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1.
J Colloid Interface Sci ; 672: 1-11, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38823218

RESUMO

In this work, we reported that by using a strong thiol ligand as the morphology-directing reagent, a series of Au nanoparticles with plate-like surface sub-structures could be successfully obtained via a one-pot seedless synthesis. The size and the density of the plates on the surface of Au can be readily tuned with the amount of the thiol ligand, resembling different roughness of the surface. Arising from the different surface roughness, the localized surface plasmon resonance (LSPR) of these shape and morphological alike Au nanoparticles can be continuously tuned within the visible-NIR region. The broad LSPR absorptions and feasible tunability make the Au nanoparticles suitable candidate for plasmonic-related applications. Interestingly, huge SERS enhancement was simultaneously achieved based on the specific surface roughness. Our results demonstrate the great potentials for tuning the LSPR and SERS of Au nanostructures through the engineering of the surface morphologies, which would assist for the design, synthesis, and applications of Au-based plasmonic nanomaterials in various fields.

2.
Structure ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38537643

RESUMO

Endolysosomal exonucleases PLD3 and PLD4 (phospholipases D3 and D4) are associated with autoinflammatory and autoimmune diseases. We report structures of these enzymes, and the molecular basis of their catalysis. The structures reveal an intra-chain dimer topology forming a basic active site at the interface. Like other PLD superfamily members, PLD3 and PLD4 carry HxKxxxxD/E motifs and participate in phosphodiester-bond cleavage. The enzymes digest ssDNA and ssRNA in a 5'-to-3' manner and are blocked by 5'-phosphorylation. We captured structures in apo, intermediate, and product states and revealed a "link-and-release" two-step catalysis. We also unexpectedly demonstrated phosphatase activity via a covalent 3-phosphohistidine intermediate. PLD4 contains an extra hydrophobic clamp that stabilizes substrate and could affect oligonucleotide substrate preference and product release. Biochemical and structural analysis of disease-associated mutants of PLD3/4 demonstrated reduced enzyme activity or thermostability and the possible basis for disease association. Furthermore, these findings provide insight into therapeutic design.

3.
Adv Mater ; : e2400421, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430204

RESUMO

Thanks to the extensive efforts toward optimizing perovskite crystallization properties, high-quality perovskite films with near-unity photoluminescence quantum yield are successfully achieved. However, the light outcoupling efficiency of perovskite light-emitting diodes (PeLEDs) is impeded by insufficient light extraction, which poses a challenge to the further advancement of PeLEDs. Here, an anisotropic multifunctional electron transporting material, 9,10-bis(4-(2-phenyl-1H-benzo[d]imidazole-1-yl)phenyl) anthracene (BPBiPA), with a low extraordinary refractive index (ne ) and high electron mobility is developed for fabricating high-efficiency PeLEDs. The anisotropic molecular orientations of BPBiPA can result in a low ne of 1.59 along the z-axis direction. Optical simulations show that the low ne of BPBiPA can effectively mitigate the surface plasmon polariton loss and enhance the photon extraction efficiency in waveguide mode, thereby improving the light outcoupling efficiency of PeLEDs. In addition, the high electron mobility of BPBiPA can facilitate balanced carrier injection in PeLEDs. As a result, high-efficiency green PeLEDs with a record external quantum efficiency of 32.1% and a current efficiency of 111.7 cd A-1 are obtained, which provides new inspirations for the design of electron transporting materials for high-performance PeLEDs.

4.
Redox Biol ; 70: 103064, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38320455

RESUMO

Amyloid-beta (Aß) is a key factor in the onset and progression of Alzheimer's disease (AD). Selenium (Se) compounds show promise in AD treatment. Here, we revealed that selenoprotein K (SELENOK), a selenoprotein involved in immune regulation and potentially related to AD pathology, plays a critical role in microglial immune response, migration, and phagocytosis. In vivo and in vitro studies corroborated that SELENOK deficiency inhibits microglial Aß phagocytosis, exacerbating cognitive deficits in 5xFAD mice, which are reversed by SELENOK overexpression. Mechanistically, SELENOK is involved in CD36 palmitoylation through DHHC6, regulating CD36 localization to microglial plasma membranes and thus impacting Aß phagocytosis. CD36 palmitoylation was reduced in the brains of patients and mice with AD. Se supplementation promoted SELENOK expression and CD36 palmitoylation, enhancing microglial Aß phagocytosis and mitigating AD progression. We have identified the regulatory mechanisms from Se-dependent selenoproteins to Aß pathology, providing novel insights into potential therapeutic strategies involving Se and selenoproteins.


