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Futile reperfusion is a phenomenon of inadequate perfusion despite successful recanalization after acute ischemic stroke (AIS). It is associated with poor patient outcomes and has received increasing interest due to its clinical diagnosis becoming more common. However, the underlying mechanisms remain elusive, and experimental studies are focused on the pathological background of futile reperfusion. Our recent study has confirmed that poor primary collateralization plays a crucial role in the insufficiency of reperfusion after AIS in mice. Specifically, the absence of primary collaterals in the circle of Willis (CoW) promoted the development of spreading depolarizations (SDs) during AIS. In our experimental stroke model, the occurrence of SDs during ischemia always predicted futile reperfusion. Conversely, in mice with a complete CoW, no SDs were observed, and reperfusion was complete. Importantly, the human CoW displays variation in the primary collaterals in approximately 50% of the population. Therefore, futile reperfusion may result from SD evolution in AIS patients. Our purpose here is to emphasize the crucial role of SD in the development of futile reperfusion. We propose that adequate collateral recruitment can prevent SD occurrence, leading to improved reperfusion and AIS outcomes.
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Here, we report for the first time on the mechanisms of action of the essential oil of Ruta graveolens (REO) against the plant pathogen Colletotrichum gloeosporioides. In particular, the presence of REO drastically affected the morphology of hyphae by inducing changes in the cytoplasmic membrane, such as depolarization and changes in the fatty acid profile where straight-chain fatty acids (SCFAs) increased by up to 92.1%. In addition, REO induced changes in fungal metabolism and triggered apoptosis-like responses to cell death, such as DNA fragmentation and the accumulation of reactive oxygen species (ROS). The production of essential enzymes involved in fungal metabolism, such as acid phosphatase, ß-galactosidase, ß-glucosidase, and N-acetyl-ß-glucosaminidase, was significantly reduced in the presence of REO. In addition, C. gloeosporioides activated naphthol-As-BI phosphohydrolase as a mechanism of response to REO stress. The data obtained here have shown that the essential oil of Ruta graveolens has a strong antifungal effect on C. gloeosporioides. Therefore, it has the potential to be used as a surface disinfectant and as a viable replacement for fungicides commonly used to treat anthracnose in the postharvest testing phase.
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Antifúngicos , Colletotrichum , Óleos Voláteis , Espécies Reativas de Oxigênio , Ruta , Colletotrichum/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Ruta/química , Antifúngicos/farmacologia , Antifúngicos/química , Espécies Reativas de Oxigênio/metabolismo , Doenças das Plantas/microbiologia , Testes de Sensibilidade Microbiana , Fragmentação do DNA/efeitos dos fármacosRESUMO
The delivery of functional molecules to the cell nucleus enables the visualization of nuclear function and the development of effective medical treatments. In this study, we successfully modified the Hoechst molecule, which is a well-documented nuclear-staining agent, using the strain-promoted azide-alkyne cycloaddition (SPAAC) reaction. We prepared Hoechst derivatives bearing an azide group (Hoe-N3) and characterized their SPAAC reactions in the presence of corresponding molecules with a dibenzylcyclooctyne unit (DBCO). The SPAAC reaction of Hoe-N3 with alkylamine bearing DBCO, fluorescent TAMRA, or Cy5 molecules bearing DBCO led to the formation of the coupling products Hoe-Amine, Hoe-TAMRA, and Hoe-Cy5, respectively. These Hoechst derivatives retained their DNA-binding properties. In addition, Hoe-TAMRA and Hoe-Cy5 exhibited properties of dual accumulation in the cell nucleus and mitochondria. Initial incubation of these molecules in living cells resulted in its accumulation in mitochondria, while after mitochondrial depolarization, it was smoothly released from mitochondria and translocated into the cell nucleus. Thus, mitochondrial depolarization could be monitored by measuring the emission of Hoe-TAMRA and Hoe-Cy5 at the cell nucleus.
