Preparation of Original and Calcined Layered Double Hydroxide as Low-Cost Adsorbents: The Role of the Trivalent Cation on Methylene Blue Adsorption.

Layered double hydroxides with the hydrotalcite-like structure, containing Mg2+, Al3+, and Fe3+ (with different Al/Fe ratios) in the layers, have been synthesized and fully characterized, as have the mixed oxides formed upon their calcination at 500 °C. Both series of solids (original and calcined ones) have been tested for methylene blue adsorption. In the case of the Fe-containing sample, oxidation of methylene blue takes place simultaneously with adsorption. For the calcined samples, their reconstruction to the hydrotalcite-like structure plays an important role in their adsorption ability.

Strong Coupling and Nonextensive Thermodynamics.

We propose a Hamiltonian-based approach to the nonextensive thermodynamics of small systems, where small is a relative term comparing the size of the system to the size of the effective interaction region around it. We show that the effective Hamiltonian approach gives easy accessibility to the thermodynamic properties of systems strongly coupled to their surroundings. The theory does not rely on the classical concept of dividing surface to characterize the system's interaction with the environment. Instead, it defines an effective interaction region over which a system exchanges extensive quantities with its surroundings, easily producing laws recently shown to be valid at the nanoscale.

Negative Thermophoretic Force in the Strong Coupling Regime.

Negative thermophoresis (a particle moving up the temperature gradient) is a somewhat counterintuitive phenomenon which has thus far eluded a simple thermostatistical description. The purpose of this Letter is to show that a thermodynamic framework based on the formulation of a Hamiltonian of mean force has the descriptive ability to capture this interesting and elusive phenomenon in an unusually elegant and straightforward fashion. We propose a mechanism that describes the advent of a thermophoretic force acting from cold to hot on systems that are strongly coupled to a nonisothermal heat bath. When a system is strongly coupled to the heat bath, the system's eigenenergies E_{j} become effectively temperature dependent. This adjustment of the energy levels allows the system to take heat from the environment, +d⟨E_{j}⟩, and return it as work, -d⟨TdE_{j}/dT⟩. This effect can make the temperature dependence of the effective energy profile nonmonotonic. As a result, particles may experience a force in either direction depending on the temperature.

Inhibition of cyclin-dependent kinase CDK1 by oxindolimine ligands and corresponding copper and zinc complexes.

Oxindolimine-copper(II) and zinc(II) complexes that previously have shown to induce apoptosis, with DNA and mitochondria as main targets, exhibit here significant inhibition of kinase CDK1/cyclin B protein. Copper species are more active than the corresponding zinc, and the free ligand shows to be less active, indicating a major influence of coordination in the process, and a further modulation by the coordinated ligand. Molecular docking and classical molecular dynamics provide a better understanding of the effectiveness and kinase inhibition mechanism by these compounds, showing that the metal complex provides a stronger interaction than the free ligand with the ATP-binding site. The metal ion introduces charge in the oxindole species, giving it a more rigid conformation that then becomes more effective in its interactions with the protein active site. Analogous experiments resulted in no significant effect regarding phosphatase inhibition. These results can explain the cytotoxicity of these metal complexes towards different tumor cells, in addition to its capability of binding to DNA, and decreasing membrane potential of mitochondria.

Correction: Temperature-dependent energy levels and size-independent thermodynamics.

Correction for 'Temperature-dependent energy levels and size-independent thermodynamics' by Rodrigo de Miguel, Phys. Chem. Chem. Phys., 2015, 17, 15691-15693.

Temperature-dependent energy levels and size-independent thermodynamics.

We show that, by properly adopting the notion of temperature-dependent energy levels, the standard tools of differential thermodynamics can be used for a consistent thermostatistical description irrespective of system size. In this framework the paradigmatic (yet not always descriptive) large-system limit is no longer a necessary assumption for differential thermodynamics. We present a generalized relation between temperature and internal energy which extends thermodynamics all the way to isolated quantum systems.

Quantifying flare combustion efficiency using an imaging Fourier transform spectrometer.

