Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
1.
Opt Express ; 32(7): 10948-10961, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38570956

RESUMO

Folded lenses offer advantages in terms of lightness and thinness, but they have limitations when it comes to correcting aberrations. In this paper, we propose a novel approach to address this issue by incorporating metasurfaces in the design of folded optical systems. Specifically, a folded refractive-metasurface hybrid annular aperture folded lens (AFL) is introduced. The structural characteristics of the AFL imaging system are analyzed to investigate the blocking ratio, thickness, and light collection capability of the ring aperture system. Additionally, a hybrid optical integration design using Zemax software is proposed for the metasurfaces. A quadruple-folded AFL working in the mid-infrared waveband is then designed. The superstructure surface is analyzed, and its processability is discussed. The results demonstrate that the reflective-metasurface hybrid AFL significantly improves the imaging quality of this type of optical system while meeting the required design accuracy.

2.
Mol Plant ; 17(5): 807-823, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38664971

RESUMO

The plant apoplast, which serves as the frontline battleground for long-term host-pathogen interactions, harbors a wealth of disease resistance resources. However, the identification of the disease resistance proteins in the apoplast is relatively lacking. In this study, we identified and characterized the rice secretory protein OsSSP1 (Oryza sativa secretory small protein 1). OsSSP1 can be secreted into the plant apoplast, and either in vitro treatment of recombinant OsSSP1 or overexpression of OsSSP1 in rice could trigger plant immune response. The expression of OsSSP1 is suppressed significantly during Magnaporthe oryzae infection in the susceptible rice variety Taibei 309, and OsSSP1-overexpressing lines all show strong resistance to M. oryzae. Combining the knockout and overexpression results, we found that OsSSP1 positively regulates plant immunity in response to fungal infection. Moreover, the recognition and immune response triggered by OsSSP1 depend on an uncharacterized transmembrane OsSSR1 (secretory small protein receptor 1) and the key co-receptor OsBAK1, since most of the induced immune response and resistance are lost in the absence of OsSSR1 or OsBAK1. Intriguingly, the OsSSP1 protein is relatively stable and can still induce plant resistance after 1 week of storage in the open environment, and exogenous OsSSP1 treatment for a 2-week period did not affect rice yield. Collectively, our study reveals that OsSSP1 can be secreted into the apoplast and percepted by OsSSR1 and OsBAK1 during fungal infection, thereby triggering the immune response to enhance plant resistance to M. oryzae. These findings provide novel resources and potential strategies for crop breeding and disease control.


Assuntos
Resistência à Doença , Oryza , Doenças das Plantas , Proteínas de Plantas , Oryza/microbiologia , Oryza/genética , Oryza/metabolismo , Oryza/imunologia , Resistência à Doença/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas , Imunidade Vegetal , Magnaporthe/fisiologia , Ascomicetos/fisiologia
3.
Front Neurosci ; 18: 1340164, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38550560

RESUMO

Implantable neuromodulation devices have significantly advanced treatments for neurological disorders such as Parkinson's disease, epilepsy, and depression. Traditional open-loop devices like deep brain stimulation (DBS) and spinal cord stimulators (SCS) often lead to overstimulation and lack adaptive precision, raising safety and side-effect concerns. Next-generation closed-loop systems offer real-time monitoring and on-device diagnostics for responsive stimulation, presenting a significant advancement for treating a range of brain diseases. However, the high false alarm rates of current closed-loop technologies limit their efficacy and increase energy consumption due to unnecessary stimulations. In this study, we introduce an artificial intelligence-integrated circuit co-design that targets these issues and using an online demonstration system for closed-loop seizure prediction to showcase its effectiveness. Firstly, two neural network models are obtained with neural-network search and quantization strategies. A binary neural network is optimized for minimal computation with high sensitivity and a convolutional neural network with a false alarm rate as low as 0.1/h for false alarm rejection. Then, a dedicated low-power processor is fabricated in 55 nm technology to implement the two models. With reconfigurable design and event-driven processing feature the resulting application-specific integrated circuit (ASIC) occupies only 5mm2 silicon area and the average power consumption is 142 µW. The proposed solution achieves a significant reduction in both false alarm rates and power consumption when benchmarked against state-of-the-art counterparts.