Assuntos
Doença de Alzheimer , Antígenos CD36 , Microglia , Selenoproteínas , Animais , Humanos , Camundongos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças , Lipoilação , Camundongos Transgênicos , Microglia/metabolismo , Fagocitose , Selenoproteínas/genética , Selenoproteínas/metabolismo , Antígenos CD36/metabolismo
5.
Chem Biol Interact ; 388: 110830, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38103880

RESUMO

Microglial polarization modulation has been considered the potential therapeutic strategy for relieving cognitive impairment in sepsis survivors. Rosmarinic acid (RA), a water-soluble polyphenolic natural compound, processes a strong protective effect on various types of neurological disorders including Parkinson's disease, depression, and anxiety. However, its role and potential molecular mechanisms in sepsis-associated cognitive impairment remain unclear. To investigate the preventive and therapeutic effect of RA on sepsis-associated cognitive impairment and elucidate the potential mechanism of RA on regulating microglial polarization, we established a CLP-induced cognitive impairment model in mice and a lipopolysaccharide-induced microglia polarization cell model in BV-2. RACK1 siRNA was designed to identify the potential molecular mechanism of RACK1 on microglial polarization. The preventive and therapeutic effect of RA on cognitive impairment followed by PET-CT and behavioral tests including open-field test and tail suspension test. RACK1/HIF-1α pathway and microglial morphology in the hippocampus or BV-2 cells were measured. The results showed that RA significantly ameliorated the CLP-induced depressive and anxiety-like behaviors and promoted whole-brain glucose uptake in mice. Moreover, RA markedly improved CLP-induced hippocampal neuron loss and microglial activation by inhibiting microglial M1 polarization. Furthermore, experiments showed RACK1 was involved in the regulation of LPS-induced microglial M1 polarization via HIF-1α, and RA suppressed lipopolysaccharide or sepsis-associated microglial M1 polarization via RACK1/HIF-1α pathway (rescued the decrease of RACK1 and increase of HIF-1α). Taken together, RA could be a potential preventive and therapeutic medication in improving cognitive impairment through RACK1/HIF-1α pathway-regulated microglial polarization.


Assuntos
Disfunção Cognitiva , Ácido Rosmarínico , Sepse , Animais , Camundongos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Microglia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores de Quinase C Ativada/efeitos dos fármacos , Receptores de Quinase C Ativada/metabolismo , Ácido Rosmarínico/farmacologia , Ácido Rosmarínico/uso terapêutico , Sepse/complicações , Sepse/tratamento farmacológico , Transdução de Sinais , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
6.
bioRxiv ; 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-38045427

RESUMO

Endolysosomal exonucleases PLD3 and PLD4 (phospholipases D3 and D4) are associated with autoinflammatory and autoimmune diseases. We report structures of these enzymes, and the molecular basis of their catalysis. The structures reveal an intra-chain dimer topology forming a basic active site at the interface. Like other PLD superfamily members, PLD3 and PLD4 carry HxKxxxxD/E motifs and participate in phosphodiester-bond cleavage. The enzymes digest ssDNA and ssRNA in a 5'-to-3' manner and are blocked by 5'-phosphorylation. We captured structures in apo, intermediate, and product states and revealed a 'link-and-release' two-step catalysis. We also unexpectedly demonstrated phosphatase activity via a covalent 3' phosphistidine intermediate. PLD4 contains an extra hydrophobic clamp that stabilizes substrate and could affect oligonucleotide substrate preference and product release. Biochemical and structural analysis of disease-associated mutants of PLD3/4 demonstrated reduced enzyme activity or thermostability and the possible basis for disease association. Furthermore, these findings provide insight into therapeutic design.