Mid-wavelength infrared (MWIR) imaging Fourier transform spectrometers (IFTSs) are a promising technology for measuring flare combustion efficiency (CE) and destruction removal efficiency (DRE). These devices generate spectrally resolved intensity images of the flare plume, which may then be used to infer column densities of relevant species along each pixel line-of-sight. In parallel, a 2D projected velocity field may be inferred from the apparent motion of flow features between successive images. Finally, the column densities and velocity field are combined to estimate the mass flow rates for the species needed to calculate the CE or DRE. Since the MWIR IFTS can measure key carbon-containing species in the flare plume, it is possible to measure CE without knowing the fuel flow rate, which is important for fenceline measurements. This work demonstrates this approach on a laboratory heated vent, and then deploys the technique on two working flares: a combustor burning natural gas at a known rate, and a steam-assisted flare at a petrochemical refinery. Analysis of the IFTS data highlights the potential of this approach, but also areas for future development to transform this approach into a reliable technique for quantifying flare emissions.Implications: Our research is motivated by the need to assess hydrocarbon emissions from flaring, which is a critical problem of global significance. For example, recent studies have shown that methane destruction efficiency of flaring from upstream oil may be significantly lower than the commonly assumed figure of 98%; work by Plant et al. , in particular, suggest that this discrepancy amounts to CO2 emissions from 2 to 8 million automobiles annually, considering the US alone. Similarly, the international energy agency (IEA) estimates a global flare efficiency of 92%, which translates in 8 million tons of CH4 emitted by flares in 2020. Highlighted by these studies and supported by the World Bank initiatives toward zero routine flaring emissions, there is an urgent need for oil and gas industry to assess their flare methane emission, and overall hydrocarbon emissions. At the very least, it is critical to identify problematic flare operating conditions and means to mitigate flare emissions. Focusing on remote quantification of plume species, the measurement technique and quantification method presented in this paper is a considerable step forward in that direction by computing combustion efficiency and key components for destruction efficiency.

Topical delivery of seriniquinone for treatment of skin cancer and fungal infections is enabled by a liquid crystalline lamellar phase.

Seriniquinone (SQ) was initially described by our group as an antimelanoma drug candidate and now also as an antifungal drug candidate. Despite its promising in vitro effects, SQ translation has been hindered by poor water-solubility. In this paper, we described the challenging nanoformulation process of SQ, which culminated in the selection of a phosphatidylcholine-based lamellar phase (PLP1). Liposomes and nanostructured lipid carriers were also evaluated but failed to encapsulate the compound. SQ-loaded PLP1 (PLP1-SQ) was characterized for the presence of sedimented or non-dissolved SQ, rheological and thermal behavior, and irritation potential with hen's egg test on the chorioallantoic membrane (HET-CAM). PLP1 influence on transepidermal water loss (TEWL) and skin penetration of SQ was assessed in a porcine ear skin model, while biological activity was evaluated against melanoma cell lines (SK-MEL-28 and SK-MEL-147) and C. albicans SC5314. Despite the presence of few particles of non-dissolved SQ (observed under the microscope 2 days after formulation obtainment), PLP1 tripled SQ retention in viable skin layers compared to SQ solution at 12 h. This effect did not seem to relate to formulation-induced changes on the barrier function, as no increases in TEWL were observed. No sign of vascular toxicity in the HET-CAM model was observed after cutaneous treatment with PLP1. SQ activity was maintained on melanoma cells after 48 h-treatment (IC50 values of 0.59-0.98 µM) whereas the minimum inhibitory concentration (MIC) against C. albicans after 24 h-treatment was 32-fold higher. These results suggest that a safe formulation for SQ topical administration was developed, enabling further in vivo studies.

Rayleigh-Schrödinger Perturbation Theory and Nonadditive Thermodynamics.

