In vitro antiproliferative effects of Vatairea macrocarpa (Benth.) Ducke lectin on human tumor cell lines and in vivo evaluation of its toxicity in Drosophila melanogaster.

Tumor cells may develop alterations in glycosylation patterns during the initial phase of carcinogenesis. These alterations may be important therapeutic targets for lectins with antitumor action. This work aimed to evaluate the in vitro cytotoxicity of VML on tumor and non-tumor cells (concentration of 25 µg/mL and then microdiluted) and evaluate its in vivo toxicity at different concentrations (1.8, 3.5 and 7.0 µg/mL), using Drosophila melanogaster. Toxicity in D. melanogaster evaluated mortality rate, as well as oxidative stress markers (TBARS, iron levels, nitric oxide levels, protein and non-protein thiols). The cytotoxicity assay showed that VML had cytotoxic effect on leukemic lines HL-60 (IC50 = 3.5 µg/mL), KG1 (IC50 = 18.6 µg/mL) and K562 (102.0 µg/mL). In the toxicity assay, VML showed no reduction in survival at concentrations of 3.5 and 7.0 µg/mL and did not alter oxidative stress markers at any concentrations tested. Cytotoxicity of VML from HL-60, KG1 and K562 cells could arise from the interaction between the lectin and specific carbohydrates of tumor cells. In contrast, effective concentrations of VML against no-tumor cells human keratinocyte - HaCat and in the D. melanogaster model did not show toxicity, suggesting that VML is a promising molecule in vivo studies involving leukemic cells.

A Supramolecular Injectable Methacryloyl Chitosan-Tricine-Based Hydrogel with 3D Printing Potential for Tissue Engineering Applications.

Printable hydrogels have attracted significant attention as versatile, tunable, and spatiotemporally controlled biomaterials for tissue engineering (TE) applications. Several chitosan-based systems are reported presenting low or no solubility in aqueous solutions at physiological pH. Herein, a novel neutrally charged, biomimetic, injectable, and cytocompatible dual-crosslinked (DC) hydrogel system based on a double functionalized chitosan (CHT) with methacryloyl and tricine moieties (CHTMA-Tricine), completely processable at physiological pH, with promising three-dimensional (3D) printing potential is presented. Tricine, an amino acid typically used in biomedicine, is capable of establishing supramolecular interactions (H-bonds) and is never explored as a hydrogel component for TE. CHTMA-Tricine hydrogels demonstrate significantly greater toughness (ranging from 656.5 ± 82.2 to 1067.5 ± 121.5 kJ m-3 ) compared to CHTMA hydrogels (ranging from 382.4 ± 44.1 to 680.8 ± 104.5 kJ m-3 ), highlighting the contribution of the supramolecular interactions for the overall reinforced 3D structure provided by tricine moieties. Cytocompatibility studies reveal that MC3T3-E1 pre-osteoblasts cells remain viable for 6 days when encapsulated in CHTMA-Tricine constructs, with semi-quantitative analysis showing ≈80% cell viability. This system's interesting viscoelastic properties allow the fabrication of multiple structures, which couple with a straightforward approach, will open doors for the design of advanced chitosan-based biomaterials through 3D bioprinting for TE.

A quantum computing approach for minimum loss problems in electrical distribution networks.

This paper presents an application of a novel quadratic unconstrained binary optimization (QUBO) formulation to the minimum loss problem in distribution networks. The proposed QUBO formulation was conceived to be employed in quantum annealing-a quantum computing paradigm useful for solving combinatorial optimization problems. Quantum annealing is expected to provide better and/or faster solutions to optimization problems when compared to the ones provided by classical computers. With the problem at stake, better solutions result in lower energy losses, and faster solutions contribute to the same outcome given the future need for frequent reconfiguration of distribution networks to accommodate highly volatile demand, as anticipated by recent low-carbon solutions. The paper presents the results obtained through a hybrid quantum-classical solver for a standard 33-node test network and compares them with the ones obtained from classical solvers. Our main conclusion is that quantum annealing has potential to show advantage in the near future in terms of solution quality and time-to-solution, as quantum annealers and hybrid solvers continue to improve their performance.

