Tunable supramolecular chirogenesis in the self-assembling of amphiphilic porphyrin triggered by chiral amines

Supramolecular chirality is one of the most important issues in different branches of science and technology, as stereoselective molecular recognition, catalysis, and sensors. In this paper, we report on the self-assembly of amphiphilic porphyrin derivatives possessing a chiral information on the periphery of the macrocycle (i.e., D-or L-proline moieties), in the presence of chiral amines as co-solute, such as chiral benzylamine derivatives. The aggregation process, steered by hydrophobic effect, has been studied in aqueous solvent mixtures by combined spectroscopic and topographic techniques. The results obtained pointed out a dramatic effect of these ligands on the morphology and on the supramolecular chirality of the final self-assembled structures. Scanning electron microscopy topography, as well as fluorescence microscopy studies revealed the formation of rod-like structures of micrometric size, different from the fractal structures formerly observed when the self-assembly process is carried out in the absence of chiral amine co-solutes. On the other hand, comparative experiments with an achiral porphyrin analogue strongly suggested that the presence of the prolinate moiety is mandatory for the achievement of the observed highly organized suprastructures. The results obtained would be of importance for unraveling the intimate mechanisms operating in the selection of the homochirality, and for the preparation of sensitive materials for the detection of chiral analytes, with tunable stereoselectivity and morphology

A spectroscopic and molecular dynamics study on the aggregation process of a long-acting lipidated therapeutic peptide: the case of semaglutide

The aggregation properties of semaglutide, a lipidated peptide drug agonist of the Glucagon-like peptide 1 receptor recently approved for the treatment of type 2 diabetes, have been investigated by spectroscopic techniques (UV-Vis absorption, steady-state and time-resolved fluorescence, and electronic circular dichroism) and molecular dynamics simulations. We show that in the micromolar concentration region, in aqueous solution, semaglutide is present as monomeric and dimeric species, with a characteristic monomer-to-dimer transition occurring at around 20 μM. The lipid chain stabilizes a globular morphology of the monomer and dimer species, giving rise to a locally well-defined polar outer surface where the lipid and peptide portions are packed to each other. At very long times, these peptide clusters nucleate the growth of larger aggregates characterized by blue luminescence and a β-sheet arrangement of the peptide chains. The understanding of the oligomerization and aggregation potential of peptide candidates is key for the development of long acting and stable drugs

Cytokine Storm in COVID-19: Immunopathogenesis and Therapy

A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors. However, the challenge is still far from being met, and other therapeutic strategies are being tested in the hope that we can eventually overcome the disease

The role of SARS-COV-2 infection in promoting abnormal immune response and sepsis: A comparison between SARS-COV-2-related sepsis and sepsis from other causes

Background: COVID-19 caused by SARS-CoV-2 virus is characterized by respiratory compromise and immune system involvement, even leading to serious disorders, such as cytokine storm. Methods: We then conducted a literature review on the topic of sepsis and covid-19, and in parallel conducted an experimental study on the histological finding of patients who died from SARS-Covid 19 infection and a control group. Results: Sepsis associated with covid-19 infection has some similarities and differences from that from other causes. Conclusion: In this paper the complex interplay between the 2 disorders was discussed, focusing on the similarities and on the effect that one could have on the other. A preliminary experimental section that demonstrates the multisystemic involvement in subjects who die from SARS-CoV-2 is also proposed

An UWB-UHF semi-passive RFID System for localization and tracking applications

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Trauma coagulopathy and its outcomes

