Experimental and computational optimization of eco-friendly mortar blocks for high temperature thermal energy storage of concentrated solar power plants

New avenues for thermal energy storage (TES) need to be investigated due to the lack of competitiveness of concentrated solar power (CSP) technologies. Solutions must be found to replace molten salt tanks which have a major economic impact and are difficult to maintain due to corrosion problems. In this sense, concrete represented an attractive candidate by proving excellent sensible TES in CSP. However, its main phase, made of Portland cement (PC), has significant environmental consequences. The production of PC is known to emit high levels of polluting gases, particularly the CO2. It is estimated to be responsible for between 5% and 7% of the world's CO2 emissions, making it a major contributor to climate change. This work presents greener cementitious materials, made of alkaline cements and hybrids cements, to be used as alternative eco-friendly TES media in CSP plants. An experimental campaign is presented which shows that these eco-efficient materials can have better mechanical properties, than the ordinary PC mortar, when exposed to high temperatures, in addition, can offer improvements of their thermal properties (thermal conductivity or specific heat). Second part of the work is devoted to Finite Element simulations, with the aim to find the best configuration, in terms of selection of materials and geometry, which are more efficient as TES system. The work is showing the following advancements in CSP technology by using alternative eco-friendly binders: the installation volume can be reduced by 17%, compared to a molten salt tank, while the heat exchanger's surface area can be resized by 29%, compared to the reference system using PC. These improvements enable wider variations in CSP operational efficiency and dynamic capabilities and represent important progress towards developing more efficient and sustainable CSP technologies.This study was funded by MCIN/AEI/10.13039/501100011033 and Europe Union NextGenerationEU/PRTR under the National Project TED2021-130633B-I00 and under the National Project PID2021-125810OB-C22.Publicad

Impact of Previous Physical Activity Levels on Symptomatology, Functionality, and Strength during an Acute Exacerbation in COPD Patients

The main objective of this study is to determine the relationship between physical activity (PA) level prior to hospitalization and the pulmonary symptomatology, functionality, exercise capacity, and strength of acute exacerbated chronic obstructive pulmonary disease (COPD) patients. In this observational study, all data were taken during the patient’s first day in hospital. Patients were divided into two groups (a PA group, and a physical inactivity (PI) group), according to the PA level evaluated by the Baecke questionnaire. Cough status was evaluated by the Leicester Cough Questionnaire (LCQ), and dyspnea was assessed using the modified Medical Research Council dyspnea scale (mMRC). Functionality was measured by the Functional Independence Measure (FIM) and the London Chest Activity of Daily Living scale (LCADL). Exercise capacity was evaluated by the two-minute step-in-place (2MSP) test, and strength assessed by dynamometry. A total of 151 patients were included in this observational study. Patients in the PI group obtained worse results compared to the PA group, and significant differences (p < 0.05) were found in all of the variables. Those COPD patients who regularly perform PA have less dyspnea and cough, as well as better functionality, exercise capacity and strength during an exacerbation, without relationship to the severity of the pathology.The author JRT has received financial support through a FPU (“Formación Profesorado Universitario”) grant (FPU:16/01531) of the Spanish Ministry of Education. The author LLL has received financial support through a FPU grant (FPU: 17/00408) of the Spanish Ministry of Education (Spain)

Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic

[EN] The induction of senescence produces a stable cell cycle arrest in cancer cells, thereby inhibiting tumor growth; however, the incomplete immune cell-mediated clearance of senescent cells may favor tumor relapse, limiting the long-term anti-tumorigenic effect of such drugs. A combination of senescence induction and the elimination of senescent cells may, therefore, represent an efficient means to inhibit tumor relapse. In this study, we explored the antitumor efficacy of a combinatory senogenic and targeted senolytic therapy in an immunocompetent orthotopic mouse model of the aggressive triple negative breast cancer subtype. Following palbociclib-induced senogenesis and senolysis by treatment with nano-encapsulated senolytic agent navitoclax, we observed inhibited tumor growth, reduced metastases, and a reduction in the systemic toxicity of navitoclax. We believe that this combination treatment approach may have relevance to other senescence-inducing chemotherapeutic drugs and additional tumor types. Significance: While the application of senescence inducers represents a successful treatment strategy in breast cancer patients, some patients still relapse, perhaps due to the subsequent accumulation of senescent cells in the body that can promote tumor recurrence. We now demonstrate that a combination treatment of a senescence inducer and a senolytic nanoparticle selectively eliminates senescent cells, delays tumor growth, and reduces metastases in a mouse model of aggressive breast cancer. Collectively, our results support targeted senolysis as a new therapeutic opportunity to improve outcomes in breast cancer patients.The M.O. laboratory members thank the financial support from the Spanish Government (project SAF2017-84689-R (MINECO/AEI/FEDER, EU)) and the Generalitat Valenciana (project PROMETEO/2019/065). The R.M. laboratory members thank the financial support from the Spanish Government (projects RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/FEDER, EU) and the Generalitat Valenciana (project PROMETEO 2018/024). Both I.G. and B.L-T. are grateful to the Generalitat Valenciana and the Spanish Ministry of Economy, respectively, for their Ph.D. grants. I.G. would like to thank I. Borreda and J. Forteza and the Instituto Valenciano de Patologia for their special collaboration and F. Sancenon for his appreciated helpGaliana, I.; Lozano-Torres, B.; Sancho, M.; Alfonso-Navarro, M.; Bernardos Bau, A.; Bisbal, V.; Serrano, M.... (2020). Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic. Journal of Controlled Release. 323:624-634. https://doi.org/10.1016/j.jconrel.2020.04.045S624634323Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018). Hallmarks of Cellular Senescence. Trends in Cell Biology, 28(6), 436-453. doi:10.1016/j.tcb.2018.02.001Acosta, J. C., & Gil, J. (2012). Senescence: a new weapon for cancer therapy. Trends in Cell Biology, 22(4), 211-219. doi:10.1016/j.tcb.2011.11.006Sieben, C. J., Sturmlechner, I., van de Sluis, B., & van Deursen, J. M. (2018). Two-Step Senescence-Focused Cancer Therapies. Trends in Cell Biology, 28(9), 723-737. doi:10.1016/j.tcb.2018.04.006Goldman, J. W., Shi, P., Reck, M., Paz-Ares, L., Koustenis, A., & Hurt, K. C. (2016). Treatment Rationale and Study Design for the JUNIPER Study: A Randomized Phase III Study of Abemaciclib With Best Supportive Care Versus Erlotinib With Best Supportive Care in Patients With Stage IV Non–Small-Cell Lung Cancer With a Detectable KRAS Mutation Whose Disease Has Progressed After Platinum-Based Chemotherapy. Clinical Lung Cancer, 17(1), 80-84. doi:10.1016/j.cllc.2015.08.003Finn, R. S., Dering, J., Conklin, D., Kalous, O., Cohen, D. J., Desai, A. J., … Slamon, D. J. (2009). PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Research, 11(5). doi:10.1186/bcr2419Geoerger, B., Bourdeaut, F., DuBois, S. G., Fischer, M., Geller, J. I., Gottardo, N. G., … Chi, S. N. (2017). A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors. Clinical Cancer Research, 23(10), 2433-2441. doi:10.1158/1078-0432.ccr-16-2898Kwapisz, D. (2017). Cyclin-dependent kinase 4/6 inhibitors in breast cancer: palbociclib, ribociclib, and abemaciclib. Breast Cancer Research and Treatment, 166(1), 41-54. doi:10.1007/s10549-017-4385-3Pernas, S., Tolaney, S. M., Winer, E. P., & Goel, S. (2018). CDK4/6 inhibition in breast cancer: current practice and future directions. Therapeutic Advances in Medical Oncology, 10, 175883591878645. doi:10.1177/1758835918786451Sutherland, R. L., & Musgrove, E. A. (2009). CDK inhibitors as potential breast cancer therapeutics: new evidence for enhanced efficacy in ER+disease. Breast Cancer Research, 11(6). doi:10.1186/bcr2454Beaver, J. A., Amiri-Kordestani, L., Charlab, R., Chen, W., Palmby, T., Tilley, A., … Cortazar, P. (2015). FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor–Positive, HER2-Negative Metastatic Breast Cancer. Clinical Cancer Research, 21(21), 4760-4766. doi:10.1158/1078-0432.ccr-15-1185Chiu, J. W., Kwok, G., Yau, T., & Leung, R. (2017). Editorial to «Palbociclib and letrozole in advanced breast cancer». Translational Cancer Research, 6(S2), S376-S379. doi:10.21037/tcr.2017.03.21Traina, T., Cadoo, K., & Gucalp, A. (2014). Palbociclib: an evidence-based review of its potential in the treatment of breast cancer. Breast Cancer: Targets and Therapy, 123. doi:10.2147/bctt.s46725Turner, N. C., Ro, J., André, F., Loi, S., Verma, S., Iwata, H., … Cristofanilli, M. (2015). Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer. New England Journal of Medicine, 373(3), 209-219. doi:10.1056/nejmoa1505270Cristofanilli, M., Turner, N. C., Bondarenko, I., Ro, J., Im, S.-A., Masuda, N., … Slamon, D. (2016). Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. The Lancet Oncology, 17(4), 425-439. doi:10.1016/s1470-2045(15)00613-0Lee, S., & Schmitt, C. A. (2019). The dynamic nature of senescence in cancer. Nature Cell Biology, 21(1), 94-101. doi:10.1038/s41556-018-0249-2Giaimo, S., & d’ Adda di Fagagna, F. (2012). Is cellular senescence an example of antagonistic pleiotropy? Aging Cell, 11(3), 378-383. doi:10.1111/j.1474-9726.2012.00807.xMuñoz-Espín, D., & Serrano, M. (2014). Cellular senescence: from physiology to pathology. Nature Reviews Molecular Cell Biology, 15(7), 482-496. doi:10.1038/nrm3823Rodier, F., & Campisi, J. (2011). Four faces of cellular senescence. Journal of Cell Biology, 192(4), 547-556. doi:10.1083/jcb.201009094He, S., & Sharpless, N. E. (2017). Senescence in Health and Disease. Cell, 169(6), 1000-1011. doi:10.1016/j.cell.2017.05.015McHugh, D., & Gil, J. (2017). Senescence and aging: Causes, consequences, and therapeutic avenues. Journal of Cell Biology, 217(1), 65-77. doi:10.1083/jcb.201708092Ewald, J. A., Desotelle, J. A., Wilding, G., & Jarrard, D. F. (2010). Therapy-Induced Senescence in Cancer. JNCI: Journal of the National Cancer Institute, 102(20), 1536-1546. doi:10.1093/jnci/djq364Gordon, R. R., & Nelson, P. S. (2012). Cellular senescence and cancer chemotherapy resistance. Drug Resistance Updates, 15(1-2), 123-131. doi:10.1016/j.drup.2012.01.002Wieland, E., Rodriguez-Vita, J., Liebler, S. S., Mogler, C., Moll, I., Herberich, S. E., … Fischer, A. (2017). Endothelial Notch1 Activity Facilitates Metastasis. Cancer Cell, 31(3), 355-367. doi:10.1016/j.ccell.2017.01.007Milanovic, M., Fan, D. N. Y., Belenki, D., Däbritz, J. H. M., Zhao, Z., Yu, Y., … Schmitt, C. A. (2017). Senescence-associated reprogramming promotes cancer stemness. Nature, 553(7686), 96-100. doi:10.1038/nature25167Parrinello, S., Coppe, J.-P., Krtolica, A., & Campisi, J. (2005). Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. Journal of Cell Science, 118(3), 485-496. doi:10.1242/jcs.01635Kirkland, J. L., Tchkonia, T., Zhu, Y., Niedernhofer, L. J., & Robbins, P. D. (2017). The Clinical Potential of Senolytic Drugs. Journal of the American Geriatrics Society, 65(10), 2297-2301. doi:10.1111/jgs.14969Childs, B. G., Gluscevic, M., Baker, D. J., Laberge, R.-M., Marquess, D., Dananberg, J., & van Deursen, J. M. (2017). Senescent cells: an emerging target for diseases of ageing. Nature Reviews Drug Discovery, 16(10), 718-735. doi:10.1038/nrd.2017.116Lozano-Torres, B., Estepa-Fernández, A., Rovira, M., Orzáez, M., Serrano, M., Martínez-Máñez, R., & Sancenón, F. (2019). The chemistry of senescence. Nature Reviews Chemistry, 3(7), 426-441. doi:10.1038/s41570-019-0108-0Zhu, Y., Tchkonia, T., Fuhrmann‐Stroissnigg, H., Dai, H. M., Ling, Y. Y., Stout, M. B., … Kirkland, J. L. (2016). Identification of a novel senolytic agent, navitoclax, targeting the Bcl‐2 family of anti‐apoptotic factors. Aging Cell, 15(3), 428-435. doi:10.1111/acel.12445Baar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., … de Keizer, P. L. J. (2017). Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging. Cell, 169(1), 132-147.e16. doi:10.1016/j.cell.2017.02.031Zhu, Y., Tchkonia, T., Pirtskhalava, T., Gower, A. C., Ding, H., Giorgadze, N., … Kirkland, J. L. (2015). The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell, 14(4), 644-658. doi:10.1111/acel.12344Chang, J., Wang, Y., Shao, L., Laberge, R.-M., Demaria, M., Campisi, J., … Zhou, D. (2015). Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nature Medicine, 22(1), 78-83. doi:10.1038/nm.4010Kile, B. T. (2014). The role of apoptosis in megakaryocytes and platelets. British Journal of Haematology, 165(2), 217-226. doi:10.1111/bjh.12757Aznar, E., Oroval, M., Pascual, L., Murguía, J. R., Martínez-Máñez, R., & Sancenón, F. (2016). Gated Materials for On-Command Release of Guest Molecules. Chemical Reviews, 116(2), 561-718. doi:10.1021/acs.chemrev.5b00456Llopis-Lorente, A., Lozano-Torres, B., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2017). Mesoporous silica materials for controlled delivery based on enzymes. Journal of Materials Chemistry B, 5(17), 3069-3083. doi:10.1039/c7tb00348jSu, Y.-L., & Hu, S.-H. (2018). Functional Nanoparticles for Tumor Penetration of Therapeutics. Pharmaceutics, 10(4), 193. doi:10.3390/pharmaceutics10040193Giménez, C., de la Torre, C., Gorbe, M., Aznar, E., Sancenón, F., Murguía, J. R., … Amorós, P. (2015). Gated Mesoporous Silica Nanoparticles for the Controlled Delivery of Drugs in Cancer Cells. Langmuir, 31(12), 3753-3762. doi:10.1021/acs.langmuir.5b00139Agostini, A., Mondragón, L., Bernardos, A., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., … Murguía, J. R. (2012). Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 51(42), 10556-10560. doi:10.1002/anie.201204663Bernardos, A., Mondragón, L., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., … Amorós, P. (2010). Enzyme-Responsive Intracellular Controlled Release Using Nanometric Silica Mesoporous Supports Capped with «Saccharides». ACS Nano, 4(11), 6353-6368. doi:10.1021/nn101499dKaur, P., Nagaraja, G. M., Zheng, H., Gizachew, D., Galukande, M., Krishnan, S., & Asea, A. (2012). A mouse model for triple-negative breast cancer tumor-initiating cells (TNBC-TICs) exhibits similar aggressive phenotype to the human disease. BMC Cancer, 12(1). doi:10.1186/1471-2407-12-120Foulkes, W. D., Smith, I. E., & Reis-Filho, J. S. (2010). Triple-Negative Breast Cancer. New England Journal of Medicine, 363(20), 1938-1948. doi:10.1056/nejmra1001389Collado, M., & Serrano, M. (2010). Senescence in tumours: evidence from mice and humans. Nature Reviews Cancer, 10(1), 51-57. doi:10.1038/nrc2772Goel, S., DeCristo, M. J., Watt, A. C., BrinJones, H., Sceneay, J., Li, B. B., … Zhao, J. J. (2017). CDK4/6 inhibition triggers anti-tumour immunity. Nature, 548(7668), 471-475. doi:10.1038/nature23465Asghar, U. S., Barr, A. R., Cutts, R., Beaney, M., Babina, I., Sampath, D., … Turner, N. C. (2017). Single-Cell Dynamics Determines Response to CDK4/6 Inhibition in Triple-Negative Breast Cancer. Clinical Cancer Research, 23(18), 5561-5572. doi:10.1158/1078-0432.ccr-17-0369Lee, B. Y., Han, J. A., Im, J. S., Morrone, A., Johung, K., Goodwin, E. C., … Hwang, E. S. (2006). Senescence-associated β-galactosidase is lysosomal β-galactosidase. Aging Cell, 5(2), 187-195. doi:10.1111/j.1474-9726.2006.00199.xPotter, D. S., & Letai, A. (2016). To Prime, or Not to Prime: That Is the Question. Cold Spring Harbor Symposia on Quantitative Biology, 81, 131-140. doi:10.1101/sqb.2016.81.030841Billard, C. (2013). BH3 Mimetics: Status of the Field and New Developments. Molecular Cancer Therapeutics, 12(9), 1691-1700. doi:10.1158/1535-7163.mct-13-0058Reers, M., Smiley, S. T., Mottola-Hartshorn, C., Chen, A., Lin, M., & Chen, L. B. (1995). [29] Mitochondrial membrane potential monitored by JC-1 dye. Mitochondrial Biogenesis and Genetics Part A, 406-417. doi:10.1016/0076-6879(95)60154-6Sugrue, M. M., Wang, Y., Rideout, H. J., Chalmers-Redman, R. M. E., & Tatton, W. G. (1999). Reduced Mitochondrial Membrane Potential and Altered Responsiveness of a Mitochondrial Membrane Megachannel in p53-Induced Senescence. Biochemical and Biophysical Research Communications, 261(1), 123-130. doi:10.1006/bbrc.1999.0984Wang, D., Liu, Y., Zhang, R., Zhang, F., Sui, W., Chen, L., … Ji, J. (2016). Apoptotic transition of senescent cells accompanied with mitochondrial hyper-function. Oncotarget, 7(19), 28286-28300. doi:10.18632/oncotarget.8536Collado, M., Gil, J., Efeyan, A., Guerra, C., Schuhmacher, A. J., Barradas, M., … Serrano, M. (2005). Senescence in premalignant tumours. Nature, 436(7051), 642-642. doi:10.1038/436642aBaker, D. J., Wijshake, T., Tchkonia, T., LeBrasseur, N. K., Childs, B. G., van de Sluis, B., … van Deursen, J. M. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 479(7372), 232-236. doi:10.1038/nature10600Jaskelioff, M., Muller, F. L., Paik, J.-H., Thomas, E., Jiang, S., Adams, A. C., … DePinho, R. A. (2010). Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature, 469(7328), 102-106. doi:10.1038/nature09603Lehmann, M., Korfei, M., Mutze, K., Klee, S., Skronska-Wasek, W., Alsafadi, H. N., … Königshoff, M. (2017). Senolytic drugs target alveolar epithelial cell function and attenuate experimental lung fibrosisex vivo. European Respiratory Journal, 50(2), 1602367. doi:10.1183/13993003.02367-2016Schafer, M. J., White, T. A., Iijima, K., Haak, A. J., Ligresti, G., Atkinson, E. J., … LeBrasseur, N. K. (2017). Cellular senescence mediates fibrotic pulmonary disease. Nature Communications, 8(1). doi:10.1038/ncomms14532Hecker, L., Logsdon, N. J., Kurundkar, D., Kurundkar, A., Bernard, K., Hock, T., … Thannickal, V. J. (2014). Reversal of Persistent Fibrosis in Aging by Targeting Nox4-Nrf2 Redox Imbalance. Science Translational Medicine, 6(231). doi:10.1126/scitranslmed.3008182Sanders, Y. Y., Liu, H., Liu, G., & Thannickal, V. J. (2015). Epigenetic mechanisms regulate NADPH oxidase-4 expression in cellular senescence. Free Radical Biology and Medicine, 79, 197-205. doi:10.1016/j.freeradbiomed.2014.12.008Soto-Gamez, A., & Demaria, M. (2017). Therapeutic interventions for aging: the case of cellular senescence. Drug Discovery Today, 22(5), 786-795. doi:10.1016/j.drudis.2017.01.004Burd, C. E., Sorrentino, J. A., Clark, K. S., Darr, D. B., Krishnamurthy, J., Deal, A. M., … Sharpless, N. E. (2013). Monitoring Tumorigenesis and Senescence In Vivo with a p16INK4a-Luciferase Model. Cell, 152(1-2), 340-351. doi:10.1016/j.cell.2012.12.010Correia-Melo, C., & Passos, J. F. (2015). Mitochondria: Are they causal players in cellular senescence? Biochimica et Biophysica Acta (BBA) - Bioenergetics, 1847(11), 1373-1379. doi:10.1016/j.bbabio.2015.05.01

