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1.
J Chem Phys ; 160(11)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38488078

RESUMO

In this work, we have evaluated the influence of temperature and pressure on the mechanism of furan oxidation by the OH radical. The stationary points on the potential energy surface were described at the M06-2X/aug-cc-pVTZ level of theory. In the kinetic treatment at the high-pressure limit (HPL), we have combined the multistructural canonical variational theory with multidimensional small-curvature tunneling corrections and long-range transition state theory. The system-specific quantum Rice-Ramsperger-Kassel theory was employed to estimate the pressure-dependent rate. In the HPL, the OH addition on the α carbon is the dominant pathway in the mechanism, producing a product via the ring-opening process, also confirmed by the product branching ratio calculations. The overall rate constant, obtained by a kinetic Monte Carlo simulation, reads the form koverall=5.22×10-13T/3001.10⁡exp1247(K/T) and indicates that the furan oxidation by OH radicals is a pressure-independent reaction under tropospheric conditions.

2.
Science ; 383(6686): 946-949, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38422142

RESUMO

Conventional supply-side approaches overlook potential benefits.

3.
Chemphyschem ; 25(7): e202400022, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38269625

RESUMO

The factors governing the acceleration of the oxidative addition of methyl iodide to pincer rhodium(I)-complexes induced by coronene have been computationally explored in detail using quantum chemical methods. Both the parent reaction and the coronene-mediated process proceed via a stepwise SN2-type mechanism. It is found that the acceleration of the process derives from the formation of an initial supramolecular complex, mainly stabilized by electrostatic and π-π interactions, which significantly increases the electron richness of the complex. The impact of this effect on the reaction barrier has been quantitatively analyzed by applying the activation strain model in combination with the energy decomposition analysis method. In addition, the influence of other polycyclic aromatic hydrocarbons on the oxidative reaction has been also considered.

4.
Sci Rep ; 13(1): 14695, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679479

RESUMO

Seismic reflection (2D/3D), borehole and bathymetric data are used to recognize a new gravitational complex in the Gulf of Squillace, Southern Italy, named the Squillace Complex. The complex has a NE-striking headwall connected to a basal detachment formed between Messinian evaporites and Tortonian shales. Its sense of movement changes to a W-E direction in the toe region. In plan view, the Squillace Complex is marked by the presence of sinuous and continuous seafloor scarps, just a few kilometers offshore, over an elongated morphological high. Seismic-well ties reveal that the complex was initiated in the Zanclean (~ 4 Ma) and continued its movement into the Gelasian (~ 2.1 Ma) at an average rate of 1.9 mm/year. Movement slowed down in the Calabrian (middle Pleistocene) and continued until the present day at a lower rate of 0.1 mm/year. Gravitational collapse of the Squillace Complex correlates with discrete contractional/transpressional events affecting the Calabrian region, which caused basin shortening and the temporary arrest of Calabrian Arc migration. These episodes resulted in tectonic uplift in the study area after 0.45 Ma (Late Pleistocene). Conversely, the complex's slower movement recorded since the Calabrian (middle Pleistocene) is associated with slab rollback of the Ionian plate under the Calabrian Arc.

5.
Org Biomol Chem ; 21(38): 7767-7775, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37698053

RESUMO

The reactivity and endo/exo selectivity of the Diels-Alder cycloaddition reactions involving furan and substituted furans as dienes have been computationally explored. In comparison to cyclopentadiene, it is found that furan is comparatively less reactive and also less endo-selective in the reaction with maleic anhydride as the dienophile. Despite that, both the reactivity and the selectivity can be successfully modified by the presence of substituents at either 2- or 3-positions of the heterocycle. In this sense, it is found that the presence of strong electron-donor groups significantly increases the reactivity of the system while the opposite is found in the presence of electron-withdrawing groups. The observed trends in both the reactivity and selectivity are analyzed quantitatively in detail by means of the activation strain model of reactivity in combination with the energy decomposition analysis methods.