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BACKGROUND: Impairment in cerebral autoregulation has been proposed as a potentially targetable factor in patients with aneurysmal subarachnoid hemorrhage (aSAH); however, there are different continuous measures that can be used to calculate the state of autoregulation. In addition, it has previously been proposed that there may be an association of impaired autoregulation with the occurrence of spreading depolarization (SD) events. METHODS: Study participants with invasive multimodal monitoring and aSAH were enrolled in an observational study. Autoregulation indices were prospectively calculated from this database as a 10 s moving correlation coefficient between various cerebral blood flow (CBF) surrogates and mean arterial pressure (MAP). In study participants with subdural electrocorticography (ECoG) monitoring, SD was also scored. Associations between clinical outcomes using the modified Rankin scale and occurrence of either isolated or clustered SD were assessed. RESULTS: A total of 320 study participants were included, 47 of whom also had ECoG SD monitoring. As expected, baseline severity factors, such as modified Fisher scale score and World Federation of Neurosurgical Societies scale grade, were strongly associated with the clinical outcome. SD probability was related to blood pressure in a triphasic pattern, with a linear increase in probability below MAP of ~ 100 mm Hg. Multiple autoregulation indices were available for review based on moving correlations between mean arterial pressure (MAP) and various surrogates of cerebral blood flow (CBF). We calculated the pressure reactivity (PRx) using two different sources for intracranial pressure (ICP). We calculated the oxygen reactivity (ORx) using the partial pressure of brain tissue oxygen (PbtO2) from the Licox probe. We calculated the cerebral blood flow reactivity (CBFRx) using perfusion measurements from the Bowman perfusion probe. Finally, we calculated the cerebral oxygen saturation reactivity (OSRx) using regional cerebral oxygen saturation measured by near-infrared spectroscopy from the INVOS sensors. Only worse ORx and OSRx were associated with worse clinical outcomes. Both ORx and OSRx also were found to increase in the hour prior to SD for both sporadic and clustered SD. CONCLUSIONS: Impairment in autoregulation in aSAH is associated with worse clinical outcomes and occurrence of SD when using ORx and OSRx. Impaired autoregulation precedes SD occurrence. Targeting the optimal MAP or cerebral perfusion pressure in patients with aSAH should use ORx and/or OSRx as the input function rather than intracranial pressure.
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A Mueller matrix polarimetry system at 532 nm wavelength is developed for noninvasive glucose sensing in turbid media such as human's fingertip. The system extracts mean absorbance and anisotropic properties, demonstrated numerically and experimentally with phantom glucose samples. It is found that mean absorbance ( A e $$ {A}_e $$ ), depolarization index (Δ), and linear dichroism (LD) show linear variation with glucose concentration 100-500 mg/dL. In addition, LightTools simulations indicate proportional scaling of scattering effects with A e $$ {A}_e $$ , Δ, and LD. Real-world tests on fingertip show a strong correlation between these properties and blood glucose levels with a mean absolute relative deviation (MARD) of 12.56% and a correlation coefficient (R2) of 0.875 in prediction by a neural network (NN) model, highlighting the advantages of Mueller matrix in extracting more parameters related to blood glucose.
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The effectiveness of activated Ia afferents to discharge ᵯC-motoneurons is decreased during passive muscle lengthening compared with static and shortening muscle conditions. Evidence suggests that these regulations are explained by (1) greater post-activation depression induced by homosynaptic post-activation depression (HPAD) and (2) primary afferent depolarization (PAD). It remains uncertain whether muscle length impacts the muscle lengthening-related aspect of regulation of the effectiveness of activated Ia afferents to discharge ᵯC-motoneurons, HPAD, PAD and heteronymous Ia facilitation (HF). We conducted a study involving 15 healthy young individuals. We recorded conditioned or non-conditioned soleus Hoffmann (H) reflex with electromyography (EMG) to estimate the effectiveness of activated Ia afferents to discharge ᵯC-motoneurons, HPAD, PAD and HF during passive lengthening, shortening and static muscle conditions at short, intermediate and long lengths. Our results show that the decrease of effectiveness of activated Ia afferents to discharge ᵯC-motoneurons and increase of post-activation depression during passive muscle lengthening occur at all muscle lengths. For PAD and HF, we found that longer muscle length increases the magnitude of regulation related to muscle lengthening. To conclude, our findings support an inhibitory effect (resulting from increased post-activation depression) of muscle lengthening and longer muscle length on the effectiveness of activated Ia afferents to discharge α-motoneurons. The increase in post-activation depression associated with muscle lengthening can be attributed to the amplification of Ia afferents discharge.
