Soundscape Characterization Using Autoencoders and Unsupervised Learning.

Passive acoustic monitoring (PAM) through acoustic recorder units (ARUs) shows promise in detecting early landscape changes linked to functional and structural patterns, including species richness, acoustic diversity, community interactions, and human-induced threats. However, current approaches primarily rely on supervised methods, which require prior knowledge of collected datasets. This reliance poses challenges due to the large volumes of ARU data. In this work, we propose a non-supervised framework using autoencoders to extract soundscape features. We applied this framework to a dataset from Colombian landscapes captured by 31 audiomoth recorders. Our method generates clusters based on autoencoder features and represents cluster information with prototype spectrograms using centroid features and the decoder part of the neural network. Our analysis provides valuable insights into the distribution and temporal patterns of various sound compositions within the study area. By utilizing autoencoders, we identify significant soundscape patterns characterized by recurring and intense sound types across multiple frequency ranges. This comprehensive understanding of the study area's soundscape allows us to pinpoint crucial sound sources and gain deeper insights into its acoustic environment. Our results encourage further exploration of unsupervised algorithms in soundscape analysis as a promising alternative path for understanding and monitoring environmental changes.

The HIV-1 Matrix Protein p17 Does Cross the Blood-Brain Barrier.

Human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorder (HAND) remains an important neurological manifestation in HIV-1-infected (HIV+) patients. Furthermore, detection of the HIV-1 matrix protein p17 (p17) in the central nervous system (CNS) and its ability to form toxic assemblies in the brain have been recently confirmed. Here, we show for the first time, using both an in vitro blood-brain barrier (BBB) model and in vivo biodistribution studies in healthy mice, that p17 can cross the BBB. There is rapid brain uptake with 0.35% ± 0.19% of injected activity per gram of tissue (IA/g) 2 min after administration, followed by brain accumulation with 0.28% ± 0.09% IA/g after 1 h. The interaction of p17 with chemokine receptor 2 (CXCR2) at the surface of brain endothelial cells triggers transcytosis. The present study supports the hypothesis of a direct role of free p17 in neuronal dysfunction in HAND by demonstrating its intrinsic ability to reach the CNS. IMPORTANCE The percentage of patients affected by HIV-1-associated neurocognitive disorder (HAND) ranges from 30% to 50% of HIV-infected (HIV+) patients. The mechanisms leading to HAND development need to be elucidated, but the roles of secreted viral proteins, chemokines, and proinflammatory molecules appear to be clear. In particular, the blood-brain barrier (BBB) represents a route for entry into the central nervous system (CNS) and thus plays an important role in HAND. Several findings suggest a key role for the HIV-1 matrix protein p17 (p17) as a microenvironmental factor capable of inducing neurocognitive disorders. Here, we show the ability of the p17 to cross the BBB and to reach the CNS, thus playing a crucial role in neuronal dysfunction in HAND.

Radiolabeled Gold Nanoseeds Decorated with Substance P Peptides: Synthesis, Characterization and In Vitro Evaluation in Glioblastoma Cellular Models.

Despite some progress, the overall survival of patients with glioblastoma (GBM) remains extremely poor. In this context, there is a pressing need to develop innovative therapy strategies for GBM, namely those based on nanomedicine approaches. Towards this goal, we have focused on nanoparticles (AuNP-SP and AuNP-SPTyr8) with a small gold core (ca. 4 nm), carrying DOTA chelators and substance P (SP) peptides. These new SP-containing AuNPs were characterized by a variety of analytical techniques, including TEM and DLS measurements and UV-vis and CD spectroscopy, which proved their high in vitro stability and poor tendency to interact with plasma proteins. Their labeling with diagnostic and therapeutic radionuclides was efficiently performed by DOTA complexation with the trivalent radiometals 67Ga and 177Lu or by electrophilic radioiodination with 125I of the tyrosyl residue in AuNP-SPTyr8. Cellular studies of the resulting radiolabeled AuNPs in NKR1-positive GBM cells (U87, T98G and U373) have shown that the presence of the SP peptides has a crucial and positive impact on their internalization by the tumor cells. Consistently, 177Lu-AuNP-SPTyr8 showed more pronounced radiobiological effects in U373 cells when compared with the non-targeted congener 177Lu-AuNP-TDOTA, as assessed by cell viability and clonogenic assays and corroborated by Monte Carlo microdosimetry simulations.