6.
Phys Chem Chem Phys ; 25(29): 19512-19523, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37458056

RESUMO

Thermal rate constants for the hydrogen abstraction reaction of methyl pentanoate were calculated using the multistructural canonical variational theory with small-curvature tunneling (MS-CVT/SCT). The conformational search for the stationary points generated by these reactions was performed with an algorithm that combines systematic and stochastic searches at dual-level. At the high-level (MPWB1K/6-31+G(d,p)), 244 geometries for methyl pentanoate and transition states were found. A systematic estimative of the efficiency of the truncation of multistructural rovibrational partition functions and its effects on thermal rate constants was carried out. In this analysis, we observed that rotation about -OCH3 group (ϕ4) of the ester generates unstable structures with little contribution to the magnitude of the partition function. We also estimate that the truncation of the partition functions in a small set of conformations can produce deviations up to 75% compared to converged theoretical results.

7.
Mar Pollut Bull ; 193: 115154, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37429157

RESUMO

Offshore oil spills often result in severe environmental and socio-economic consequences. This work focuses on a busy, yet poorly studied part of NW Europe, the Irish Sea, to assess the impact of future oil spills on the nearby coast. By integrating numerical models and shoreline sensitivity analyses for two confined areas, Liverpool Bay and Milford Haven, this work acknowledges wind direction and speed as principal controls on the movement of oil under winter/storm conditions and in shallow waters. Ocean currents play a secondary role, but are significant in deeper waters and in low-wind summer conditions. The temporal elements used in the modelling thus stress that when the spill occurs is just as important as where. As a corollary, the fate of spilled oil is determined in this work for distinct scenarios and types. Response strategies are recommended to minimise the impact of future spills on coastal populations.


Assuntos
Poluição por Petróleo , Poluição por Petróleo/análise , Modelos Teóricos , Vento , Estações do Ano , Europa (Continente) , Monitoramento Ambiental
8.
J Phys Chem A ; 127(19): 4317-4327, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37026895

RESUMO

We investigate the photoionization pathways of naphthalene, 1-cyanonaphthalene, and 2-cyanonaphthalene upon complexation with the water dimer, aiming to understand the photodissociation process under conditions of the interstellar medium (ISM). We analyze the intermolecular bonding pattern, equilibrium rotational properties, energy complexation, far-IR spectra, and ionic trends of the possible photoproducts using dispersion-corrected density functional theory (DFT-D) and time-dependent DFT (TD-DFT). For the different configurations, we evaluate the possible charge-transfer (CT) excitations near the photoionization limit. Our results indicate that, in high-radiation regions of the ISM (>8.0 eV), CT excitations occur from localized occupied molecular orbitals (MOs) in the aromatic molecules to mixed unoccupied MOs in the complexes, favoring cationic aromatic species in these conditions. We notice that the photoabsorption spectra depend on the type of intermolecular interaction (H-bonds or O-H···π bonds) in the complexes, as well as the presence and position (1 or 2) of the cyano-functional group in naphthalene. For hydrated naphthalene, the O-H···π complexes assume a more relevant role for photodissociation. In the case of the cyano-substituted derivatives, the H-bonded structures are more favorable to be considered as prereactive models. However, the cyano group at position 2 indicates that CT excitations toward the water dimer are more likely to occur.

