The potential of third-generation biodiesel from Tolypothrix sp. CACIAM22 as a feedstock.

Renewable energy has been recognized as an alternative to fossil fuels as a step to transform the energy produced and consumed worldwide. Cyanobacteria and microalgae are currently being considered as substitutes to the traditional feedstock used to produce biofuels due to their ability to achieve high amounts of lipids under cellular stress conditions. The aim of this study was to investigate the utilization of Tolypothrix sp. CACIAM 22 cyanobacterial biomass as a feedstock for biodiesel production, specifically by examining the effects of supplementing with hydrolysate of Brazil nutshell (HBNS) on biomass generation, lipid production, fatty acid composition, and quality of synthesized biodiesel. The supplementation of HBNS led to a significant increase of 12g.L-1 in wet biomass production. The lipid content reached 41 % of the biomass produced in HBNS supplemented cultures when nitrate source was deprived. The quality evaluation of cyanobacteria-derived biodiesel was performed using Biodiesel Analyzer ver 2.2 software, revealing superior quality compared to biodiesel produced from plant sources. The biodiesel exhibited values of 23 h for oxidative stability, 65 for cetane number, and an iodine index of 31 (g I2. 100 g-1 fat), indicating promising potential as a renewable source. This study is the first to utilize HBNS as an organic supplement for cyanobacteria culture medium and assess its impact on biomass and lipid production in Tolypothrix sp., supporting the hypothesis of utilizing this biomass as a renewable feedstock for biodiesel production as a viable alternative to plant sources based on biomass production, lipid productivity, and biodiesel quality.

Misclassification of a frequent variant from PMS2CL pseudogene as a PMS2 loss of function variant in Brazilian patients.

PMS2, a Lynch Syndrome gene, presents challenges in genetic testing due to the existence of multiple pseudogenes. This study aims to describe a series of cases harboring a variant in the PMS2CL pseudogene that has been incorrectly assigned to PMS2 with different nomenclatures. We reviewed data from 647 Brazilian patients who underwent multigene genetic testing at a single center to identify those harboring the PMS2 V1:c.2186_2187delTC or V2:c.2182_2184delACTinsG variants, allegedly located at PMS2 exon 13. Gene-specific PCR and transcript sequencing was performed. Among the 647 individuals, 1.8% (12) carried the investigated variants, with variant allele frequencies ranging from 15 to 34%. By visually inspecting the alignments, we confirmed that both V1 and V2 represented the same variant and through gene-specific PCR and PMS2 transcript analysis, we demonstrated that V1/V2 is actually located in the PMS2CL pseudogene. Genomic databases (ExAC and gnomAD) report an incidence of 2.5 - 5.3% of this variant in the African population. Currently, V1 is classified as "uncertain significance" and V2 as "conflicting" in ClinVar, with several laboratories classifying them as "pathogenic". We identified a frequent African PMS2CL variant in the Brazilian population that is misclassified as a PMS2 variant. It is likely that V1/V2 have been erroneously assigned to PMS2 in several manuscripts and by clinical laboratories, underscoring a disparity-induced matter. Considering the limitations of short-read NGS differentiating between certain regions of PMS2 and PMS2CL, using complementary methodologies is imperative to provide an accurate diagnosis.

Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells.

Aim: Multidrug resistance (MDR) is frequent in non-small cell lung cancer (NSCLC) patients, which can be due to its fibrotic stroma. This work explores the combination of pentoxifylline, an anti-fibrotic and chitinase 3-like-1 (CHI3L1) inhibitor drug, with conventional chemotherapy to improve NSCLC treatment. Methods: The effect of pentoxifylline in the expression levels of P-glycoprotein (P-gp), CHI3L1 and its main downstream proteins, as well as on cell death, cell cycle profile, and P-gp activity was studied in two pairs of sensitive and MDR counterpart NSCLC cell lines (NCI-H460/NCI-H460/R and A549/A549-CDR2). Association studies between CHI3L1 gene expression and NSCLC patients' survival were performed using The Cancer Genome Atlas (TCGA) analysis. The sensitizing effect of pentoxifylline to different drug regimens was evaluated in both sensitive and MDR NSCLC cell lines. The cytotoxicity of the drug combinations was assessed in MCF10A non-tumorigenic cells. Results: Pentoxifylline slightly decreased the expression levels of CHI3L1, ß-catenin and signal transducer and activator of transcription 3 (STAT3), and caused a significant increase in the G1 phase of the cell cycle in both pairs of NSCLC cell lines. A significant increase in the % of cell death was observed in the sensitive NCI-H460 cell line. TCGA analysis revealed that high levels of CHI3L1 are associated with low overall survival (OS) in NSCLC patients treated with vinorelbine. Moreover, pentoxifylline sensitized both pairs of sensitive and MDR NSCLC cell lines to the different drug regimens, without causing significant toxicity to non-tumorigenic cells. Conclusion: This study suggests the possibility of combining pentoxifylline with chemotherapy to increase NSCLC therapeutic response, even in cases of MDR.

