Biocompatible hybrids based on nanographene oxide covalently linked to glycolporphyrins: synthesis, characterization and biological evaluation

The major limitation in the development of hybrids based on graphene oxide (GO) and porphyrins is their dispersibility and stability in aqueous systems due to the hydrophobic character induced by porphyrins. Most of the previous approaches reported the direct functionalization of GO with polyethylene glycol (PEG) chains followed by the self-assembly of porphyrins by π-π interactions. Here, new hybrids were prepared using porphyrins previously functionalized with different number/types of glycol branches to be covalently attached through esterification to the carboxyl groups of GO sheets of nanometric dimensions. The number of the glycol chains and its relative position in the porphyrin core showed to be fundamental to improve the hybrids dispersion and stability in aqueous solutions. The best performing hybrids were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared, UV-Vis absorption and fluorescence spectroscopy. The in vitro biocompatibility assessment of these hybrids was conducted using human Saos-2 cells. Their effects on cell proliferation and viability, the generation of reactive oxygen species as well as the cell morphology after cell uptake were analysed. The results demonstrate the biocompatibility of these hybrid nanomaterials with human Saos-2 cells, which is very promising for future application in biomedicine namely in cancer therapy.publishe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. Methods: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model—a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates—with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality—which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. Findings: The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2–100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1–290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1–211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4–48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3–37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7–9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. Interpretation: Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. Funding: Bill & Melinda Gates Foundation

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions. Funding: Bill & Melinda Gates Foundation

Mechanistic insights on the site selectivity in successive 1,3-dipolar cycloadditions to meso-tetraarylporphyrins

A DFT study on site selectivity in successive 1,3-dipolar cycloadditions of meso-tetraarylporphyrins with azomethine ylide and N-methylnitrone has been carried out. The calculation of the thermodynamic stability of both ylide and nitrone-derived adducts reveals that bacteriochlorins are more stable and have stronger aromatic character than isobacteriochlorins. Calculations of whole reaction pathways show that cycloadditions of azomethine ylide on porphyrin and its derived chlorin are irreversible and hence kinetically controlled. Solvent influence on the site selectivity of this reaction has also been considered, and appears to be decisive in controlling the site selectivity. In contrast, cycloadditions of nitrone over porphyrin and chlorin are clearly reversible, pointing to a thermodynamic control of these reactions.This work was supported by the Ministerio de Ciencia y Tecnología (projects CTQ2005-08016 and Consolider Ingenio 2010 CSD2006-00), the University of Aveiro, the Fundação para a Ciência e a Tecnologia (grant SFRH/BPD/8374/2002 of A.M.G.S.) and FEDER for funding the Organic Chemistry Research Unit.Peer reviewe

Screening of wild type Streptomyces isolates able to overproduce clavulanic acid

The selection of new microorganisms able to produce antimicrobial compounds is hoped for to reduce their production costs and the side effects caused by synthetic drugs. Clavulanic acid is a \u3b2-lactam antibiotic produced by submerged culture, which is widely used in medicine as a powerful inhibitor of \u3b2-lactamases, enzymes produced by bacteria resistant to antibiotics such penicillin and cephalosporin. The purpose of this work was to select the best clavulanic acid producer among strains of Streptomyces belonging to the Microorganism Collection of the Department of Antibiotics of the Federal University of Pernambuco (DAUFPE). Initially, the strains were studied for their capacity to inhibit the action of \u3b2-lactamases produced by Klebsiella aerogenes ATCC 15380. From these results, five strains were selected to investigate the batch kinetics of growth and clavulanic acid production in submerged culture carried out in flasks. The results were compared with the ones obtained by Streptomyces clavuligerus ATCC 27064 selected as a control strain. The best clavulanic acid producer was Streptomyces DAUFPE 3060, molecularly identified as Streptomyces variabilis, which increased the clavulanic acid production by 28% compared to the control strain. This work contributes to the enlargement of knowledge on new Streptomyces wild strains able to produce clavulanic acid by submerged culture

Mapping wood volume in seasonally dry vegetation of Caatinga in Bahia State, Brazil

The Caatinga biome in Brazil comprises the largest and most continuous expanse of the seasonally dry tropical forest (SDTF) worldwide; nevertheless, it is among the most threatened and least studied, despite its ecological and biogeographical importance. The spatial distribution of volumetric wood stocks in the Caatinga and the relationship with environmental factors remain unknown. Therefore, this study intends to quantify and analyze the spatial distribution of wood volume as a function of environmental variables in Caatinga vegetation in Bahia State, Brazil. Volumetric estimates were obtained at the plot and fragment level. The multiple linear regression techniques were adopted, using environmental variables in the area as predictors. Spatial modeling was performed using the geostatistical kriging approach with the model residuals. The model developed presented a reasonable fit for the volume m3 ha with r2 of 0.54 and Root Mean Square Error (RMSE) of 10.9 m3 ha–1. The kriging of ordinary residuals suggested low error estimates in unsampled locations and balance in the under and overestimates of the model. The regression kriging approach provided greater detailing of the global wood volume stock map, yielding volume estimates that ranged from 0.01 to 109 m3 ha–1. Elevation, mean annual temperature, and precipitation of the driest month are strong environmental predictors for volume estimation. This information is necessary to development action plans for sustainable management and use of the Caatinga SDTF in Bahia State, Brazil