4.
Chem Commun (Camb) ; 60(31): 4218-4221, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38525863

RESUMO

Heterostructured Fe2O3/Fe7S8 hollow fibers were rationally designed and synthesized via the electrospinning technique, followed by a calcination process and sulfuration treatment. Benefitting from the synergistic effect of the hollow structure and the built-in electric field induced by the heterostructure, the as-prepared Fe2O3/Fe7S8 composite anode exhibits high specific capacity (947 mA h g-1 after 100 cycles at 0.2 A g-1), excellent rate capability, and long-term cycling stability (730 mA h g-1 after 1000 cycles at 1 A g-1).

5.
Cytokine ; 177: 156556, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38417214

RESUMO

BACKGROUND: Impaired wound healing in traumatic skin injuries remains a severe clinical challenge due to impaired re-vascularization, harmful bacteria infection, and inflammation dysregulation. Macrophages are recognized as prominent immune cells in tissue regeneration and wound healing. Consequently, the modulation of macrophages provides a promising therapeutic target for wound healing disorders. Here, we aimed to explore whether a novel constructed combination of thermosensitive hydrogel Pluronic F-127 (PF-127) and phillyrin (PH, the main active compound of forsythia suspensa) could improve skin wound healing. METHODS: Firstly, the biological effects of pH on the phenotype and inflammation of macrophages were assessed by flow cytometry and ELISA. The biocompatibility of the PF-127 plus PH combination was investigated on keratinocytes and red blood cells. The biological effect of PF-127/PH hydrogel on the migratory ability of keratinocytes in vitro was evaluated using the scratch and transwell migration assays. In addition,S. aureusandE. coliwere employed to test the antibacterial properties of the PF-127 plus PH combination. Finally, PF-127 plus PH scaffold was appliedto the full-thickness skin defect in mice. Histomorphological evaluation and immunochemistry were performed to explore the wound-healing activity of PF-127/PH hydrogel. RESULTS: PH can promote the polarization of macrophages from the M1 (pro-inflammatory) phenotype to the M2 (anti-inflammatory) phenotype. The PF-127/PH hydrogel was highly biocompatible and showed a potent stimulative effect on the migration of keratinocytesin vitro. The combination of PF-127 and PH exerted a pronounced antibacterial activity onS. aureusandE. coli in vitro.PF-127/PH hydrogel potently accelerates the healing of full-thickness skin defects by promoting skin cell proliferation, accelerating angiogenesis, and inhibiting inflammation. CONCLUSIONS: Our study suggests that PF-127/PH hydrogel has excellent potential for treating traumatic skin defects.


Assuntos
Glucosídeos , Hidrogéis , Cicatrização , Camundongos , Animais , Hidrogéis/farmacologia , Macrófagos , Poloxâmero/farmacologia , Antibacterianos/farmacologia , Inflamação
6.
Plant Cell ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376990

RESUMO

In adverse environments, the number of fertilizable female gametophytes (FGs) in plants is reduced, leading to increased survival of remaining offspring. How the maternal plant perceives internal growth cues and external stress conditions to alter FG development remains largely unknown. We report that homeostasis of the stress signaling molecule nitric oxide (NO) plays a key role in controlling FG development under both optimal and stress conditions. NO homeostasis is precisely regulated by S-nitrosoglutathione reductase (GSNOR). Prior to fertilization, GSNOR protein is exclusively accumulated in sporophytic tissues and indirectly controls FG development in Arabidopsis (Arabidopsis thaliana). In GSNOR null mutants, NO species accumulated in the degenerating sporophytic nucellus and auxin efflux into the developing FG was restricted, which inhibited FG development, resulting in reduced fertility. Importantly, restoring GSNOR expression in maternal, but not gametophytic tissues, or increasing auxin efflux substrate significantly increased the proportion of normal FGs and fertility. Furthermore, GSNOR overexpression or added auxin efflux substrate increased fertility under drought and salt stress. These data indicate that NO homeostasis is critical to normal auxin transport and maternal control of FG development, which in turn determine seed yield. Understanding this aspect of fertility control could contribute to mediating yield loss under adverse conditions.

