Integration of Transcriptomics and Metabolomics to Reveal the Molecular Mechanisms Underlying Rhodium Nanoparticles-Based Photodynamic Cancer Therapy

Rhodium nanoparticles have recently been described as promising photosensitizers due to their low toxicity in the absence of near-infrared irradiation, but their high cytotoxicity when irradiated. Irradiation is usually carried out with a laser source, which allows the treatment to be localized in a specific area, thus avoiding undesirable side effects on healthy tissues. In this study, a multi-omics approach based on the combination of microarray-based transcriptomics and mass spectrometry-based untargeted and targeted metabolomics has provided a global picture of the molecular mechanisms underlying the anti-tumoral effect of rhodium nanoparticle-based photodynamic therapy. The results have shown the ability of these nanoparticles to promote apoptosis by suppressing or promoting anti- and pro-apoptotic factors, respectively, and by affecting the energy machinery of tumor cells, mainly blocking the β-oxidation, which is reflected in the accumulation of free fatty acids and in the decrease in ATP, ADP and NAD+ levels.Depto. de Química AnalíticaFac. de Ciencias QuímicasTRUEMinisterio de Ciencia, Innovaciónpu

EFFECT OF PARAMETERS OF MULTIGRID METHOD ASSOCIATED WITH EXTRAPOLATORS IN CFD PROBLEMS

The focus of this work is analyzing the behavior of the following parameters: the iteration error, the processing time (CPU time) and the convergence factors for two problems of Computational Fluid Dynamics (CFD): the two-dimensional linear heat diffusion problem, governed by a Poisson-like equation, with Dirichlet's boundary conditions, and it is solved by using the Geometric Multigrid Method associated to the following extrapolation methods: Aitken, Empiric, Mitin, Epsilon (scalar and topological), Rho (scalar and topological), Multiple Aitken Extrapolations and Multiple Mitin Extrapolations; and the square lid-driven cavity, governed by Burgers’ equations, with Dirichlet's boundary conditions, solved by using the Geometric Multigrid associated to the Topological Epsilon Extrapolation Method during the Multigrid cycles. According to numerical results, it was observed: the reduction of the magnitude of iteration error, the reduction of non-dimensional residual based on the initial estimate and the reduction of the convergence factor, with a CPU time compatible to the pure Multigrid Method for both problems

Estabilidade de 3-deoxiantocianidinas em grãos e farinha de sorgo durante o armazenamento.

O sorgo possui compostos bioativos que lhe conferem alta capacidade antioxidante, porém, o genótipo, as condições de plantio, de armazenamento e de processamento podem ter efeito nos teores e na estabilidade desses compostos. Assim, objetivou-se avaliar a estabilidade das 3- deoxiantocianidinas (3-DXAs) em grãos e farinhas de sorgo após 60 e 180 dias de armazenamento a 4, 25 e 40°C. Não houve efeito do tipo de produto (grão ou farinha), da temperatura e das interações sobre os teores de 3-DXAs. Apenas o tempo de armazenamento influenciou a estabilidade desses compostos. Houve redução nos teores das 3-DXAs nos 60 dias iniciais, entretanto, não houve diferença entre os tempos 60 e 180 dias em ambas matrizes. Após 180 dias, a farinha e os grãos de sorgo ainda apresentaram retenção, respectivamente, de 62,9 e 77,9% de luteolinidina, 56,1 e 71,4% de apigeninidina, 63,1 e 72,3% de 5-metoxiluteolinidina e 61,5 e 69,0% de 7-metoxiapigeninidina

Joint ancestry and association test indicate two distinct pathogenic pathways involved in classical dengue fever and dengue shock syndrome

Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway. We conducted functional analyses for PPP2R5E, revealing by immunofluorescence imaging that the coded protein co-localizes with both DENV1 and DENV2 NS5 proteins. Interestingly, only DENV2-NS5 migrated to the nucleus, and a deletion of the predicted top-linking motif in NS5 abolished the nuclear transfer. These observations support the existence of differences between serotypes in their cellular dynamics, which may contribute to differential infection outcome risk. The contribution of the identified genes to the genetic risk render Southeast and Northeast Asian populations more susceptible to both phenotypes, while African populations are best protected against DSS and intermediately protected against DF, and Europeans the best protected against DF but the most susceptible against DSS.The research leading to these results has received funding from the European Commission Seventh Framework Programme [FP7/2007-2013] for the DENFREE project under Grant Agreement no. 282378. MO has a PhD grant from FCT (The Portuguese Foundation for Science and Technology - SFRH/BD/95626/2013). I3S is financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Competitiveness and Internationalization Operational Programme (POCI), Portugal 2020, and by Portuguese funds through FCT/Ministério da Ciência, Tecnologia e Inovação in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Tratamento com Flunixin meglumine não previne efeitos do benzoato de estradiol sobre a função luteal durante a ressincronização precoce de vacas leiteiras.