An initiative of cooperation in Zika virus research: the experience of the ZIKABRA study in Brazil.

BACKGROUND: The Zika virus outbreak has triggered a set of local and global actions for a rapid, effective, and timely public health response. A World Health Organization (WHO) initiative, supported by the Department of Chronic Condition Diseases and Sexually Transmitted Infections (DCCI) of the Health Surveillance Secretariat (SVS), Brazil Ministry of Health (MoH) and other public health funders, resulted in the start of the "Study on the persistence of Zika virus in body fluids of patients with ZIKV infection in Brazil - ZIKABRA study". The ZIKABRA study was designed to increase understanding of how long ZIKV persists in bodily fluids and informing best measures to prevent its transmission. Data collection began in July 2017 and the last follow up visit occurred in 06/26/2020. METHODS: A framework for the ZIKABRA Cooperation initiative is provided through a description and analysis of the mechanisms, strategies and the ethos that have guided the models of international governance and technical cooperation in health for scientific exchange in the context of a public health emergency. Among the methodological strategies, we included a review of the legal documents that supported the ZIKABRA Cooperation; weekly documents produced in the meetings and working sessions; technical reports; memorandum of understanding and the research protocol. CONCLUSION: We highlight the importance of working in cooperation between different institutional actors to achieve more significant results than that obtained by each group working in isolation. In addition, we point out the advantages of training activities, ongoing supervision, the construction of local installed research capacity, training academic and non-academic human resources, improvement of laboratory equipment, knowledge transfer and the availability of the ZIKABRA study protocol for development of similar studies, favoring the collective construction of knowledge to provide public health emergency responses. Strategy harmonization; human resources and health services; timing and recruiting particularities and processing institutional clearance in the different sites can be mentioned as challenges in this type of initiative.

Impact of Urgent Chemotherapy in Critically Ill Patients.

OBJECTIVE: Compare the mortality between critically ill patients who received urgent chemotherapy for a cancer-related life-threatening complication with matched patients (controls) who did not received it. DESIGN: Propensity score-matched retrospective study. SETTING: Adult intensive care unit in an oncological hospital. PARTICIPANTS: All adults with solid tumor or hematological malignancies who received at least 1 day of urgent intravenous chemotherapy for a cancer-related life-threatening complication. Using the propensity score method adjusted for 10 variables, patients who received urgent chemotherapy were matched to patients who did not. INTERVENTIONS: None. MAIN OUTCOMES MEASURES: Intensive care unit and hospital mortality. RESULTS: Forty-seven patients (57% with solid tumors and 43% with hematological malignancies) who received urgent chemotherapy were matched to 94 controls. At intensive care unit admission, patients were similar except that those who received urgent chemotherapy were less likely to have received chemotherapy previously (36% vs 85%; P < .01). The intensive care unit (48.9% vs 23.4%; P < .01) and hospital (76.6% vs 46.8%; P < .01) mortality of the patients who received urgent chemotherapy was higher than the controls. The subgroup analysis showed that the higher mortality was limited to patients with solid tumor. CONCLUSION: The use of urgent chemotherapy is associated with an increase in the intensive care unit and hospital mortality of unselected critically ill patients with solid tumors but not in patients with hematological malignancies.

Overexpression of AtNCED3 gene improved drought tolerance in soybean in greenhouse and field conditions.

Water deficit is an important climatic problem that can impair agriculture yield and economy. Genetically modified soybean plants containing the AtNCED3 gene were obtained aiming drought-tolerance improvement. The NCED3 gene encodes a 9-cis-epoxycarotenoid dioxygenase (NCED, EC 1.13.11.51), an important enzyme in abscisic acid biosynthesis. ABA activates the expression of drought-responsive genes, in water-deficit conditions, targeting defense mechanisms and enabling plants to survive under low water availability. Results from greenhouse experiments showed that the transgene AtNCED3 and the endogenous genes GmAREB1, GmPP2C, GmSnRK2 and GmAAO3 presented higher expression under water deficit (WD) in the event 2Ha11 than in WT-plants. No significant correlation was observed between the plant materials and WD conditions for growth parameters; however, gas exchange measurements decreased in the GM event, which also showed 80% higher intrinsic water use when compared to WT plants. In crop season 2015/16, event 2Ha11 showed higher total number of pods, higher number of pods with seeds and yield than WT plants. ABA concentration was also higher in GM plants under WD. These results obtained in field screenings suggest that AtNCED3 soybean plants might outperform under drought, reducing economic and yield losses, thus being a good candidate line to be incorporated in the soybean-breeding program to develop drought-tolerant cultivars.

