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1.
Opt Express ; 32(6): 8929-8936, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571138

RESUMO

A modified two-level model is proposed to study the spatially resolved current density distribution of GaN-based green miniaturized light-emitting diodes (mini-LEDs), combining with microscopic hyperspectral imaging. We found that the spatially resolved current density distribution reveals both the radiative and non-radiative recombination mappings, which can also be provided separately by this model. In addition, higher current density is not necessarily correlated with higher photon emission, especially for the regions around the electrode edges, where the high current density suggests current crowding and defect-related non-radiative recombination. The current density distribution of mini-LEDs is further verified by the laser-beam-induced current (LBIC) and the spatially resolved mappings of peak wavelength and FWHM. The modified two-level model also offers radiative/non-radiative mappings and is proved to be beneficial to determine the micro-zone current density distribution and to reveal the intrinsic radiative/non-radiative recombination mechanism of mini-LEDs.

2.
Nat Commun ; 15(1): 2051, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448408

RESUMO

Transmembrane channels play a vital role in regulating the permeation process, and have inspired recent development of biomimetic channels. Herein, we report a class of artificial biomimetic nanochannels based on DNAzyme-functionalized glass nanopipettes to realize delicate control of channel permeability, whereby the surface wettability and charge can be tuned by metal ions and DNAzyme-substrates, allowing reversible conversion between different permeability states. We demonstrate that the nanochannels can be reversibly switched between four different permeability states showing distinct permeability to various functional molecules. By embedding the artificial nanochannels into the plasma membrane of single living cells, we achieve selective transport of dye molecules across the cell membrane. Finally, we report on the advanced functions including gene silencing of miR-21 in single cancer cells and selective transport of Ca2+ into single PC-12 cells. In this work, we provide a versatile tool for the design of rectifying artificial nanochannels with on-demand functions.


Assuntos
DNA Catalítico , Membrana Celular , Biomimética , Inativação Gênica , Permeabilidade
3.
Angew Chem Int Ed Engl ; : e202401189, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506220

RESUMO

This study introduces a novel approach for synthesizing Benzoxazine-centered Polychiral Polyheterocycles (BPCPHCs) via an innovative asymmetric carbene-alkyne metathesis-triggered cascade. Overcoming challenges associated with intricate stereochemistry and multiple chiral centers, the catalytic asymmetric Carbene Alkyne Metathesis-mediated Cascade (CAMC) is employed using dirhodium catalyst/Brønsted acid co-catalysis, ensuring precise stereo control as validated by X-ray crystallography. Systematic substrate scope evaluation establishes exceptional diastereo- and enantioselectivities, creating a unique library of BPCPHCs. Pharmacological exploration identifies twelve BPCPHCs as potent Nav ion channel blockers, notably compound 8 g. In vivo studies demonstrate that intrathecal injection of 8 g effectively reverses mechanical hyperalgesia associated with chemotherapy-induced peripheral neuropathy (CIPN), suggesting a promising therapeutic avenue. Electrophysiological investigations unveil the inhibitory effects of 8 g on Nav1.7 currents. Molecular docking, dynamics simulations and surface plasmon resonance (SPR) assay provide insights into the stable complex formation and favorable binding free energy of 8 g with C5aR1. This research represents a significant advancement in asymmetric CAMC for BPCPHCs and unveils BPCPHC 8 g as a promising, uniquely acting pain blocker, establishing a C5aR1-Nav1.7 connection in the context of CIPN.

4.
JACS Au ; 4(2): 402-410, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38425918

RESUMO

We presented the construction of the ring-in-ring and Russian doll complexes on the basis of triptycene-derived carbon nanoring (TP-[12]CPP), which not only acts as a host for pillar[5]arene (P5A) but also serves as an energy donor for building Förster resonance energy transfer (FRET) systems. We also demonstrated that their hierarchical assembly processes could be efficiently monitored in real time using FRET. NMR, UV-vis and fluorescence, and mass spectroscopy analyses confirmed the successful encapsulation of the guests P5A/P5A-An by TP-[12]CPP, facilitated by C-H···π and ···π interactions, resulting in the formation of a distinct ring-in-ring complex with a binding constant of Ka = 2.23 × 104 M-1. The encapsulated P5A/P5A-An can further reverse its role to be a host for binding energy acceptors to form Russian doll complexes, as evidenced by the occurrence of FRET and mass spectroscopy analyses. The apparent binding constant of the Russian doll complexes was up to 3.6 × 104 M-1, thereby suggesting an enhanced synergistic effect. Importantly, the Russian doll complexes exhibited both intriguing one-step and sequential FRET dependent on the subcomponent P5A/P5A-An during hierarchical assembly, reminiscent of the structure and energy transfer of the light-harvesting system presented in purple bacteria.

