A New Heteroleptic Zn(II) Complex with Schiff Bases Sensitizes Triple-Negative Breast Cancer Cells to Doxorubicin and Paclitaxel.

: Triple-negative breast cancer (TNBC) is the most challenging molecular subtype of breast cancer (BC) in clinical practice, associated with a worse prognosis due to limited treatment strategies and its insensitivity to conventional drugs. Zinc is an important trace element for homeostasis, and its Schiff base metal complexes have shown promise in treating advanced tumors. In this study, four new heteroleptic Zn(II) complexes (-) with Schiff bases were synthesized, characterized, and evaluated for their activity in BC cells.

Analysis of goal, feedback and rewards on sustained attention via machine learning.

Introduction: Sustaining attention is a notoriously difficult task as shown in a recent experiment where reaction times (RTs) and pupillometry data were recorded from 350 subjects in a 30-min vigilance task. Subjects were also presented with different types of goal, feedback, and reward.

Methods: In this study, we revisit this experimental data and solve three families of machine learning problems: (i) RT-regression problems, to predict subjects' RTs using all available data, (ii) RT-classification problems, to classify responses more broadly as attentive, semi-attentive, and inattentive, and (iii) to predict the subjects' experimental conditions from physiological data.

Rhenium(I) and technetium(I) complexes with megazol derivatives: towards the development of a theranostic platform for Chagas disease.

The diagnosis and treatment of Chagas disease (CD) in the chronic phase remains a challenge. With that in mind, a potential theranostic device based on the trypanocidal agent known as megazol and the -M(CO) (M = Re or Tc) fragment is proposed in the present work. The peripheral structure of megazol (L) was modified to obtain the compounds L (R1 = H, R2 = Me and R1 = R2 = Me), which were used in the syntheses of complexes of composition [ReBr(CO)L].

Reconstructing rodent brain signals during euthanasia with eigensystem realization algorithm (ERA).

We accurately reconstruct the Local Field Potential time series obtained from anesthetized and awake rats, both before and during CO euthanasia. We apply the Eigensystem Realization Algorithm to identify an underlying linear dynamical system capable of generating the observed data. Time series exhibiting more intricate dynamics typically lead to systems of higher dimensions, offering a means to assess the complexity of the brain throughout various phases of the experiment.

Gold(I) and Silver(I) Complexes Containing Hybrid Sulfonamide/Thiourea Ligands as Potential Leishmanicidal Agents.

Leishmaniasis is a group of parasitic diseases with the potential to infect more than 1 billion people; however, its treatment is still old and inadequate. In order to contribute to changing this view, this work consisted of the development of complexes derived from M metal ions with thioureas, aiming to obtain potential leishmanicidal agents. The thiourea ligands (HL) were obtained by reactions of -toluenesulfohydrazide with R-isothiocyanates and were used in complexation reactions with Ag and Au, leading to the formation of complexes of composition [M(HL)]X (M = Ag or Au; X = NO or Cl).

Selective vulnerability and resilience to Alzheimer's disease tauopathy as a function of genes and the connectome.

Brain regions in Alzheimer's (AD) exhibit distinct vulnerability to the disease's hallmark pathology, with the entorhinal cortex and hippocampus succumbing early to tau tangles while others like primary sensory cortices remain resilient. The quest to understand how local/regional genetic factors, pathogenesis, and network-mediated spread of pathology together govern this selective vulnerability (SV) or resilience (SR) is ongoing. Although many risk genes in AD are known from gene association and transgenic studies, it is still not known whether and how their baseline expression signatures confer SV or SR to brain structures.

Cellular underpinnings of the selective vulnerability to tauopathic insults in Alzheimer's disease.

Neurodegenerative diseases such as Alzheimer's disease (AD) exhibit pathological changes in the brain that proceed in a stereotyped and regionally specific fashion, but the cellular and molecular underpinnings of regional vulnerability are currently poorly understood. Recent work has identified certain subpopulations of neurons in a few focal regions of interest, such as the entorhinal cortex, that are selectively vulnerable to tau pathology in AD. However, the cellular underpinnings of regional susceptibility to tau pathology are currently unknown, primarily because whole-brain maps of a comprehensive collection of cell types have been inaccessible.

Effect of essential oil of Alpinia zerumbet on cardiovascular and autonomic function in rats with isoproterenol induced acute myocardial infarction.

Alpinia zerumbet is a plant popularly used to treat hypertension and anxiety. Studies with Alpinia zerumbet demonstrate antihypertensive and vasodilator effects, among others. The objective of this study was to analyze the effect of essential oil of Alpinia zerumbet (EOAz) on cardiovascular and autonomic function in rats with isoproterenol-induced myocardial infarction.

Gold-Based Coronands as Hosts for M Metal Ions: Ring Size Matters.