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BACKGROUND: Neurogenic meningeal inflammation is regarded as a key driver of migraine headache. Multiple evidence show importance of inflammatory processes in the dura mater for pain generation but contribution of the leptomeninges is less clear. We assessed effects of cortical spreading depolarization (CSD), the pathophysiological mechanism of migraine aura, on expression of inflammatory mediators in the leptomeninges. METHODS: A single CSD event was produced by a focal unilateral microdamage of the cortex in freely behaving rats. Three hours later intact cortical leptomeninges and parenchyma of ipsi-lesional (invaded by CSD) and sham-treated contra-lesional (unaffected by CSD) hemispheres were collected and mRNA levels of genes associated with inflammation (Il1b, Tnf, Ccl2; Cx3cl1, Zc3h12a) and endocannabinoid CB2 receptors (Cnr2) were measured using qPCR. RESULTS: Three hours after a single unilateral CSD, most inflammatory factors changed their expression levels in the leptomeninges, mainly on the side of CSD. The meninges overlying affected cortex increased mRNA expression of all proinflammatory cytokines (Il1b, Tnf, Ccl2) and anti-inflammatory factors Zc3h12a and Cx3cl1. Upregulation of proinflammatory cytokines was found in both meninges and parenchyma while anti-inflammatory markers increased only meningeal expression. CONCLUSION: A single CSD is sufficient to produce pronounced leptomeningeal inflammation that lasts for at least three hours and involves mostly meninges overlying the cortex affected by CSD. The prolonged post-CSD inflammation of the leptomeninges can contribute to mechanisms of headache generation following aura phase of migraine attack.
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Depressão Alastrante da Atividade Elétrica Cortical , Meninges , Animais , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Ratos , Masculino , Meninges/fisiopatologia , Inflamação/fisiopatologia , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Modelos Animais de Doenças , Ratos Wistar , Quimiocina CX3CL1/metabolismo , Quimiocina CX3CL1/genéticaRESUMO
Mitochondrial function is tightly linked to morphology, and fragmentation of dendritic mitochondria during noxious conditions suggests loss of function. In the normoxic cortex, spreading depolarization (SD) is a phenomenon underlying migraine aura. It is unknown whether mitochondria structure is affected by normoxic SD. In vivo two-photon imaging followed by quantitative serial section electron microscopy (ssEM) was used to monitor dendritic mitochondria in the normoxic cortex of urethane-anesthetized mature male and female mice during and after SD initiated by focal KCl microinjection. Structural dynamics of dendrites and their mitochondria were visualized by transfecting excitatory, glutamatergic neurons of the somatosensory cortex with bicistronic AAV, which induced tdTomoto labeling in neuronal cytoplasm and mitochondria labeling with roGFP. Normoxic SD triggered rapidly reversible fragmentation of dendritic mitochondria alongside dendritic beading; however, mitochondria took significantly longer to recover. Several rounds of SD resulted in transient mitochondrial fragmentation and dendritic beading without accumulating injury, as both recovered. SsEM corroborated normoxic SD-elicited dendritic and mitochondrial swelling and transformation of the filamentous mitochondrial network into shorter, swollen tubular, and globular structures. Our results revealed normoxic SD-induced disruption of the dendritic mitochondrial structure that might impact mitochondrial bioenergetics during migraine with aura.
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The present study explores the intricacies of CALIPSO Level 3 optimized Aerosol Optical Depth (AOD) and Dust Aerosol Optical Depth (DAOD) products. Hence, the study focused on regions in the Middle East and North Africa (MENA) across different seasons from January 2007 to December 2020. The study utilizes a refined 1° × 1° grid resolution to analyze horizontal distribution patterns, seasonal variations, and the interplay of various aerosol constituents. The Middle East (ME) stands out with intensified AOD during transitional periods, and the Saharan-Sahel Dust (SSD) belt exhibits higher DAOD during specific seasons. Regions with significant industrialization and human activities exhibit high non-dust AOD values, while major dust sources like the SSD and the Arabian Desert showed high DAOD values in the spring and summer seasons. The study reveals seasonal variations in AOD and DAOD, with different regions showing distinct characteristics influenced by topographic and environmental factors. Observational evidence on the vertical distribution of dust layers is crucial for modeling studies to assess the impact of airborne dust particles on radiation and clouds. However, there are challenges in assimilating dust into atmospheric models due to limited ground measurements near dust sources. Further, the statistical metrics highlight regional and seasonal variations in DAOD, Dust Center of Mass, and Dust Top Height. The analysis extends to particle depolarization ratio, aerosol classification, spatial deviation in dust composition, AOD, and cloud properties (e.g., cloud optical thickness and cloud fraction). This has been influenced by several factors such as atmospheric circulation patterns, temperature, humidity, and land cover changes. Trends in AOD and DAOD over timescale indicate regional variations in aerosol concentrations. The study offers valuable insights into the complex atmospheric phenomena shaping the examined regions over the 13 years.