Infrared spectroscopy for fast screening of diabetes and periodontitis.

SIGNIFICANCE: FT-IR is an important and emerging tool, providing information related to the biochemical composition of biofluids. It is important to demonstrate that there is an efficacy in separating healthy and diseased groups, helping to establish FT-IR uses as fast screening tool. AIM: Via saliva diagnosis evaluate the accuracy of FT-IR associate with machine learning model for classification among healthy (control group), diabetic (D) and periodontitis (P) patients and the association of both diseases (DP). APPROACH: Eighty patients diagnosed with diabetes and periodontitis through conventional methods were recruited and allocated in one of the four groups. Saliva samples were collected from participants of each group (n = 20) and were processed using Bruker Alpha II spectrometer in a FT-IR spectral fingerprint region between 600 and-1800 cm-1, followed by data preprocessing and analysis using machine learning tools. RESULTS: Various FTI-R peaks were detectable and attributed to specific vibrational modes, which were classified based on confusion matrices showed in paired groups. The highest true positive rates (TPR) appeared between groups C vs D (93.5 % ± 2.7 %), groups C vs. DP (89.2 % ± 4.1 %), and groups D and P (90.4 % ± 3.2 %). However, P vs DP presented higher TPR for DP (84.1 % ±3.1 %) while D vs. DP the highest rate for DP was 81.7 % ± 4.3 %. Analyzing all groups together, the TPR decreased. CONCLUSION: The system used is portable and robust and can be widely used in clinical environments and hospitals as a new diagnostic technique. Studies in our groups are being conducted to solidify and expand data analysis methods with friendly language for healthcare professionals. It was possible to classify healthy patients in a range of 78-93 % of accuracy. Range over 80 % of accuracy between periodontitis and diabetes were observed. A general classification model with lower TPR instead of a pairwise classification would only have advantages in scenarios where no prior patient information is available regarding diabetes and periodontitis status.

Mass spectrometry-based quantification of immunostimulatory gliadin proteins and peptides in coloured wheat varieties: Implications for Celiac Disease.

Pigmented wheat varieties (Triticum aestivum spp.) are getting increasingly popular in modern nutrition and thoroughly researched for their functional and nutraceutical value. The colour of these wheat grains is caused by the expression of natural pigments, including carotenoids and anthocyanins, that can be restricted to either the endosperm, pericarp and/or aleurone layers. While contrasts in phytochemical synthesis give rise to variations among purple, blue, dark and yellow grain's antioxidant and radical scavenging capacities, little is known about their influence on gluten proteins expression, digestibility and immunogenic potential in a Celiac Disease (CD) framework. Herein, it has been found that the expression profile and immunogenic properties of gliadin proteins in pigmented wheat grains might be affected by anthocyanins and carotenoids upregulation, and that the spectra of peptide released upon simulated gastrointestinal digestion is also significantly different. Interestingly, anthocyanin accumulation, as opposed to carotenoids, correlated with a lower immunogenicity and toxicity of gliadins at both protein and peptide levels. Altogether, this study provides first-level evidence on the impact modern breeding practices, seeking higher expression levels of health promoting phytochemicals at the grain level, may have on wheat crops functionality and CD tolerability.

Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases.

