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Building bridges between environmental and political agendas is essential nowadays in face of the increasing human pressure on natural environments, including wetlands. Wetlands provide critical ecosystem services for humanity and can generate a considerable direct or indirect income to the local communities. To meet many of the sustainable development goals, we need to move our trajectory from the current environmental destructive development to a wiser wetland use. The current article contain a proposed agenda for the Pantanal aiming the improvement of public policy for conservation in the Pantanal, one of the largest, most diverse, and continuous inland wetland in the world. We suggest and discuss a list of 11 essential interfaces between science, policy, and development in region linked to the proposed agenda. We believe that a functional science network can booster the collaborative capability to generate creative ideas and solutions to address the big challenges faced by the Pantanal wetland.

Cellulose nanocrystals (CNC) were obtained from macauba and gravata fibers. Macauba (or Bocaiuva) is a palm tree found throughout most of Brazil and Gravata is an abundant kind of bromelia with 1–2m long leaves, found in Brazilian Pantanal and Cerrado. The raw fibers of both fibers were mercerized with NaOH solutions and bleached; they were then submitted to acid hydrolysis using H2SO4 at 45 °C, varying the hydrolysis time from 15 up to 75 min. The fibers were analyzed by X-ray diffraction (XRD), FTIR Spectroscopy, scanning electron microscopy (SEM) and thermal stability by thermogravimetric analysis (TG). XRD patterns did not present changes in the crystal structure of cellulose after mercerization, but it was observed a decrease of hemicellulose and lignin contents, and consequently an increase of cellulose content with the increase of NaOH solution concentration in the mercerization. After acid hydrolysis, the cellulose nanocrystals (CNC) were also analyzed by transmission electron microscopy (TEM) which showed an acicular or rod-like aspect and nanometric dimensions of CNC from both fibers, but the higher values of aspect ratio (L/D) were found on CNC obtained from gravata after 45 min of acid hydrolysis. The mercerization and subsequent bleaching of fibers influenced the crystallinity index and thermal stability of the resulting CNC, but their properties are mainly influenced by the hydrolysis time, i. e., there is an increase in crystallinity and thermal stability up to 45 min of hydrolysis, after this time, both properties decrease, probably due to the cellulose degradation by the sulfuric acid.

The VCP ATPase has been linked to cancer, but the lack of well-defined, selective inhibitors has limited further investigation. A million-molecule screen now identifies a covalent inhibitor as well as an allosteric inhibitor that may freeze the enzyme in an ADP-bound conformation. VCP (also known as p97 or Cdc48p in yeast) is an AAA + ATPase regulating endoplasmic reticulum–associated degradation. After high-throughput screening, we developed compounds that inhibit VCP via different mechanisms, including covalent modification of an active site cysteine and a new allosteric mechanism. Using photoaffinity labeling, structural analysis and mutagenesis, we mapped the binding site of allosteric inhibitors to a region spanning the D1 and D2 domains of adjacent protomers encompassing elements important for nucleotide-state sensing and ATP hydrolysis. These compounds induced an increased affinity for nucleotides. Interference with nucleotide turnover in individual subunits and distortion of interprotomer communication cooperated to impair VCP enzymatic activity. Chemical expansion of this allosteric class identified NMS-873, the most potent and specific VCP inhibitor described to date, which activated the unfolded protein response, interfered with autophagy and induced cancer cell death. The consistent pattern of cancer cell killing by covalent and allosteric inhibitors provided critical validation of VCP as a cancer target.

