Exploiting Co(III)-Cyclopentadienyl Complexes To Develop Anticancer Agents.

In recent years, organometallic complexes have attracted much attention as anticancer therapeutics aiming at overcoming the limitations of platinum drugs that are currently marketed. Still, the development of half-sandwich organometallic cobalt complexes remains scarcely explored. Four new cobalt(III)-cyclopentadienyl complexes containing N,N-heteroaromatic bidentate, and phosphane ligands were synthesized and fully characterized by elemental analysis, spectroscopic techniques, and DFT methods. The cytotoxicity of all complexes was determined in vitro by the MTS assay in colorectal (HCT116), ovarian (A2780), and breast (MDA-MB-231 and MCF-7) human cancer cell lines and in a healthy human cell line (fibroblasts). The complexes showed high cytotoxicity in cancer cell lines, mostly due to ROS production, apoptosis, autophagy induction, and disruption of the mitochondrial membrane. Also, these complexes were shown to be nontoxic in vivo in an ex ovo chick embryo yolk sac membrane (YSM) assay.

Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study.

BACKGROUND: Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia. METHODS: This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged ≥ 60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year, and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events. RESULTS: Among 1,556 patients included in the study, 405 (4.5%) had a diagnosis of dementia and 1,151 were matched controls. When compared to matched controls, patients with dementia had a lower frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia; and higher frequency of fever and delirium. They also had a lower frequency of ICU admission (32.7% vs. 47.1%, p < 0.001) and shorter ICU length of stay (7 vs. 9 days, p < 0.026), and a lower frequency of sepsis (17% vs. 24%, p = 0.005), KRT (6.4% vs. 13%, p < 0.001), and IVM (4.6% vs. 9.8%, p = 0.002). There were no differences in hospital mortality between groups. CONCLUSION: Clinical manifestations of COVID-19 differ between older inpatients with and without dementia. We observed that dementia alone could not explain the higher short-term mortality following severe COVID-19. Therefore, clinicians should consider other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of older adults with dementia hospitalised with COVID-19.

Combining dynamic Monte Carlo with machine learning to study nanoparticle translocation.

Resistive pulse sensing (RPS) measurements of nanoparticle translocation have the ability to provide information on single-particle level characteristics, such as diameter or mobility, as well as ensemble averages. However, interpreting these measurements is complex and requires an understanding of nanoparticle dynamics in confined spaces as well as the ways in which nanoparticles disrupt ion transport while inside a nanopore. Here, we combine Dynamic Monte Carlo (DMC) simulations with Machine Learning (ML) and Poisson-Nernst-Planck calculations to simultaneously simulate nanoparticle dynamics and ion transport during hundreds of independent particle translocations as a function of nanoparticle size, electrophoretic mobility, and nanopore length. The use of DMC simulations allowed us to explicitly investigate the effects of Brownian motion and nanoparticle/nanopore characteristics on the amplitude and duration of translocation signals. Simulation results were verified with experimental RPS measurements and found to be in quantitative agreement.

A Comprehensive Review on Photoacoustic-Based Devices for Biomedical Applications.

The photoacoustic effect is an emerging technology that has sparked significant interest in the research field since an acoustic wave can be produced simply by the incidence of light on a material or tissue. This phenomenon has been extensively investigated, not only to perform photoacoustic imaging but also to develop highly miniaturized ultrasound probes that can provide biologically meaningful information. Therefore, this review aims to outline the materials and their fabrication process that can be employed as photoacoustic targets, both biological and non-biological, and report the main components' features to achieve a certain performance. When designing a device, it is of utmost importance to model it at an early stage for a deeper understanding and to ease the optimization process. As such, throughout this article, the different methods already implemented to model the photoacoustic effect are introduced, as well as the advantages and drawbacks inherent in each approach. However, some remaining challenges are still faced when developing such a system regarding its fabrication, modeling, and characterization, which are also discussed.

Metamaterial Vivaldi Antenna Array for Breast Cancer Detection.