5.
ACS Chem Neurosci ; 15(6): 1063-1073, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38449097

RESUMO

Chronic pain is a growing global health problem affecting at least 10% of the world's population. However, current chronic pain treatments are inadequate. Voltage-gated sodium channels (Navs) play a pivotal role in regulating neuronal excitability and pain signal transmission and thus are main targets for nonopioid painkiller development, especially those preferentially expressed in dorsal root ganglial (DRG) neurons, such as Nav1.6, Nav1.7, and Nav1.8. In this study, we screened in virtual hits from dihydrobenzofuran and 3-hydroxyoxindole hybrid molecules against Navs via a veratridine (VTD)-based calcium imaging method. The results showed that one of the molecules, 3g, could inhibit VTD-induced neuronal activity significantly. Voltage clamp recordings demonstrated that 3g inhibited the total Na+ currents of DRG neurons in a concentration-dependent manner. Biophysical analysis revealed that 3g slowed the activation, meanwhile enhancing the inactivation of the Navs. Additionally, 3g use-dependently blocked Na+ currents. By combining with selective Nav inhibitors and a heterozygous expression system, we demonstrated that 3g preferentially inhibited the TTX-S Na+ currents, specifically the Nav1.7 current, other than the TTX-R Na+ currents. Molecular docking experiments implicated that 3g binds to a known allosteric site at the voltage-sensing domain IV(VSDIV) of Nav1.7. Finally, intrathecal injection of 3g significantly relieved mechanical pain behavior in the spared nerve injury (SNI) rat model, suggesting that 3g is a promising candidate for treating chronic pain.


Assuntos
Dor Crônica , Indóis , Neuralgia , Ratos , Animais , Simulação de Acoplamento Molecular , Canal de Sódio Disparado por Voltagem NAV1.8 , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Gânglios Espinais/metabolismo
6.
Chempluschem ; : e202300770, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38236013

RESUMO

Electrochromic devices (ECDs) possess the performance advantages in terms of color adjustability, low power consumption, and visual friendliness, emerging as one of the ideal candidates for energy-efficient smart windows, next-generation displays, and wearable electronics. The optical and electrical characteristics of ECDs can be adjusted by modifying the materials or structure of devices. This review summarizes the recent developments of innovative technologies and key materials of ECDs for display applications, highlighting the key issues and development trends in this area.