9.
Redox Biol ; 60: 102616, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36746004

RESUMO

OBJECTIVE: Rheumatoid arthritis is an inflammatory joint disease in which synovial iron deposition has been described. Transferrin receptor 2 (Tfr2) represents a critical regulator of systemic iron levels. Loss of Tfr2 function in humans and mice results in iron overload. As iron contributes to inflammatory processes, we investigated whether Tfr2-deletion affects the pathogenesis of inflammatory arthritis in an iron-dependent manner. METHODS: Using a global and conditional genetic disruption of Tfr2, we assessed the relevance of Tfr2 in K/BxN serum-transfer arthritis (STA) and macrophage polarization. RESULTS: Male Tfr2-/- mice subjected to STA developed pronounced joint swelling, and bone erosion as compared to Tfr2+/+ littermate-controls (P < 0.01). Furthermore, an increase of neutrophils and macrophages/monocytes was observed in the inflammatory infiltrate within the paws of Tfr2-/- mice. To elucidate whether Tfr2 in myeloid cells has a direct role in the pathogenesis of arthritis or whether the effects were mediated via the systemic iron overload, we induced STA in Tfr2fl/fl-LysMCre + mice, which showed normal iron-loading. Cre + female mice displayed increased disease development compared to Cre-controls. As macrophages regulate iron availability and innate immunity, we hypothesized that Tfr2-deficiency would polarize macrophages toward a pro-inflammatory state (M1) that contributes to arthritis progression. In response to IFN-γ stimulation, Tfr2-/- macrophages showed increased expression of M1-like cytokines, IFN-γ-target genes, nitric-oxide production, and prolonged STAT1 activation compared to Tfr2+/+ macrophages (P < 0.01), while pre-treatment with ruxolitinib abolished Tfr2-driven M1-like polarization. CONCLUSION: Taken together, these findings suggest a protective role of Tfr2 in macrophages on the progression of arthritis via suppression of M1-like polarization.


Assuntos
Artrite , Sobrecarga de Ferro , Humanos , Camundongos , Masculino , Feminino , Animais , Camundongos Knockout , Ferro/metabolismo , Sobrecarga de Ferro/patologia , Macrófagos/metabolismo , Artrite/metabolismo , Receptores da Transferrina/genética
10.
FEBS Lett ; 597(2): 309-319, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36114012

RESUMO

Uncoupling protein-3 (UCP3) is a mitochondrial transmembrane protein highly expressed in the muscle that has been implicated in regulating the efficiency of mitochondrial oxidative phosphorylation. Increasing UCP3 expression in skeletal muscle enhances proton leak across the inner mitochondrial membrane and increases oxygen consumption in isolated mitochondria, but its precise function in vivo has yet to be fully elucidated. To examine whether muscle-specific overexpression of UCP3 modulates muscle mitochondrial oxidation in vivo, rates of ATP synthesis were assessed by 31 P magnetic resonance spectroscopy (MRS), and rates of mitochondrial oxidative metabolism were measured by assessing the rate of [2-13 C]acetate incorporation into muscle [4-13 C]-, [3-13 C]-glutamate, and [4-13 C]-glutamine by high-resolution 13 C/1 H MRS. Using this approach, we found that the overexpression of UCP3 in skeletal muscle was accompanied by increased muscle mitochondrial inefficiency in vivo as reflected by a 42% reduction in the ratio of ATP synthesis to mitochondrial oxidation.


Assuntos
Canais Iônicos , Mitocôndrias , Animais , Camundongos , Trifosfato de Adenosina/metabolismo , Canais Iônicos/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias Musculares , Proteínas Mitocondriais/metabolismo , Músculo Esquelético/metabolismo , Prótons , Proteína Desacopladora 3/análise , Proteína Desacopladora 3/metabolismo
11.
J Cachexia Sarcopenia Muscle ; 14(1): 298-309, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36418015