Application of thermography to estimate respiratory rate in the emergency room: The journal Temperature toolbox.

Among the vital signs collected during hospital triage, respiratory rate is an important parameter associated with physiological, pathophysiological, and emotional changes. In recent years, the importance of its verification in emergency centers due to the severe acute respiratory syndrome 2 (SARS2) pandemic has become very clear, although it is still one of the least evaluated and collected vital signs. In this context, infrared imaging has been shown to be a reliable estimator of respiratory rate, with the advantage of not requiring physical contact with patients. The objective of this study was to evaluate the potential of analyzing a sequence of thermal images as an estimator of respiratory rate in the clinical routine of an emergency room. We used an infrared thermal camera (T540, Flir Systems) to obtain the respiratory rate data of 136 patients, based on nostrils' temperature fluctuation, during the peak of the COVID-19 pandemic in Brazil and compared it with the chest incursion count method, commonly employed in the emergency screening procedures. We found a good agreement between both methods, with Bland-Altman limits of agreement ranging from -4 to 4 min-1, no proportional bias (R2 = 0.021, p = 0.095), and a strong correlation between them (r = 0.95, p < 0.001). Our results suggest that infrared thermography has potential to be a good estimator of respiratory rate in the routine of an emergency room.

The Southern Ocean mixed layer and its boundary fluxes: fine-scale observational progress and future research priorities.

Interactions between the upper ocean and air-ice-ocean fluxes in the Southern Ocean play a critical role in global climate by impacting the overturning circulation and oceanic heat and carbon uptake. Remote and challenging conditions have led to sparse observational coverage, while ongoing field programmes often fail to collect sufficient information in the right place or at the time-space scales required to constrain the variability occurring in the coupled ocean-atmosphere system. Only within the last 10 years have we been able to directly observe and assess the role of the fine-scale ocean and rapidly evolving atmospheric marine boundary layer on the upper limb of the Southern Ocean's overturning circulation. This review summarizes advances in mechanistic understanding, arising in part from observational programmes using autonomous platforms, of the fine-scale processes (1-100 km, hours-seasons) influencing the Southern Ocean mixed layer and its variability. We also review progress in observing the ocean interior connections and the coupled interactions between the ocean, atmosphere and cryosphere that moderate air-sea fluxes of heat and carbon. Most examples provided are for the ice-free Southern Ocean, while major challenges remain for observing the ice-covered ocean. We attempt to elucidate contemporary research gaps and ongoing/future efforts needed to address them. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

Southern Ocean phytoplankton dynamics and carbon export: insights from a seasonal cycle approach.

Quantifying the strength and efficiency of the Southern Ocean biological carbon pump (BCP) and its response to predicted changes in the Earth's climate is fundamental to our ability to predict long-term changes in the global carbon cycle and, by extension, the impact of continued anthropogenic perturbation of atmospheric CO2. There is little agreement, however, in climate model projections of the sensitivity of the Southern Ocean BCP to climate change, with a lack of consensus in even the direction of predicted change, highlighting a gap in our understanding of a major planetary carbon flux. In this review, we summarize relevant research that highlights the important role of fine-scale dynamics (both temporal and spatial) that link physical forcing mechanisms to biogeochemical responses that impact the characteristics of the seasonal cycle of phytoplankton and by extension the BCP. This approach highlights the potential for integrating autonomous and remote sensing observations of fine scale dynamics to derive regionally optimized biogeochemical parameterizations for Southern Ocean models. Ongoing development in both the observational and modelling fields will generate new insights into Southern Ocean ecosystem function for improved predictions of the sensitivity of the Southern Ocean BCP to climate change. This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.

Determining the Proximity Effect-Induced Magnetic Moment in Graphene by Polarized Neutron Reflectivity and X-ray Magnetic Circular Dichroism.

