RESUMO
Ganglioside GM1 is a class of glycolipids predominantly located in the nervous system. Comprising a ceramide anchor and an oligosaccharide chain containing sialic acid, GM1 plays a pivotal role in various cellular processes, including signal transduction, cell adhesion, and membrane organization. Moreover, GM1 has been implicated in the pathogenesis of several neurological disorders, such as Parkinson's disease, Alzheimer's disease, and stroke. In this study, by creating a neural cell model membrane simulation system and employing rigorous molecular models, we utilize a coarse-grained molecular dynamics approach to explore the structural and dynamic characteristics of multi-component neuronal plasma membranes at varying GM1 ganglioside concentrations. The simulation results reveal that as GM1 concentration increases, a greater number of hydrogen bonds form between GM1 molecules, resulting in the formation of larger clusters, which leads to reduced membrane fluidity, increased lipid ordering, decreased membrane thickness and surface area and higher levels of GM1 dissociation. Through a meticulous analysis, while considering GM1's structural attributes, we offer valuable insights into the structural and dynamic traits of the cell membrane. This study provides a robust methodology for exploring membrane characteristics and enhances our comprehension of GM1 molecules, serving as a resource for both experimental and computational researchers in this field.
Assuntos
Membrana Celular , Gangliosídeo G(M1) , Simulação de Dinâmica Molecular , Gangliosídeo G(M1)/química , Gangliosídeo G(M1)/metabolismo , Membrana Celular/química , Membrana Celular/metabolismo , Ligação de Hidrogênio , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismoRESUMO
BACKGROUND: The use of antibiotics is essential in the treatment of sepsis and septic shock, and delaying their administration may impact patient mortality outcomes. However, there is currently a controversial debate surrounding this issue. In this meta-analysis, we aimed to explore the association between delayed antibiotic use and mortality in patients with sepsis and septic shock. METHODS: A systematic search was conducted on PubMed, EMBASE, Web of Science, and Cochrane Library to identify relevant studies published from 2013 to 2023. These studies focused on patients with sepsis or septic shock and provided information on various antibiotic administration times and mortality rates. Two independent reviewers screened and extracted the data. The quality of each study was assessed using the Newcastle-Ottawa Scale, and the collected data were analyzed using STATA 15.1 software. RESULTS: A total of 29 studies were included, consisting of 17 prospective cohort studies and 12 retrospective cohort studies. The meta-analysis showed that compared to administration of antibiotics within 1 h, each hour of delay in antibiotic administration increased the in-hospital mortality (IHM) (OR = 1.041, 95 % CI: 1.021-1.062), and ministration of antibiotics after 1 h increased the IHM (OR = 1.205, 95 % CI: 1.123-1.293). There was no significant change in the 28-day mortality (OR = 1.297, 95 % CI: 0.882-1.906), 90-day mortality (OR = 1.172, 95 % CI: 0.846-1.622), and 1-year mortality (OR = 0.986, 95 % CI: 0.422-2.303). Administration of antibiotics within 3 h may reduce the IHM (OR = 1.297, 95 % CI: 1.011-1.664, p = 0.041), while administration of antibiotics within 6 h showed no significant association with the IHM. CONCLUSION: The administration of antibiotics beyond 1 h after emergency triage or disease identification is strongly associated with an increased IHM in patients with sepsis or septic shock, and each hour of delay in antibiotic administration may be associated with an increase in the IHM. Furthermore, the use of antibiotics identification beyond 3 h after emergency triage / sepsis or septic shock may also increase the IHM.
Assuntos
Antibacterianos , Mortalidade Hospitalar , Sepse , Choque Séptico , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Choque Séptico/tratamento farmacológico , Choque Séptico/mortalidade , Sepse/tratamento farmacológico , Sepse/mortalidade , Tempo para o Tratamento , Resultado do Tratamento , Fatores de TempoRESUMO
In this work, a set of quasi-intrinsic photosensitizers are theoretically proposed based on the 2-amino-8-(1'-ß-d-2'-deoxyribofuranosyl)-imidazo[1,2-α]-1,3,5-triazin-4(8H)-one (P), which could pair with the 6-amino-5-nitro-3-(1'-ß-d-2'-deoxyribofuranosyl)-2(1H)-pyridone (Z) and keep the essential structural characters of nucleic acid. It is revealed that the ring expansion and electron-donating/electron-withdrawing substitution bring enhanced two-photon absorption and bright photoluminescence of these monomers, thereby facilitating the selective excitation and tumor localization through fluorescence imaging. However, instead of undergoing radiative transition (S1 â S0), the base pairing induced fluorescence quenching and rapid intersystem crossing (S1 â Tn) are observed and characterized by the reduced singlet-triplet energy gaps and large spin-orbit coupling values. To ensure the phototherapeutic properties of the considered base pairs in long-lived T1 state, we examined the vertical electron affinity as well as vertical ionization potential for production of superoxide anions via Type I photoreaction, and their required T1 energy (0.98 eV) to generate singlet oxygen 1O2 via Type II mechanism.