NMR Insights into the Structure-Function Relationships in the Binding of Melanocortin Analogues to the MC1R Receptor.

Linear and cyclic analogues of the α-melanocyte stimulating hormone (α-MSH) targeting the human melanocortin receptor 1 (MC1R) are of pharmacological interest for detecting and treating melanoma. The central sequence of α-MSH (His-Phe-Arg-Trp) has been identified as being essential for receptor binding. To deepen current knowledge on the molecular basis for α-MSH bioactivity, we aimed to understand the effect of cycle size on receptor binding. To that end, we synthesised two macrocyclic isomeric α-MSH analogues, c[NH-NO2-C6H3-CO-His-DPhe-Arg-Trp-Lys]-Lys-NH2 (CycN-K6) and c[NH-NO2-C6H3-CO-His-DPhe-Arg-Trp-Lys-Lys]-NH2 (CycN-K7). Their affinities to MC1R receptor were determined by competitive binding assays, and their structures were analysed by ¹H and 13C NMR. These results were compared to those of the previously reported analogue c[S-NO2-C6H3-CO-His-DPhe-Arg-Trp-Cys]-Lys-NH2 (CycS-C6). The MC1R binding affinity of the 22-membered macrocyclic peptide CycN-K6 (IC50 = 155 ± 16 nM) is higher than that found for the 25-membered macrocyclic analogue CycN-K7 (IC50 = 495 ± 101 nM), which, in turn, is higher than that observed for the 19-membered cyclic analogue CycS-C6 (IC50 = 1770 ± 480 nM). NMR structural study indicated that macrocycle size leads to changes in the relative dispositions of the side chains, particularly in the packing of the Arg side chain relative to the aromatic rings. In contrast to the other analogues, the 22-membered cycle's side chains are favorably positioned for receptor interaction.

Isostructural Re(I)/(99m)Tc(I) tricarbonyl complexes for cancer theranostics.

Merging classical organic anticancer drugs with metal-based compounds in one single molecule offers the possibility of exploring new approaches for cancer theranostics, i.e. the combination of diagnostic and therapeutic modalities. For this purpose, we have synthesized and biologically evaluated a series of Re(I)/(99m)Tc(I) tricarbonyl complexes (Re1­Re4 and Tc1­Tc4, respectively) stabilized by a cysteamine-based (N,S,O) chelator and containing 2-(4'-aminophenyl)benzothiazole pharmacophores. With the exception of Re1, all the Re complexes have shown a moderate cytotoxicity in MCF7 and PC3 cancer cells (IC50 values in the 15.9­32.1 µM range after 72 h of incubation). The cytotoxic activity of the Re complexes is well correlated with cellular uptake that was quantified using the isostructural (99m)Tc congeners. There is an augmented cytotoxic effect for Re3 and Re4 (versusRe1 and Re2), and the highest cellular uptake for Tc3 and Tc4, which display a long ether-containing linker to couple the pharmacophore to the (N,S,O)-chelator framework. Moreover, fluorescence microscopy clearly confirmed the cytosolic accumulation of the most cytotoxic compound (Re3). Biodistribution studies of Tc1­Tc4 in mice confirmed that these moderately lipophilic complexes (logDo/w = 1.95­2.32) have a favorable bioavailability. Tc3 and Tc4 presented a faster excretion, as they undergo metabolic transformations, in contrast to complexes Tc1 and Tc2. In summary, our results show that benzothiazole-containing Re(I)/(99m)Tc(I) tricarbonyl complexes stabilized by cysteamine-based (N,S,O)-chelators have potential to be further applied in the design of new tools for cancer theranostics.

Phenotyping soybean plants transformed with rd29A:AtDREB1A for drought tolerance in the greenhouse and field.