7.
Cell Rep ; 42(10): 113194, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37777966

RESUMO

The ability of the human immune system to generate antibodies to any given antigen can be strongly influenced by immunoglobulin V-gene allelic polymorphisms. However, previous studies have provided only limited examples. Therefore, the prevalence of this phenomenon has been unclear. By analyzing >1,000 publicly available antibody-antigen structures, we show that many V-gene allelic polymorphisms in antibody paratopes are determinants for antibody binding activity. Biolayer interferometry experiments further demonstrate that paratope allelic polymorphisms on both heavy and light chains often abolish antibody binding. We also illustrate the importance of minor V-gene allelic polymorphisms with low frequency in several broadly neutralizing antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus. Overall, this study not only highlights the pervasive impact of V-gene allelic polymorphisms on antibody binding but also provides mechanistic insights into the variability of antibody repertoires across individuals, which in turn have important implications for vaccine development and antibody discovery.


Assuntos
Anticorpos , Região Variável de Imunoglobulina , Humanos , Região Variável de Imunoglobulina/genética , Sítios de Ligação de Anticorpos , Polimorfismo Genético , Anticorpos Neutralizantes , Anticorpos Antivirais
8.
Angew Chem Int Ed Engl ; 62(40): e202310047, 2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37593817

RESUMO

The current availability of multi-resonance thermally activated delayed fluorescence (MR-TADF) materials with excellent color purity and high device efficiency in the deep-blue region is appealing. To address this issue in the emerged nitrogen/carbonyl MR-TADF system, we propose a spiro-lock strategy. By incorporating spiro functionalization into a concise molecular skeleton, a series of emitters (SFQ, SOQ, SSQ, and SSeQ) can enhance molecular rigidity, blue-shift the emission peak, narrow the emission band, increase the photoluminescence quantum yield by over 92 %, and suppress intermolecular interactions in the film state. The referent CZQ without spiro structure has a more planar skeleton, and its bluer emission in the solution state redshifts over 40 nm with serious spectrum broadening and a low PLQY in the film state. As a result, SSQ achieves an external quantum efficiency of 25.5 % with a peak at 456 nm and a small full width at half maximum of 31 nm in a simple unsensitized device, significantly outperforming CZQ. This work discloses the importance of spiro-junction in modulating deep-blue MR-TADF emitters.

9.
ACS Nano ; 17(17): 16731-16742, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37651715

RESUMO

Micro-/nanorobots (MNRs) are envisioned to act as "motile-targeting" platforms for biomedical tasks due to their ability to propel and navigate in challenging, hard-to-reach biological environments. However, it remains a great challenge for current swarming MNRs to accurately report and regulate therapeutic doses during disease treatment. Here we present the development of swarming multifunctional heater-thermometer nanorobots (HT-NRs) and their application in precise feedback photothermal hyperthermia delivery. The HT-NRs are designed as photothermal-responsive photonic nanochains consisting of magnetic Fe3O4 nanoparticles arranged periodically in one dimension and encapsulated in a temperature-responsive hydrogel shell. The HT-NRs exhibit energetic and controllable swarming motions under a rotating magnetic field, while simultaneously functioning as motile nanoheaters and nanothermometers, utilizing their photothermal conversion and (photo)thermal-responsive structural color changes (photothermochromism). Consequently, the HT-NRs can be quickly deployed to a remote target area (e.g., a superficial tumor lesion) using their collective motion and selectively eliminate diseased cells in a specific targeted region by utilizing their self-reporting photothermochromism as visual feedback for precisely regulating external light irradiation. This work may inspire the development of intelligent multifunctional theranostic micro-/nanorobots and their practical applications in precise disease treatment.


Assuntos
Hipertermia Induzida , Termômetros , Retroalimentação , Temperatura , Hidrogéis
10.
J Dairy Sci ; 106(8): 5253-5265, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37414601

RESUMO

Whey protein powder (PP), which is mainly derived from bovine milk, is rich in milk fat globule membrane (MFGM). The MGFM has been shown to play a role in promoting neuronal development and cognition in the infant brain. However, its role in Alzheimer's disease (AD) has not been elucidated. Here, we showed that the cognitive ability of 3×Tg-AD mice (a triple-transgenic mouse model of AD) could be improved by feeding PP to mice for 3 mo. In addition, PP ameliorated amyloid peptide deposition and tau hyperphosphorylation in the brains of AD mice. We found that PP could alleviate AD pathology by inhibiting neuroinflammation through the peroxisome proliferator-activated receptor γ (PPARγ)-nuclear factor-κB signaling pathway in the brains of AD mice. Our study revealed an unexpected role of PP in regulating the neuroinflammatory pathology of AD in a mouse model.