We report the magnitude of the induced magnetic moment in CVD-grown epitaxial and rotated-domain graphene in proximity with a ferromagnetic Ni film, using polarized neutron reflectivity (PNR) and X-ray magnetic circular dichroism (XMCD). The XMCD spectra at the C K-edge confirm the presence of a magnetic signal in the graphene layer, and the sum rules give a magnetic moment of up to ∼0.47 µB/C atom induced in the graphene layer. For a more precise estimation, we conducted PNR measurements. The PNR results indicate an induced magnetic moment of ∼0.41 µB/C atom at 10 K for epitaxial and rotated-domain graphene. Additional PNR measurements on graphene grown on a nonmagnetic Ni9Mo1 substrate, where no magnetic moment in graphene is measured, suggest that the origin of the induced magnetic moment is due to the opening of the graphene's Dirac cone as a result of the strong C pz-Ni 3d hybridization.

It Takes Two to Tango, Part II: Synthesis of A-Ring Functionalised Quinones Containing Two Redox-Active Centres with Antitumour Activities.

In 2021, our research group published the prominent anticancer activity achieved through the successful combination of two redox centres (ortho-quinone/para-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. The combination of two naphthoquinoidal substrates towards a synergetic product was indicated, but not fully explored. Herein, we report the synthesis of 15 new quinone-based derivatives prepared from click chemistry reactions and their subsequent evaluation against nine cancer cell lines and the murine fibroblast line L929. Our strategy was based on the modification of the A-ring of para-naphthoquinones and subsequent conjugation with different ortho-quinoidal moieties. As anticipated, our study identified several compounds with IC50 values below 0.5 µM in tumour cell lines. Some of the compounds described here also exhibited an excellent selectivity index and low cytotoxicity on L929, the control cell line. The antitumour evaluation of the compounds separately and in their conjugated form proved that the activity is strongly enhanced in the derivatives containing two redox centres. Thus, our study confirms the efficiency of using A-ring functionalized para-quinones coupled with ortho-quinones to obtain a diverse range of two redox centre compounds with potential applications against cancer cell lines. Here as well, it literally takes two for an efficient tango!

Multidecadal trend of increasing iron stress in Southern Ocean phytoplankton.

Southern Ocean primary productivity is principally controlled by adjustments in light and iron limitation, but the spatial and temporal determinants of iron availability, accessibility, and demand are poorly constrained, which hinders accurate long-term projections. We present a multidecadal record of phytoplankton photophysiology between 1996 and 2022 from historical in situ datasets collected by Biogeochemical Argo (BGC-Argo) floats and ship-based platforms. We find a significant multidecadal trend in irradiance-normalized nonphotochemical quenching due to increasing iron stress, with concomitant declines in regional net primary production. The observed trend of increasing iron stress results from changing Southern Ocean mixed-layer physics as well as complex biological and chemical feedback that is indicative of important ongoing changes to the Southern Ocean carbon cycle.

Incorporation of a molybdenum atom in a Rubredoxin-type Centre of a de novo-designed α3DIV-L21C three-helical bundle peptide.

The rational design and functionalization of small, simple, and stable peptides scaffolds is an attractive avenue to mimic catalytic metal-centres of complex proteins, relevant for the design of metalloenzymes with environmental, biotechnological and health impacts. The de novo designed α3DIV-L21C framework has a rubredoxin-like metal binding site and was used in this work to incorporate a Mo-atom. Thermostability studies using differential scanning calorimetry showed an increase of 4 °C in the melting temperature of the Mo-α3DIV-L21C when compared to the apo-α3DIV-L21C. Circular dichroism in the visible and far-UV regions corroborated these results showing that Mo incorporation provides stability to the peptide even though there were almost no differences observed in the secondary structure. A formal reduction potential of ∼ -408 mV vs. NHE, pH 7.6 was determined. Combining electrochemical results, EPR and UV-visible data we discuss the oxidation state of the molybdenum centre in Mo-α3DIV-L21C and propose that is mainly in a Mo (VI) oxidation state.