7.
Anesth Analg ; 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37968831

RESUMO

BACKGROUND: Chronic orofacial pain (COP) therapy is challenging, as current medical treatments are extremely lacking. Moutan Cortex (MC) is a traditional Chinese medicine herb widely used for chronic inflammatory diseases. However, the mechanism behind MC in COP therapy has not been well-established. The purpose of this study was to identify the active ingredients of MC and their specific underlying mechanisms in COP treatment. METHODS: In this study, the main active ingredients and compound-target network of MC in COP therapy were identified through network pharmacology and bioinformatics analysis. Adult male Sprague-Dawley rats received oral mucosa lipopolysaccharide (LPS) injection to induce COP. Pain behaviors were evaluated by orofacial mechanical nociceptive assessment after intraganglionar injection. In vitro inflammatory cytokines in LPS-pretreated human periodontal ligament stem cells (hPDLSCs) and rat primary cultural trigeminal ganglion (TG) neurons were quantified by real-time quantitative polymerase chain reaction (RT-qPCR). Schrödinger software was used to verify the molecular docking of quercetin and critical targets. Whole-cell recording electrophysiology was used to evaluate the effect of quercetin on voltage-gated sodium (Na v ) channel in rat TG neurons. RESULTS: The assembled compound-target network consisted of 4 compounds and 46 targets. As 1 of the active components of MC correlated with most related targets, quercetin alleviated mechanical allodynia in LPS-induced rat model of COP (mechanical allodynia threshold median [interquartile range (IQR) 0.5 hours after drug administration: vehicle 1.3 [0.6-2.0] g vs quercetin 7.0 [6.0-8.5] g, P = .002). Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that immune response and membrane functions play essential roles in MC-COP therapy. Five of the related targets were identified as core targets by protein-protein interaction analysis. Quercetin exerted an analgesic effect, possibly through blocking Na v channel in TG sensory neurons (peak current density median [IQR]: LPS -850.2 [-983.6 to -660.7] mV vs LPS + quercetin -589.6 [-711.0 to -147.8] mV, P = .006) while downregulating the expression level of proinflammatory cytokines-FOS (normalized messenger RNA [mRNA] level mean ± standard error of mean [SEM]: LPS [2. 22 ± 0.33] vs LPS + quercetin [1. 33 ± 0.14], P = .034) and TNF-α (normalized mRNA level mean ± SEM: LPS [8. 93 ± 0.78] vs LPS + quercetin [3. 77 ± 0.49], P < .0001). CONCLUSIONS: Identifying Na v as the molecular target of quercetin clarifies the analgesic mechanism of MC, and provides ideas for the development of novel selective and efficient chronic pain relievers.

8.
Chem Sci ; 14(40): 11121-11130, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37860654

RESUMO

In this study, we synthesized and reported the heterotopic bisnanohoops P5-[8,10]CPPs containing cycloparaphenylenes (CPPs) and a pillar[5]arene unit, which act not only as energy donors but also as a host for binding energy acceptors. We demonstrated that a series of elegant FRET systems could be constructed successfully through self-assembly between donors P5-[8,10]CPPs and acceptors with different emissions via host-guest interaction. These FRET systems further allow us to finely adjust the donors P5-[8,10]CPPs and acceptors (BODIPY-Br and Rh-Br) for achieving multiple color-tunable emissions, particularly white-light emission. More importantly, these host-guest complexes were successfully utilized in the fabrication of white-light fluorescent films and further integrated with a 365 nm LED lamp to create white LED devices. The findings highlight a new application of carbon nanorings in white-light emission materials, beyond the common recognition of π-conjugated molecules.

9.
Nanoscale ; 15(43): 17232-17248, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37856207

RESUMO

Micro-LED displays have been recognized as the next-generation display technology. This review focuses on the pixel-driving technology of micro-LED displays. The performance of pixel driving on micro-LED displays is discussed in terms of brightness uniformity, driving speed, grayscale, and frame rate under various driving architectures. Since the memristors possess characteristics similar to those of biological synaptic neurons due to the ion migration mechanism, the neural network approach which combines the memristor arrays with the pixel driving circuit of micro-LEDs could promote the development of smart and efficient displays.

10.
Appl Opt ; 62(19): 5294-5300, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37707234

RESUMO

We present a high-absorption optical stack design for aluminum (Al) kinetic inductance detectors (KIDs). Aluminum can be easily processed in micro-fabrication and is the most conventional superconducting material for KIDs. However, it is challenging to achieve high absorption in the Al absorber because of its high reflection at optical wavelengths. By embedding the thin Al film between an anti-reflection (AR) coating layer and a dielectric-based distributed Bragg reflector, we show that close-to-unity absorption can be achieved around a single wavelength (e.g., ≈98.9% at 1518 nm). The reflection and transmission measurements agree well with the calculation based on the transmission matrix model. We also show our preliminary results of absorption ≥70% in a broader wavelength range (≈230n m) with multilayer AR coatings. The absorber design in a lumped-element KID is discussed. Our work paves the way to high-efficiency photon-counting and energy-resolving Al-based KIDs in the optical to NIR range.