Antibodies can block immune receptor engagement or trigger the receptor machinery to initiate signaling. We hypothesized that antibody agonists trigger signaling by sterically excluding large receptor-type protein tyrosine phosphatases (RPTPs) such as CD45 from sites of receptor engagement. An agonist targeting the costimulatory receptor CD28 produced signals that depended on antibody immobilization and were sensitive to the sizes of the receptor, the RPTPs, and the antibody itself. Although both the agonist and a non-agonistic anti-CD28 antibody locally excluded CD45, the agonistic antibody was more effective. An anti-PD-1 antibody that bound membrane proximally excluded CD45, triggered Src homology 2 domain-containing phosphatase 2 recruitment, and suppressed systemic lupus erythematosus and delayed-type hypersensitivity in experimental models. Paradoxically, nivolumab and pembrolizumab, anti-PD-1-blocking antibodies used clinically, also excluded CD45 and were agonistic in certain settings. Reducing these agonistic effects using antibody engineering improved PD-1 blockade. These findings establish a framework for developing new and improved therapies for autoimmunity and cancer.

Automated statistical analysis of raman spectra of nanomaterials.

Both at the academic and the industrial level, material scientists are exploring routes for mass production and functionalization of graphene, carbon nanotubes (CNT), carbon dots, 2D materials, and heterostructures of these. Proper application of the novel materials requires fast and thorough characterization of the samples. Raman spectroscopy stands out as a standard non-invasive technique capable of giving key information on the structure and electronic properties of nanomaterials, including the presence of defects, degree of functionalization, diameter (in the case of CNT), different polytypes, doping, etc. Here, we present a computational tool to automatically analyze the Raman spectral features of nanomaterials, which we illustrate with the example of CNT and graphene. The algorithm manages hundreds of spectra simultaneously and provides statistical information (distribution of Raman shifts, average values of shifts and relative intensities, standard deviations, correlation between different peaks, etc.) of the main spectral features defining the structure and electronic properties of the samples, as well as publication-ready graphical material.

Non-Isothermal Crystallization Kinetics of Polyamide 6/Graphene Nanoplatelets Nanocomposites Obtained via In Situ Polymerization: Effect of Nanofiller Size.

Thermoplastic resin transfer molding (T-RTM) technology was applied to synthesize graphene nanoplatelets-based nanocomposites via anionic ring-opening polymerization (AROP). Polyamide 6 (PA6) was obtained by AROP and was used as the polymeric matrix of the developed nanocomposites. The non-isothermal crystallization behavior of PA6 and nanocomposites was analyzed by differential scanning calorimetry (DSC). Nanocomposites with 0.5 wt.% of graphene nanoplatelets (GNPs) with two different diameter sizes were prepared. Results have shown that the crystallization temperature shifted to higher values in the presence of GNPs. This behavior is more noticeable for the nanocomposite prepared with smaller GNPs (PA6/GN). The crystallization kinetic behavior of all samples was assessed by Avrami and Liu's models. It was observed that GNPs increased the crystallization rate, thus revealing a nucleating ability, and also validated the reduction of half-time crystallization values. Such tendency was also supported by the lower activation energy values determined by Friedman's method.

Evidence of increased gluten-induced perturbations in the nucleophilic tone and detoxifying defences of intestinal epithelial cells impaired by gastric disfunction.

It has been increasingly demonstrated over the past few years that some proteolytically resistant gluten peptides may directly affect intestinal cell structure and functions by modulating pro-inflammatory gene expression and oxidative stress. The relationship between oxidative cell damage and Celiac Disease (CD) is supported by several studies on human intestinal epithelial cell lines, such as the Caco-2 cell model, already shown to be particularly sensitive to the pro-oxidative and pro-apoptotic properties of gluten protein digests. Through providing valuable evidence concerning some of the pathophysiological mechanisms that may be at play in gluten-related disorders, most of these in vitro studies have been employing simplified digestion schemes and intestinal cell systems that do not fully resemble mature enterocytes in terms of their characteristic tight junctions, microvilli and membrane transporters. Herein the peptide profile and pro-oxidative effect of two different gastrointestinal gliadin digestions was thoroughly characterized and comprehensively compared: one following the complete INFOGEST workflow and a second one by-passing gastric processing, to assess the dependence of gliadin-triggered downstream cell effects on pepsin activity. In both matrices, gluten-derived immunogenic peptide sequences were identified by non-targeted LC-MS/MS. Altogether, this study provides first-hand data concerning the still unexplored peptide composition, gastric-dependence and immunogenicity of physiologically representative gliadin protein digests as well as foundational clues stressing the need for more complex and integrated in vitro cell systems when modelling and exploiting gluten-induced perturbations in the nucleophilic tone and inflammatory status of intestinal epithelial cells.

Predicting Quality of Life in Women with Breast Cancer Who Engage in Physical Exercise: The Role of Psychological Variables.