The objective of this work is the design and validation of a directional Vivaldi antenna to detect tumor cells' electromagnetic waves with a frequency of around 5 GHz. The proposed antenna is 33% smaller than a traditional Vivaldi antenna due to the use of metamaterials in its design. It has an excellent return loss of 25 dB at 5 GHz and adequate radiation characteristics as its gain is 6.2 dB at 5 GHz. The unit cell size of the proposed metamaterial is 0.058λ × 0.054λ at the operation frequency of 5 GHz. The proposed antenna was designed and optimized in CST microwave software, and the measured and simulated results were in good agreement. The experimental study demonstrates that an array composed with the presented antennas can detect the existence of tumors in a liquid breast phantom with positional accuracy through the analysis of the minimum amplitude of Sii.

Maternal Fluoride Exposure Exerts Different Toxicity Patterns in Parotid and Submandibular Glands of Offspring Rats.

There is currently a controversial and heated debate about the safety and ethical aspects of fluoride (F) used for human consumption. Thus, this study assessed the effects of prenatal and postnatal F exposure of rats on the salivary glands of their offspring. Pregnant rats were exposed to 0, 10, or 50 mg F/L from the drinking water, from the first day of gestation until offspring weaning (42 days). The offspring rats were euthanized for the collection of the parotid (PA) and submandibular (SM) glands, to assess the oxidative biochemistry and to perform morphometric and immunohistochemical analyses. F exposure was associated with a decrease in the antioxidant competence of PA in the 10 mg F/L group, contrasting with the increase observed in the 50 mg F/L group. On the other hand, the antioxidant competence of the SM glands was decreased at both concentrations. Moreover, both 10 and 50 mg F/L groups showed lower anti-α-smooth muscle actin immunostaining area in SM, while exposure to 50 mg F/L was associated with changes in gland morphometry by increasing the duct area in both glands. These findings demonstrate a greater susceptibility of the SM glands of the offspring to F at high concentration in comparison to PA, reinforcing the need to adhere to the optimum F levels recommended by the regulatory agencies. Such findings must be interpreted with caution, especially considering their translational meaning.

Biological Activity of Copaiba in Damage to the Alveolar Bone in a Model of Periodontitis Induced in Rats.

Several studies have investigated the effects of natural products in the treatment of diseases. Traditional Amazonian populations commonly use copaiba due to its well-known anti-inflammatory, antibacterial, and healing properties. In this study, we aimed to investigate the effects of systemic administration of copaiba oleoresin (Copaifera reticulata Ducke) on ligature-induced periodontitis in rats. To do so, 21 adult rats were divided into three groups (n = 7 each): a control group, ligature-induced periodontitis group, and ligature-induced periodontitis group treated with copaiba oleoresin (200 mg/kg/day). The ligature remained from day 0 to 14, and the copaiba oleoresin was administered via oral gavage during the last seven days. On day 14, the animals were euthanized, and mandibles were collected for histopathological evaluation and microcomputed tomography analysis. Our data showed that the administration of copaiba considerably reduced the inflammatory profile. Moreover, copaiba oleoresin limited alveolar bone loss, increased trabecular thickness and bone-to-tissue volume ratio, and decreased the number of trabeculae compared with those of the untreated experimental periodontitis group. Our findings provide pioneering evidence that supports the potential of copaiba oleoresin in reducing periodontitis-induced alveolar bone damage in rats.

Ab initio screening of Pt-based transition-metal nanoalloys using descriptors derived from the adsorption and activation of CO2.