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Better techniques for imaging ferroelectric polarization would aid the development of new ferroelectrics and the refinement of old ones. Here we show how scanning transmission electron microscope (STEM) electron beam-induced current (EBIC) imaging reveals ferroelectric polarization with obvious, simply interpretable contrast. Planar imaging of an entire ferroelectric hafnium zirconium oxide (Hf0.5Zr0.5O2, HZO) capacitor shows an EBIC response that is linearly related to the polarization determined in situ with the positive-up, negative-down (PUND) method. The contrast is easily calibrated in MV/cm. The underlying mechanism is magnification-independent, operating equally well on micrometer-sized devices and individual nanoscale domains. Coercive-field mapping reveals that individual domains are biased "positive" and "negative", as opposed to being "easy" and "hard" to switch. The remanent background E-fields generating this bias can be isolated and mapped. Coupled with STEM's native capabilities for structural identification, STEM EBIC imaging provides a revolutionary tool for characterizing ferroelectric materials and devices.
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BACKGROUND: The initiation of migraine headaches and the involvement of neuroinflammatory signaling between parenchymal and meningeal cells remain unclear. Experimental evidence suggests that a cascade of inflammatory signaling originating from neurons may extend to the meninges, thereby inducing neurogenic inflammation and headache. This review explores the role of parenchymal inflammatory signaling in migraine headaches, drawing upon recent advancements. BODY: Studies in rodents have demonstrated that sterile meningeal inflammation can stimulate and sensitize meningeal nociceptors, culminating in headaches. The efficacy of relatively blood-brain barrier-impermeable anti-calcitonin gene-related peptide antibodies and triptans in treating migraine attacks, both with and without aura, supports the concept of migraine pain originating in meninges. Additionally, PET studies utilizing inflammation markers have revealed meningeal inflammatory activity in patients experiencing migraine with aura, particularly over the occipital cortex generating visual auras. The parenchymal neuroinflammatory signaling involving neurons, astrocytes, and microglia, which eventually extends to the meninges, can link non-homeostatic perturbations in the insensate brain to pain-sensitive meninges. Recent experimental research has brought deeper insight into parenchymal signaling mechanisms: Neuronal pannexin-1 channels act as stress sensors, initiating the inflammatory signaling by inflammasome formation and high-mobility group box-1 release in response to transient perturbations such as cortical spreading depolarization (CSD) or synaptic metabolic insufficiency caused by transcriptional changes induced by migraine triggers like sleep deprivation and stress. After a single CSD, astrocytes respond by upregulating the transcription of proinflammatory enzymes and mediators, while microglia are involved in restoring neuronal structural integrity; however, repeated CSDs may prompt microglia to adopt a pro-inflammatory state. Transcriptional changes from pro- to anti-inflammatory within 24 h may serve to dampen the inflammatory signaling. The extensive coverage of brain surface and perivascular areas by astrocyte endfeet suggests their role as an interface for transporting inflammatory mediators to the cerebrospinal fluid to contribute to meningeal nociception. CONCLUSION: We propose that neuronal stress induced by CSD or synaptic activity-energy mismatch may initiate a parenchymal inflammatory signaling cascade, transmitted to the meninges, thereby triggering lasting headaches characteristic of migraine, with or without aura. This neuroinflammatory interplay between parenchymal and meningeal cells points to the potential for novel targets for migraine treatment and prophylaxis.