In this study, we aimed to conduct a descriptive analysis of the primary physiological and psychological factors influencing the quality of life in women with breast cancer who engage in physical exercise. The study examined the key psychological variables predicting patients' quality of life, perceived support from family and friends, and the perception of physical condition. The sample consisted of 46 women from Cáceres (Spain) aged between 30 and 75 years undergoing breast cancer treatment. The Functional Evaluation Scale in Cancer Therapy (FACT-B+4) was used to measure quality of life; the Basic Psychological Needs Satisfaction Scale was used to measure autonomy, competence, and social relationships; the Behavior Regulation Questionnaire in Exercise (BREQ-3) was used to measure the types of self-determined motivation for sports participation; the General Evaluation of Self-Esteem Scale was used to measure self-esteem; the International Fitness Scale (IFIS) was used to measure perceived physical condition; and the Perceived Autonomy Support Scale for Exercise Settings (PASSES) was used to measure the perceived autonomy support from family and friends. A multiple regression analysis revealed that perceived physical condition and self-esteem were significant positive predictors of a variance in quality of life, while intrinsic motivation did not significantly predict it. The findings underscore the importance of promoting autonomous motivation in patients to enhance their physical and psychological well-being through physical activity.

Palliative Care in Advanced Liver Disease: Similar or Different Palliative Care Needs in Patients with a Prospect of Transplantation? Prospective Study from a Portuguese University Hospital and Transplantation Center.

Background and Aims: End-stage liver disease (ESLD) is an important cause of morbidity and mortality, comparable to a large extent to other organ insufficiencies. The need for palliative care (PC) in patients with ESLD is high. In Portugal, in the only identified study, more than 80% of patients hospitalized with ESLD had criteria for PC. No results specified which needs they identified or their transplantation prospect status. Methods: Prospective observational study including 54 ESLD patients who presented to a university hospital and transplantation center, between November 2019 and September 2020. Assessment of their PC needs through the application of NECPAL CCOMS-ICO© and IPOS, considering their transplantation perspective status. Results: Of the 54 patients, 5 (9.3%) were on active waiting list for transplantation and 8 (14.8%) under evaluation. NECPAL CCOMS-ICO© identified 23 patients (n = 42.6%) that would benefit from PC. Assessment of PC needs by clinicians, functional markers and significant comorbidities were the most frequent criteria (47.8%, n = 11). IPOS also revealed a different sort of needs: on average, each patient identified about 9 needs (8.9 ±2.8). Among the symptoms identified, weakness (77.8%), reduced mobility (70.3%), and pain (48.1%) stood out, as well as the psychoemotional symptoms of depression (66.7%) and anxiety (77.8%). There were no significant differences between the subgroups of patients analyzed. Only 4 patients (7.4%) were followed by the PC team. Conclusion: All the ESLD patients included, independently of the group they belonged to, presented with PC needs. No significant differences between the subgroups of patients were identified, confirming that even patients with a transplantation prospect have important needs for PC.

Introdução e objetivos: A doença hepática avançada (DHA) é uma causa importante de morbilidade e mortalidade, comparável em grande medida a outras insuficiências de órgão. A necessidade de cuidados paliativos (CP) em doentes com DHA é elevada. Em Portugal, no único estudo identificado até ao momento, mais de 80% dos doentes hospitalizados com DHA apresentavam critérios para CP. Não foram especificadas que necessidades de CP nem a perspetiva de transplante dos referidos doentes, que com o presente estudo se pretende ajudar a esclarecer. Métodos: Estudo prospectivo observacional incluindo 54 doentes com DHA assistidos num hospital universitário e centro de transplante, entre novembro de 2019 e setembro de 2020. Avaliação das necessidades de CP por meio da aplicação do NECPAL CCOMS-ICO© e IPOS, considerando a sua perspectiva de transplante. Resultados: Dos 54 doentes, cinco (9,3%) estavam em lista de espera ativa para transplante e oito (14,8%) em avaliação. O NECPAL CCOMS-ICO© identificou 23 doentes (n = 42,6%) que beneficiariam de CP. A avaliação das necessidades de CP por médicos, os marcadores funcionais e as comorbidades significativas foram os critérios mais frequentes (47,8%, n = 11). O IPOS também revelou diversas necessidades de CP: em média, cada doente identificou cerca de 9 necessidades (8,9 + −2,8). Entre os sintomas identificados, destacaram-se a fraqueza (77,8%), a mobilidade reduzida (70,3%) e a dor (48,1%), bem como os sintomas psicoemocionais de depressão (66,7%) e ansiedade (77,8%). Não houve diferenças significativas entre os subgrupos de doentes analisados. Apenas 4 doentes (7,4%) foram acompanhados pela equipa intra-hospitalar de CP. Conclusão: Todos os doentes com DHA incluídos, independentemente do grupo a que pertenciam, apresentaram necessidades de CP. Não foram identificadas diferenças significativas entre os subgrupos de doentes, confirmando que mesmo os doentes com perspectiva de transplante têm importantes necessidades de CP.