Effectiveness of salivary stimulation using xylitol-malic acid tablets as coadjuvant treatment in patients with gastro-oesophageal reflux disease : early findings

Besides dental erosion syndrome, other oral syndromes could benefit from the stimulation of salivary secretion, in patients with gastro-oesophageal reflux disease (GORD). Our aims is evaluate the improvement of oral extra-oesophageal manifestations in patients with GORD using xylitol?malic acid tablets to stimulate salivary secretion. The effectiveness of salivary stimulation using xylitol?malic acid tablets (as a supplement to omeprazole 40 mg/day) was assessed in a clinical trial (n = 14) lasting six months with patients with prior positive pH-metry, through GORD extra-oesophageal clinical signs, GerdQ and RDQ questionnaires, odontological variables, basal salivary secretion, stimulated salivary secretion, pH and buffer capacity, mucosal erythema index and dental wear. Statistics: chi-square (Haberman post-hoc), ANOVA, and Mann-Whitney U; variables between visits were evaluated with McNemar?s Student?s t and Wilcoxon tests; p < 0.05. 100% of patients not taking xylitol?malic acid presented xerostomia, but only 14.3% of patients taking xylitol?malic acid (p < 0.01) did. The mean saliva-buffer capacity at the last visit for patients not taking xylitol?malic acid was 2.14 ± 0.38, versus 2.71 ± 0.49 for patients taking xylitol?malic acid (p < 0.05). Retro-sternal burning (p < 0.05), heartburn (p < 0.05) and regurgitation (p < 0.05) were also reduced. Xylitol?malic acid tablets improve quality of life among patients with GORD, by reducing dry mouth, increasing saliva buffering and reducing heartburn, retro-sternal burning and regurgitation

Real-Time In Vivo Detection of Cellular Senescence through the Controlled Release of the NIR Fluorescent Dye Nile Blue