11.
Environ Sci Pollut Res Int ; 30(41): 94623-94638, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37535281

RESUMO

Dissolved organic matter (DOM) transported by inflowing rivers can considerably contribute to the organic loadings of lakes. The current study characterized the DOM properties and source apportionment in the inflowing rivers of Dianchi Lake, the sixth largest freshwater lake in China suffering from organic pollution, during the rainy season by using spectroscopic and carbon stable isotope techniques, and the regulation role of land use was assessed. The results showed that land use (urbanized, agricultural, or mixed) largely affected DOM properties. Greater concentrations and fluorescence intensities of DOM with low aromaticity and dominant autochthonous sources were observed in the urban rivers than in the agricultural rivers. The proportion of humic-like substances increased, while that of tryptophan-like matter decreased from upstream to downstream of two main urban rivers. DOM in the agricultural rivers was characterized by more amounts of aromatic humic-like substances with dominant allochthonous sources compared to that in the urban rivers. Stable isotope analysis showed that the decomposition of macrophytes and input of terrestrial sources from C3 plant-dominated soil and sewage were the major DOM origins in the rivers. The positive linear relationship between the chemical oxygen demand (COD) concentration and fluorescence intensities of terrigenous DOM components implied the necessity of controlling exogenous inputs to alleviate organic pollution in the Dianchi Lake.


Assuntos
Matéria Orgânica Dissolvida , Lagos , Lagos/química , Espectrometria de Fluorescência , Rios/química , China
12.
J Environ Manage ; 344: 118489, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37393880

RESUMO

Significant progress has been made in the development of phosphorus recovery adsorbents and photocatalysts for degradation of pesticides. However, the bifunctional materials for phosphorus recovery and photocatalytic degradation of pesticides have not been designed, and the mechanism of the interaction between photocatalysis and P adsorption remains unexplored. Herein, we develop biochar-g-C3N4-MgO composites (BC-g-C3N4-MgO) with bi-function application to minimize water toxicity and eutrophication. The results show phosphorus adsorption capacity of the BC-g-C3N4-MgO composite reaches 111.0 mg·g-1, and its degradation ratio of dinotefuran reaches 80.1% within 260 min. The mechanism studies show that MgO can play variety roles in BC-g-C3N4-MgO composite, in which can improve the adsorption capacity of phosphorus, enhance the utilization efficiency of visible light and the separation efficiency of photoinduced electron-hole pairs. The biochar existed in BC-g-C3N4-MgO serves as charge transporter with a good conductivity, which promotes the fluent transfer of photo-generated charge carriers. The ESR indicates that both •O2- and •OH generated from BC-g-C3N4-MgO are responsible for dinotefuran degradation. Finally, pot experiments reveal that P laden BC-g-C3N4-MgO promotes the growth of pepper seedlings with high P utilization efficiency of 49.27%.


Assuntos
Praguicidas , Fósforo , Óxido de Magnésio , Fertilizantes
13.
Nanotechnology ; 34(33)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37192605

RESUMO

The temperature-dependent external quantum efficiency (EQE) droops of 265 nm, 275 nm, 280 nm, and 285 nm AlGaN-based ultraviolet-c light-emitting diodes (UVC-LEDs) differed in Al contents have been comprehensively investigated. The modifiedABCmodel (R = An+Bn2+Cn3) with the current-leakage related term,f(n)= Dn4, has been employed to analyze the recombination mechanisms in these UVC-LED samples. Experimental results reveal that, at relatively low electrical-current levels, the contribution of Shockley-Read-Hall (SRH) recombination exceeds those of the Auger recombination and carrier leakage. At relatively high electrical-current levels, the Auger recombination and carrier leakage jointly dominate the EQE droop phenomenon. Moreover, the inactivation efficiencies of 222 nm excimer lamp, 254 nm portable Mercury lamp, 265 nm, 280 nm, and 285 nm UVC-LED arrays in the inactivation ofEscherichia colihave been experimentally investigated, which could provide a technical reference for fighting against the new COVID-19.