Microcapsules based on alginate and guar gum for co-delivery of hydrophobic antitumor bioactives.

The main goal was the development of a polysaccharide microcapsule for anticancer application based on guar gum and sodium alginate for the controlled release of hesperidin and betulinic acid by spray drying technique. The microcapsule showed an Encapsulation Efficiency of 98.15 ± 0.34 % for hesperidin and 99.76 ± 0.22 % for betulinic acid. In the release study, the Korsmeyer-Peppas mathematical model was identified as the most adequate to explain the observed release mechanism. In vivo tests were performed in zebrafish model, revealing that the microcapsules did not alter the locomotor activity and were not toxic within 96 h by oral administration, suggesting their biological safety. In vitro cytotoxic activity against HL-60 cells confirmed an IC50 value of 2.52 ± 0.23 µg mL-1 in 72 h. Additionally, a decrease in the cytotoxic activity of betulinic acid against L-929 (non-tumor) cells was evidenced. Therefore, the microcapsules synthesized in this work represent a promising formulation for anticancer applications.

Cysteine-Assisted Click-Chemistry for Proximity-Driven, Site-Specific Acetylation of Histones.

Post-translational modifications of histones are essential in the regulation of chromatin structure and function. Among these modifications, lysine acetylation is one of the most established. Earlier studies relied on the use of chromatin containing heterogeneous mixtures of histones acetylated at multiple sites. Differentiating the individual contribution of single acetylation events towards chromatin regulation is thus of great relevance. However, it is difficult to access homogeneous samples of histones, with a single acetylation, in sufficient quantities for such studies. By engineering histone H3 with a cysteine in proximity of the lysine of interest, we demonstrate that conjugation with maleimide-DBCO followed by a strain-promoted alkyne-azide cycloaddition reaction results in the acetylation of a single lysine in a controlled, site-specific manner. The chemical precision offered by our click-to-acetylate approach will facilitate access to and the study of acetylated histones.

Two new species of geckos of the genus Phyllopezus Peters, 1878 (Squamata: Gekkota: Phyllodactylidae) from northeastern Brazil.

We describe two new species of Brazilian geckos of the genus Phyllopezus based on morphological and molecular data. The first species is currently known from a relictual Cerrado enclavecampos rupestres, in the mountains of the Serra do Espinhao in the state of Bahia. The second species is known from northeastern Atlantic Forest and transitional areas with Caatinga biome in the state of Alagoas. The two new species are sister taxa and together are the sister clade to the remaining species in the Phyllopezus pollicaris species complex. These new species can be morphologically distinguished from their congeners by meristic and morphometric characters, in addition to color pattern and genetic differentiation.

Network biology and artificial intelligence drive the understanding of the multidrug resistance phenotype in cancer.

Globally with over 10 million deaths per year, cancer is the most transversal disease across countries, cultures, and ethnicities, affecting both developed and developing regions. Tumorigenesis is dynamically altered by distinct events and can be lethal when untreated. Despite the innovative therapeutics available, multidrug resistance (MDR) to chemotherapy remains the major hindrance to the success of cancer therapy. The multiple mechanisms by which cancer cells evade cell death are diverse, indicating that MDR involves complex interconnected biological networks. Molecular profiling is currently able to stratify cancer into its distinct subtypes and help identify the best therapeutics, leading to "translational systems medicine". Highly specialized methodologies are generating a large amount of "omics" data - including epigenetics, genomics, transcriptomics, proteomics, metabolomics, as well as pharmacogenomics. Many of the resulting databases store data in non-standard formats, which need to be converted, interpreted, and merged into readable formats. The latest development of artificial intelligence (AI) methodologies and tools, coupled with advancements in large-scale data management and powerful graphic processing computing units, potentiate the integration of these large data sources into relevant biological networks, which will enhance our understanding of cancer MDR. In this review, we revisit common MDR mechanisms and compile a list of the most relevant "omics" public databases. We highlight examples of AI methods that are now decisively contributing to clear advances in cancer research, such as identification of new drugs from large databases and prediction of relevant drug, target, and system properties. An overview of several freely available "ready-to-use" algorithms is also provided. The described molecular scale AI algorithms and tools will undoubtedly guide important improvements in efficiency and efficacy of traditional methods of cancer diagnostics and treatment.