8.
BMC Psychiatry ; 23(1): 665, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700243

RESUMO

BACKGROUND: Mental health disorders affect millions of US adults, however, the trends and related factors for mental health care utilization in the US remain unknown. AIMS: Our study aimed to assess the trend of mental health utilization and related socio-demographic factors in the US. METHODS: The study included 55,052 individuals from the National Health and Nutrition Examination Survey (NHANES) in 1999-2018. Temporal trends in the percentages of mental health care utilizers were estimated across survey cycles. Trends and linked factors of mental health care utilization were assessed by a logistic regression model, while the non-linearity was estimated by restricted cubic splines. RESULTS: From 1999 to 2018, the percentage of mental health care utilizers in the US adult population increased from 7.0 to 11.3% (P < 0.001); meanwhile, the trends in males and females were consistent. The percentage increased positively with age in individuals aged 20-39 (P < 0.001) or aged 60 and over (P = 0.003). The trends were consistent in three race/ethnicity groups (P < 0.05). The logistic regression analysis revealed that several disparities existed in the subpopulations. Older age, female, lower family poverty-income ratio (PIR), chronic diseases, higher educational level, and smoking were estimated to be associated with a higher percentage of mental health care. CONCLUSIONS: The percentage of mental health care utilizers took on an increasing trend in the US adult population from 1999 to 2018. These trends were also observed in the subpopulations, but with disparities. Future research for exploring factors associated with mental health care utilizations is necessary.


Assuntos
Saúde Mental , Aceitação pelo Paciente de Cuidados de Saúde , Masculino , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Inquéritos Nutricionais , Etnicidade , Renda
9.
Neuropsychologia ; 189: 108667, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37619937

RESUMO

When searching for a target defined by a set of objects, attention can be directed toward task-relevant objects by creating a category-based attentional template (CAT). Previous studies have found that CAT can be activated before the onset of the target. However, the time course of CAT pre-activation and whether the category framework (prototypical or semantic) can modulate it remain unclear. To explore the time course of CAT pre-activation, we employed a rapid serial probe presentation paradigm (RSPP) with event-related potentials (ERPs). To investigate the effect of the category framework on the time course of CAT pre-activation, the target category was defined as the prototypical category (Experiment 1) or the semantic category (Experiment 2). The results showed that the prototype-based CAT was pre-activated 300 ms prior to the target, whereas the semantics-based CAT was pre-activated 1500 ms before the onset of the target. The difference in the time course of pre-activation between the two CAT types indicates that the category framework can modulate the time course of CAT pre-activation. Additionally, during the attentional selection phase, an overall comparison of the target revealed that a larger N2pc was elicited by the prototype-based CAT than by the semantics-based CAT, suggesting that the prototype-based CAT could capture more attention than the semantics-based CAT. The findings on the difference between the two CAT frameworks in the preparatory and attentional selection phases provide more evidence for categorical information in visual search and extend our understanding of the mechanism of categorical attentional selection.

10.
Biomed Opt Express ; 14(7): 3152-3171, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37497518

RESUMO

We introduce a novel system for geometrically accurate, continuous, live, volumetric middle ear optical coherence tomography imaging over a 10.9mm×30∘×30∘ field of view (FOV) from a handheld imaging probe. The system employs a discretized spiral scanning (DC-SC) pattern to rapidly collect volumetric data and applies real-time scan conversion and lateral angular distortion correction to reduce geometric inaccuracies to below the system's lateral resolution over 92% of the FOV. We validate the geometric accuracy of the resulting images through comparison with co-registered micro-computed tomography (micro-CT) volumes of a phantom target and a cadaveric middle ear. The system's real-time volumetric imaging capabilities are assessed by imaging the ear of a healthy subject while performing dynamic pressurization of the middle ear in a Valsalva maneuver.