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Meninges , Transtornos de Enxaqueca , Doenças Neuroinflamatórias , Transdução de Sinais , Humanos , Transtornos de Enxaqueca/metabolismo , Transtornos de Enxaqueca/fisiopatologia , Doenças Neuroinflamatórias/fisiopatologia , Animais , Transdução de Sinais/fisiologia , Neurônios/metabolismoRESUMO
The tau protein is a microtubule-associated protein that promotes microtubule stabilization. The phosphorylation of the tau protein has been linked to its dissociation from microtubules. Here, we examined the relationship between neuronal depolarization activity and tau protein phosphorylation by employing model systems in culture as well as in vivo. The KCl-evoked depolarization of cultured neurons has often been used to investigate the effects of neuronal activity. We found dephosphorylation at AT8 sites (S202, T205), T212, AT180 sites (T231, S235), and S396 in KCl-simulated cultured neurons. We also found that the KCl-induced tau protein dephosphorylation increases the level of the tau protein fractionated with stable microtubules. In an in vivo experiment, we demonstrated that the exposure of mice to a new environment activates protein phosphatase 1 in the mouse hippocampus and induces tau protein dephosphorylation. We also found an increased amount of the tau protein in a stable microtubule fraction, suggesting that the dephosphorylation of the tau protein may lead to its increased microtubule association in vivo. These results suggest that the association of microtubules with tau proteins may be regulated by the tau protein phosphorylation status affected by neuronal electrical activity.
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Despite its existence for more than 80 years, the titanium industry is still challenged by massive carbon emissions, high production costs, and large resource waste. More than one hundred million tons of Ti-bearing blast furnace slag (TB-slag) has been discarded in China because of the difficulty of reutilization, which requires efficient titanium extraction and recovery technologies. This paper describes a low-cost, carbon-emission-free method for Ti extraction and oxygen evolution via molten oxide electrolysis (MOE) vacuum distillation. After a comprehensive analysis of the binding energies and activities of liquid metals, the highlights of our study are as follows. 1) Sb has the best preferential deposition of Ti among a series of high-Ti-affinitive liquid metal cathodes (Cu, Ni, Pb, Sn, and Sb). 2) The Ir anode was first used in TB-slag with IrO2 formed on its surface to protect it from further corrosion. 3) An alloy containing Ti and Ca can be obtained by MOE, and Ti and Ca metals can be refined by further vacuum distillation. 4) A closed loop is formed in the overall process owing to the recyclable Sb cathode and continuous feeding of TB-slag into the electrolyte. This simple, low-cost, and environmentally friendly method can realize the efficient utilization of Ti resources and achieve carbon neutrality.
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Significance: The depolarization of circularly polarized light (CPL) caused by scattering in turbid media reveals structural information about the dispersed particles, such as their size, density, and distribution, which is useful for investigating the state of biological tissue. However, the correlation between depolarization strength and tissue parameters is unclear. Aim: We aimed to examine the generalized correlations of depolarization strength with the particle size and wavelength, yielding depolarization diagrams. Approach: The correlation between depolarization intensity and size parameter was examined for single and multiple scattering using the Monte Carlo simulation method. Expanding the wavelength width allows us to obtain depolarization distribution diagrams as functions of wavelength and particle diameter for reflection and transparent geometries. Results: CPL suffers intensive depolarization in a single scattering against particles of various specific sizes for its wavelength, which becomes more noticeable in the multiple scattering regime. Conclusions: The depolarization diagrams with particle size and wavelength as independent variables were obtained, which are particularly helpful for investigating the feasibility of various particle-monitoring methods. Based on the obtained diagrams, several applications have been proposed, including blood cell monitoring, early embryogenesis, and antigen-antibody interactions.