Physical chemists reconcile the empirical theory of classical thermodynamics with the quantum nature of matter and energy when they recover thermodynamics from a statistical mechanical treatment of the individual particles' quantized eigenspectrum. The conclusion is that, when systems are very large collections of particles, interactions between adjacent systems are comparatively negligible, resulting in an additive thermodynamic framework where the energy of a composite system AB may be expressed as the sum of the individual energies of subsystems A and B. This powerful theory is consistent with quantum theory, and it accurately describes the macroscopic properties of sufficiently large systems subject to comparatively short-ranged interactions. Nevertheless, classical thermodynamics has its limitations. Its main drawback is the theory's failure to accurately describe systems not sufficiently large for the aforementioned interaction to be neglected. This shortcoming was addressed by the celebrated chemist Terrell L. Hill in the 1960s when he generalized classical thermodynamics by adding a phenomenological energy term to describe systems not captured by the additivity ansatz (i.e., AB ≠ A + B) of classical thermodynamics. Despite its elegance and success, Hill's generalization mostly remained a specialist tool rather than becoming part of the standard chemical thermodynamics corpus. A probable reason is that, in contrast to the classical large-system case, Hill's small-system framework does not reconcile with a thermostatistical treatment of quantum mechanical eigenenergies. In this work we show that, by introducing a temperature-dependent perturbation in the particles' energy spectrum, Hill's generalized framework is in fact recovered with a simple thermostatistical analysis accessible to physical chemists.

Synthetic beidellite clay as nanocarrier for delivery of antitumor oxindolimine-metal complexes.

Studies on the immobilization of oxindolimine­copper(II) or zinc(II) complexes [ML] in synthetic beidellite (BDL) clay were developed to obtain a suitable inorganic carrier capable of promoting the modified-release of metallopharmaceuticals. Previous investigations have shown that the studied metal complexes are promising antitumor agents, targeting DNA, mitochondria, and some proteins. They can bind to DNA, causing oxidative damage via formation of reactive oxygen species (ROS). In mitochondria they lead to a decrease in membrane potential, acting as decoupling agents, and therefore efficiently inducing apoptosis. Additionally, they inhibit human topoisomerase IB and cyclin dependent kinases, proteins involved in the cell cycle. BDL clays in the sodium form were synthesized under hydrothermal conditions and characterized by a set of physicochemical techniques while the BDL-[ML] hybrid materials were prepared by ion exchange method. The characterization of pristine clay and the obtained hybrids were performed by Infrared, Raman, electron paramagnetic resonance and energy dispersive X-ray spectroscopies, thermogravimetric analysis, scanning electron microscopy, X-ray powder diffraction, specific surface area, zeta potential and surface ionic charge measurements. The [ML] release assays under the same cell incubation conditions were performed monitoring metals by X-ray fluorescence. The BDL-[CuL] hybrid materials were stable and able to derail tumor HeLa cells, with corresponding IC50 values in the 0.11-0.41 mg mL-1 range. By contrast, the analogous hybrid samples of zinc(II) and the pristine BDL proved to be non-toxic facing the same cells. These results indicate a promising possibility of using synthetic beidellite as a carrier of such antitumor metal complexes.

Dispersal-induced resilience to stochastic environmental fluctuations in populations with Allee effect.

Many species are unsustainable at small population densities (Allee effect); i.e., below the so-called Allee threshold, the population decreases instead of growing. In a closed local population, environmental fluctuations always lead to extinction. Here, we show how, in spatially extended habitats, dispersal can lead to a sustainable population in a region, provided the amplitude of environmental fluctuations is below an extinction threshold. We have identified two types of sustainable populations: high-density and low-density populations (through a mean-field approximation, valid in the limit of large dispersal length). Our results show that patches where population is high, low, or extinct coexist when the population is close to global extinction (even for homogeneous habitats). The extinction threshold is maximum for characteristic dispersal distances much larger than the spatial scale of synchrony of environmental fluctuations. The extinction threshold increases proportionally to the square root of the dispersal rate and decreases with the Allee threshold. The low-population-density solution can allow understanding of difficulties in recovery after harvesting. This theoretical framework provides a unique approach to address other factors, such as habitat fragmentation or harvesting, impacting population resilience to environmental fluctuations.

Beyond Formulation: Contributions of Nanotechnology for Translation of Anticancer Natural Products into New Drugs.

Nature is the largest pharmacy in the world. Doxorubicin (DOX) and paclitaxel (PTX) are two examples of natural-product-derived drugs employed as first-line treatment of various cancer types due to their broad mechanisms of action. These drugs are marketed as conventional and nanotechnology-based formulations, which is quite curious since the research and development (R&D) course of nanoformulations are even more expensive and prone to failure than the conventional ones. Nonetheless, nanosystems are cost-effective and represent both novel and safer dosage forms with fewer side effects due to modification of pharmacokinetic properties and tissue targeting. In addition, nanotechnology-based drugs can contribute to dose modulation, reversion of multidrug resistance, and protection from degradation and early clearance; can influence the mechanism of action; and can enable drug administration by alternative routes and co-encapsulation of multiple active agents for combined chemotherapy. In this review, we discuss the contribution of nanotechnology as an enabling technology taking the clinical use of DOX and PTX as examples. We also present other nanoformulations approved for clinical practice containing different anticancer natural-product-derived drugs.