11.
Front Plant Sci ; 14: 1176359, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37324696

RESUMO

Tree peony ( Paeonia suffruticosa Andr.) is a popular cut flower among ornamental plants. However, its short vase life severely hinders the production and application of cut tree peony flowers. To extend the postharvest longevity and improve the horticultural value, silver nanoparticles (Ag-NPs) was applied for reducing bacterial proliferation and xylem blockage in cut tree peony flowers in vitro and in vivo. Ag-NPs was synthesized with the leaf extract of Eucommia ulmoides and characterized. The Ag-NPs aqueous solution showed inhibitory activity against bacterial populations isolated from stem ends of cut tree peony 'Luoyang Hong' in vitro. The minimum inhibitory concentration (MIC) was 10 mg L-1. Compared with the control, pretreatments with Ag-NPs aqueous solution at 5 and 10 mg L-1 for 24 h increased flower diameter, relative fresh weight (RFW), and water balance of tree peony 'Luoyang Hong' flowers. Additionally, malondialdehyde (MDA) and H2O2 content in pretreated petals were lower than the control during the vase life. The activities of superoxide dismutase (SOD) and catalase (CAT) in pretreated petals were lower than that of the control at the early vase stage and higher at the late vase life. Furthermore, pretreatments with Ag-NPs aqueous solution at 10 mg L-1 for 24 h could reduce bacterial proliferation in the xylem vessels on the stem ends by confocal laser scanning microscope (CLSM) and scanning electron microscope (SEM). Overall, pretreatments with green synthesized Ag-NPs aqueous solution effectively reduced bacteria-induced xylem blockage of cut tree peony, resulting in improved water uptake, extended vase life, and enhanced postharvest quality. Therefore, this technique can be used as a promising postharvest technology in the cut flower industry.

12.
IEEE Trans Biomed Circuits Syst ; 17(3): 598-609, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37074883

RESUMO

Versatile and energy-efficient neural signal processors are in high demand in brain-machine interfaces and closed-loop neuromodulation applications. In this paper, we propose an energy-efficient processor for neural signal analyses. The proposed processor utilizes three key techniques to efficiently improve versatility and energy efficiency. 1) Hybrid neural network design: The processor supports artificial neural network (ANN)- and spiking neural network (SNN)-based neuromorphic processing where ANN is used to support the processing of ExG signals and SNN is used for handling neural spike signals. 2) Event-driven processing: The processor can perform always-on binary neural network (BNN)-based event detection with low-energy consumption, and it only switches to the high-accuracy convolutional neural network (CNN)-based recognition mode when events are detected. 3) Reconfigurable architecture: By exploiting the computational similarity of different neural networks, the processor supports critical BNN, CNN, and SNN operations with the same processing elements, achieving significant area reduction and energy efficiency improvement over those of a naive implementation. It achieves 90.05% accuracy and 4.38 uJ/class in a center-out reaching task with an SNN and 99.4% sensitivity, 98.6% specificity, and 1.93 uJ/class in an EEG-based seizure prediction task with dual neural network-based event-driven processing. Moreover, it achieves a classification accuracy of 99.92%, 99.38%, and 86.39% and energy consumption of 1.73, 0.99, and 1.31 uJ/class for EEG-based epileptic seizure detection, ECG-based arrhythmia detection, and EMG-based gesture recognition, respectively.


Assuntos
Interfaces Cérebro-Computador , Redes Neurais de Computação , Humanos
13.
Org Biomol Chem ; 21(13): 2729-2741, 2023 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-36916165

RESUMO

A series of DAB-peptide and DAB-dipeptide derivatives were synthesized from D-tartrate-derived nitrone 18. The DAB peptides 16 are derivatives of trans,trans-3,4-dihydroxy-L-proline. Glycosidase inhibition assay found four of them to be weak and selective bovine liver ß-galactosidase inhibitors, and the C-2' methyl substituted compound 23b showed the most potent ß-galactosidase inhibition (IC50 = 0.66 µM). Molecular docking studies revealed different docking modes of compound 23b compared to those of other DAB-peptides, and partial similarity of compound 23b to DGJ.