The controlled, self-assembled synthesis of multinuclear coordination compounds can be performed via different approaches. Frequently, steric, geometric and/or electronic factors located at the ligand systems predefine the way in which metal ions can assemble them to large aggregates. For the compounds in the present paper, also the Pearson's acidities and preferred coordination geometries of the metal ions were used as organization principles.

Vasorelaxant effect of Alpinia zerumbet's essential oil on rat resistance artery involves blocking of calcium mobilization.

Alpinia zerumbet is a plant from the Zingiberaceae family, popularly used for hypertension treatment. Several studies have demonstrated Alpinia zerumbet vasodilator effect on conductance vessels but not on resistance vessels. Thereby, the aim of this study was to verify the vasodilator effect of the essential oil of Alpinia zerumbet (EOAz) on isolated rat resistance arteries and characterize its mechanism of action.

New ruthenium(II) complexes with cyclic thio- and semicarbazone: evaluation of cytotoxicity and effects on cell migration and apoptosis of lung cancer cells.

We describe the synthesis, physicochemical characterization, and antitumor assays of four novel analogous ruthenium(II) complexes with general formula -[Ru(N-L)(P-P)]PF, where P-P = bis(diphenylphosphine)methane (dppm, in complexes 1 and 2) or bis(diphenylphosphine)ethane (dppe, in complexes 3 and 4) and N-L = 5,6-diphenyl-4,5-dihydro-2-[1,2,4]triazine-3-thione (Btsc, in complexes 1 and 3) or 5,6-diphenyltriazine-3-one (Bsc, in complexes 2 and 4). The data were consistent with arrangement of the biphosphine ligands. For the Btsc and Bsc ligands, the data pointed to monoanionic bidentate coordination to ruthenium(II) through , and ,, respectively.

Influence of nitro ruthenium isomerization on photochemically induced nitric oxide release: Vasorelaxant activities.

We have synthesized cis-[Ru(bpy)(NO-κN)L] and cis-[Ru(bpy)(NO-κO)L ] (bpy = 2,2'-bipyridine; k = indication of the coordinated center to Ruthenium; L = pyridine type ligand) by reacting cis-[Ru(bpy)(HO)L] with sodium nitrite or conducting basic cis-[Ru(bpy)NO(L)] hydrolysis. Photolysis at the metal-ligand charge transfer band (MLCT) of the isomers yielded nitric oxide (NO) as determined by NO measurement. The NO photorelease rates obtained upon 447 nm laser irradiation of the ruthenium complexes showed that cis-[Ru(bpy)(NO-κO)L] released NO three times faster than cis-[Ru(bpy)(NO-κN)L].

Electrocatalytic properties of a novel ruthenium(II) terpyridine-based complex towards CO reduction.

The electrocatalytic properties of Ru complexes are of great technological interest given their potential application in reactions such water splitting and CO reduction. In this work, a novel terpyridine-based Ru(II) complex, [RuCl(trpy)(acpy)], trpy = 2,2':6',2''-terpyridine, acpy = 2-pyridylacetate was synthesized and its spectroscopic, electrochemical and catalytic properties were explored in detail. In dry acetonitrile, the complex exhibits two reduction peaks at -1.

Peritoneal Dialysis Exit-Site Care Protocols in Portugal and Its Association with Catheter-Related Infections.

Introduction: Exit-site infection (ESi) prevention is a key factor in lowering the risk of peritonitis. This study aimed to evaluate the associations between exit-site (ES) care protocols and the annual incidence rates of ESi and peritonitis in Portugal.

Methods: We performed a national survey using two questionnaires: one about the incidence of catheter-related infections and the other characterizing patients' education and ES care protocols.

The effects of microglia on tauopathy progression can be quantified using Nexopathy in silico (Nexis) models.

The prion-like transsynaptic propagation of misfolded tau along the brain's connectome has previously been modeled using connectome-based network diffusion models. In addition to the connectome, interactions between the general neurological "milieu" in the neurodegenerative brain and proteinopathic species can also contribute to pathology propagation. Such a molecular nexopathy framework posits that the distinct characteristics of neurodegenerative disorders stem from interactions between the network and surrounding molecular players.

Are there synergies in the decarbonization of aviation and shipping? An integrated perspective for the case of Brazil.

Aviation and shipping account for 22% of total transport-related CO emissions. Low-carbon fuels (such as biofuels and e-fuels) are the most promising alternatives to deeply decarbonize air and maritime transport. A number of technological routes focused on the production of renewable jet fuel can coproduce marine fuels, emulating the economies of scope of crude oil refineries.

Zinc(II) complexes bearing N,N,S ligands: Synthesis, crystal structure, spectroscopic analysis, molecular docking and biological investigations about its antifungal activity.