Selective two-photon absorption in carbon dots: a piece of the photoluminescence emission puzzle

Carbon nanodots (Cdots) are now emerging as promising nonlinear fluorophores for applications in biological environments. A thorough and systematic approach to the two-photon induced emission of Cdots that could provide design guidelines to control their nonlinear emission properties is still missing. In this work, we address the nonlinear optical spectroscopy of Cdots prepared by controlled chemical cutting of graphene oxide (GO). The two-photon absorption in the 700–1000 nm region and the corresponding emission spectrum are carefully investigated. The highest two-photon absorption cross-section estimated was 130 GM at 720 nm. This value is comparable with the one reported for graphene nanoribbons with push–pull architecture. The emission spectrum depends on the excitation mode. At the same excitation energy, nonlinear excitation results in excitation-wavelength independent emission, while upon linear excitation the emission is excitation-wavelength dependent. The biphotonic interaction seems to be selective towards sp2 clusters bearing electron donor and acceptor groups found in push–pull architectures. Both linear and nonlinear emission can be understood based on the existence of isolated sp2 clusters involved in π–π stacking interactions with clusters in adjacent layers.The authors are grateful to Fundação para a Ciência e Tecnologia (FCT, Portugal), European Union, QREN, FEDER and COMPETE for funding the QOPNA, TEMA, and CQFM research unit (project Pest-C/QUI/UI0062/2013, UID/EMS/ 00481/2013 and UID/NAN/50024/2013). FCT is acknowledged for the Post-Doctoral grants of C. I. M. S., S. N. P and I. F. A. M., and for supporting the individual work contract of E. M., I. B. and P. A. A. P. M. within the Investigador FCT program (SFRH/BPD/105478/2014, SFRH/BPD/92409/2013, SFRH/BPD/ 75782/2011, IF/00759/2013, IF/00582/2015 and IF/00917/ 2013). G. G. gratefully acknowledges the funding by European Commission under individual fellowship Marie SklodowskaCurie (NANOTER, Grant Agreement 708351).Peer reviewe

New fluorescent probes based on gallium(III) corrole complexes for the recognition of hydrogen sulfide: a journey from solution to intracellular site

In this work, three fluorescent probes for detection of hydrogen sulfide (H2S) where prepared based on gallium (III) corrole complexes bearing nitro groups at beta-pyrrolic positions. Two of the compounds selected, the 3-nitro5,10,15- tris(pentafluorophenyl)corrolatogallium(III)(pyridine) (CGa-NO2) and the 3,17-dinitro-5,10,15-tris (pentafluorophenyl)corrolatogallium(III)(pyridine) (CGa-2NO2) present one and two nitro groups directly linked to the beta-pyrrolic position. The third compound, the (E)-3-(2-nitroprop-1-en-1-yl)-5,10,15-tris(pentafluorophenyl)corrolatogallium(III)(pyridine) (CGa-EtNO2), has a carbon-carbon double bond spacer between the corrole unit and the nitro group. All these derivatives were obtained from 5,10,15-tris(pentafluorophenyl)corrolatogallium(III)(pyridine) (CGa). The precursor CGa and the derivative CGa-EtNO2 behaved as turn-OFF probes, while compound CGa-NO2 responded as a turn-ON probe in the presence of H2S in the pH range of 5-9. Mechanistic studies show that the interaction of H2S with the probes involves its coordination with gallium(III) and in some cases the reduction of the nitro group to a new aminated corrole. While the formation of the coordination complex with H2S is almost immediate, the kinetics of the reduction is slow. Interestingly, for CGaNO2 the two processes can be explored in a ratiometric sensing of H2S in a non-aqueous solution showing a good linearity over an extended concentration range (5-200 mu M). The response of the corroles to H2S in intracellular medium was studied in 2D cultured cells (HeLa).LISBOA-01-0145-FEDER-029319; LA/P/0056/2020info:eu-repo/semantics/publishedVersio

An insight into the gas-phase fragmentations of potential molecular sensors with porphyrin-chalcone structures

Porphyrin-chalcone derivatives with potential cation sensing ability have been studied by ESI-MS and multistage ESI-MS. The presence of conjugated C=C and C=O double bonds in the chalcone moiety is responsible for the formation of diagnostic fragment ions common to all the studied meta and para chalcones. The ortho isomers show different fragmentation patterns that can be explained by different electronic charge distributions. (C) 2015 Elsevier B.V. All rights reserved