RESUMO

BACKGROUND: The detrimental impact of malnutrition and cachexia in cancer patients subjected to surgical resection is well established. However, how systemic and local metabolic alterations in cancer patients impact the serum metabolite signature, thereby leading to cancer-specific differences, is poorly defined. In order to implement metabolomics as a potential tool in clinical diagnostics and disease follow-up, targeted metabolite profiling based on quantitative measurements is essential. We hypothesized that the quantitative metabolic profile assessed by 1 H nuclear magnetic resonance (NMR) spectroscopy can be used to identify cancer-induced catabolism and potentially distinguish between specific tumour entities. Importantly, to prove tumour dependency and assess metabolic normalization, we additionally analysed the metabolome of patients' sera longitudinally post-surgery in order to assess metabolic normalization. METHODS: Forty two metabolites in sera of patients with tumour entities known to cause malnutrition and cachexia, namely, upper gastrointestinal cancer and pancreatic cancer, as well as sera of healthy controls, were quantified by 1 H NMR spectroscopy. RESULTS: Comparing serum metabolites of patients with gastrointestinal cancer with healthy controls and pancreatic cancer patients, we identified at least 15 significantly changed metabolites in each comparison. Principal component and pathway analysis tools showed a catabolic signature in preoperative upper gastrointestinal cancer patients. The most specifically upregulated metabolite group in gastrointestinal cancer patients was ketone bodies (3-hydroxybutyrate, P < 0.0001; acetoacetate, P < 0.0001; acetone, P < 0.0001; false discovery rate [FDR] adjusted). Increased glycerol levels (P < 0.0001), increased concentration of the ketogenic amino acid lysine (P = 0.03) and a significant correlation of 3-hydroxybutyrate levels with branched-chained amino acids (leucine, P = 0.02; isoleucine, P = 0.04 [FDR adjusted]) suggested that ketone body synthesis was driven by lipolysis and amino acid breakdown. Interestingly, the catabolic signature was independent of the body mass index, clinically assessed malnutrition using the nutritional risk screening score, and systemic inflammation assessed by CRP and leukocyte count. Longitudinal measurements and principal component analyses revealed a quick normalization of key metabolic alterations seven days post-surgery, including ketosis. CONCLUSIONS: Together, the quantitative metabolic profile obtained by 1 H NMR spectroscopy identified a tumour-induced catabolic signature specific to upper gastrointestinal cancer patients and enabled monitoring restoration of metabolic homeostasis after surgery. This approach was critical to identify the obtained metabolic profile as an upper gastrointestinal cancer-specific signature independent of malnutrition and inflammation.


Assuntos
Neoplasias Gastrointestinais , Desnutrição , Neoplasias Pancreáticas , Humanos , Ácido 3-Hidroxibutírico , Caquexia/etiologia , Caquexia/metabolismo , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/metabolismo , Inflamação/metabolismo , Leucina , Desnutrição/etiologia , Desnutrição/metabolismo , Neoplasias Pancreáticas/metabolismo , Metabolômica
12.
Arthrosc Sports Med Rehabil ; 4(6): e1993-e2003, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36579050

RESUMO

Purpose: To evaluate the influence of lateral posterior tibial slope (LPTS) and meniscal bone angle (MBA) on primary anterior cruciate ligament (ACL) tear risk in an adult population through the LPTS-MBA ratio. Methods: A retrospective case-control study was performed with patients from a tertiary hospital who underwent primary ACL surgery and had preoperative magnetic resonance imaging (MRI). These subjects were matched by age and sex in a 1:1 ratio to patients who had an MRI without ACL tear. LPTS and MBA were measured on MRI scan. Quantitative data are presented in the median ± interquartile range (IQR). Identification of independent risk factors for primary ACL tear was performed using multivariable logistic regression. Receiver operating characteristics curves detected any variable with strong discriminative capacity. Results: In total, 95 patients with primary ACL tear confirmed on MRI were matched with 95 controls (N = 190). Nearly 80% were male subjects, with a median age of 26 years. In the ACL tear group, the median value of LPTS-MBA ratio was 0.20 (IQR 0.11-0.37) versus 0.12 (IQR 0.08-0.19) in the control group (P = .001). LPTS had a median value of 4.20° in the ACL tear group (IQR 2.05-7.35°) and 2.90° in the control group (IQR, 2.05-5.00°) (P = .026), whereas MBA was 19° (IQR, 16-24°) versus 26° (IQR, 24-30°) (P = .001), respectively. Logistic regression showed that LPTS (odds ratio 1.20, 95% confidence interval 1.03-1.42, P = .021) and MBA (odds ratio 0.78, 95% confidence interval 0.71-0.85, P = .001) were independent predictors. The area under the curve (AUC) of LPTS-MBA ratio was 0.69, greater than that of LPTS alone (AUC = 0.61) but lower than that for MBA (AUC = 0.82). Conclusions: In this study, a reduced MBA was the strongest predictive variable associated with a primary ACL tear. A threshold of 22.35° of MBA was associated with an increased risk of ACL tear, with a sensitivity of 70% and specificity of 84%. A cut-off of 0.22 of LPTS-MBA was associated with an increased risk of ACL tear, with a sensitivity of 55% and specificity of 87%. Level of Evidence: Level III, case-control study.