14.
Angew Chem Int Ed Engl ; 62(28): e202304623, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37193936

RESUMO

We report the synthesis and chiroptical properties of novel chiral carbon nanorings Sp-/Rp-[12]PCPP containing a planar chiral [2.2]PCP unit, and demonstrate that Sp-/Rp-[12]PCPP can not only host crown ether 18-Crown-6 to form ring-in-ring complexes with a binding constant 3.35×103  M-1 , but also accommodate the complexes of 18-Crown-6 and S/R-protonated amines to form homochiral S@Sp-/R@Rp- and heterochiral S@Rp-/R@Sp- ternary complexes, displaying significantly larger binding constants of up to 3.31×105  M-1 depending on the chiral guests. Importantly, homochiral S@Sp-/R@Rp- ternary complexes exhibit an enhanced CD signal, while the heterochiral S@Rp-/R@Sp- ones have a constant CD signal compared with the chiral carbon nanorings, respectively, which suggests that homochiral S@Sp-/R@Rp- ternary complexes display a highly narcissistic chiral self-recognition for S/R-protonated chiral amines, respectively. Finally, the chiral ternary complexes can be further applied to determine the ee values of chiral guests. The findings highlight a new application of carbon nanorings in supramolecular sensors, beyond the common recognition of π-conjugated molecules.

15.
Nat Biotechnol ; 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37217750

RESUMO

Little is known about the biological roles of glycosylated RNAs (glycoRNAs), a recently discovered class of glycosylated molecules, because of a lack of visualization methods. We report sialic acid aptamer and RNA in situ hybridization-mediated proximity ligation assay (ARPLA) to visualize glycoRNAs in single cells with high sensitivity and selectivity. The signal output of ARPLA occurs only when dual recognition of a glycan and an RNA triggers in situ ligation, followed by rolling circle amplification of a complementary DNA, which generates a fluorescent signal by binding fluorophore-labeled oligonucleotides. Using ARPLA, we detect spatial distributions of glycoRNAs on the cell surface and their colocalization with lipid rafts as well as the intracellular trafficking of glycoRNAs through SNARE protein-mediated secretory exocytosis. Studies in breast cell lines suggest that surface glycoRNA is inversely associated with tumor malignancy and metastasis. Investigation of the relationship between glycoRNAs and monocyte-endothelial cell interactions suggests that glycoRNAs may mediate cell-cell interactions during the immune response.

16.
Org Lett ; 25(21): 3972-3977, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37204179

RESUMO

We report a metal- and oxidant-free aromatic C-C bond cleavage in the curved corannulene skeleton. Reaction of 1-aminocorannulene with hydrazonyl chloride generates an amidrazone intermediate that undergoes facile intramolecular proton migrations and ring annulation to give a 1,2,4-triazole derivative of planar benzo[ghi]fluoranthene, in which the release of strain associated with the curved π-surface and the formation of an aromatic triazole moiety are the driving forces. This report provides new insights into the aromatic C-C bond cleavage.

17.
Sci Adv ; 9(16): eade7622, 2023 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-37075105

RESUMO

Visualizing redox-active metal ions, such as Fe2+ and Fe3+ ions, are essential for understanding their roles in biological processes and human diseases. Despite the development of imaging probes and techniques, imaging both Fe2+ and Fe3+ simultaneously in living cells with high selectivity and sensitivity has not been reported. Here, we selected and developed DNAzyme-based fluorescent turn-on sensors that are selective for either Fe2+ or Fe3+, revealing a decreased Fe3+/Fe2+ ratio during ferroptosis and an increased Fe3+/Fe2+ ratio in Alzheimer's disease mouse brain. The elevated Fe3+/Fe2+ ratio was mainly observed in amyloid plaque regions, suggesting a correlation between amyloid plaques and the accumulation of Fe3+ and/or conversion of Fe2+ to Fe3+. Our sensors can provide deep insights into the biological roles of labile iron redox cycling.


Assuntos
Doença de Alzheimer , Camundongos , Animais , Humanos , Doença de Alzheimer/diagnóstico por imagem , Ferro , Metais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Placa Amiloide , Peptídeos beta-Amiloides/metabolismo
18.
J Environ Manage ; 330: 117232, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36610197