This is the peer reviewed version of the following article: B. Lozano-Torres, J. F. Blandez, I. Galiana, A. García-Fernández, M. Alfonso, M. D. Marcos, M. Orzáez, F. Sancenón, R. Martínez-Máñez, Angew. Chem. Int. Ed. 2020, 59, 15152., which has been published in final form at https://doi.org/10.1002/anie.202004142. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] In vivo detection of cellular senescence is accomplished by using mesoporous silica nanoparticles loaded with the NIR-FDA approved Nile blue (NB) dye and capped with a galactohexasaccharide (S3). NB emission at 672 nm is highly quenched inside S3, yet a remarkable emission enhancement is observed upon cap hydrolysis in the presence of beta-galactosidase and dye release. The efficacy of the probe to detect cellular senescence is tested in vitro in melanoma SK-Mel-103 and breast cancer 4T1 cells and in vivo in palbociclib-treated BALB/cByJ mice bearing breast cancer tumor.R.M. thanks financial support from the Spanish Government (RTI2018-100910-B-C41 and RTI2018-101599-B-C22 (MCUI/AEI/FEDER, UE)) and the Generalitat Valenciana (PROMETEO 2018/024). M.O. thanks the financial support from SAF2017-84689-R project and MINECO/AEI/FEDER, UE and the Generalitat Valenciana (PROMETEO/2019/065). B.L.-T. is grateful to the Spanish Ministry of Economy for her PhD grant. I.G. thanks her contract from IDM. J.F.-B. and M.A. thank the UPV for their postdoctoral fellowship.Lozano-Torres, B.; Blandez, JF.; Galiana, I.; García-Fernández, A.; Alfonso-Navarro, M.; Marcos Martínez, MD.; Orzáez, M.... (2020). Real-Time In Vivo Detection of Cellular Senescence through the Controlled Release of the NIR Fluorescent Dye Nile Blue. Angewandte Chemie International Edition. 59(35):15152-15156. https://doi.org/10.1002/anie.202004142S15152151565935He, S., & Sharpless, N. E. (2017). Senescence in Health and Disease. Cell, 169(6), 1000-1011. doi:10.1016/j.cell.2017.05.015Lozano-Torres, B., Estepa-Fernández, A., Rovira, M., Orzáez, M., Serrano, M., Martínez-Máñez, R., & Sancenón, F. (2019). The chemistry of senescence. Nature Reviews Chemistry, 3(7), 426-441. doi:10.1038/s41570-019-0108-0Muñoz-Espín, D., & Serrano, M. (2014). Cellular senescence: from physiology to pathology. Nature Reviews Molecular Cell Biology, 15(7), 482-496. doi:10.1038/nrm3823Hernandez-Segura, A., Nehme, J., & Demaria, M. (2018). Hallmarks of Cellular Senescence. Trends in Cell Biology, 28(6), 436-453. doi:10.1016/j.tcb.2018.02.001Baker, D. J., Childs, B. G., Durik, M., Wijers, M. E., Sieben, C. J., Zhong, J., … van Deursen, J. M. (2016). Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature, 530(7589), 184-189. doi:10.1038/nature16932Soto-Gamez, A., & Demaria, M. (2017). Therapeutic interventions for aging: the case of cellular senescence. Drug Discovery Today, 22(5), 786-795. doi:10.1016/j.drudis.2017.01.004Kirkland, J. L., Tchkonia, T., Zhu, Y., Niedernhofer, L. J., & Robbins, P. D. (2017). The Clinical Potential of Senolytic Drugs. Journal of the American Geriatrics Society, 65(10), 2297-2301. doi:10.1111/jgs.14969Niedernhofer, L. J., & Robbins, P. D. (2018). Senotherapeutics for healthy ageing. Nature Reviews Drug Discovery, 17(5), 377-377. doi:10.1038/nrd.2018.44Hayflick, L., & Moorhead, P. S. (1961). The serial cultivation of human diploid cell strains. Experimental Cell Research, 25(3), 585-621. doi:10.1016/0014-4827(61)90192-6Zhang, R., & Adams, P. D. (2007). Heterochromatin and its Relationship to Cell Senescence and Cancer Therapy. Cell Cycle, 6(7), 784-789. doi:10.4161/cc.6.7.4079Campisi, J. (2005). Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors. Cell, 120(4), 513-522. doi:10.1016/j.cell.2005.02.003Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., … Pereira-Smith, O. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proceedings of the National Academy of Sciences, 92(20), 9363-9367. doi:10.1073/pnas.92.20.9363Lozano-Torres, B., Galiana, I., Rovira, M., Garrido, E., Chaib, S., Bernardos, A., … Sancenón, F. (2017). An OFF–ON Two-Photon Fluorescent Probe for Tracking Cell Senescence in Vivo. Journal of the American Chemical Society, 139(26), 8808-8811. doi:10.1021/jacs.7b04985Asanuma, D., Sakabe, M., Kamiya, M., Yamamoto, K., Hiratake, J., Ogawa, M., … Urano, Y. (2015). Sensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo. Nature Communications, 6(1). doi:10.1038/ncomms7463Muñoz-Espín, D. (2019). Nanocarriers targeting senescent cells. Translational Medicine of Aging, 3, 1-5. doi:10.1016/j.tma.2019.01.001Ekpenyong-Akiba, A. E., Canfarotta, F., Abd H., B., Poblocka, M., Casulleras, M., Castilla-Vallmanya, L., … Macip, S. (2019). Detecting and targeting senescent cells using molecularly imprinted nanoparticles. Nanoscale Horizons, 4(3), 757-768. doi:10.1039/c8nh00473kAlberti, S., Soler-Illia, G. J. A. A., & Azzaroni, O. (2015). Gated supramolecular chemistry in hybrid mesoporous silica nanoarchitectures: controlled delivery and molecular transport in response to chemical, physical and biological stimuli. Chemical Communications, 51(28), 6050-6075. doi:10.1039/c4cc10414eDe la Torre, C., Casanova, I., Acosta, G., Coll, C., Moreno, M. J., Albericio, F., … Martínez-Máñez, R. (2014). Gated