Time trends and social inequalities in infant and young child feeding practices: national estimates from Brazil's Food and Nutrition Surveillance System, 2008-2019.

OBJECTIVE: To describe the time trends and socio-economic inequalities in infant and young child feeding practices in accordance with the Brazilian deprivation index (BDI). DESIGN: This time-series study analysed the prevalence of multiple breast-feeding and complementary feeding indicators based on data from the Brazilian Food and Nutrition Surveillance System, 2008-2019. Prais-Winsten regression models were used to analyse time trends. Annual percent change (APC) and 95 % CI were calculated. SETTING: Primary health care services, Brazil. PARTICIPANTS: Totally, 911 735 Brazilian children under 2 years old. RESULTS: Breast-feeding and complementary feeding practices differed between the extreme BDI quintiles. Overall, the results were more favourable in the municipalities with less deprivation (Q1). Improvements in some complementary feeding indicators were observed over time and evidenced such disparities: minimum dietary diversity (Q1: Δ 47·8-52·2 %, APC + 1·44, P = 0·006), minimum acceptable diet (Q1: Δ 34·5-40·5 %, APC + 5·17, P = 0·004) and consumption of meat and/or eggs (Q1: Δ 59·7-80·3 %, APC + 6·26, P < 0·001; and Q5: Δ 65·7-70·7 %, APC + 2·20, P = 0·041). Stable trends in exclusive breast-feeding and decreasing trends in the consumption of sweetened drinks and ultra-processed foods were also observed regardless the level of the deprivation. CONCLUSIONS: Improvements in some complementary food indicators were observed over time. However, the improvements were not equally distributed among the BDI quintiles, with children from the municipalities with less deprivation benefiting the most.

Moisture Sorption Isotherms and Thermodynamic Properties of Biodegradable Polymers for Application in Food Packaging Industry.

This work aims to evaluate the influence of two starch-based materials (B16 and B20) on the moisture sorption isotherms, determined at 30, 40, and 50 °C, where B16 contains 5% (w/w) more starch than B20. Thermodynamic functions (differential enthalpy (∆Hdif), differential entropy (∆Sdif), integral enthalpy (Δhint), integral entropy (ΔSint), free Gibbs energy (∆G), and spreading pressure (φ)) were used to understand the water-binding behaviors and the energy requirements to remove the moisture content from the surface of these materials. The moisture sorption isotherms exhibited type III behavior, and the Guggenheim-Anderson-de Boer (GAB) model was the most suitable to fit the experimental moisture adsorption data. The adsorption isotherms of microparticles were enthalpy-controlled, with isokinetic temperature values of 221.45 and 279.77 K for B16 and B20, respectively, being higher than the harmonic mean temperature (312.94 K). The values of ∆G were positive (45.274 and 44.307 kJmol-1 for B16 and B20, respectively), indicating a non-spontaneous process. The spreading pressure values increased with increasing water activity (aw) for all isotherms. Higher values of ∆Hdif and ∆Sdif obtained from B16 confirmed its higher number of sorption sites available for binding with water molecules when compared to B20, making it less suitable for application in the food packaging industry.

Boosting the Catalytic Performance of AuAg Alloyed Nanoparticles Grafted on MoS2 Nanoflowers through NIR-Induced Light-to-Thermal Energy Conversion.

