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ABSTRACT Microbiota, and the plethora of signalling molecules that they generate, are a major driving force that underlies a striking range of inter-individual physioanatomic and behavioural consequences for the host organism. Among the bacterial effectors, one finds peptidoglycan, the major constituent of the bacterial cell surface. In the steady-state, fragments of peptidoglycan are constitutively liberated from bacterial members of the gut microbiota, cross the gut epithelial barrier and enter the host system. The fate of these peptidoglycan fragments, and the outcome for the host, depends on the molecular nature of the peptidoglycan, as well the cellular profile of the recipient tissue, mechanism of cell entry, the expression of specific processing and recognition mechanisms by the cell, and the local immune context. At the target level, physiological processes modulated by peptidoglycan are extremely diverse, ranging from immune activation to small molecule metabolism, autophagy and apoptosis. In this review, we bring together a fragmented body of literature on the kinetics and dynamics of peptidoglycan interactions with the mammalian host, explaining how peptidoglycan functions as a signalling molecule in the host under physiological conditions, how it disseminates within the host, and the cellular responses to peptidoglycan. A comprehensive review of the diverse mechanisms acting in the mammalian host to facilitate the uptake, biodistribution, processing and recognition of the major bacterial cell wall constituent, peptidoglycan, a key microbiome effector molecule influencing host physiology during health and disease.

Alzheimer’s disease (AD) is a progressive and neurodegenerative disorder of the cortex and hippocampus, which eventually leads to cognitive impairment. Although the etiology of AD remains unclear, the presence of β-amyloid (Aβ) peptides in these learning and memory regions is a hallmark of AD. Therefore, the inhibition of Aβ peptide aggregation has been considered the primary therapeutic strategy for AD treatment. Many studies have shown that resveratrol has antioxidant, anti-inflammatory, and neuroprotective properties and can decrease the toxicity and aggregation of Aβ peptides in the hippocampus of AD patients, promote neurogenesis, and prevent hippocampal damage. In addition, the antioxidant activity of resveratrol plays an important role in neuronal differentiation through the activation of silent information regulator-1 (SIRT1). SIRT1 plays a vital role in the growth and differentiation of neurons and prevents the apoptotic death of these neurons by deacetylating and repressing p53 activity; however, the exact mechanisms remain unclear. Resveratrol also has anti-inflammatory effects as it suppresses M1 microglia activation, which is involved in the initiation of neurodegeneration, and promotes Th2 responses by increasing anti-inflammatory cytokines and SIRT1 expression. This review will focus on the antioxidant and anti-inflammatory neuroprotective effects of resveratrol, specifically on its role in SIRT1 and the association with AD pathophysiology.

This paper examines the relationship between the destination of exports and the input prices paid by firms, using detailed customs and firm-product-level data from Portugal. Both ordinary least squares regressions and an instrumental-variable strategy using exchange-rate movements (interacted with indicators for initial exports) as a source of variation in destinations indicate that exporting to richer countries leads firms to pay higher prices for inputs, other things equal. The results are supportive of what we call the income-based quality-choice channel: selling to richer destinations leads firms to raise the average quality of goods they produce and to purchase higher-quality inputs.

Peptidoglycan, the major structural polymer forming the cell wall of bacteria, is an important mediator of physiological and behavioral effects in mammalian hosts. These effects are frequently linked to its translocation from the intestinal lumen to host tissues. However, the modality and regulation of this translocation across the gut barrier has not been precisely addressed. In this study, we characterized the absorption of peptidoglycan across the intestine and its systemic dissemination. We report that peptidoglycan has a distinct tropism for host organs when absorbed via the gut, most notably by favoring access to the brain. We demonstrate that intestinal translocation of peptidoglycan occurs through a microbiota-induced active process. This process is regulated by the parasympathetic pathway via the muscarinic acetylcholine receptors. Together, this study reveals fundamental parameters concerning the uptake of a major microbiota molecular signal from the steady-state gut.