Assuntos
Dipeptídeos , Glicosídeo Hidrolases , Animais , Bovinos , Simulação de Acoplamento Molecular , Peptídeo C , beta-Galactosidase , Relação Estrutura-Atividade , Estrutura Molecular
14.
Eur J Med Chem ; 247: 115056, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36603505

RESUMO

A series of α-1-C-alkyl DAB (1,4-dideoxy-1,4-imino-d-arabinitol) and LAB (1,4-dideoxy-1,4-imino-l-arabinitol) derivatives with aryl substituents have been designed as analogues of broussonetine W (12), and assayed as glycosidase inhibitors. While the inhibition spectrum of α-1-C-alkyl DAB derivative 16 showed a good correlation to that of broussonetine W (12), introduction of substituents on the terminal aryl (17a-f) or hydroxyl groups at C-1' position of the alkyl chains (18a-e) decreased their α-glucosidase inhibitions but greatly improved their inhibitions of bovine liver ß-glucosidase and ß-galactosidase. Furthermore, epimerization of C-1' configurations of compounds 18a-e clearly lowered their inhibition potency of bovine liver ß-glucosidase and ß-galactosidase. Notably, some of the α-1-C-alkyl DAB derivatives were also found to have potent human lysosome ß-glucosidase inhibitions. In contrast, enantiomers of compounds 18a-e and 1'-epi-18a-e generally showed increased α-glucosidase inhibitions, but sharply decreased bovine liver ß-glucosidase and ß-galactosidase inhibitions. Molecular docking calculations unveiled the novel two set of binding modes for each series of compounds; introduction of C-1' hydroxyl altered the conformations of the pyrrolidine rings and orientation of their long chains, resulting in improved accommodation in the hydrophobic grooves. The compounds reported herein are very potent ß-glucosidase and ß-galactosidase inhibitions with novel binding mode; and the structure-activity relationship provides guidance for design and development of more pyrrolidine pharmacological chaperones for lysosomal storage diseases.


Assuntos
alfa-Glucosidases , beta-Glucosidase , Animais , Bovinos , Humanos , alfa-Glucosidases/metabolismo , beta-Galactosidase , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Simulação de Acoplamento Molecular , Pirrolidinas/farmacologia , Relação Estrutura-Atividade
15.
Front Plant Sci ; 13: 1037989, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325559

RESUMO

Hexaploid wheat is a major food crop and is sensitive to heat stress. It is necessary to discover genes related to thermotolerance in wheat. Fes1s is a class of nucleotide exchange factor of heat shock protein 70s, proven to be participated in heat response in human, yeast, and Arabidopsis. However, little is known about Fes1s in hexaploid wheat. In this study, we identified nine Fes1s in hexaploid wheat (TaFes1s) and found that they present as three triads. A phylogenetic relationship analysis revealed that these Fes1s grouped into Fes1A, Fes1B and Fes1C subclades, and Fes1As and Fes1Bs were divergent in monocots, but possibly not in dicots. The sequences, gene structures and protein motifs of TaFes1s homoeologues within a triad were highly conserved. Through cis-elements analysis including heat shock elements, and miRNA targets prediction, we found that regulation of three TaFes1s homoeologues may be different, while the expression patterns of three homoeologues were similar. The expression levels of TaFes1As were higher than those of TaFes1Bs and TaFes1Cs, and based on these expressions, TaFes1As were chosen for functional characterization. Intriguingly, neither TaFes1A-5A nor TaFes1A-5D could not rescue the thermotolerance defect of Arabidopsis fes1a mutants at seedling stage, but in the transgenic plants seed germination was accelerated under normal and heat stress condition. The functional characterization indicated that roles of Fes1As would be different in Arabidopsis and hexaploid wheat, and function retention of TaFes1As may occur during wheat evolution. In conclusion, our study comprehensively characterized the distribution and expression of Fes1s in hexaploid wheat and found that two TaFes1As could accelerate seed germination under normal and heat stress condition.