The development of drought tolerant plants is a high priority because the area suffering from drought is expected to increase in the future due to global warming. One strategy for the development of drought tolerance is to genetically engineer plants with transcription factors (TFs) that regulate the expression of several genes related to abiotic stress defense responses. This work assessed the performance of soybean plants overexpressing the TF DREB1A under drought conditions in the field and in the greenhouse. Drought was simulated in the greenhouse by progressively drying the soil of pot cultures of the P58 and P1142 lines. In the field, the performance of the P58 line and of 09D-0077, a cross between the cultivars BR16 and P58, was evaluated under four different water regimes: irrigation, natural drought (no irrigation) and water stress created using rain-out shelters in the vegetative or reproductive stages. Although the dehydration-responsive element-binding protein (DREB) plants did not outperform the cultivar BR16 in terms of yield, some yield components were increased when drought was introduced during the vegetative stage, such as the number of seeds, the number of pods with seeds and the total number of pods. The greenhouse data suggest that the higher survival rates of DREB plants are because of lower water use due to lower transpiration rates under well watered conditions. Further studies are needed to better characterize the soil and atmospheric conditions under which these plants may outperform the non-transformed parental plants.

Evaluation of a Radioiodinated G-quadruplex Binder in Cervical Cancer Models.

We herein describe the radiosynthesis of a 125I-labeled acridine orange derivative ([125I]-C8), acting as a G-quadruplex binder, and its biological evaluation in cervical cancer models, aiming to enlighten its potential as a radioligand for Auger Electron Radiopharmaceutical Therapy (AE-RPT) of cancer. [125I]-C8 was synthesized with a moderate radiochemical yield (ca. 60 %) by a [125I]iodo-destannylation reaction. Its evaluation in cervical cancer HeLa cells demonstrated that the radiocompound has a significant cellular internalization with a notorious accumulation in the cell nucleus. In line with these results, [125I]-C8 strongly compromised the viability of HeLa cells in a dose-dependent manner, inducing non-repairable DNA lesions that are most probably due to the AEs emitted by 125I in close proximity to  the DNA. Biodistribution studies in a murine HeLa xenograft model showed that [125I]-C8 has fast blood clearance and high in vivo stability but poor tumor uptake, after systemic administration. The respective supramolecular conjugate with the AS1411 aptamer ([125I]-C8/AS1411) led to a slower blood clearance in the same animal tumor model, although without improving the tumor uptake. To take advantage of the radiotoxicity of [125I]-C8 against cervical cancer cells other strategies need to be studied, based namely on alternative nanodelivery carriers and/or intratumoral injection approaches.

Microorganism community structure: A characterisation of agrosystems from Madeira Archipelago.

Microbial diversity profoundly influences soil ecosystem functions, making it vital to monitor community dynamics to comprehend its structure. Our study focused on six agrosystems in Madeira Archipelago, analysing bacteria, archaea, fungi and AMF through classical microbiology and molecular techniques. Despite distinct edaphoclimatic conditions and management practices, bacterial structures exhibited similarities, with Alphaproteobacteria at 18%-20%, Bacilli at 11%-18% and Clostridia at 9%-14%. The predominance of copiothrophic groups suggested that soil nutrient content was the driver of these communities. Regarding archaea, the communities changed among sites, and it was evident that agrosystems provided niches for methanogens. The Crenarchaeota varied between 15% and 29%, followed by two classes of Euryarchaeota, Methanomicrobia (17%-25%) and Methanococci (4%-32%). Fungal communities showed consistent composition at the class level but had differing diversity indices due to management practices and soil texture. Sordaryomycetes (21%-28%) and Agaricomycetes (15%-23%) were predominant. Conversely, AMF communities appeared to be also influenced by the agrosystem, with Glomus representing over 50% of the community in all agrosystems. These insights into microbial groups' susceptibilities to environmental conditions are crucial for maintaining healthy soil and predicting climate change effects on agrosystems' productivity, resilience and sustainability. Additionally, our findings enable the development of more robust prediction models for agricultural practices.

RNA-based liposomes for oral cancer: From biophysical characterization to biological evaluation.