Garcinia is a genus of Clusiaceae, distributed throughout tropical Asia, Africa, New Caledonia, Polynesia, and Brazil. Garcinia plants contain a broad range of biologically active metabolites which, in the last few decades, have received considerable attention due to the chemical compositions of their extracts, with compounds which have been shown to have beneficial effects in several diseases. Our work had the objective of reviewing the benefits of five Garcinia species (G. brasiliensis, G. gardneriana, G. pedunculata, G. cambogia, and G. mangstana). These species provide a rich natural source of bioactive compounds with relevant therapeutic properties and anti-inflammatory effects, such as for the treatment of skin disorders, wounds, pain, and infections, having demonstrated antinociceptive, antioxidant, antitumoral, antifungal, anticancer, antihistaminic, antiulcerogenic, antimicrobial, antiviral, vasodilator, hypolipidemic, hepatoprotective, nephroprotective, and cardioprotective properties. This demonstrates the relevance of the genus as a rich source of compounds with valuable therapeutic properties, with potential use in the prevention and treatment of nontransmissible chronic diseases.

This study was designed to evaluate a spray-dried multivalent polyclonal antibody preparation (PAP) against lactate-producing bacteria as an alternative to monensin (MON) to control ruminal acidification. Holstein cows (677 ± 98 kg) fitted with ruminal cannulas were allocated in an incomplete Latin square design with two 20 days period. Cows were randomly assigned to control (CTL), PAP, or MON treatments. For each period, cows were fed a forage diet in the first 5 days (d−5 to d−1), composed of sugarcane, urea and a mineral supplement, followed by a 74% concentrate diet for 15 days (d 0 to d 14). There were no treatment main effects ( P > 0.05) on dry matter intake (DMI) and microbial protein synthesis. However, there was a large peak ( P < 0.01) of intake on d 0 (18.29 kg), followed by a large decline on d 1 (3.67 kg). From d2, DMI showed an increasing pattern (8.34 kg) and stabilized around d 8 (12.96 kg). Higher mean pH was measured ( P < 0.01) in cattle-fed MON (6.06 vs. PA P = 5.89 and CTL = 5.91). The ruminal NH 3 -N concentration of CTL-fed cows was lower ( P < 0.01) compared to those fed MON or PAP. The molar concentration of acetate and lactate was not affected ( P > 0.23) by treatments, but feeding MON increased ( P = 0.01) propionate during the first 4 days after the challenge. Feeding MON and PAP reduced ( P = 0.01) the molar proportion of butyrate. MON was effective in controlling pH and improved ruminal fermentation of acidosis-induced cows. However, PAP was not effective in controlling acidosis. The acidosis induced by the challenge was caused by the accumulation of SCFAs. Therefore, the real conditions for evaluation of this feed additive were not reached in this experiment, since this PAP was proposed to work against lactate-producing bacteria.

Background: The relationship between superinfection by multidrug-resistant Gram-negative bacteria and mortality among SARS-CoV-2 hospitalized patients is still unclear. Carbapenem-resistant Acinetobacter baumannii and carbapenemase-producing Enterobacterales are among the most frequently isolated species when it comes to hospital-acquired superinfections among SARS-CoV-2 patients. Methods: Herein, a retrospective study was carried out using data from adult patients hospitalized for COVID-19. The interaction between in-hospital mortality and rectal carriage and superinfection by carbapenemase-producing Enterobacterales and/or carbapenem-resistant Acinetobacter baumannii was assessed. Results: The incidence of KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii rectal carriage was 30%. Bloodstream infection and/or pneumonia due to KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii occurred in 20% of patients. A higher Charlson comorbidity index (OR 1.41, 95% CI 1.24–1.59), being submitted to invasive mechanical ventilation/ECMO ≥ 96 h (OR 6.34, 95% CI 3.18–12.62), being treated with systemic corticosteroids (OR 4.67, 95% CI 2.43–9.05) and having lymphopenia at the time of admission (OR 0.54, 95% CI 0.40–0.72) were the features most strongly associated with in-hospital mortality. Conclusions: Although KPC-producing Klebsiella pneumoniae and/or carbapenem-resistant Acinetobacter baumannii rectal carriage, and/or bloodstream infection/pneumonia were diagnosed in a remarkable percentage of COVID-19 patients, their impact on in-hospital mortality was not significant. Further studies are needed to assess the burden of antimicrobial resistance as a legacy of COVID-19 in order to identify future prevention opportunities.