Assuntos
Doença de Alzheimer , Humanos , Camundongos , Animais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Doença de Alzheimer/veterinária , PPAR gama , Proteínas do Soro do Leite , Pós , Doenças Neuroinflamatórias/veterinária , Proteínas tau/metabolismo , Camundongos Transgênicos , Transdução de Sinais , Modelos Animais de Doenças
11.
Adv Mater ; : e2305273, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37461316

RESUMO

Efficient blue phosphors remain a formidable challenge for organic light-emitting diodes (OLEDs). To circumvent this obstacle, a series of Ir(III)-based carbene complexes bearing asymmetric di-N-aryl 6-(trifluoromethyl)-2H-imidazo[4,5-b]pyridin-2-ylidene chelates, namely, f-ct6a-c, are synthesized, and their structures and photophysical properties are comprehensively investigated. Moreover, these emitters can undergo interconversion in refluxing 1,2,4-trichlorobenzene, catalyzed by a mixture of sodium acetate (NaOAc) and p-toluenesulfonic acid monohydrate (TsOH·H2 O) without decomposition. All Ir(III) complexes present good photoluminescence quantum yield (ΦPL = 83-88%) with peak maximum (max.) at 443-452 nm and narrowed full width at half maximum (FWHM = 66-73 nm). Among all the fabricated OLED devices, f-ct6b delivers a max. external quantum efficiency (EQE) of 23.4% and Commission Internationale de L'Eclairage CIEx , y coordinates of (0.14, 0.12), whereas the hyper-OLED device based on f-ct6a and 5H,9H,11H,15H-[1,4] benzazaborino [2,3,4-kl][1,4]benzazaborino[4',3',2':4,5][1,4]benzazaborino[3,2-b]phenazaborine-7,13-diamine, N7,N7,N13,N13,5,9,11,15-octaphenyl (ν-DABNA) exhibits max. EQE of 26.2% and CIEx , y of (0.12, 0.13). Finally, the corresponding tandem OLED with f-ct6b as dopant gives a max. luminance of over 10 000 cd m-2 and max. EQE of 42.1%, confirming their candidacies for making true-blue OLEDs.

12.
bioRxiv ; 2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37333077

RESUMO

The ability of human immune system to generate antibodies to any given antigen can be strongly influenced by immunoglobulin V gene (IGV) allelic polymorphisms. However, previous studies have provided only a limited number of examples. Therefore, the prevalence of this phenomenon has been unclear. By analyzing >1,000 publicly available antibody-antigen structures, we show that many IGV allelic polymorphisms in antibody paratopes are determinants for antibody binding activity. Biolayer interferometry experiment further demonstrates that paratope allelic mutations on both heavy and light chain often abolish antibody binding. We also illustrate the importance of minor IGV allelic variants with low frequency in several broadly neutralizing antibodies to SARS-CoV-2 and influenza virus. Overall, this study not only highlights the pervasive impact of IGV allelic polymorphisms on antibody binding, but also provides mechanistic insights into the variability of antibody repertoires across individuals, which in turn have important implications for vaccine development and antibody discovery.

13.
bioRxiv ; 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37162858

RESUMO

Developing broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the XBB.1.5. Structural studies revealed that group 1 bnAbs use recurrent germline-encoded CDRH3 features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-characterized "site V" on the RBD and destabilize spike trimer. The site V has remained largely unchanged in SARS-CoV-2 variants and is highly conserved across diverse sarbecoviruses, making it a promising target for broad coronavirus vaccine development. Our findings suggest that targeted vaccine strategies may be needed to induce effective B cell responses to escape resistant subdominant spike RBD bnAb sites.

14.
Nanomicro Lett ; 15(1): 141, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37247162

RESUMO

Micro/nanorobots can propel and navigate in many hard-to-reach biological environments, and thus may bring revolutionary changes to biomedical research and applications. However, current MNRs lack the capability to collectively perceive and report physicochemical changes in unknown microenvironments. Here we propose to develop swarming responsive photonic nanorobots that can map local physicochemical conditions on the fly and further guide localized photothermal treatment. The RPNRs consist of a photonic nanochain of periodically-assembled magnetic Fe3O4 nanoparticles encapsulated in a responsive hydrogel shell, and show multiple integrated functions, including energetic magnetically-driven swarming motions, bright stimuli-responsive structural colors, and photothermal conversion. Thus, they can actively navigate in complex environments utilizing their controllable swarming motions, then visualize unknown targets (e.g., tumor lesion) by collectively mapping out local abnormal physicochemical conditions (e.g., pH, temperature, or glucose concentration) via their responsive structural colors, and further guide external light irradiation to initiate localized photothermal treatment. This work facilitates the development of intelligent motile nanosensors and versatile multifunctional nanotheranostics for cancer and inflammatory diseases.