Mesoporous Silica Nanoparticles Using a Double-Role Circular Peptide for the Controlled and Target-Preferential Release of Doxorubicin in CXCR4-Expresing Lymphoma Cells. Advanced Functional Materials, 25(5), 687-695. doi:10.1002/adfm.201403822Bernardos, A., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Amorós, P. (2009). Enzyme-Responsive Controlled Release Using Mesoporous Silica Supports Capped with Lactose. Angewandte Chemie International Edition, 48(32), 5884-5887. doi:10.1002/anie.200900880Bernardos, A., Aznar, E., Marcos, M. D., Martínez-Máñez, R., Sancenón, F., Soto, J., … Amorós, P. (2009). Enzyme-Responsive Controlled Release Using Mesoporous Silica Supports Capped with Lactose. Angewandte Chemie, 121(32), 5998-6001. doi:10.1002/ange.200900880Agostini, A., Mondragón, L., Bernardos, A., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., … Murguía, J. R. (2012). Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles. Angewandte Chemie International Edition, 51(42), 10556-10560. doi:10.1002/anie.201204663Agostini, A., Mondragón, L., Bernardos, A., Martínez-Máñez, R., Marcos, M. D., Sancenón, F., … Murguía, J. R. (2012). Targeted Cargo Delivery in Senescent Cells Using Capped Mesoporous Silica Nanoparticles. Angewandte Chemie, 124(42), 10708-10712. doi:10.1002/ange.201204663Muñoz‐Espín, D., Rovira, M., Galiana, I., Giménez, C., Lozano‐Torres, B., Paez‐Ribes, M., … Serrano, M. (2018). A versatile drug delivery system targeting senescent cells. EMBO Molecular Medicine, 10(9). doi:10.15252/emmm.201809355Mérian, J., Gravier, J., Navarro, F., & Texier, I. (2012). Fluorescent Nanoprobes Dedicated to in Vivo Imaging: From Preclinical Validations to Clinical Translation. Molecules, 17(5), 5564-5591. doi:10.3390/molecules17055564Fu, W., Yan, C., Guo, Z., Zhang, J., Zhang, H., Tian, H., & Zhu, W.-H. (2019). Rational Design of Near-Infrared Aggregation-Induced-Emission-Active Probes: In Situ Mapping of Amyloid-β Plaques with Ultrasensitivity and High-Fidelity. Journal of the American Chemical Society, 141(7), 3171-3177. doi:10.1021/jacs.8b12820Ovchinnikov, O. V., Evtukhova, A. V., Kondratenko, T. S., Smirnov, M. S., Khokhlov, V. Y., & Erina, O. V. (2016). Manifestation of intermolecular interactions in FTIR spectra of methylene blue molecules. Vibrational Spectroscopy, 86, 181-189. doi:10.1016/j.vibspec.2016.06.016Aznar, E., Oroval, M., Pascual, L., Murguía, J. R., Martínez-Máñez, R., & Sancenón, F. (2016). Gated Materials for On-Command Release of Guest Molecules. Chemical Reviews, 116(2), 561-718. doi:10.1021/acs.chemrev.5b00456Llopis-Lorente, A., Lozano-Torres, B., Bernardos, A., Martínez-Máñez, R., & Sancenón, F. (2017). Mesoporous silica materials for controlled delivery based on enzymes. Journal of Materials Chemistry B, 5(17), 3069-3083. doi:10.1039/c7tb00348jGarcía‐Fernández, A., Aznar, E., Martínez‐Máñez, R., & Sancenón, F. (2019). New Advances in In Vivo Applications of Gated Mesoporous Silica as Drug Delivery Nanocarriers. Small, 16(3), 1902242. doi:10.1002/smll.201902242Kozlovskaya, V., Xue, B., & Kharlampieva, E. (2016). Shape-Adaptable Polymeric Particles for Controlled Delivery. Macromolecules, 49(22), 8373-8386. doi:10.1021/acs.macromol.6b01740Mishra, D. K., Shandilya, R., & Mishra, P. K. (2018). Lipid based nanocarriers: a translational perspective. Nanomedicine: Nanotechnology, Biology and Medicine, 14(7), 2023-2050. doi:10.1016/j.nano.2018.05.021Seidi, F., Jenjob, R., Phakkeeree, T., & Crespy, D. (2018). Saccharides, oligosaccharides, and polysaccharides nanoparticles for biomedical applications. Journal of Controlled Release, 284, 188-212. doi:10.1016/j.jconrel.2018.06.026Chen, W., Zhou, S., Ge, L., Wu, W., & Jiang, X. (2018). Translatable High Drug Loading Drug Delivery Systems Based on Biocompatible Polymer Nanocarriers. Biomacromolecules, 19(6), 1732-1745. doi:10.1021/acs.biomac.8b00218Vázquez-González, M., & Willner, I. (2018). DNA-Responsive SiO2 Nanoparticles, Metal–Organic Frameworks, and Microcapsules for Controlled Drug Release. Langmuir, 34(49), 14692-14710. doi:10.1021/acs.langmuir.8b00478Farid, R. M., Youssef, N. A. H. A., & Kassem, A. A. (2018). Platform for Lipid Based Nanocarriers’ Formulation Components and their Potential Effects: A Literature Review. Current Pharmaceutical Design, 23(43), 6613-6629. doi:10.2174/1381612824666171128104814Lombardo, D., Calandra, P., Barreca, D., Magazù, S., & Kiselev, M. (2016). Soft Interaction in Liposome Nanocarriers for Therapeutic Drug Delivery. Nanomaterials, 6(7), 125. doi:10.3390/nano6070125Bansal, A., & Zhang, Y. (2014). Photocontrolled Nanoparticle Delivery Systems for Biomedical Applications. Accounts of Chemical Research, 47(10), 3052-3060. doi:10.1021/ar500217wKamaly, N., Yameen, B., Wu, J., & Farokhzad, O. C. (2016). Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release. Chemical Reviews, 116(4), 2602-2663. doi:10.1021/acs.chemrev.5b00346Trewyn, B. G., Slowing, I. I., Giri, S., Chen, H.-T., & Lin, V. S.-Y. (2007). Synthesis and Functionalization of a Mesoporous Silica Nanoparticle Based on the Sol–Gel Process and Applications in Controlled Release. Accounts of Chemical Research, 40(9), 846-853. doi:10.1021/ar600032