There is some consensus on the foreign policy of Dilma Rousseff’s government that Brazil lost prestige and international influence because of her lesser personal dedication. Against this consensus, the paper presents two alternative hypotheses for explaining its unsatisfactory outcomes: that there was no change in policy objectives but an adaptation to a more hostile context and that its limitations were structurally related to dependency on global corporations and to the increasing rejection of South-South politics by domestic business. If this analysis is correct, the structural limitations described require that the struggle to achieve an independent foreign policy involve deeper political and ideological battles and a more radical questioning of neoliberal capitalism. Há certo consenso sobre a política econômica externa do governo Dilma Rousseff: o Brasil perdeu prestígio e influência internacional por causa de sua menor dedicação pessoal. Contra este consenso, o artigo apresenta duas hipóteses para explicar os resultados piores: que não houve mudança nos objetivos da política, mas sua adaptação a contexto mais hostil, e que os limites da política externa relacionam-se, estruturalmente, à dependência das corporações globais e, politicamente, à gradual rejeição da política Sul-Sul por parte do empresariado interno. Se esta análise estiver correta, a existência dos limites estruturais apontados exige que, no futuro, a luta para assegurar uma política externa independente envolva batalhas políticas e ideológicas mais profundas e um questionamento mais radical do capitalismo neoliberal.

Evaluation of the growth model of the PT governments based on the contributions of Celso Furtado reveals that the recent growth cycle has alleviated the typical characteristics of underdevelopment by developing a mass consumption market and improving labor market conditions. However, the limitations of the model prevented modernizing the structure of production to sustain changes on the demand side, including labor in sectors with higher productivity, limiting the control of foreign subsidiaries, and reducing the structural vulnerability inherent in specialization in basic commodities exports. The limits of the model were aggravated by the crisis of 2008–2009, revealing the difficulty of incorporating a peripheral economy like the Brazilian into global capitalism. Uma avaliação do modelo de crescimento dos governos do PT a partir da contribuição de Celso Furtado revela que o ciclo de crescimento recente amenizou características típicas do subdesenvolvimento ao desenvolver um mercado de consumo de massa no Brasil e ao melhorar as condições no mercado de trabalho. No entanto, as limitações do modelo não permitiram modernizar a estrutura produtiva de forma a sustentar as transformações do lado da demanda, incluir a mão de obra em setores de maior produtividade, limitar o controle das filiais estrangeiras, e diminuir a vulnerabilidade estrutural inerente à especialização em exportações de commodities básicas. Os limites do modelo de desenvolvimento adotado se agravaram após a crise de 2008–2009, revelando as dificuldades de inserção de uma economia periférica como a brasileira no capitalismo global.

This study evaluates single and joint endocrine disruptor toxicities of thyroid hormone, levothyroxine, and amiodarone in the embryo-larval stages of Danio rerio. Single toxicity experiments were carried out in concentrations based on the environmental concentration and increasing concentrations of 10, 100, and 1000 times the environmental concentration. Joint toxicity experiments evaluated the combined effects of these compounds. Toxic effects were examined during zebrafish embryonic development, and the parameters analyzed were apical sublethal, teratogenicity, mortality endpoints, and morphometry. Thyroid hormone exhibited the highest toxicity. However, the results showed that the environmental concentrations for all 3 compounds had low risk in relation to the parameters studied, such as teratogenic effects and morphometry. The larvae were more affected than embryos, where embryos needed higher concentrations in all experiments, possibly due to the absence of the chorion. The same type of effects were observed in the joint toxicity test, except that a possible antagonistic effect was detected. However, high concentrations showed stronger effects of these toxic compounds on fish development.