Background and Objectives: Trauma coagulopathy begins at the moment of trauma. This study investigated whether coagulopathy upon arrival in the emergency room (ER) is correlated with increased hemotransfusion requirement, more hemodynamic instability, more severe anatomical damage, a greater need for hospitalization, and hospitalization in the intensive care unit (ICU). We also analyzed whether trauma coagulopathy is correlated with unfavorable indices, such as acidemia, lactate increase, and base excess (BE) increase. Material and Methods: We conducted a prospective, monocentric, observational study of all patients (n = 503) referred to the Department of Emergency and Acceptance, IRCCS Fondazione Policlinico San Matteo, Pavia, for major trauma from 1 January 2018 to 30 January 2019. Results: Of the 503 patients, 204 had trauma coagulopathy (group 1), whereas 299 patients (group 2) did not. Group 1 had a higher hemotransfusion rate than group 2. In group 1, 15% of patients showed hemodynamic instability compared with only 8% of group 2. The shock index (SI) distribution was worse in group 1 than in group 2. Group 1 was more often hypotensive, tachycardic, and with low oxygen saturation, and had a more severe injury severity score than group 2. In addition, 47% of group 1 had three or more body districts involved compared with 23% of group 2. The hospitalization rate was higher in group 1 than in group 2 (76% vs. 58%). The length of hospitalization was >10 days for 45% of group 1 compared with 28% of group 2. The hospitalization rate in the ICU was higher in group 1 than in group 2 (22% vs. 14.8%). The average duration of ICU hospitalization was longer in group 1 than in group 2 (12.5 vs. 9.78 days). Mortality was higher in group 1 than in group 2 (3.92% vs. 0.98%). Group 1 more often had acidemia and high lactates than group 2. Group 1 also more often had BE <−6. Conclusions: Trauma coagulopathy patients, upon arrival in the ER, have greater hemotransfusion (p = 0.016) requirements and need hospitalization (p = 0.032) more frequently than patients without trauma coagulopathy. Trauma coagulopathy seems to be more present in patients with a higher injury severity score (ISS) (p = 0.000) and a greater number of anatomical districts involved (p = 0.000). Head trauma (p = 0.000) and abdominal trauma (p = 0.057) seem related to the development of trauma coagulopathy. Males seem more exposed than females in developing trauma coagulopathy (p = 0.018). Upon arrival in the ER, the presence of tachycardia or alteration of SI and its derivatives can allow early detection of patients with trauma coagulopathy

Genetic and environmental determinants of diastolic heart function

Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends on myocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processes and is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiac motion analysis to measure diastolic functional traits in 39,559 participants of the UK Biobank and perform a genome-wide association study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomeric function under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes were independent predictors of diastolic function and we found a causal relationship between genetically-determined ventricular stiffness and incident heart failure. Our results provide insights into the genetic and environmental factors influencing diastolic function that are relevant for identifying causal relationships and potential tractable targets

Footprint Pro Carbono: a calculadora para a pegada de carbono de commodities agrícolas.

A gravidade das mudanças climáticas globais exige medidas urgentes. no Brasil, o setor agropecuário é o principal responsável pelas emissões de gases de efeito estufa (GEE), respondendo por 33,2% do total das emissões do país, segundo a Quarta Comunicação Nacional do Brasil à Convenção Quadro das Nações Unidas sobre Clima (Brasil, 2021). Para que as ações de mitigação ou remoção de GEE na agropecuária sejam efetivas, são necessários métodos, ferramentas e políticas setoriais e públicas que promovam a identificação das fontes de emissão e orientem a sua gestão – como a Footprint PRO Carbono , ferramenta para estimar a pegada de carbono de commodities agrícolas

Genetic and environmental determinants of diastolic heart function

Diastole is the sequence of physiological events that occur in the heart during ventricular filling and principally depends on myocardial relaxation and chamber stiffness. Abnormal diastolic function is related to many cardiovascular disease processes and is predictive of health outcomes, but its genetic architecture is largely unknown. Here, we use machine learning cardiac motion analysis to measure diastolic functional traits in 39,559 participants of the UK Biobank and perform a genome-wide association study. We identified 9 significant, independent loci near genes that are associated with maintaining sarcomeric function under biomechanical stress and genes implicated in the development of cardiomyopathy. Age, sex and diabetes were independent predictors of diastolic function and we found a causal relationship between genetically-determined ventricular stiffness and incident heart failure. Our results provide insights into the genetic and environmental factors influencing diastolic function that are relevant for identifying causal relationships and potential tractable targets