The effect of mechanochemistry on the preparation of heterogeneous catalysts: Reduction of furfural to obtain furfuryl alcohol.

In this context, mechanochemistry is receiving increasing attention for the synthesis of many chemical compounds in the solid state, considered by IUPAC as one of the 10 methodologies to change the world.Mechanochemistry is the part of chemistry that uses mechanical energy for the transformation of matter. This methodology will be used to study the effect caused by mechanochemistry in the precursor (Mg(OH)2), which is activated at 450 º C to obtain the active phase (MgO). This phase displays Lewis basic sites, which catalyzes the hydrogenation reaction of furfural to furfuryl alcohol. This catalyst will be used in the reduction of furfural to furfuryl alcohol (FFA) using isopropanol as hydrogen donor agent and dissolution medium.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Hidrocalumita: preparación por el método mecanoquímico y su aplicacion en la isomerización de glucosa a fructosa.

La fructosa es la llave para la formación de diversas moléculas plataformas tales como, furfural, 5-hidroximetilfurfural (HMF), acido levulinico, ácido fórmico y acido láctico. Actualmente en la industria se utilizan mayormente enzimas debido a los mejores resultados de selectividad y rendimiento del proceso de glucosa a fructosa. Es por este motivo que la búsqueda de catalizadores heterogéneos, que no necesiten condiciones de reacción tan singulares, hace que sea un amplio campo de investigación dentro de la catálisis.DEASYL SA Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A Two-Photon Probe Based on Naphthalimide-Styrene Fluorophore for the In Vivo Tracking of Cellular Senescence

Cellular senescence is a state of stable cell cycle arrest that can negatively affect the regenerative capacities of tissues and can contribute to inflammation and the progression of various aging-related diseases. Advances in the in vivo detection of cellular senescence are still crucial to monitor the action of senolytic drugs and to assess the early onset or accumulation of senescent cells. Here, we describe a naphthalimide-styrene-based probe (HeckGal) for the detection of cellular senescence both in vitro and in vivo. HeckGal is hydrolyzed by the increased lysosomal β-galactosidase activity of senescent cells, resulting in fluorescence emission. The probe was validated in vitro using normal human fibroblasts and various cancer cell lines undergoing senescence induced by different stress stimuli. Remarkably, HeckGal was also validated in vivo in an orthotopic breast cancer mouse model treated with senescence-inducing chemotherapy and in a renal fibrosis mouse model. In all cases, HeckGal allowed the unambiguous detection of senescence in vitro as well as in tissues and tumors in vivo. This work is expected to provide a potential technology for senescence detection in aged or damaged tissues

The OTELO survey. A case study of [O III]4959,5007 emitters at <z> = 0.83

The OTELO survey is a very deep, blind exploration of a selected region of the Extended Groth Strip and is designed for finding emission-line sources (ELSs). The survey design, observations, data reduction, astrometry, and photometry, as well as the correlation with ancillary data used to obtain a final catalogue, including photo-z estimates and a preliminary selection of ELS, were described in a previous contribution. Here, we aim to determine the main properties and luminosity function (LF) of the [O III] ELS sample of OTELO as a scientific demonstration of its capabilities, advantages, and complementarity with respect to other surveys. The selection and analysis procedures of ELS candidates obtained using tunable filter (TF) pseudo-spectra are described. We performed simulations in the parameter space of the survey to obtain emission-line detection probabilities. Relevant characteristics of [O III] emitters and the LF([O III]), including the main selection biases and uncertainties, are presented. A total of 184 sources were confirmed as [O III] emitters at a mean redshift z=0.83. The minimum detectable line flux and equivalent width (EW) in this ELS sample are $\sim$5 $\times$ 10$^{-19}$ erg s$^{-1}$ cm$^{2}$ and $\sim$6 \AA, respectively. We are able to constrain the faint-end slope ($\alpha = -1.03\pm0.08$) of the observed LF([O III]) at z=0.83. This LF reaches values that are approximately ten times lower than those from other surveys. The vast majority (84\%) of the morphologically classified [O III] ELSs are disc-like sources, and 87\% of this sample is comprised of galaxies with stellar masses of M$_\star$ $<$ 10$^{10}$ M$_{\odot}$.Comment: v1: 16 pages, 6 figures. Accepted in Astronomy \& Astrophysics. v2: Author added in metadat