Preparation of highly active phosphated TiO2 catalysts via continuous sol–gel synthesis in a microreactor

Microreactors, featuring μm-sized tubes, offer greater flexibility and precise control of chemical processes compared to conventional large-scale reactors, due to their elevated surface-to-volume ratio and modular construction. However, their application in catalyst production has been largely neglected. Herein, we present the development of a microreactor process for the one-step sol–gel preparation of phosphated TiO2 – a catalyst which has been recently demonstrated to be an eco-friendly material for the selective synthesis of the platform chemical 5-hydroxymethylfurfural (5-HMF) from bio-derived glucose. In order to establish catalyst preparation–property–performance relationships, 18 samples were prepared according to a D-optimal experimental plan with a central point. The key properties of these samples (porosity, crystallite size, mole bulk fraction of P) were correlated, using quadratic and interaction models, with the catalytic performance (conversion, selectivity, reaction rate) of 5-HMF synthesis as a test reaction. The optimal calculated catalyst features were set as target parameters to optimise catalyst synthesis applying quadratic correlation functions. An optimal catalyst was obtained, validating the models employed, with a yield of almost 100% and a space–time yield of ca. 3 orders of magnitude higher than that of a conventional batch process. The high yield could be mainly attributed to the optimal hydrolysis ratio and temperature. Controlling the TiO2 crystallite size and surface acidity in conjunction with fine-tuning of the porous properties in the microreactor led to increased glucose conversion, surface based formation rates of 5-HMF, and selectivity towards 5-HMF of the optimal catalyst in relation to the batch-prepared material

W, Z and photon production in CMS

The production of electroweak bosons (photons, W and Z particles) in PbPb and pp collisions at sqrt(s) = 2.76 TeV per interacting nucleon pair has been measured with the CMS detector at the LHC. Direct photon production is studied using samples of isolated photons. W and Z bosons are reconstructed through their leptonic decay into muons. Their production rate in PbPb data is studied as a function of the centrality of the collision and compared to that in pp interactions, once normalized by the number of binary nucleon-nucleon interactions. The results are also compared to next-to-leading-order perturbative QCD calculations.Comment: Proceedings from Plenary Talk at 5th International Conference on Hard and Electromagnetic Probes of High-Energy Nuclear Collisions (Hard Probes 2012) at Cagliari (Italia

Metformin and Breast Cancer: Where Are We Now?

Breast cancer is the most prevalent cancer and the leading cause of cancer-related death among women worldwide. Type 2 diabetes-associated metabolic traits such as hyperglycemia, hyperinsulinemia, inflammation, oxidative stress, and obesity are well-known risk factors for breast cancer. The insulin sensitizer metformin, one of the most prescribed oral antidiabetic drugs, has been suggested to function as an antitumoral agent, based on epidemiological and retrospective clinical data as well as preclinical studies showing an antiproliferative effect in cultured breast cancer cells and animal models. These benefits provided a strong rationale to study the effects of metformin in routine clinical care of breast cancer patients. However, the initial enthusiasm was tempered after disappointing results in randomized controlled trials, particularly in the metastatic setting. Here, we revisit the current state of the art of metformin mechanisms of action, critically review past and current metformin-based clinical trials, and briefly discuss future perspectives on how to incorporate metformin into the oncologist's armamentarium for the prevention and treatment of breast cancer

Active Rho is localized to podosomes induced by oncogenic Src and is required for their assembly and function

Transformation of fibroblasts by oncogenic Src causes disruption of actin stress fibers and formation of invasive adhesions called podosomes. Because the small GTPase Rho stimulates stress fiber formation, Rho inactivation by Src has been thought to be necessary for stress fiber disruption. However, we show here that Rho[GTP] levels do not decrease after transformation by activated Src. Inactivation of Rho in Src-transformed fibroblasts by dominant negative RhoA or the Rho-specific inhibitor C3 exoenzyme disrupted podosome structure as judged by localization of podosome components F-actin, cortactin, and Fish. Inhibition of Rho strongly inhibited Src-induced proteolytic degradation of the extracellular matrix. Furthermore, development of an in situ Rho[GTP] affinity assay allowed us to detect endogenous Rho[GTP] at podosomes, where it colocalized with F-actin, cortactin, and Fish. Therefore, Rho is not globally inactivated in Src-transformed fibroblasts, but is necessary for the assembly and function of structures implicated in tumor cell invasion