15.
Nat Commun ; 14(1): 1181, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36864033

RESUMO

Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Cardiopatias , Doenças Metabólicas , Masculino , Animais , Camundongos , Cardiomiopatias Diabéticas/genética , Vitamina A , Diabetes Mellitus Experimental/complicações , Tretinoína , Camundongos Knockout , Miócitos Cardíacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética
16.
Nat Commun ; 14(1): 390, 2023 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693830

RESUMO

Statins play an important role in the treatment of diabetic nephropathy. Increasing attention has been given to the relationship between statins and insulin resistance, but many randomized controlled trials confirm that the therapeutic effects of statins on diabetic nephropathy are more beneficial than harmful. However, further confirmation of whether the beneficial effects of chronic statin administration on diabetic nephropathy outweigh the detrimental effects is urgently needed. Here, we find that long-term statin administration may increase insulin resistance, interfere with lipid metabolism, leads to inflammation and fibrosis, and ultimately fuel diabetic nephropathy progression in diabetic mice. Mechanistically, activation of insulin-regulated phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway leads to increased fatty acid synthesis. Furthermore, statins administration increases lipid uptake and inhibits fatty acid oxidation, leading to lipid deposition. Here we show that long-term statins administration exacerbates diabetic nephropathy via ectopic fat deposition in diabetic mice.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia , Resistência à Insulina , Animais , Camundongos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Ácidos Graxos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos , Mamíferos
17.
BMC Complement Med Ther ; 22(1): 302, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36401257

RESUMO

BACKGROUND: Neuroinflammation-mediated microglia polarization is a major process in various central nervous system (CNS) diseases. Endoplasmic reticulum (ER) stress contributes to the inflammatory signals as well as to microglia polarization in lipopolysaccharide (LPS) induced neuroinflammation. Ascorbic acid 6-palmitate (L-AP) has been broadly used as a dietary antioxidant in foods and demonstrated a strong inhibitory effect on 5-LOX; however, the specific anti-inflammation mechanisms remain unclear. In this study, we investigated the effects and possible mechanisms of L-AP on LPS-induced neuroinflammation in BV-2 cells. METHODS: Immortalized murine microglia cell line BV-2 cells were employed to assess the effect of L-AP to modulate microglia M1/M2 polarization in vivo, and the molecular mechanism was evaluated by qRT-PCR and Western blotting analysis. Molecular docking was used to predict the binding activity of L-AP with protein kinase R-like ER kinase (PERK). RESULTS: L-AP at 62.5 µM significantly modulated LPS-induced microglia M1/M2 polarization (increases of interleukin (IL)-10 and arginase-1 (Arg-1) transcriptions) independent of cell growth. Besides, L-AP at 62.5 µM significantly down-regulated glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding homologous protein (CHOP) mRNA levels. Similar data were shown in the tunicamycin (TM) induced ER stress cells model. Moreover, the protective effect of L-AP on TM-induced microglia M1/M2 polarization was similar to that of 4-phenyl butyric acid (4-PBA), the ER stress inhibitor. Molecular docking results indicated L-AP might directly bind with PERK, with a binding affinity of -7.7 kcal/mol. A further study unveiled that L-AP notably inhibited LPS-induced PERK/ eukaryotic initiation factor 2α (elf2α) activation. CONCLUSION: Together, this study revealed that L-AP possessed its effect on the reconstruction of microglia M1/M2 polarization balance in LPS-stimulated BV-2 cells via modulating PERK/elF2α mediated ER stress.