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Luz , Método de Monte Carlo , Tamanho da Partícula , Espalhamento de Radiação , Simulação por Computador , Nefelometria e Turbidimetria/métodosRESUMO
SARS-CoV-2 is the causative agent of the COVID-19 pandemic, the acute respiratory disease which, so far, has led to over 7 million deaths. There are several symptoms associated with SARS-CoV-2 infections which include neurological and psychiatric disorders, at least in the case of pre-Omicron variants. SARS-CoV-2 infection can also promote the onset of glioblastoma in patients without prior malignancies. In this study, we focused on the Envelope protein codified by the virus genome, which acts as viroporin and that is reported to be central for virus propagation. In particular, we characterized the electrophysiological profile of E-protein transfected U251 and HEK293 cells through the patch-clamp technique and FURA-2 measurements. Specifically, we observed an increase in the voltage-dependent (Kv) and calcium-dependent (KCa) potassium currents in HEK293 and U251 cell lines, respectively. Interestingly, in both cellular models, we observed a depolarization of the mitochondrial membrane potential in accordance with an alteration of U251 cell growth. We, therefore, investigated the transcriptional effect of E protein on the signaling pathways and found several gene alterations associated with apoptosis, cytokines and WNT pathways. The electrophysiological and transcriptional changes observed after E protein expression could explain the impact of SARS-CoV-2 infection on gliomagenesis.
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COVID-19 , Glioblastoma , Potencial da Membrana Mitocondrial , SARS-CoV-2 , Humanos , Glioblastoma/metabolismo , Glioblastoma/virologia , Glioblastoma/patologia , Glioblastoma/genética , Células HEK293 , SARS-CoV-2/fisiologia , COVID-19/virologia , COVID-19/metabolismo , Linhagem Celular Tumoral , Proteínas do Envelope de Coronavírus/metabolismo , Proteínas do Envelope de Coronavírus/genética , Apoptose , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/virologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genéticaRESUMO
Spreading depolarizations (SD) contribute to lesion progression after experimental focal cerebral ischemia while such correlation has never been shown in stroke patients. In this prospective, diagnostic study, we investigate the association of SDs and secondary infarct progression after malignant hemispheric stroke. SDs were continuously monitored for 3-9 days with electrocorticography after decompressive hemicraniectomy for malignant hemispheric stroke. To ensure valid detection and analysis of SDs, a threshold based on the electrocorticographic baseline activity was calculated to identify valid electrocorticographic recordings. Subsequently SD characteristics were analyzed in association to infarct progression based on serial MRI. Overall, 62 patients with a mean stroke volume of 289.6 ± 68 cm3 were included. Valid electrocorticographic recordings were found in 44/62 patients with a mean recording duration of 139.6 ± 26.5 hours and 52.5 ± 39.5 SDs per patient. Infarct progression of more than 5% was found in 21/44 patients. While the number of SDs was similar between patients with and without infarct progression, the SD-induced depression duration per day was significantly longer in patients with infarct progression (593.8 vs. 314.1 minutes; *p = 0.046). Therefore, infarct progression is associated with a prolonged SD-induced depression duration. Real-time analysis of electrocorticographic recordings may identify secondary stroke progression and help implementing targeted management strategies.
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Multidrug resistance (MDR) is a rising threat to global health because the number of essential antibiotics used for treating MDR infections is increasingly compromised. In this work we report a group of new amphiphilic peptides (AMPs) derived from the well-studied G3 (G(IIKK)3I-NH2) to fight infections from Gram-positive bacteria including susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA), focusing on membrane interactions. Time-dependent killing experiments revealed that substitutions of II by WW (GWK), II by FF (GFK) and KK by RR (GIR) resulted in improved bactericidal efficiencies compared to G3 (GIK) on both S. aureus and MRSA, with the order of GWK > GIR > GFK > GIK. Electronic microscopy imaging revealed structural disruptions of AMP binding to bacterial cell walls. Fluorescence assays including AMP binding to anionic lipoteichoic acids (LTA) in cell-free and cell systems indicated concentration and time-dependent membrane destabilization associated with bacterial killing. Furthermore, AMP's binding to anionic plasma membrane via similar fluorescence assays revealed a different extent of membrane depolarization and leakage. These observations were supported by the penetration of AMPs into the LTA barrier and the subsequent structural compromise to the cytoplasmic membrane as revealed from SANS (small angle neutron scattering). Both experiments and molecular dynamics (MD) simulations revealed that GWK and GIR could make the membrane more rigid but less effective in diffusive efficiency than GIK and GFK through forming intramembrane peptide nanoaggregates associated with hydrophobic mismatch and formation of fluidic and rigid patches. The reported peptide-aggregate-induced phase-separation emerged as a crucial factor in accelerated membrane disintegration and fast bacterial killing. This work has demonstrated the importance of membrane interactions to the development of more effective AMPs and the relevance of the approaches as reported in assisting this area of research.