In this study, we report an ab initio screening, based on density functional theory calculations, of Pt-based transition-metal nanoalloys using physicochemical descriptors derived from the adsorption and activation of CO2 on 55-atom nanoclusters, namely, PtnTM55-n, with n = 0, 13, 42, 55, TM = Fe, Co, Ni, Cu, Ru, Rh, Pd, Ag, Os, Ir, Au. From the adsorption on the unary and binary nanoclusters, at the chemisorption regime (bent CO2), we identified a linear correlation between the interaction energy and charge transfer from the nanoclusters towards CO2 and the bent CO2 angle; moreover, the interaction energy is enhanced for larger values of the molecular charge and angle. The alloying of Cu55, Ag55, and Au55 with Pt provides a path to change the CO2 adsorption from physisorption (linear, non-activated) to chemisorption (enhanced interaction energies, bent, activated), while the strong interaction energy of CO2 with Os55, Ru55, and Fe55 can be decreased by alloying with Pt using different structural configurations, i.e., the trends are similar for core-shell and segregated structures. Thus, based on our results and analyses, we can select different combinations of PtnTM55-n nanoalloys to yield the desired interaction strength and magnitude of the charge transfer towards the activated anionic CO2, which can help in the design of nanocatalysts for CO2 activation or different chemical reactions in which charge transfer plays a crucial role.

Role of the OH-group in the adsorption properties of methanol, ethanol, and ethylene glycol on 15-atom 3d, 4d, and 5d transition-metal clusters.

The adsorption of alcohols on transition-metal (TM) substrates has received the attention of many researchers due to the applications of alcohols in several technological fields. However, our atomic-level understanding is still far from satisfactory, in particular for the interaction of alcohols with finite-size TM clusters, where new effects can arise due to the presence of quantum-size effects. In this work, we report a theoretical investigation of the adsorption properties of methanol, ethanol, and ethylene glycol on 12 different 3d, 4d, and 5d TM15 clusters based on density functional theory calculations within the semi-empirical D3 van der Waals corrections. From the correlation analysis of all the lowest- and high-energy configurations, we identified the adsorption modes of methanol, ethanol, and ethylene glycol on the TM15 clusters, in which the OH group binds to the cationic TM sites via the O-TM and H-TM interactions. Due to the relatively weak alcohol-TM15 interaction, the changes induced on the TM15 clusters are small, except for Au15 and Ru15, where the bare cluster changes its structure to a nearby minimum in the potential energy surface. The adsorption energy for the alcohol/TM15 systems is correlated to the combination of several parameters, in which the main contribution is connected with the O-TM interaction and the HOTM angles. Furthermore, the TM electronegativity is an important descriptor for the methanol and ethanol adsorption energies, while charge transfer is important for ethylene glycol.

Drone Swarms as Networked Control Systems by Integration of Networking and Computing.

The study of multi-agent systems such as drone swarms has been intensified due to their cooperative behavior. Nonetheless, automating the control of a swarm is challenging as each drone operates under fluctuating wireless, networking and environment constraints. To tackle these challenges, we consider drone swarms as Networked Control Systems (NCS), where the control of the overall system is done enclosed within a wireless communication network. This is based on a tight interconnection between the networking and computational systems, aiming to efficiently support the basic control functionality, namely data collection and exchanging, decision-making, and the distribution of actuation commands. Based on a literature analysis, we do not find revision papers about design of drone swarms as NCS. In this review, we introduce an overview of how to develop self-organized drone swarms as NCS via the integration of a networking system and a computational system. In this sense, we describe the properties of the proposed components of a drone swarm as an NCS in terms of networking and computational systems. We also analyze their integration to increase the performance of a drone swarm. Finally, we identify a potential design choice, and a set of open research challenges for the integration of network and computing in a drone swarm as an NCS.

Frequency-Spectra-Based High Coding Capacity Chipless RFID Using an UWB-IR Approach.

A novel methodology is proposed to reliably predict the resonant characteristics of a multipatch backscatter-based radio frequency identification (RFID) chipless tag. An ultra-wideband impulsion radio (UWB-IR)-based reader interrogates the chipless tag with a UWB pulse, and analyzes the obtained backscatter in the time domain. The RFID system consists of a radar cross-section (RCS)-based chipless tag containing a square microstrip patch antenna array in which the chipless tag is interrogated with a UWB pulse by an UWB-IR-based reader. The main components of the backscattered signal, the structural mode, and the antenna mode were identified and their spectral quality was evaluated. The study revealed that the antenna-mode backscatter includes signal carrying information, while the structural mode backscatter does not include any tag information. The simulation findings were confirmed by experimental measurements obtained in an anechoic chamber environment using a 6-bit multipatch chipless RFID tag. Finally, the novel technique does not use calibration tags and can freely orient tags with respect to the reader.