In the present work, the synthesis, characterization, antifungal activity, molecular docking study and in silico approach of five thiosemicarbazone derivatives and their corresponding zinc(II) complexes are described. The compounds were characterized by elemental analysis, IR, UV-Vis and NMR spectroscopic measurements, molar conductivity measurements, emission spectra, high-resolution mass spectrometry and X ray study. The antifungal activity of the free ligands and synthesized compounds was preliminarily evaluated against Candida albicans (ATCC 90028), Candida tropicalis (ATCC 13803) and Candida glabrata (ATCC 2001), by the minimum inhibitory concentration (MIC) assay.

Matrix Inversion and Subset Selection (MISS): A pipeline for mapping of diverse cell types across the murine brain.

The advent of increasingly sophisticated imaging platforms has allowed for the visualization of the murine nervous system at single-cell resolution. However, current experimental approaches have not yet produced whole-brain maps of a comprehensive set of neuronal and nonneuronal types that approaches the cellular diversity of the mammalian cortex. Here, we aim to fill in this gap in knowledge with an open-source computational pipeline, Matrix Inversion and Subset Selection (MISS), that can infer quantitatively validated distributions of diverse collections of neural cell types at 200-μm resolution using a combination of single-cell RNA sequencing (RNAseq) and in situ hybridization datasets.

Modeling seeding and neuroanatomic spread of pathology in amyotrophic lateral sclerosis.

The neurodegenerative disorder amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of upper and lower motor neurons, with pathological involvement of cerebral motor and extra-motor areas in a clinicopathological spectrum with frontotemporal dementia (FTD). A key unresolved issue is how the non-random distribution of pathology in ALS reflects differential network vulnerability, including molecular factors such as regional gene expression, or preferential spread of pathology via anatomical connections. A system of histopathological staging of ALS based on the regional burden of TDP-43 pathology observed in postmortem brains has been supported to some extent by analysis of distribution of in vivo structural MRI changes.

Mechanistic investigation of the aerobic oxidation of 2-pyridylacetate coordinated to a Ru(II) polypyridyl complex.

A new ruthenium polypyridyl complex, [Ru(bpy)(acpy)] (acpy = 2-pyridylacetate, bpy = 2,2'-bipyridine), was synthesized and fully characterized. Distinct from the previously reported analog, [Ru(bpy)(pic)] (pic = 2-pyridylcarboxylate), the new complex is unstable under aerobic conditions and undergoes oxidation to yield the corresponding α-keto-2-pyridyl-acetate (acpyoxi) coordinated to the Ru center. The reaction is one of the few examples of C-H activation at mild conditions using O as the primary oxidant and can provide mechanistic insights with important implications for catalysis.

Emergence of directional bias in tau deposition from axonal transport dynamics.

Defects in axonal transport may partly underpin the differences between the observed pathophysiology of Alzheimer's disease (AD) and that of other non-amyloidogenic tauopathies. Particularly, pathological tau variants may have molecular properties that dysregulate motor proteins responsible for the anterograde-directed transport of tau in a disease-specific fashion. Here we develop the first computational model of tau-modified axonal transport that produces directional biases in the spread of tau pathology.

Copper(II) complexes based on thiosemicarbazone ligand: Preparation, crystal structure, Hirshfeld surface, energy framework, antiMycobacterium activity, in silico and molecular docking studies.

Considering the promising previous results on the remarkable activity exhibited by cobalt(III) and manganese(II) thiosemicarbazone compounds as antibacterial agents, the present study aimed to prepare and then evaluate the antibacterial activity of two different types of Cu(II) complexes based on a 2-acetylpyridine-N(4)-methyl-thiosemicarbazone ligand (Hatc-Me), a monomer complex [CuCl(atc-Me)] and a novel dinuclear complex [{Cu(μ-atc-Me)}μ-SO]. The compounds were characterized by infrared spectra, ultraviolet visible and CHN elemental analysis. In addition, the crystalline structures of the complexes were determined by single-crystal X-ray diffraction.

A Computational Model for Pain Processing in the Dorsal Horn Following Axonal Damage to Receptor Fibers.

Computational modeling of the neural activity in the human spinal cord may help elucidate the underlying mechanisms involved in the complex processing of painful stimuli. In this study, we use a biologically-plausible model of the dorsal horn circuitry as a platform to simulate pain processing under healthy and pathological conditions. Specifically, we distort signals in the receptor fibers akin to what is observed in axonal damage and monitor the corresponding changes in five quantitative markers associated with the pain response.

Built to Last: Functional and Structural Mechanisms in the Moth Olfactory Network Mitigate Effects of Neural Injury.

Most organisms suffer neuronal damage throughout their lives, which can impair performance of core behaviors. Their neural circuits need to maintain function despite injury, which in particular requires preserving key system outputs. In this work, we explore whether and how certain structural and functional neuronal network motifs act as injury mitigation mechanisms.