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Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Cátions/química , Tensoativos/química , Tensoativos/farmacologia , Simulação de Dinâmica MolecularRESUMO
The relatively low thermal depolarization temperature (Td) has hindered the development and practical application of lead-free Bi0.5Na0.5TiO3-based systems; therefore, a feasible strategy is urgently needed to defer the depolarization behavior. In this work, a perovskite/metal 0.78 Bi0.5Na0.5TiO3-0.22 Bi0.5K0.5TiO3/xAg (BNT-22BKT/xAg) composite ceramic is designed and successfully prepared. The introduction of metal Ag with a larger thermal expansion coefficient leads to an increased fraction and enhanced lattice distortion of the rhombohedral phase, as well as an enlarged domain size. The thermal stability thus is effectively improved, and the optimal Td value of 166 °C is obtained at x = 0.03, which is about 60 °C higher than that of prototype ceramics. This research provides a perovskite/metal composite scheme to increase the depolarization temperature of BNT-based ceramics and promotes their potential for practical applications.
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Nimodipine is used to prevent delayed ischemic deficit in patients with aneurysmal subarachnoid hemorrhage (aSAH). Spreading depolarization (SD) is recognized as a factor in the pathomechanism of aSAH and other acute brain injuries. Although nimodipine is primarily known as a cerebral vasodilator, it may have a more complex mechanism of action due to the expression of its target, the L-type voltage-gated calcium channels (LVGCCs) in various cells in neural tissue. This study was designed to investigate the direct effect of nimodipine on SD, ischemic tissue injury, and neuroinflammation. SD in control or nimodipine-treated live mouse brain slices was induced under physiological conditions using electrical stimulation, or by subjecting the slices to hypo-osmotic stress or mild oxygen-glucose deprivation (mOGD). SD was recorded applying local field potential recording or intrinsic optical signal imaging. Histological analysis was used to estimate tissue injury, the number of reactive astrocytes, and the degree of microglia activation. Nimodipine did not prevent SD occurrence in mOGD, but it did reduce the rate of SD propagation and the cortical area affected by SD. In contrast, nimodipine blocked SD occurrence in hypo-osmotic stress, but had no effect on SD propagation. Furthermore, nimodipine prevented ischemic injury associated with SD in mOGD. Nimodipine also exhibited anti-inflammatory effects in mOGD by reducing reactive astrogliosis and microglial activation. The results demonstrate that nimodipine directly inhibits SD, independent of nimodipine's vascular effects. Therefore, the use of nimodipine may be extended to treat acute brain injuries where SD plays a central role in injury progression.
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Isquemia Encefálica , Encéfalo , Depressão Alastrante da Atividade Elétrica Cortical , Nimodipina , Animais , Nimodipina/farmacologia , Camundongos , Depressão Alastrante da Atividade Elétrica Cortical/efeitos dos fármacos , Masculino , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/patologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Pressão Osmótica/efeitos dos fármacosRESUMO
Introduced here is the on-line coupling of hollow-fiber flow field-flow fractionation (HF5) to depolarized multi-angle static light scattering (D-MALS). HF5 is a size-based separation alternative to size-exclusion and hydrodynamic chromatography and asymmetric flow field-flow fractionation. HF5 can separate larger sizes than its chromatographic counterparts and provides several advantages over its fractionation counterpart, including reduced sample consumption and greater ease of operation. D-MALS is a variant of MALS in which the depolarized scattering from the analyte solution is measured at a variety of angles simultaneously. Measurements of depolarized scattering have previously been employed in studying the optical properties of solutions or suspensions, to determine the length of rod-like analytes, and to gain increased accuracy in the determination of analyte molar mass. The coupling HF5/D-MALS allows for the depolarization ratio of a solution or suspension to be measured continuously across the fractogram. This is demonstrated here for a Teflon latex the size range of which extends beyond that accessible to commercial size-exclusion columns. The results presented provide the first reported on-line HF5/D-MALS coupling, showing the feasibility of the technique as well as its realized potential for providing continuous depolarization measurements, inter alia.