A Dynamic Threshold Cancellation Technique for a High-Power Conversion Efficiency CMOS Rectifier.

Power conversion efficiency (PCE) has been one of the key concerns for power management circuits (PMC) due to the low output power of the vibrational energy harvesters. This work reports a dynamic threshold cancellation technique for a high-power conversion efficiency CMOS rectifier. The proposed rectifier consists of two stages, one passive stage with a negative voltage converter, and another stage with an active diode controlled by a threshold cancellation circuit. The former stage conducts the signal full-wave rectification with a voltage drop of 1 mV, whereas the latter reduces the reverse leakage current, consequently enhancing the output power delivered to the ohmic load. As a result, the rectifier can achieve a voltage and power conversion efficiency of over 99% and 90%, respectively, for an input voltage of 0.45 V and for low ohmic loads. The proposed circuit is designed in a standard 130 nm CMOS process and works for an operating frequency range from 800 Hz to 51.2 kHz, which is promising for practical applications.

Reducing the Training Samples for Damage Detection of Existing Buildings through Self-Space Approximation Techniques.

Data-driven methodologies are among the most effective tools for damage detection of complex existing buildings, such as heritage structures. Indeed, the historical evolution and actual behaviour of these assets are often unknown, no physical models are available, and the assessment must be performed only based on the tracking of a set of damage-sensitive features. Selecting the most representative state indicators to monitor and sampling them with an adequate number of records are therefore essential tasks to guarantee the successful performance of the damage detection strategy. Despite their relevance, these aspects have been frequently taken for granted and little attention has been paid to them by the scientific community working in the field of Structural Health Monitoring. The present paper aims to fill this gap by proposing a multistep strategy to drive the selection of meaningful pairs of correlated features in order to support the damage detection as a one-class classification problem. Numerical methods to reduce the number of necessary acquisitions and estimate the performance of approximation techniques are also provided. The analyses carried out to test and validate the proposed strategy exploit a dense dataset collected during the long-term monitoring of an outstanding heritage structure, i.e., the Church of 'Santa Maria de Belém' in Lisbon.

Is the von Mises criterion generally applicable to soft solids?

The purely viscoplastic paradigm has forged the understanding of yield stress materials, leading to misconceptions associated to the set of quantities that are needed to characterize yielding transition and also to the significance of the measured quantities (Thompson et al., 2018). The following assertions, usually taken for granted, are actually simplistic constitutive assumptions: (i) there exists a scalar that represents the yielding condition, (ii) there is a universal rule that maps the yield stress tensor onto that scalar, (iii) the von Mises yielding criterion holds (Thompson et al., 2018). That is, these statements are not necessarily true for a general yield stress material. In the present study we investigate the yielding of seven materials in two extensional loading conditions: traction and compression. We show that the von Mises criterion does not perform well for the yielding of these materials. A new criterion that includes the third invariant of the (deviatoric) yield stress tensor is proposed to handle the differences between traction and compression values of the stress at the yielding point. Even this criterion is not able to accommodate the yielding obtained in shear loading for these materials. In this regard, the most likely scenario is that no universal criterion exists for all kinds of yield stress materials.

Ab initio investigation of the role of transition-metal dopants in the adsorption properties of ethylene glycol on doped Pt(100) surfaces.