13.
J Phys Chem A ; 126(29): 4791-4800, 2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35839446

RESUMO

Thermal rate coefficients for the hydrogen abstraction reactions of prenol (3-methyl-2-butenol) by a hydrogen atom were calculated with the multipath canonical variational theory with small-curvature tunneling (MP-CVT/SCT). The conformational search was performed with a dual-level approach, and the multistructural torsional anharmonicity effects were corrected through the rovibrational partition function calculated with the multistructural method based on a coupled torsional potential (MS-T(C)). This methodology allows us to estimate the thermal rate constants in the temperature range of 200-2500 K and fit them into two analytical expressions. Differences between the number of conformations on the torsional potential energy surfaces for prenol and the transition state decrease the thermal rate constants for the H-abstraction at the α carbon. An opposite behavior was detected for the abstractions on the δ site. The product branching ratios were calculated using single-structure and multipath approaches. The product distributions from the former are shown to be inadequate for studying the mechanism under combustion conditions. The values estimated from MP-CVT/SCT rate coefficients indicated that the radicals from (Rα) and (Rδ)/(Rδ') are formed in considerable amounts. These species are fundamental in comprehending the inhibition and promotion of the autoignition phenomena.


Assuntos
Biocombustíveis , Hidrogênio , Compreensão , Hemiterpenos , Hidrogênio/química , Cinética , Pentanóis
14.
Opt Express ; 30(6): 9623-9642, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35299385

RESUMO

Quantum and neuromorphic computational platforms in integrated photonic circuits require next-generation optical functionalities. Often, increasingly complex on-chip light-routing that allow superpositions not attainable by planar technologies are paramount e.g. for artificial neural networks. Versatile 3D waveguides are achievable via two-photon polymerization (TPP)-based microprinting. Here, a 3D morphology prediction tool which considers experimental TPP parameters, is presented, enabling on-chip 3D waveguide performance simulations. The simulations allow reducing the cost-intensive systematic experimental optimization process. Fabricated 3D waveguides show optical transmission properties in agreement with simulations, demonstrating that the developed morphology prediction methodology is beneficial for the development of versatile on-chip and potentially inter-chip photonic interconnect technology.

15.
iScience ; 25(1): 103610, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35005554

RESUMO

Thousands of biomedical scientific articles, including those describing genes associated with human diseases, are published every week. Computational methods such as text mining and machine learning algorithms are now able to automatically detect these associations. In this study, we used a cognitive computing text-mining application to construct a knowledge network comprising 3,723 genes and 99 diseases. We then tracked the yearly changes on these networks to analyze how our knowledge has evolved in the past 30 years. Our systems approach helped to unravel the molecular bases of diseases and detect shared mechanisms between clinically distinct diseases. It also revealed that multi-purpose therapeutic drugs target genes that are commonly associated with several psychiatric, inflammatory, or infectious disorders. By navigating this knowledge tsunami, we were able to extract relevant biological information and insights about human diseases.

16.
Semin Cancer Biol ; 82: 94-119, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-33290846

RESUMO

Metabolic reprogramming is one of the main hallmarks of cancer cells. It refers to the metabolic adaptations of tumor cells in response to nutrient deficiency, microenvironmental insults, and anti-cancer therapies. Metabolic transformation during tumor development plays a critical role in the continued tumor growth and progression and is driven by a complex interplay between the tumor mutational landscape, epigenetic modifications, and microenvironmental influences. Understanding the tumor metabolic vulnerabilities might open novel diagnostic and therapeutic approaches with the potential to improve the efficacy of current tumor treatments. Prostate cancer is a highly heterogeneous disease harboring different mutations and tumor cell phenotypes. While the increase of intra-tumor genetic and epigenetic heterogeneity is associated with tumor progression, less is known about metabolic regulation of prostate cancer cell heterogeneity and plasticity. This review summarizes the central metabolic adaptations in prostate tumors, state-of-the-art technologies for metabolic analysis, and the perspectives for metabolic targeting and diagnostic implications.