Assuntos
Lipopolissacarídeos , Microglia , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Estresse do Retículo Endoplasmático , Simulação de Acoplamento Molecular , Ácido Ascórbico/metabolismo , Ácido Ascórbico/farmacologia , Palmitatos/metabolismo , Palmitatos/farmacologia
18.
Biomater Adv ; 140: 213029, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36058016

RESUMO

Wound infections, especially infections with multidrug-resistant bacteria, are a serious public health issue worldwide. In addition, the accumulation microbial biofilm of multidrug-resistant Pseudomonas aeruginosa increases the risk and physically obstruct its healing activity at the wound site. Therefore, the development of an eminent agent to control wound infection is urgently needed. Here, we report a novel chitosan (a natural biological macromolecule)-modified self-nanoemulsifying system (CSN) with lipophilic chlorhexidine acetate (CAA, a poorly water-soluble agent) that was designed and prepared using low-energy emulsification methods. We found that CSN displays better antibacterial efficacy, which occurs more quickly than its aqueous solution, in destroying the structure of the bacterial cell membrane and promoting the leakage of nucleic acids, proteins, K+, and Mg2+ from Pseudomonas aeruginosa cells. Importantly, CSN also accelerates skin wound healing after Pseudomonas aeruginosa infection by inhibiting biofilm formation and eradicating mature biofilms. Moreover, the proteomic results suggested that CSN altered membrane permeability and cellular membrane metabolism, allowing more drug molecules to enter the cytosol. Based on these results, this lipophilic self-nanoemulsifying system may be applied in the treatment of skin wounds caused by multidrug-resistant bacteria, especially Pseudomonas aeruginosa.


Assuntos
Quitosana , Infecção dos Ferimentos , Antibacterianos/farmacologia , Biofilmes , Membrana Celular , Quitosana/farmacologia , Humanos , Proteômica , Pseudomonas aeruginosa , Infecção dos Ferimentos/tratamento farmacológico
19.
Vaccines (Basel) ; 10(8)2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-36016204

RESUMO

Background: By 16 May 2022, 12,186,798,032 people had been vaccinated with COVID-19 vaccines. Our study found that myocarditis/pericarditis may occur in adolescents after COVID-19 vaccination. Methods: In this regard, we conducted a meta-analysis of seven groups of adolescents aged 12-19 years to compare the incidence of myocarditis/pericarditis after vaccination and compare the relative risk incidence after the first and second doses of a COVID-19 vaccine, and between males and females for risk incidence. Results: We analyzed 22,020,997 subjects from seven studies, including 130 cases of confirmed myocarditis/pericarditis. The overall mean incidence rate was 1.69 cases per 100,000 person-years. Of these, 19 of the 12,122,244 people who received a first dose of a COVID-19 vaccine had myocarditis/pericarditis, an incidence rate of 0.0022% (95% CI 0.0001-0.0034), and 111 of the 1,008,753 people who received a second dose had myocarditis/pericarditis, an incidence rate of 0.0107% (95% CI 0.0059-0.0155). The prevalence relative ratio (RR) after the first and second doses was RR = 5.53 (95% CI: 3.01-10.16), with a higher prevalence after the second dose than after the first dose of a COVID-19 vaccine. After a second dose of a COVID-19 vaccine, the RR for males relative to females was RR = 13.91 (95% CI: 4.30-44.95), with a more pronounced risk of disease in males than in females. Conclusions: Our study showed that myocarditis/pericarditis occurred after vaccination with the BNT162b2 or Comirnaty vaccine, especially after the second vaccination in male adolescents, but the incidence of myocarditis/pericarditis after vaccination with the above vaccines was very rare (0.0022%). Therefore, it is recommended that adolescents should be vaccinated with the COVID-19 universal vaccine as soon as possible and closely monitored for subsequent adverse reactions, which can be treated promptly.

20.
Molecules ; 27(13)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35807295

RESUMO

The employment of thermally activated delayed fluorescence (TADF) emitters is one of the most promising ways to realize the external quantum efficiency (EQE) of over 25% for organic light-emitting diodes (OLEDs). In addition, the TADF emitter based on oxygen-bridged boron (BO) fragment can maintain blue emission with high color purity. Herein, we constructed two blue TADF emitters, 3TBO and 5TBO, for OLEDs application. Both emitters consist of three donors linked at the oxygen-bridged boron acceptor. OLED devices based on 3TBO and 5TBO exhibited both high excellent device efficiency and high color purity with a maximum EQE; full-width at half-maximum (FWHM); and CIE coordinates of 17.3%, 47 nm, (0.120, 0.294), and 26.2%, 57 nm, (0.125, 0.275), respectively.

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