Storms drive outgassing of CO2 in the subpolar Southern Ocean.

The subpolar Southern Ocean is a critical region where CO2 outgassing influences the global mean air-sea CO2 flux (FCO2). However, the processes controlling the outgassing remain elusive. We show, using a multi-glider dataset combining FCO2 and ocean turbulence, that the air-sea gradient of CO2 (∆pCO2) is modulated by synoptic storm-driven ocean variability (20 µatm, 1-10 days) through two processes. Ekman transport explains 60% of the variability, and entrainment drives strong episodic CO2 outgassing events of 2-4 mol m-2 yr-1. Extrapolation across the subpolar Southern Ocean using a process model shows how ocean fronts spatially modulate synoptic variability in ∆pCO2 (6 µatm2 average) and how spatial variations in stratification influence synoptic entrainment of deeper carbon into the mixed layer (3.5 mol m-2 yr-1 average). These results not only constrain aliased-driven uncertainties in FCO2 but also the effects of synoptic variability on slower seasonal or longer ocean physics-carbon dynamics.

It takes two to tango: synthesis of cytotoxic quinones containing two redox active centers with potential antitumor activity.

We report the synthesis of 47 new quinone-based derivatives via click chemistry and their subsequent evaluation against cancer cell lines and the control L929 murine fibroblast cell line. These compounds combine two redox centers, such as an ortho-quinone/para-quinone or quinones/selenium with the 1,2,3-triazole nucleus. Several of these compounds present IC50 values below 0.5 µM in cancer cell lines with significantly lower cytotoxicity in the control cell line L929 and good selectivity index. Hence, our study confirms the use of a complete and very diverse range of quinone compounds with potential application against certain cancer cell lines.

Arylethynyltrifluoroborate Dienophiles for on Demand Activation of IEDDA Reactions.

Strained alkenes and alkynes are the predominant dienophiles used in inverse electron demand Diels-Alder (IEDDA) reactions. However, their instability, cross-reactivity, and accessibility are problematic. Unstrained dienophiles, although physiologically stable and synthetically accessible, react with tetrazines significantly slower relative to strained variants. Here we report the development of potassium arylethynyltrifluoroborates as unstrained dienophiles for fast, chemically triggered IEDDA reactions. By varying the substituents on the tetrazine (e.g., pyridyl- to benzyl-substituents), cycloaddition kinetics can vary from fast (k2 = 21 M-1 s-1) to no reaction with an alkyne-BF3 dienophile. The reported system was applied to protein labeling both in the test tube and fixed cells and even enabled mutually orthogonal labeling of two distinct proteins.

Styrylpyrazoles: Properties, Synthesis and Transformations.

The pyrazole nucleus and its reduced forms, pyrazolines and pyrazolidine, are privileged scaffolds in medicinal chemistry due to their remarkable biological activities. A huge number of pyrazole derivatives have been studied and reported over time. This review article gives an overview of pyrazole derivatives that contain a styryl (2-arylvinyl) group linked in different positions of the pyrazole backbone. Although there are studies on the synthesis of styrylpyrazoles dating back to the 1970s and even earlier, this type of compound has rarely been studied. This timely review intends to summarize the properties, biological activity, methods of synthesis and transformation of styrylpyrazoles; thus, highlighting the interest and huge potential for application of this kind of compound.

Correction: Boronic acids as building blocks for the construction of therapeutically useful bioconjugates.

Correction for 'Boronic acids as building blocks for the construction of therapeutically useful bioconjugates' by João P. M. António et al., Chem. Soc. Rev., 2019, 48, 3513-3536, DOI: .