Large cell neuroendocrine carcinoma of the urinary bladder. Bibliographic review.

OBJECTIVES: Large cell neuroendocrine carcinoma (LCNEC) of the urinary bladder is very rare. We intend to update diagnostic criteria, pathologic and immunohistochemical characteristics, prognosis and treatment options. All published articles related with LCNEC of the urinary bladder have been reviewed and a descriptive study has been done. RESULTS: A total of 17 LCNEC of the bladder has been found. The 50% of all LCNEC of the bladder are mixed histological variant. This variant implies a better prognosis than the pure variant. The 70% of LCNEC of the bladder were ≥T3 at the time of diagnosis and the survival rate was 25%, whereas T2 tumors showed a survival rate of 100%. Radical cystectomy with lymphadenectomy combined with chemotherapy can sometimes reduce local and distant recurrence and improve survival of LCNEC of the bladder. CONCLUSIONS: LCNEC of the bladder is a tumor with high rate of local and distant recurrence, as well as low survival, requiring early diagnosis and aggressive combined treatment.

Hypebaric oxygen treatment in urology.

OBJECTIVES: Hyperbaric oxygen therapy (HBO) has been successfully used in several disorders derived from tissue hypoxia, due to the extra oxygen supply to the tissues it enables. In this manuscript we performed a systematic review including all the existing data published until 2010 about HBO in urologic disorders. METHODS: We performed a Medline search using the terms "hyperbaric oxygen", "radical cystitis", "interstitial cystitis", "hemorrhagic cystitis", "urological/pelvic fistula"and "Fournier's gangrene". The search was restricted to human clinical trials published in any language. RESULTS: We found 56 papers: 1 randomized controlled trial, 7 reviews and 48 case reports; only one of them was a prospective study. A total of 695 patients were included. Just one study used tissue oxygen measurement to define hypoxia. The number of hyperbaric oxygen therapy sessions ranged from 4 to 44 (mean 19.2 sessions/patient). CONCLUSIONS: The level of evidence from most reviewed papers is low because most of them are case series. Nevertheless, results of most of those studies regarding patient management are good or very good. So it seems that HBO can be very useful in urological diseases related to tissue hypoxia.

Multivariate probing of antitumor metal-based complexes damage on living cells through Raman imaging.

Intracellular modifications caused by two metal-based antitumor compounds were assessed by confocal Raman imaging assisted by multivariate curve resolution method, a very powerful deconvolution tool that can be used to extract the characteristic spectral profile of the individual or "purest" components from an image dataset. The use of this Raman methodology has the advantage of being non-invasive and totally label-free. Four main different intracellular processes were observed under the Raman imaging and multivariate approach combination, and even, significant differences could be identified between the treatments with both metallodrugs. Leakage of the nucleus and nucleolus content into the cytoplasm, along with releasing of cytochrome c were observed for the treatment with the Cu-based complex. At the same time, changes of hydrogen-bonding network were also evidenced, indicating an apoptotic cellular death process, consistent with complementary Total Reflection X-Ray fluorescence (TXRF) and fluorescence experiments attesting mitochondria and DNA as main targets after uptake of the complex by cells. For treatment with the Zn-based complex, changes associated with cytochrome c were not detected, neither a rapid leakage of nucleus content upon 24 h treatment. The hydrogen-bonding network also followed a quite different pattern, suggesting that with this metallodrug, the cellular death follows a different mechanism.

AMPK-deficiency forces metformin-challenged cancer cells to switch from carbohydrate metabolism to ketogenesis to support energy metabolism.