Oral cancer incidence and mortality are increasing over time. The most common therapies for oral cancers are surgery and radiotherapy, either used alone or combined, and immunotherapy can be also an option. Although there are several therapeutic options, none of them are completely effective, and in addition, there are numerous associated side effects. To overcome these limitations, researchers have been trying to reduce these drawbacks by using drug delivery systems that carry drugs for specific delivery to cancer cells. For that purpose, RNA-coated liposomes to selectively deliver the ligands C8 (acridine orange derivative) and dexamethasone to oral cancer cells were produced, characterized, and biologically evaluated. Firstly, the RNA structure and binding interaction with ligands (C8 and dexamethasone) were evaluated by circular dichroism (CD), thermal difference spectroscopy (TDS), nuclear magnetic resonance (NMR) and fluorescence titrations. The biophysical assays evidenced the formation of an RNA hairpin and duplex structure. Moreover, steady-state and time-resolved fluorescence intensity and anisotropy experiments show that C8 forms a complex with RNA and adopts an open conformation upon RNA binding. Then, RNA-coated liposomes were characterized by dynamic light scattering, and diameters near 160 nm were observed. Time-resolved anisotropy measurements of C8 loaded in RNA-functionalized liposomes indicate the co-existence of free C8 in solution (inside the liposome) and C8 bound to RNA at the external liposome surface. The RNA-functionalized liposomes loaded with C8 or dexamethasone mediated a significant reduction in the cell viability of malignant UPCI-SCC-154 cells while maintaining viable non-malignant NHDF cells. Additionally, the liposomes were able to internalize the cells, with higher uptake by the malignant cell line. Overall, the results obtained in this work can contribute to the development of new drug delivery systems based on RNA-coated liposomes.

Molecularly designed layer-by-layer (LbL) films to detect catechol using information visualization methods.

The control of molecular architectures has been exploited in layer-by-layer (LbL) films deposited on Au interdigitated electrodes, thus forming an electronic tongue (e-tongue) system that reached an unprecedented high sensitivity (down to 10(-12) M) in detecting catechol. Such high sensitivity was made possible upon using units containing the enzyme tyrosinase, which interacted specifically with catechol, and by processing impedance spectroscopy data with information visualization methods. These latter methods, including the parallel coordinates technique, were also useful for identifying the major contributors to the high distinguishing ability toward catechol. Among several film architectures tested, the most efficient had a tyrosinase layer deposited atop LbL films of alternating layers of dioctadecyldimethylammonium bromide (DODAB) and 1,2-dipalmitoyl-sn-3-glycero-fosfo-rac-(1-glycerol) (DPPG), viz., (DODAB/DPPG)5/DODAB/Tyr. The latter represents a more suitable medium for immobilizing tyrosinase when compared to conventional polyelectrolytes. Furthermore, the distinction was more effective at low frequencies where double-layer effects on the film/liquid sample dominate the electrical response. Because the optimization of film architectures based on information visualization is completely generic, the approach presented here may be extended to designing architectures for other types of applications in addition to sensing and biosensing.

Introduction of the rd29A:AtDREB2A CA gene into soybean (Glycine max L. Merril) and its molecular characterization in leaves and roots during dehydration.

The loss of soybean yield to Brazilian producers because of a water deficit in the 2011-2012 season was 12.9%. To reduce such losses, molecular biology techniques, including plant transformation, can be used to insert genes of interest into conventional soybean cultivars to produce lines that are more tolerant to drought. The abscisic acid (ABA)-independent Dehydration Responsive Element Binding (DREB) gene family has been used to obtain plants with increased tolerance to abiotic stresses. In the present study, the rd29A:AtDREB2A CA gene from Arabidopsis thaliana was inserted into soybean using biolistics. Seventy-eight genetically modified (GM) soybean lines containing 2-17 copies of the AtDREB2A CA gene were produced. Two GM soybean lines (P1397 and P2193) were analyzed to assess the differential expression of the AtDREB2A CA transgene in leaves and roots submitted to various dehydration treatments. Both GM lines exhibited high expression of the transgene, with the roots of P2193 showing the highest expression levels during water deficit. Physiological parameters examined during water deficit confirmed the induction of stress. This analysis of AtDREB2A CA expression in GM soybean indicated that line P2193 had the greatest stability and highest expression in roots during water deficit-induced stress.

Assessment of Aptamer as a Potential Drug Targeted Delivery for Retinal Angiogenesis Inhibition.