Os objetivos foram 1) determinar se o tratamento com benzoato de estradiol (BE) e implante de progesterona (P4) no D12 alteram o estradiol (E2) circulante e afetam a função do corpo lúteo (CL; P4 plasmática); 2) avaliar se o tratamento com flunixin meglumine (FLU) poderia prevenir efeitos negativo do BE sobre o CL. Vacas em lactação Holandês x Gir (n=45) foram submetidas a protocolo de sincronização da ovulação à base de BE e P4 (D-10: 2 mg BE+ implante de P4; D-2: remoção do implante+PGF2&#945;; D-1: 1 mg BE; D0: estro). No D12, as vacas foram divididas aleatoriamente em quatro grupos/tratamentos: A) controle (CTL), salina im; B) 2 mg BE im, implante de P4 (BE-P4); C) 2 mg BE im, implante de P4, 1.1 mg/Kg FLU im (BE-P4-FLU); e D) implante de P4 no D12, remoção do folículo dominante por OPU no D15 (OPU-P4). Amostras de sangue foram coletadas diariamente e o plasma armazenado a -20ºC. RIA em fase-sólida foi utilizado para dosagens diárias de P4 (D12 a D22) e estradiol plasmático a cada 48h (D13 a D21). Os dados foram analisados pelo PROC MIXED do SAS para medidas repetidas. Foram analisados efeitos de grupo, dia do ciclo, e sua interação. Foram observados efeitos de grupo (P=0,0075 e P=0,0068), dia do cicloe (P<0,0001 e P<0,001), e interação grupo*dia (P=0,0001 e P=0,0012) para E2 e P4, respectivamente. No D13, BE-P4 e BE-P4-FLU tiveram maior E2 comparados com OPU-P4 e CTL (21,7±2,7; 18,0±3,4 vs 3,7±0,9; e 8,76±6,3 pg/mL, respectivamente; P<0,001). O E2 plasmático não diferiu entre grupos e dia do ciclo a partir do D15. A P4 plasmática decresceu do D12 ao D22 em todos os grupos, mas a taxa de redução diferiu. Em grupos que receberam BE, P4 diminuiu do D12 até atingir concentrações significativamente menores no D17 (3,6±0,3 vs 1,4±0,2 ng/mL e 4,2±0,4 vs 1,9±0,4 ng/mL para BE-P4 e BEP4-FLU, respectivamente; P<0,0001), enquanto P4 atingiu valores baixos somente no D20 no OPU-P4 (4,0±0,3 vs 1,5±0,3 ng/mL, D12 vs D20, respectivamente; P<0,0001) e D19 no CTL (3,1±0,4 vs 1,3±0,4 ng/mL, D12 vs D19; P=0,0045). No grupo OPU-P4, o pico de P4 foi no D17 (4,0±0,6 ng/mL) e permaneceu alta no D18 (3,2±0,5), maior (P<0.03) do que nos grupos BE-P4 (1,4±0,2 e 1,0±0,2; D17 e D18) e BE-P4-FLU (1,9±0,4 e 1,3±0,4; respectivamente). Conclui-se que a ressincronização com BE no D12 aumenta o E2 plasmático no D13 e pode ter antecipado a luteólise funcional. Tratamento concomitante com FLU não impediu este efeito

A Novel Technology for Processing Urban Waste Compost as a Fast-Releasing Nitrogen Source to Improve Soil Properties and Broccoli and Lettuce Production.

This study evaluated nitrogen (N) mineralization dynamics in three soils after the addition of heat-treated urban waste amendments or urban waste compost (UWC). The effects of UWC and urea on soil properties and broccoli and lettuce production were compared.Published online: 20 March 2021