MoS2 nanoflowers (NFs) obtained through a hydrothermal approach were used as the substrate for the deposition of tiny spherical bimetallic AuAg or monometallic Au nanoparticles (NPs), leading to novel photothermal-assisted catalysts with different hybrid nanostructures and showing improved catalytic performance under NIR laser irradiation. The catalytic reduction of pollutant 4-nitrophenol (4-NF) to the valuable product 4-aminophenol (4-AF) was evaluated. The hydrothermal synthesis of MoS2 NFs provides a material with a broad absorption in the Vis-NIR region of the electromagnetic spectrum. The in situ grafting of alloyed AuAg and Au NPs of very small size (2.0-2.5 nm) was possible through the decomposition of organometallic complexes [Au2Ag2(C6F5)4(OEt2)2]n and [Au(C6F5)(tht)] (tht = tetrahydrothiophene) using triisopropilsilane as reducing agent, leading to nanohybrids 1-4. The new nanohybrid materials display photothermal properties arising from NIR light absorption of the MoS2 NFs component. The AuAg-MoS2 nanohybrid 2 showed excellent photothermal-assisted catalytic activity for the reduction of 4-NF, which is better than that of the monometallic Au-MoS2 nanohybrid 4. The obtained nanohybrids were characterised by transmission electron microscopy (TEM), High Angle Annular Dark Field-Scanning Transmission Electron Microscopy-Energy Dispersive X-ray Spectroscopy (HAADF-STEM-EDS), X-ray photoelectron spectroscopy and UV-Vis-NIR spectroscopy.

Amplicon-based NGS test for assessing MLH1 promoter methylation and its correlation with BRAF mutation in colorectal cancer patients.

Detecting MLH1 promoter methylation is highly relevant to differentiate between possible Lynch syndrome patients or patients with sporadic causes of MLH1/PMS2 deficiency in colorectal (CRC) and endometrial cancers. Here, we aimed to develop a test for assessing MLH1 promoter methylation based in next generation sequencing (NGS), and to evaluate the concordance of MLH1 methylation and BRAF-V600 mutation status in CRC. For that, we performed a series of experiments with DNA from tumor, saliva and commercial control samples and our in house developed amplicon-based NGS test. In patients' samples, MLH1 methylation above 10% was only observed in tumors with MLH1/PMS2 loss. We confirmed the reproducibility and accuracy of MLH1 promoter analysis performing a serial dilution experiment with completely methylated and unmethylated control DNAs and a comparison between two NGS platforms (Ion Proton and Illumina). In MLH1/PMS2 deficient tumors, the MLH1 methylation status was concordant with the BRAF mutation status in 90% (18/20) of the cases. Our amplicon-based NGS test showed a great sensitivity and specificity for detecting MLH1 methylation in CRC samples, with a high agreement with the evaluation of BRAF mutation. This simple and affordable test could be used as a reflex test to identify patients with sporadic causes of MLH1/PMS2 deficiency in CRC, aiding to genetic test referral and identification of Lynch syndrome patients.

Vitamin A deficiency and associated risk factors in children aged 12-59 months living in poorest municipalities in the South Region of Brazil.

OBJECTIVE: To estimate the prevalence of vitamin A deficiency (VAD) in children and associated risk factors. DESIGN: Analysis of data from a cross-sectional multicentre study performed in the primary care units of the municipalities from January to June 2015. The children's legal guardians answered a socio-economic questionnaire, and the children's blood samples were obtained by venipuncture. Plasma retinol was determined by HPLC. Plasma retinol values of <0·70 µmol/l were considered VDA. Poisson multiple regression with robust variance was used. Values of P < 0·05 were considered significant. The data were analysed in the SPSS software, 21.0. SETTING: Forty-eight poorest municipalities in the South Region of Brazil. PARTICIPANTS: Children (n 1503) aged 12-59 months. RESULTS: The prevalence of VAD in the sample was 1·9 % (95 % CI (0·5, 6·8)). The following risk factors were associated with the outcome in the final explanatory model: family received Bolsa Familia program benefits (PR = 3·19; 95 % CI (1·69, 6·02)), child was not being breastfed (PR = 5·22; 95 % CI (1·68, 16·18)) and stunting (PR = 4·75; 95 % CI (2·10, 10·73)). CONCLUSIONS: VAD did not represent a public health problem for children living in socio-economically vulnerable municipalities in the South Region of Brazil, suggesting a new panorama of this nutritional deficiency even in regions of low socio-economic conditions in these three states. Thus, in view of the current nutritional transition scenario, it is necessary to continuously monitor and improve public policies related to vitamin A supplementation in the country.

Detection of Measurable Residual Disease Biomarkers in Extracellular Vesicles from Liquid Biopsies of Multiple Myeloma Patients-A Proof of Concept.