Background Metabolic reprogramming is a well-known marker of cancer, and it represents an early event during hepatocellular carcinoma (HCC) development. The recent approval of several molecular targeted agents has revolutionized the management of advanced HCC patients. Nevertheless, the lack of circulating biomarkers still affects patient stratification to tailored treatments. In this context, there is an urgent need for biomarkers to aid treatment choice and for novel and more effective therapeutic combinations to avoid the development of drug-resistant phenotypes. This study aims to prove the involvement of miR-494 in metabolic reprogramming of HCC, to identify novel miRNA-based therapeutic combinations and to evaluate miR-494 potential as a circulating biomarker. Methods Bioinformatics analysis identified miR-494 metabolic targets. QPCR analysis of glucose 6-phosphatase catalytic subunit (G6pc) was performed in HCC patients and preclinical models. Functional analysis and metabolic assays assessed G6pc targeting and miR-494 involvement in metabolic changes, mitochondrial dysfunction, and ROS production in HCC cells. Live-imaging analysis evaluated the effects of miR-494/G6pc axis in cell growth of HCC cells under stressful conditions. Circulating miR-494 levels were assayed in sorafenib-treated HCC patients and DEN-HCC rats. Results MiR-494 induced the metabolic shift of HCC cells toward a glycolytic phenotype through G6pc targeting and HIF-1A pathway activation. MiR-494/G6pc axis played an active role in metabolic plasticity of cancer cells, leading to glycogen and lipid droplets accumulation that favored cell survival under harsh environmental conditions. High miR-494 serum levels associated with sorafenib resistance in preclinical models and in a preliminary cohort of HCC patients. An enhanced anticancer effect was observed for treatment combinations between antagomiR-494 and sorafenib or 2-deoxy-glucose in HCC cells. Conclusions MiR-494/G6pc axis is critical for the metabolic rewiring of cancer cells and associates with poor prognosis. MiR-494 deserves attention as a candidate biomarker of likelihood of response to sorafenib to be tested in future validation studies. MiR-494 represents a promising therapeutic target for combination strategies with sorafenib or metabolic interference molecules for the treatment of HCC patients who are ineligible for immunotherapy.

The 6-minute walking test (6MWT) is a simple assessment tool to evaluate exercise capacity. The result of the test is the distance that a subject can walk at a constant and normal pace within 6 minutes (6MWD) and reflects the aerobic/fitness performance related to walking function. Use of 6MWT has been relevant to assess exercise tolerance either in healthy children or in patients with, heart, lung and metabolic diseases. Our aim was to find 6MWT reference values in healthy Italian children. The 6MWT was performed in 5614 children aged 6-11 years recruited from primary Italian schools. Age related reference percentiles of the covered distance were gender-modeled. A linear and quadratic regression model was used to predict 6MWT performance. Males walked longer distances than females, respectively 598.8±83.9 m vs 592.1±77.6 m (p = 0.0016). According to the regression analysis, 6MWD was positively related to age, gender and height, while it was negatively related to body weight [(6MWD = -160.16 + 93.35× age (years) -4.05× age2 (years) +7.34× gender (m) +2.12× weight (kg) -2.50× height (cm)]. Reference values were established for the 6MWT in healthy children. The age related 6MWD percentiles provided a useful tool in the assessment of capacity in 6-11 year children, in fact they may be helpful to evaluate the effect of a given treatment or rehabilitation program and represent a feasible measure as to prevention within the primary school context. It was found a substantial difference from other countries for 6mwd values. In our study, factors such as age, weight and height were relevant for the prediction of 6MWD, similarly to other studies. Therefore, these variables should be taken into account in context of exercise performance.

The approval of immunotherapy has revolutionized the management of hepatocellular carcinoma (HCC) patients. However, sorafenib remains a first-line therapeutic option for advanced patients and, in particular, for patients not eligible for immune checkpoint inhibitors, but its efficacy is limited by the onset of acquired resistance, highlighting the urgent need for predictive biomarkers. This study investigates the role of miR-22 in metabolic reprogramming and its potential as a biomarker in HCC. The analysis of miR-22 expression was performed in HCC patients and preclinical models by qPCR. Functional analyses in HCC cells evaluated GLUT1 as a direct miR-22 target. Cellular and metabolic assays evaluated the miR-22/GLUT1 axis’s role in metabolic changes, tumor aggressiveness, and sorafenib response. Circulating miR-22 was analyzed in sorafenib-treated HCC patients and rats. MiR-22 was downregulated in HCCs and associated with aggressive tumor features. Functionally, miR-22 modulated the HIF1A pathway, enhanced survival in stressful conditions, promoted a glycolytic shift, and enhanced cancer cell plasticity and sorafenib resistance via GLUT1 targeting. In addition, high serum miR-22 levels were associated with sorafenib resistance in HCC patients and rats. GLUT1 inhibition sensitized low miR-22-expressing HCC cells to sorafenib in preclinical models. These findings suggest that circulating miR-22 deserves attention as a predictive biomarker of sorafenib response. GLUT1 inhibition may represent a therapeutic strategy to combine with sorafenib, particularly in patients exhibiting high circulating miR-22 levels.