Different typologies of alcohol consumers in the practice of «botellon» in three Spanish cities

In this work, 6,009 youngsters (14-25 years old) who practice the «botellon» were interviewed in three cities of the Valencian Community. After a stratifi ed sampling among college and noncollege students, a two-step cluster analysis was carried out for each sample with two aims: to identify different types of alcohol consumers in the practice of the «botellon» and to carry out a crossed validation of the results obtained. The variables included in the analysis were the following: gender, age group (university students: U; adolescent students: ES), performance of intensive episodes of consumption (yes/no), number of years practicing the «botellon» and grams of alcohol ingested. The results show the validity of the structure obtained for youngsters, revealing intensive episodes of alcohol consumption, as a fourgroup structure appeared in all three samples (male U, male ES, female U, female ES), in which men were always at the top of alcohol ingestion. Furthermore, ES consumed the same amount of alcohol as U, even though they had been consuming for less time. However, the youngsters who did not report intensive episodes of alcohol consumption showed some structure variability, with a tendency among women to match men’s levels of alcohol consumptionEn este trabajo se entrevistó a 6.009 jóvenes que practican botellón (14-25 años) en tres ciudades de la Comunidad Valenciana, realizando un muestreo estratifi cado de centros de Secundaria, Bachiller, CF y Universidad. Se efectuó un análisis de conglomerados en dos fases con cada muestra con dos objetivos: identifi car tipologías de consumidores de alcohol en el botellón y realizar una validación cruzada de la solución obtenida. Las variables consideradas en los análisis fueron: sexo, grupo de edad (universitarios: U; estudiantes Secundaria: ES), realización o no de episodios intensivos de consumo, años practicando botellón y gramos de alcohol ingeridos. Los resultados muestran evidencia de validez de la estructura obtenida para los jóvenes que realizan episodios intensivos de consumo de alcohol, ya que aparece una estructura de cuatro grupos en las tres muestras (varones U, varones ES, mujeres U, mujeres ES), siendo siempre los varones quienes más consumen. Además, los ES consumen iguales cantidades de alcohol que los U, aunque llevan menos años consumiendo. Por su parte, entre los jóvenes que no realizan episodios intensivos de consumo de alcohol se observa cierta variabilidad en la estructura, siendo manifi esta la tendencia de las mujeres a igualar su consumo con el de los varone

Epidemiology, mortality, and health service use of local-level multimorbidity patterns in South Spain

Multimorbidity –understood as the occurrence of chronic diseases together–represents a major challenge for healthcare systems due to its impact on disability, quality of life, increased use of services and mortality. However, despite the global need to address this health problem, evidence is still needed to advance our understanding of its clinical and social implications. Our study aims to characterisemultimorbidity patterns in a dataset of 1,375,068 patients residing in southern Spain. Combining LCA techniques and geographic information, together with service use, mortality, and socioeconomic data, 25 chronicity profiles were identified and subsequently characterised by sex and age. The present study has led us to several findings that take a step forward in this field of knowledge. Specifically, we contribute to the identification of an extensive range of at-risk groups. Moreover, our study reveals that the complexity of multimorbidity patterns escalates at a faster rate and is associated with a poorer prognosis in local areas characterised by lower socioeconomic status. These results emphasize the persistence of social inequalities in multimorbidity, highlighting the need for targeted interventions to mitigate the impact on patients’ quality of life, healthcare utilisation, and mortality rates.University Research Institute for Sustainable Social DevelopmentBiomedical Research and Innovation Institute of Cadiz (INiBICA)University of CadizRamon y Cajal programme run by the Spanish Ministry of Science and InnovationPublic funds by the ITI call (Integrated Territorial Investment), developed by the Health Department of the Andalusian Government (ITI-0028-2019)DEMMOCAD project has been 80% co-financed by funds from the European Regional Development Fund (ERDF) operational programme of Andalusia 2014–2020INDESS (Instituto Universitario de Investigación para el Desarrollo Social Sostenible)University of Cadiz, Jerez de la Frontera, Spai