AT11-L0 is an aptamer derivative of AS1411 composed of G-rich sequences that can adopt a G-quadruplex (G4) structure and target nucleolin (NCL), a protein that acts as a co-receptor for several growth factors. Hence, this study aimed to characterize the AT11-L0 G4 structure and its interaction with several ligands for NCL targeting and to evaluate their capacity to inhibit angiogenesis using an in vitro model. The AT11-L0 aptamer was then used to functionalize drug-associated liposomes to increase the bioavailability of the aptamer-based drug in the formulation. Biophysical studies, such as nuclear magnetic resonance, circular dichroism, and fluorescence titrations, were performed to characterize the liposomes functionalized with the AT11-L0 aptamer. Finally, these liposome formulations with the encapsulated drugs were tested on the human umbilical vein endothelial cell (HUVEC) model to assess their antiangiogenic capacity. The results showed that the AT11-L0 aptamer-ligand complexes are highly stable, presenting melting temperatures from 45 °C to 60 °C, allowing for efficient targeting of NCL with a KD in the order of nM. The aptamer-functionalized liposomes loaded with ligands C8 and dexamethasone did not show cytotoxic effects in HUVEC cells compared with the free ligands and AT11-L0, as assessed by cell viability assays. AT11-L0 aptamer-functionalized liposomes encapsulating C8 and dexamethasone did not present a significant reduction in the angiogenic process when compared with the free ligands. In addition, AT11-L0 did not show anti-angiogenic effects at the concentrations tested. However, C8 shows potential as an angiogenesis inhibitor, which should be further developed and optimized in future experiments.

Network Analysis and Natural Language Processing to Obtain a Landscape of the Scientific Literature on Materials Applications.

Recent progress in natural language processing (NLP) enables mining the literature in various tasks akin to knowledge discovery. Obtaining an updated birds-eye view of key research topics and their evolution in a vast, dynamic field such as materials science is challenging even for experienced researchers. In this Perspective paper, we present a landscape of the area of applied materials in selected representative journals based on a combination of methods from network science and simple NLP strategies. We found a predominance of energy-related materials, e.g., for batteries and catalysis, organic electronics, which include flexible sensors and flexible electronics, and nanomedicine with various topics of materials used in diagnosis and therapy. As for the impact calculated through standard metrics of impact factor, energy-related materials and organic electronics are again top of the list across different journals, while work in nanomedicine has been found to have a lower impact in the journals analyzed. The adequacy of the approach to identify key research topics in materials applications was verified indirectly by comparing the topics identified in journals with diverse scopes, including journals that are not specific to materials. The approach can be employed to obtain a fast overview of a given field from the papers published in related scientific journals, which can be adapted or extended to any research area.

The efficacy of polyphenols as an antioxidant agent: An updated review.

Global production of the two major poultry products, meat and eggs, has increased quickly. This, in turn, indicates both the relatively low cost and the customers' desire for these secure and high-quality products. Natural feed additives have become increasingly popular to preserve and enhance the health and productivity of poultry and livestock. We consume a lot of polyphenols, which are a kind of micronutrient. These are phytochemicals with positive effects on cardiovascular, cognitive, anti-inflammatory, detoxifying, anti-tumor, anti-pathogen, a catalyst for growth, and immunomodulating functions, among extra health advantages. Furthermore, high quantities of polyphenols have unknown and occasionally unfavorable impacts on the digestive tract health, nutrient assimilation, the activity of digestive enzymes, vitamin and mineral assimilation, the performance of the laying hens, and the quality of the eggs. This review clarifies the numerous sources, categories, biological functions, potential limitations on usage, and effects of polyphenols on poultry performance, egg composition, exterior and interior quality traits.

Evaluation of novel 99mTc(I)-labeled homobivalent α-melanocyte-stimulating hormone analogs for melanocortin-1 receptor targeting.