RESUMO

Pyrite-based autotrophic denitrification (PAD) is an emerging biological process to diminish nitrate pollution, but the relatively low NO3--N removal rate limits its practical application. In this research, a pyrite-intensified hybrid sequencing batch biofilm reactor (PIHSBBR) was designed to treat low C/N ratio domestic wastewater. The results showed that PIHSBBR could achieve optimal removal of COD, NH4+-N, and TN under the aeration rate of 1.0 L/L∙min and the hydraulic retention time (HRT) of 8 h, with removal rates of 69.67 ± 4.37%, 77.04 ± 4.84%, and 63.92 ± 6.66%, respectively. The PAD efficiency in PIHSBBR during the stable operation was not high (13.05-31.01%), and the main nitrogen removal pathway in PIHSBBR, especially in the aerobic zone, was simultaneous nitrification and denitrification (SND). High-throughput sequencing analysis unraveled that Planctomycetota (3.65%) had a high abundance in the anoxic zone of PIHSBBR, implying that anaerobic ammonium oxidation (anammox) might have occurred in the anoxic zone. In addition, the nitrogen cycle function gene with the highest abundance was nirBD, indicating the possible presence of dissimilatory nitrate reduction to ammonium (DNRA) within the system (aerobic and anoxic zones). Our research can provide useful information for the improvement and future application of PIHSBBR.


Assuntos
Compostos de Amônio , Desnitrificação , Nitratos , Reatores Biológicos , Nitrificação , Biofilmes , Nitrogênio , Oxirredução , Esgotos
19.
Front Immunol ; 13: 1080980, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36578485

RESUMO

Background: Epidemiological observational studies have investigated the relationship between rheumatoid arthritis(RA) and pre-eclampsia, but no consistent conclusions were obtained due to various limitations. Hence, we conducted a two-sample mendelian randomization analysis to evaluate the potential causal effect of RA on pre-eclampsia. Methods: Summary-level statistics for RA were derived from a large-scale meta-analysis of datasets of genome-wide association studies(GWAS) which involved 14,361 cases and 43,923 controls. Moreover, summary statistics for pre-eclampsia or eclampsia were sourced from the Finn biobank which contained 3,903 cases and 114,735 controls. The inverse variance weighting (IVW) as well as other four effective methods including MR-Egger, weighted median, weighted mode, and simple mode were applied to deduce the potential causal relationships between RA and pre-eclampsia comprehensively. Results: The two-sample MR analysis suggested a strong causal relationship between RA and pre-eclampsia[OR,1.05;95%CI, 1.01-1.09;p<0.05]. The OR estimates obtained from the weighted mode[OR,1.09;95%CI,1.03-1.15;p<0.01] and weighted median[OR,1.07;95%CI, 1.01-1.14;p<0.05] were similar to those from the IVW method, but there was no significant association observed in MR Egger and simple mode analysis. Conclusion: This MR analysis provides evidence of a positive causal association between RA and pre-eclampsia genetically. Our findings highlight the importance of more intensive prenatal care and early intervention among pregnant women with RA to prevent potential adverse obstetric outcomes. Moreover, our study provides clues for risk factor identification and early prediction of pre-eclampsia.


Assuntos
Artrite Reumatoide , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/genética , Polimorfismo de Nucleotídeo Único , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/genética
20.
Chem Sci ; 13(43): 12818-12830, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36519059

RESUMO

The misfolded proteins or polypeptides commonly observed in neurodegenerative diseases, including Alzheimer's disease (AD), are promising drug targets for developing therapeutic agents. To target the amyloid-ß (Aß) peptide plaques and oligomers, the hallmarks of AD, we have developed twelve amphiphilic small molecules with different hydrophobic and hydrophilic fragments. In vitro fluorescence binding assays demonstrate that these amphiphilic compounds show high binding affinity to both Aß plaques and oligomers, and six of them exhibit selective binding toward Aß oligomers. These amphiphilic compounds can also label the Aß species in the brain sections of transgenic AD mice, as shown by immunostaining with an Aß antibody. Molecular docking studies were performed to obtain structure-affinity relationships. To our delight, four amphiphilic compounds can alleviate the Cu2+-Aß induced toxicity in cell viability assays. In addition, confocal fluorescence imaging studies provide evidence that two compounds, ZY-15-MT and ZY-15-OMe, can disrupt the interactions between Aß oligomers and human neuroblastoma SH-SY5Y cell membranes. Overall, these studies strongly suggest that developing compounds with amphiphilic properties that target Aß oligomers and modulate the Aß oligomer-cell membrane interactions can be an effective strategy for the development of small molecule AD therapeutics.

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