Metformin-induced preferential killing of breast cancer initiating CD44+CD24−/low cells is sufficient to overcome primary resistance to trastuzumab in HER2+ human breast cancer xenografts

Trastuzumab-refractory breast cancer stem cells (CSCs) could explain the high rate of primary resistance to single-agent trastuzumab in HER2 gene-amplified breast cancer patients. The identification of agents with strong selective toxicity for trastuzumab-resistant breast CSCs may have tremendous relevance for how HER2+ breast cancer patients should be treated. Using the human breast cancer cell line JIMT-1, which was established from the pleural metastasis of a patient who was clinically resistant to trastuzumab ab initio, we examined whether preferential killing of the putative CD44+CD24 −/low breast CSC population might be sufficient to overcome primary resistance to trastuzumab in vivo. Because recent studies have shown that the anti-diabetic biguanide metformin can exert antitumor effects by targeted killing of CSC-like cells, we explored whether metformin's ability to preferentially kill breast cancer initiating CD44+CD24 −/low cells may have the potential to sensitize JIMT-1 xenograft mouse models to trastuzumab. Upon isolation for breast cancer initiating CD44+CD24 −/low cells by employing magnetic activated cell sorting, we observed the kinetics of metformin-induced killing drastically varied among CSC and non-CSC subpopulations. Metformin's cell killing effect increased dramatically by more than 10-fold in CD44+CD24 −/low breast CSC cells compared to non-CD44+CD24 −/low immunophenotypes. While seven-weeks treatment length with trastuzumab likewise failed to reduce tumor growth of JIMT-1 xenografts, systemic treatment with metformin as single agent resulted in a significant two-fold reduction in tumor volume. When trastuzumab was combined with concurrent metformin, tumor volume decreased sharply by more than four-fold. Given that metformin-induced preferential killing of breast cancer initiating CD44+CD24 −/low subpopulations is sufficient to overcome in vivo primary resistance to trastuzumab, the incorporation of metformin into trastuzumab-based regimens may provide a valuable strategy for treatment of HER2+ breast cancer patients

Identification and characterization of miRNAs in spleens of sheep subjected to repetitive vaccination

Accumulative evidence has shown that short non-coding RNAs such as miRNAs can regulate the innate and adaptive immune responses. Aluminium hydroxide is a commonly used adjuvant in human and veterinary vaccines. Despite its extended use, its mechanism of action is not fully understood and very few in vivo studies have been done to enhance understanding at the molecular level. In this work, we took advantage of a previous long-term experiment in which lambs were exposed to three different treatments by parallel subcutaneous inoculations with aluminium-containing commercial vaccines, an equivalent dose of aluminium or mock injections. Spleen samples were used for miRNA-seq. A total of 46 and 16 miRNAs were found differentially expressed when animals inoculated with commercial vaccines or the adjuvant alone were compared with control animals, respectively. Some miRNAs previously related to macrophage polarization were found dysregulated exclusively by the commercial vaccine treatment but not in the aluminium inoculated animals. The dysregulated miRNAs in vaccine group let-7b-5p, miR-29a-3p, miR-27a and miR-101-3p are candidates for further research, since they may play key roles in the immune response induced by aluminium adjuvants added to vaccines. Finally, protein–protein interaction network analysis points towards leucocyte transendothelial migration as a specific mechanism in animals receiving adjuvant only