Monitoring measurable residual disease (MRD) is crucial to assess treatment response in Multiple Myeloma (MM). Detection of MRD in peripheral blood (PB) by exploring Extracellular Vesicles (EVs), and their cargo, would allow frequent and minimally invasive monitoring of MM. This work aims to detect biomarkers of MRD in EVs isolated from MM patient samples at diagnosis and remission and compare the MRD-associated content between BM and PB EVs. EVs were isolated by size-exclusion chromatography, concentrated by ultrafiltration, and characterized according to their size and concentration, morphology, protein concentration, and the presence of EV-associated protein markers. EVs from healthy blood donors were used as controls. It was possible to isolate EVs from PB and BM carrying MM markers. Diagnostic samples had different levels of MM markers between PB and BM paired samples, but no differences between PB and BM were found at remission. EVs concentration was lower in the PB of healthy controls than of patients, and MM markers were mostly not detected in EVs from controls. This study pinpoints the potential of PB EVs from MM remission patients as a source of MM biomarkers and as a non-invasive approach for monitoring MRD.

Mechanical interlocking of SWNTs with N-rich macrocycles for efficient ORR electrocatalysis.

Substitutional N-doping of single-walled carbon nanotubes is a common strategy to enhance their electrocatalytic properties in the oxygen-reduction reaction (ORR). Here, we explore the encapsulation of SWNTs within N-rich macrocycles as an alternative strategy to display electroactive sites on the surface of SWNTs. We design and synthesize four types of mechanically interlocked derivatives of SWNTs (MINTs) by combining two types of macrocycles and two types of SWNT samples. Comprehensive electrochemical characterization of these MINTs and their reference SWNTs allows us to establish structure-activity relationships. First, we show that all MINT samples are superior electrocatalysts compared to pristine SWNTs, which serves as general validation of our strategy. Secondly, we show that macrocycles displaying both N atoms and carbonyl groups perform better than those with N atoms only. Finally, we demonstrate that a tighter fit between macrocycles and SWNTs results in enhanced catalytic activity and stability, most likely due to a more effective charge-transfer between the SWNTs and the macrocycles. These results, focusing on the ORR as a testbed, show the possibility of understanding electrocatalytic performance of SWNTs at the molecular level and thus enable the design of more active and more stable catalysts in the future.

Ruthenium complexes show potent inhibition of AKR1C1, AKR1C2, and AKR1C3 enzymes and anti-proliferative action against chemoresistant ovarian cancer cell line.

In this study, we present the synthesis, kinetic studies of inhibitory activity toward aldo-keto reductase 1C (AKR1C) enzymes, and anticancer potential toward chemoresistant ovarian cancer of 10 organoruthenium compounds bearing diketonate (1-6) and hydroxyquinolinate (7-10) chelating ligands with the general formula [(η6-p-cymene)Ru(chel)(X)]n+ where chel represents the chelating ligand and X the chlorido or pta ligand. Our studies show that these compounds are potent inhibitors of the AKR enzymes with an uncommon inhibitory mechanism, where two inhibitor molecules bind to the enzyme in a first fast and reversible step and a second slower and irreversible step. The binding potency of each step is dependent on the chemical structure of the monodentate ligands in the metalloinhibitors with the chlorido complexes generally acting as reversible inhibitors and pta complexes as irreversible inhibitors. Our study also shows that compounds 1-9 have a moderate yet better anti-proliferative and anti-migration action on the chemoresistant ovarian cancer cell line COV362 compared to carboplatin and similar effects to cisplatin.

Single-Walled Carbon Nanotubes Encapsulated within Metallacycles.

Mechanically interlocked derivatives of carbon nanotubes (MINTs) are interesting nanotube products since they show high stability without altering the carbon nanotube structure. So far, MINTs have been synthesized using ring-closing metathesis, disulfide exchange reaction, H-bonding or direct threading with macrocycles. Here, we describe the encapsulation of single-walled carbon nanotubes within a palladium-based metallosquare. The formation of MINTs was confirmed by a variety of techniques, including high-resolution transmission electron microscopy. We find the making of these MINTs is remarkably sensitive to structural variations of the metallo-assemblies. When a metallosquare with a cavity of appropriate shape and size is used, the formation of the MINT proceeds successfully by both templated clipping and direct threading. Our studies also show indications on how supramolecular coordination complexes can help expand the potential applications of MINTs.