Ethylene glycol (EG) has been considered as a promising alcohol for direct alcohol fuel cells, however, our atomistic understanding of its interaction with doped transition-metal (TM) substrates is not well established. Here, we employed density functional theory calculations within the additive van der Waals D3 correction to improve our atomistic understanding of the role of TM dopants on the adsorption properties of EG on undoped and doped Pt(100) surfaces, namely, Pt8TM1/Pt9/Pt(100) and Pt9/Pt8TM1/Pt(100), where substitutional TM dopants (Fe, Co, Ni, Ru, Rh and Pd) are located within the topmost or subsurface Pt(100) layers, respectively. Except for Pd, all the studied TM dopants showed strong energetic preference for the subsurface layer, which can be explained by the segregation energy and charge effects, and it is not affected by the EG adsorption. In the lowest energy configurations of the undoped and doped substrates, EG binds via one OH group, with the anionic O atom located close to the on-top cationic TM site and the H atom parallel to the surface and pointing towards the bridge site. However, at slightly higher energy configurations, EG adsorbs via one OH with the C-C bond almost perpendicular to the surface, or via both OH groups. As expected, the adsorption is stronger on Pt8TM1/Pt9/Pt(100) with EG (OH group) bound to the cationic TM site and a O-TM distance of about 2 Å. Furthermore, doping enhanced the adsorption energy, and hence, decreased the distance between EG and the surface. For all substrates, adsorption induces a reduction of the work function, which is larger for the adsorption of EG via two OH groups.

Ab initio investigation of quantum size effects on the adsorption of CO2, CO, H2O, and H2 on transition-metal particles.

Adsorption is a crucial preliminary step for the conversion of CO2 into higher-value chemicals, nonetheless, the atomistic understanding of how substrate particle size affects this step is still incomplete. In this study, we employed density functional theory to investigate the effects of particle size on the adsorption of model molecules involved in the CO2 transformations (CO2, CO, H2O and H2) on Con, Nin and Cun particles with different sizes (n = 13, 55, 147) and on the respective close-packed surfaces. We found significant size-dependence of the adsorption properties for physisorbed (linear) and chemisorbed (bent) CO2 on the substrates and distinct (symmetric or asymmetric) stretching of the C-O bonds, which can play a crucial role to understand the CO2 dissociation pathways. For CO and H2, some properties showed small oscillations, due to size effects that induced alternation of the adsorption site preference for different particle sizes; for H2O, the adsorption properties were almost independent of particle size. The presence of low-coordinated adsorption sites resulted in a trend for stronger adsorption and greater charge transfer for smaller clusters. Fixing the size-independent factors (e.g., type of metal), our results show that CO2 adsorption on transition-metal clusters is significantly affected by particle size, suggesting that substrate particle size could be a key factor to understand and control the catalytic transformations of CO2.

Safety and Effectiveness of Copaiba Oleoresin (C. reticulata Ducke) on Inflammation and Tissue Repair of Oral Wounds in Rats.

In traditional communities of the Brazilian Amazon, the copaiba oleoresin (C. reticulata Ducke) is widely known for its therapeutic activity, especially its wound healing and anti-inflammatory actions. Our study aimed to evaluate these effects in oral lesions and the safety of the dosage proposed. A punch biopsy wound was induced on the ventral surface of the tongue of forty-five male Wistar rats under anesthesia. Animals were randomly allocated to one of three groups based on the treatment: control, corticoid and copaiba. A daily dose of each treatment and vehicle was administrated by oral gavage for three consecutive days. Sample collections took place on the third, seventh and 15th days post-wounding for clinical and histopathological analyses. Blood was collected on the third and seventh days for kidneys and liver function tests. Semi-quantitative analyses were performed based on scores of inflammation and reepithelization. Tissue collagen deposition was detected by PicroSirius red staining. Copaiba-treated wounds revealed a smaller wound area, decreased of acute inflammatory reaction and enhanced reepithelization. The levels of kidney and liver function tests did not reveal presence of damage post-treatments. Our findings suggest that copaiba oleoresin is a safe and effective alternative therapy for inflammation and tissue repair of oral wounds in this animal model.

The influence of hydroxy groups on the adsorption of three-carbon alcohols on Ni(111), Pd(111) and Pt(111) surfaces: a density functional theory study within the D3 dispersion correction.