Aiming to apply the multivalency concept to melanoma imaging, we have assessed the in vivo melanocortin type 1 receptor (MC1R)-targeting properties of (99m)Tc(I)-labeled homobivalent peptide conjugates which contain copies of the α-melanocyte-stimulating hormone (α-MSH) analog [Ac-Nle(4), Asp(5), D-Phe(7), Lys(11)]α-MSH4-11 separated by linkers of different length (L(2) nine atoms and L(3) 14 atoms). The MC1R-binding affinity of L(2) and L(3) is significantly higher than that of the monovalent conjugate L(1). Metallation of these conjugates yielded the complexes fac-[M(CO)(3)(k(3)-L)](+) (M is (99m)Tc/Re; 1/1a, L is L(1); 2/2a, L is L(2); 3/3a, L is L(3)), with IC(50) values in the subnanomolar and nanomolar range. The MC1R-mediated internalization of 2 and 3 is higher than that of 1 in B16F1 melanoma cells. Biodistribution studies in melanoma-bearing mice have shown low nonspecific accumulation with a tumor uptake that correlates with IC(50) values. However, no correlation between tumor uptake and valency was found. Nevertheless, 2 displayed the highest tumor retention, and the best tumor to nontarget organ ratios.

Toward the optimization of an e-tongue system using information visualization: a case study with perylene tetracarboxylic derivative films in the sensing units.

The wide variety of molecular architectures used in sensors and biosensors and the large amount of data generated with some principles of detection have motivated the use of computational methods, such as information visualization techniques, not only to handle the data but also to optimize sensing performance. In this study, we combine projection techniques with micro-Raman scattering and atomic force microscopy (AFM) to address critical issues related to practical applications of electronic tongues (e-tongues) based on impedance spectroscopy. Experimentally, we used sensing units made with thin films of a perylene derivative (AzoPTCD acronym), coating Pt interdigitated electrodes, to detect CuCl(2) (Cu(2+)), methylene blue (MB), and saccharose in aqueous solutions, which were selected due to their distinct molecular sizes and ionic character in solution. The AzoPTCD films were deposited from monolayers to 120 nm via Langmuir-Blodgett (LB) and physical vapor deposition (PVD) techniques. Because the main aspects investigated were how the interdigitated electrodes are coated by thin films (architecture on e-tongue) and the film thickness, we decided to employ the same material for all sensing units. The capacitance data were projected into a 2D plot using the force scheme method, from which we could infer that at low analyte concentrations the electrical response of the units was determined by the film thickness. Concentrations at 10 µM or higher could be distinguished with thinner films--tens of nanometers at most--which could withstand the impedance measurements, and without causing significant changes in the Raman signal for the AzoPTCD film-forming molecules. The sensitivity to the analytes appears to be related to adsorption on the film surface, as inferred from Raman spectroscopy data using MB as analyte and from the multidimensional projections. The analysis of the results presented may serve as a new route to select materials and molecular architectures for novel sensors and biosensors, in addition to suggesting ways to unravel the mechanisms behind the high sensitivity obtained in various sensors.

Radioiodinated sunitinib as a potential radiotracer for imaging angiogenesis-radiosynthesis and first radiopharmacological evaluation of 5-[125I]Iodo-sunitinib.

Sunitinib® (SU11248) is a highly potent tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR). Radiolabeled inhibitors of RTKs might be useful tools for monitoring RTKs levels in tumour tissue giving valuable information for anti-angiogenic therapy. We report here the synthesis of a (125)I-labeled derivative of sunitinib® and its first radiopharmaceutical characterization. The non-radioactive reference compound 5-iodo-sunitinib 4 was prepared by Knoevenagel condensation of 5-iodo-oxindole with the corresponding substituted 5-formyl-1H-pyrrole. In a competition binding assay against VEGFR-2 a binding constant (K(d)) of 16 nM for 4 was found. The ability of 4 to inhibit tyrosine kinase activity was demonstrated on RTK expressing cells suggesting this radiotracer as a useful tool for monitoring VEGFR expression. 5-[(125)I]lodo-sunitinib, [(125)I]-4 was obtained via destannylation of the corresponding tributylstannyl precursor with [(125)I]NaI in the presence of H(2)O(2) in high radiochemical yield (>95%) and radiochemical purity (<98%) after HPLC purification. Determination of human plasma protein binding at time intervals of 0; 1; 2; 4 and 24h suggested a low non-specific binding of 5-10%. Preliminary biodistribution studies of [(125)I]-4 in healthy CD-1 mice showed a relatively high uptake in VEGFR-2 rich tissues like kidney and lung followed by rapid washout (9.6 and 9.7; 4.5 and 3.8% ID/g of kidney and lung at 1 and 4h, respectively).