Background/Objectives: conducting fitness tests in educational settings can lead to advantages for both individuals and groups, beyond just enhancing fitness. With the aim of appropriately interpreting performance, this study was conducted to establish sex- and age-specific percentile normative data for a physical fitness (PF) protocol and to define a compound measure of physical performance. Methods: In this cross-sectional study, a short, feasible, and easy-to-administer test battery was performed for 5106 school children, aged 6–10 years. Gender- and age-specific percentiles for the PF tests were constructed, and a Physical Fitness–Motor Competence Performance Index (PF-MC PI) was calculated according to the percentiles. Results: Boys scored higher in all the PF tests when compared to girls (p < 0.001). There was also a trend towards increased PF levels as the age increased in both genders (p < 0.0001). Correlations between scores on individual test items were moderate to high (r from 0.549 to 0.700), and all individual test item scores significantly correlated with the PF-MC PI (p < 0.0001). Conclusions: the provided percentile values will enable the correct interpretation and monitoring of the fitness status of children and the PF-MC PI can be used for easily rating children’s health-related fitness qualities.

A. aegypti production and human density may vary considerably in dengue endemic areas. Understanding how interactions between these factors influence the risk of transmission could improve the effectiveness of the allocation of vector control resources. To evaluate the combined impacts of variation in A. aegypti production and human density we integrated field data with simulation modeling. Using data from seven censuses of A. aegypti pupae (2007-2009) and from demographic surveys, we developed an agent-based transmission model of the dengue transmission cycle across houses in 16 dengue-endemic urban 'patches' (1-3 city blocks each) of Armenia, Colombia. Our field data showed that 92% of pupae concentrated in only 5% of houses, defined as super-producers. Average secondary infections (R(0)) depended on infrequent, but highly explosive transmission events. These super-spreading events occurred almost exclusively when the introduced infectious person infected mosquitoes that were produced in super-productive containers. Increased human density favored R(0), and when the likelihood of human introduction of virus was incorporated into risk, a strong interaction arose between vector production and human density. Simulated intervention of super-productive containers was substantially more effective in reducing dengue risk at higher human densities. These results show significant interactions between human population density and the natural regulatory pattern of A. aegypti in the dynamics of dengue transmission. The large epidemiological significance of super-productive containers suggests that they have the potential to influence dengue viral adaptation to mosquitoes. Human population density plays a major role in dengue transmission, due to its potential impact on human-A. aegypti contact, both within a person's home and when visiting others. The large variation in population density within typical dengue endemic cities suggests that it should be a major consideration in dengue control policy.

Citrus (genus Citrus L.) fruits are essential sources of bioactive compounds with antioxidant properties, such as flavonoids. These polyphenolic compounds are divided into subclasses, in which flavanones are the most prominent. Among them, naringenin and hesperidin are emerging compounds with anticancer potential, especially for breast cancer (BC). Several mechanisms have been proposed, including the modulation of epigenetics, estrogen signaling, induction of cell death via regulation of apoptotic signaling pathways, and inhibition of tumor invasion and metastasis. However, this information is sparse in the literature and needs to be brought together to provide an overview of how naringenin and hesperidin can serve as therapeutic tools for drug development and as a successful co-adjuvant strategy against BC. This review detailed such mechanisms in this context and highlighted how naringenin and hesperidin could interfere in BC carcinogenesis and be helpful as potential alternative therapeutic sources for breast cancer treatment.

The first set of simple sequence repeat (SSR) markers for Urochloa mosambicensis (Hack.) Dandy is described in this study. SSRs were isolated from a genomic library with 3491 contigs obtained by high-throughput sequencing. Primers were designed for twenty loci , and all primer pairs were successfully amplified in 39 genotypes, yielding an average of 4.95 alleles per locus . The mean polymorphic information content (PIC) was 0.559, and the mean discriminating power (DP) was 0.520 for all loci considering also all U. mosambicensis genotypes. The non‐Bayesian clustering analysis has confirmed clustering consistency of the individuals and provides enough support for the existence of the pattern that also emerged from PCoA and UPGMA. These markers demonstrated potential transferability to U. advena , U. oligotricha , U. brachyura and U. xantholeuca . Our findings showed that the set of molecular markers described here have strong potential for fingerprinting and characterizing genetic diversity in intra-specific plant collections, whose breeding programs could be accelerated by the effective use of these molecular tools, not only in U. mosambicensis , but also within the genus Urochloa .