Assuntos
Neoplasias da Próstata , Epigênese Genética , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo
17.
Phys Chem Chem Phys ; 23(44): 25414-25423, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34751697

RESUMO

Thermal rate coefficients for the hydrogen-abstraction reactions of 3-butenal by a hydrogen atom were obtained applying multipath canonical variational theory with small-curvature tunneling (MP-CVT/SCT). Torsional anharmonicity due to the hindered rotors was taken into account by calculating the rovibrational partition function using the extended two-dimensional torsional (E2DT) method. For comparison, rovibrational partition functions were also estimated using the multistructural method with torsional anharmonicity based on a coupled torsional potential (MS-T(C)). By contrast, with (E)-2-butenal reactions, the abstraction reactions of 3-butenal proceed via five reaction channels (R1)-(R5). In a conformational search, 45 distinguishable structures of transition states were found, including enantiomers, which were separated into six conformational reaction channels (CRCs). The individual reactive paths were constructed, the recrossing and semiclassical transmission coefficients estimated, and the multipath rate constants were obtained. High torsional barriers between the wells of CRC2/CRC6 indicate a harmonic behavior. Consequently, a difference between the torsional anharmonicity of 3-butenal and the transition states is responsible for the increase in the thermal rate constants for channel (R2). Analysis of the contributions of each conformer of the transition state shows an important contribution of the high-energy rotamers in the total flux of (R1)-(R5). After fitting the rate constants in a four-parameter equation, the activation energy estimation showed a strong temperature dependence.

18.
Sci Rep ; 11(1): 16990, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417535

RESUMO

This work uses a high-quality 3D seismic volume from offshore Canterbury Basin, New Zealand, to investigate how submarine canyon systems can focus sub-surface fluid. The seismic volume was structurally conditioned to improve the contrast in seismic reflections, preserving their lateral continuity. It reveals multiple pockmarks, eroded gullies and intra-slope lobe complexes occurring in association with the Waitaki Submarine Canyon. Pockmarks are densely clustered on the northern bank of the canyon and occur at a water depth of 500-900 m. In parallel, near-seafloor strata contain channel-fill deposits, channel lobes, meandering channel belts and overbank sediments deposited downslope of the submarine canyon. We propose that subsurface fluid migrates from relatively deep Cretaceous strata through shallow channel-fill deposits and lobes to latter seep out through the canyon and associated gullies. The new, reprocessed Fluid Cube meta-attribute confirms that fluids have seeped out through the eroded walls of the Waitaki Canyon, with such a seepage generating seafloor depressions in its northern bank. Our findings stress the importance of shallow reservoirs (channel-fill deposits and lobes) as potential repositories for fluid, hydrocarbons, or geothermal energy on continental margins across the world.