Epidemiologic studies in diabetic patients as well as research in model organisms have indicated the potential of metformin as a drug candidate for the treatment of various types of cancer, including breast cancer. To date most of the anti-cancer properties of metformin have, in large part, been attributed either to the inhibition of mitochondrial NADH oxidase complex (Complex I in the electron transport chain) or the activation of AMP-activated kinase (AMPK). However, it is becoming increasingly clear that AMPK activation may be critical to alleviate metabolic and energetic stresses associated with tumor progression suggesting that it may, in fact, attenuate the toxicity of metformin instead of promoting it. Here, we demonstrate that AMPK opposes the detrimental effects of mitochondrial complex I inhibition by enhancing glycolysis at the expense of, and in a manner dependent on, pyruvate availability. We also found that metformin forces cells to rewire their metabolic grid in a manner that depends on AMPK, with AMPK-competent cells upregulating glycolysis and AMPK-deficient cell resorting to ketogenesis. In fact, while the killing effects of metformin were largely rescued by pyruvate in AMPKcompetent cells, AMPK-deficient cells required instead acetoacetate, a product of fatty acid catabolism indicating a switch from sugar to fatty acid metabolism as a central resource for ATP production in these cells. In summary, our results indicate that AMPK activation is not responsible for metformin anticancer activity and may instead alleviate energetic stress by activating glycolysis.

Statistical Mechanics at Strong Coupling: A Bridge between Landsberg's Energy Levels and Hill's Nanothermodynamics.

We review and show the connection between three different theories proposed for the thermodynamic treatment of systems not obeying the additivity ansatz of classical thermodynamics. In the 1950s, Landsberg proposed that when a system comes into contact with a heat bath, its energy levels are redistributed. Based on this idea, he produced an extended thermostatistical framework that accounts for unknown interactions with the environment. A decade later, Hill devised his celebrated nanothermodynamics, where he introduced the concept of subdivision potential, a new thermodynamic variable that accounts for the vanishing additivity of increasingly smaller systems. More recently, a thermostatistical framework at strong coupling has been formulated to account for the presence of the environment through a Hamiltonian of mean force. We show that this modified Hamiltonian yields a temperature-dependent energy landscape as earlier suggested by Landsberg, and it provides a thermostatistical foundation for the subdivision potential, which is the cornerstone of Hill's nanothermodynamics.

Thermodynamics Far from the Thermodynamic Limit.

Understanding how small systems exchange energy with a heat bath is important to describe how their unique properties can be affected by the environment. In this contribution, we apply Landsberg's theory of temperature-dependent energy levels to describe the progressive thermalization of small systems as their spectrum is perturbed by a heat bath. We propose a mechanism whereby the small system undergoes a discrete series of excitations and isentropic spectrum adjustments leading to a final state of thermal equilibrium. This produces standard thermodynamic results without invoking system size. The thermal relaxation of a single harmonic oscillator is analyzed as a model example of a system with a quantized spectrum than can be embedded in a thermal environment. A description of how the thermal environment affects the spectrum of a small system can be the first step in using environmental factors, such as temperature, as parameters in the design and operation of nanosystem properties.

On the nonequilibrium thermodynamics of large departures from Butler-Volmer behavior.

Large deviations from the behavior predicted by the Butler-Volmer equation of electrochemistry are accounted for using mesoscopic nonequilibrium thermodynamics. The nonequilibrium thermodynamic hypotheses are extended to include velocity space and cope with imperfect reactant transport leading to departures from Butler-Volmer behavior. This results in a modified Butler-Volmer equation in good agreement with experimental data. The distinct advantages of the method and its applicability to analyze other systems are briefly discussed.

Finite Systems in a Heat Bath: Spectrum Perturbations and Thermodynamics.

When a finite system is at equilibrium with a heat bath, the equilibrium temperature is dictated by the heat bath and not by the intrinsic thermostatistics of the finite system. If not sufficiently large, it may be necessary for the finite system to change its thermostatistics in order to be at equilibrium with the heat bath. We account for this process by invoking Landsberg's notion of temperature-dependent energy levels. We establish that the mismatch between the intrinsic temperature of the excited finite system and that of the heat bath drives a spectrum perturbation which enables thermal equilibrium. We show that the temperature-induced spectrum perturbation is equivalent to Hill's purely thermodynamic subdivision potential. The difference between intrinsic and equilibrium temperature provides us with a measure for how large a system can be before it no longer needs to be regarded as small. The theoretical framework proposed in this paper identifies the role of temperature in a bottom-up thermostatistical description of finite systems.