Experimentally, steric and inductive effects have been suggested as key parameters in the adsorption and reactivity of alcohols on transition-metal (TM) surfaces, however, our atomistic understanding of the behavior of alcohols in catalysis is far from satisfactory, in particular, due to the role of hydroxy groups in the adsorption properties of C3 alcohols on TM surfaces. In this study, we investigated those effects through ab initio calculations based on density functional theory employing a semilocal exchange-correlation functional within van der Waals corrections (the D3 framework) for the adsorption of C3 alcohols with different numbers and positions of OH groups, namely, propane, 1-propanol, 2-propanol, 1,2-propanediol, 1,3-propanediol and glycerol, on the compact Ni(111), Pd(111) and Pt(111) surfaces. As expected, we found that the adsorption energy is affected by the number of hydroxy groups with similar values for each pair of regioisomers, which clearly indicates the effect of the number of OH groups. Based on Bader charge analysis, we found an effective charge transfer from the C3 molecules to the substrates, which can explain the reduction in the work function due to adsorption. Upon adsorption, the alpha carbon to the OH group closest to the surface and the central carbon are the most positively charged atoms, which increases the lability of their bonded H atoms. In addition, the depletion of electron density between the C-H and O-H bonds closer to the surfaces corroborated their stretching, suggesting that the proximity of the adsorbates to the surfaces affects the acidity of these H atoms, as well as inductive effects within the molecules.

Methyl-cyclopentadienyl Ruthenium Compounds with 2,2'-Bipyridine Derivatives Display Strong Anticancer Activity and Multidrug Resistance Potential.

New ruthenium methyl-cyclopentadienyl compounds bearing bipyridine derivatives with the general formula [Ru(η5-MeCp)(PPh3)(4,4'-R-2,2'-bpy)]+ (Ru1, R = H; Ru2, R = CH3; and Ru3, R = CH2OH) have been synthesized and characterized by spectroscopic and analytical techniques. Ru1 crystallized in the monoclinic P21/ c, Ru2 in the triclinic P1̅, and Ru3 in the monoclinic P21/ n space group. In all molecular structures, the ruthenium center adopts a "piano stool" distribution. Density functional theory calculations were performed for all complexes, and the results support spectroscopic data. Ru1 and Ru3 were poor substrates of the main multidrug resistance human pumps, ABCB1, ABCG2, ABCC1, and ABCC2, while Ru2 displayed inhibitory properties of ABCC1 and ABCC2 pumps. Importantly, all compounds displayed a very high cytotoxic profile for ovarian cancer cells (sensitive and resistant) that was much more pronounced than that observed with cisplatin, making them very promising anticancer agents.

Effect of tolbutamide on tetraethylammonium-induced postsynaptic zinc signals at hippocampal mossy fiber-CA3 synapses.

The application of tetraethylammonium (TEA), a blocker of voltage-dependent potassium channels, can induce long-term potentiation (LTP) in the synaptic systems CA3-CA1 and mossy fiber-CA3 pyramidal cells of the hippocampus. In the mossy fibers, the depolarization evoked by extracellular TEA induces a large amount of glutamate and also of zinc release. It is considered that zinc has a neuromodulatory role at the mossy fiber synapses, which can, at least in part, be due to the activation of presynaptic ATP-dependent potassium (KATP) channels. The aim of this work was to study properties of TEA-induced zinc signals, detected at the mossy fiber region, using the permeant form of the zinc indicator Newport Green. The application of TEA caused a depression of those signals that was partially blocked by the KATP channel inhibitor tolbutamide. After the removal of TEA, the signals usually increased to a level above baseline. These results are in agreement with the idea that intense zinc release during strong synaptic events triggers a negative feedback action. The zinc depression, caused by the LTP-evoking chemical stimulation, turns into potentiation after TEA washout, suggesting the existence of a correspondence between the observed zinc potentiation and TEA-evoked mossy fiber LTP.