19.
Theranostics ; 11(16): 7844-7868, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335968

RESUMO

Radiotherapy is one of the curative treatment options for localized prostate cancer (PCa). The curative potential of radiotherapy is mediated by irradiation-induced oxidative stress and DNA damage in tumor cells. However, PCa radiocurability can be impeded by tumor resistance mechanisms and normal tissue toxicity. Metabolic reprogramming is one of the major hallmarks of tumor progression and therapy resistance. Specific metabolic features of PCa might serve as therapeutic targets for tumor radiosensitization and as biomarkers for identifying the patients most likely to respond to radiotherapy. The study aimed to characterize a potential role of glutaminase (GLS)-driven glutamine catabolism as a prognostic biomarker and a therapeutic target for PCa radiosensitization. Methods: We analyzed primary cell cultures and radioresistant (RR) derivatives of the conventional PCa cell lines by gene expression and metabolic assays to identify the molecular traits associated with radiation resistance. Relative radiosensitivity of the cell lines and primary cell cultures were analyzed by 2-D and 3-D clonogenic analyses. Targeting of glutamine (Gln) metabolism was achieved by Gln starvation, gene knockdown, and chemical inhibition. Activation of the DNA damage response (DDR) and autophagy was assessed by gene expression, western blotting, and fluorescence microscopy. Reactive oxygen species (ROS) and the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) were analyzed by fluorescence and luminescence probes, respectively. Cancer stem cell (CSC) properties were investigated by sphere-forming assay, CSC marker analysis, and in vivo limiting dilution assays. Single circulating tumor cells (CTCs) isolated from the blood of PCa patients were analyzed by array comparative genome hybridization. Expression levels of the GLS1 and MYC gene in tumor tissues and amino acid concentrations in blood plasma were correlated to a progression-free survival in PCa patients. Results: Here, we found that radioresistant PCa cells and prostate CSCs have a high glutamine demand. GLS-driven catabolism of glutamine serves not only for energy production but also for the maintenance of the redox state. Consequently, glutamine depletion or inhibition of critical regulators of glutamine utilization, such as GLS and the transcription factor MYC results in PCa radiosensitization. On the contrary, we found that a combination of glutamine metabolism inhibitors with irradiation does not cause toxic effects on nonmalignant prostate cells. Glutamine catabolism contributes to the maintenance of CSCs through regulation of the alpha-ketoglutarate (α-KG)-dependent chromatin-modifying dioxygenase. The lack of glutamine results in the inhibition of CSCs with a high aldehyde dehydrogenase (ALDH) activity, decreases the frequency of the CSC populations in vivo and reduces tumor formation in xenograft mouse models. Moreover, this study shows that activation of the ATG5-mediated autophagy in response to a lack of glutamine is a tumor survival strategy to withstand radiation-mediated cell damage. In combination with autophagy inhibition, the blockade of glutamine metabolism might be a promising strategy for PCa radiosensitization. High blood levels of glutamine in PCa patients significantly correlate with a shorter prostate-specific antigen (PSA) doubling time. Furthermore, high expression of critical regulators of glutamine metabolism, GLS1 and MYC, is significantly associated with a decreased progression-free survival in PCa patients treated with radiotherapy. Conclusions: Our findings demonstrate that GLS-driven glutaminolysis is a prognostic biomarker and therapeutic target for PCa radiosensitization.


Assuntos
Glutamina/metabolismo , Neoplasias da Próstata/metabolismo , Tolerância a Radiação/genética , Animais , Autofagia , Proteína 5 Relacionada à Autofagia/metabolismo , Biomarcadores Farmacológicos , Linhagem Celular Tumoral , Glutaminase/antagonistas & inibidores , Glutaminase/genética , Glutaminase/metabolismo , Humanos , Masculino , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Oxirredução , Proteínas Proto-Oncogênicas c-myc/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Sensors (Basel) ; 21(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34372288

RESUMO

The image stitching process is based on the alignment and composition of multiple images that represent parts of a 3D scene. The automatic construction of panoramas from multiple digital images is a technique of great importance, finding applications in different areas such as remote sensing and inspection and maintenance in many work environments. In traditional automatic image stitching, image alignment is generally performed by the Levenberg-Marquardt numerical-based method. Although these traditional approaches only present minor flaws in the final reconstruction, the final result is not appropriate for industrial grade applications. To improve the final stitching quality, this work uses a RGBD robot capable of precise image positing. To optimize the final adjustment, this paper proposes the use of bio-inspired algorithms such as Bat Algorithm, Grey Wolf Optimizer, Arithmetic Optimization Algorithm, Salp Swarm Algorithm and Particle Swarm Optimization in order verify the efficiency and competitiveness of metaheuristics against the classical Levenberg-Marquardt method. The obtained results showed that metaheuristcs have found better solutions than the traditional approach.


Assuntos
Algoritmos , Humanos
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