16.
Eur J Med Chem ; 244: 114852, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36332547

RESUMO

A series of C-6 fluorinated casuarine derivatives have been synthesized via organocatalytic stereoselective α-fluorination of iminosugar-based aldehydes or direct nucleophilic fluorination of polyhydroxylated pyrrolizidines. Glycosidase assays against various glycosidases allowed systematic structure-activity relationship (SAR) study using molecular docking calculations. Introduction of fluorine atom(s) at C-6 position removed the trehalase and maltase inhibitory activities of all casuarine derivatives, and greatly increased their specificity towards amyloglucosidase. Inhibition of the fluorinated casuarines depended on the configuration of C-6 fluorine, of which 6-deoxy-6-epi-6-fluoro-casuarine (24) was found approximately 40-fold potent than its parent compound 6-epi-casuarine (2) as a potent and specific inhibitor of amyloglucosidase. Molecular docking calculations showed that replacement of the C-6 hydroxyls by fluorine atom(s) removed the original interactions with trehalase, but helped to reinforce the binding with amyloglucosidase via newly established fluorine related hydrogen bonding or untypical anion-π interactions. To further investigate the quantitative SARs of casuarine derivatives, the CoMFA and CoMSIA models on amyloglucosidase were established, indicating the dominating effect of electrostatic field in amyloglucosidase inhibition. The 3D-QSAR models were validated to be reliable and can be used for further optimization of casuarine-related iminosugars, as well as design and development of anti-diabetic and immunomodulatory drugs.


Assuntos
Glucana 1,4-alfa-Glucosidase , Trealase , Simulação de Acoplamento Molecular , Glucana 1,4-alfa-Glucosidase/metabolismo , Trealase/metabolismo , Flúor , Relação Quantitativa Estrutura-Atividade , Relação Estrutura-Atividade , Glicosídeo Hidrolases
17.
Otol Neurotol ; 43(8): e824-e828, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35970156

RESUMO

OBJECTIVE: This study aimed to evaluate the ability of transtympanic middle ear optical coherence tomography (ME-OCT) to assess placement of cochlear implants (CIs) in situ. PATIENT: A 72-year-old man with bilateral progressive heredodegenerative sensorineural hearing loss due to work-related noise exposure received a CI with a slim modiolar electrode for his right ear 3 months before his scheduled checkup. INTERVENTION: A custom-built swept source ME-OCT system (λo = 1550 nm, ∆λ = 40 nm) designed for transtympanic middle ear imaging was used to capture a series of two- and three-dimensional images of the patient's CI in situ. Separately, transtympanic OCT two-dimensional video imaging and three-dimensional imaging were used to visualize insertion and removal of a CI with a slim modiolar electrode in a human cadaveric temporal bone through a posterior tympanotomy. MAIN OUTCOME MEASURE: Images and video were analyzed qualitatively to determine the visibility of implant features under ME-OCT imaging and quantitatively to determine insertion depth of the CI. RESULTS: After implantation, the CI electrode could be readily visualized in the round window niche under transtympanic ME-OCT in both the patient and the temporal bone. In both cases, characteristic design features of the slim modiolar electrode allowed us to quantify the insertion depth from our images. CONCLUSIONS: ME-OCT could potentially be used in a clinic as a noninvasive, nonionizing means to confirm implant placement. This study shows that features of the CI electrode visible under ME-OCT can be used to quantify insertion depth in the postoperative ear.


Assuntos
Implante Coclear , Implantes Cocleares , Perda Auditiva Neurossensorial , Idoso , Cóclea/cirurgia , Implante Coclear/métodos , Perda Auditiva Neurossensorial/cirurgia , Humanos , Masculino , Projetos Piloto , Janela da Cóclea/cirurgia , Tomografia de Coerência Óptica
18.
Eur J Med Chem ; 238: 114499, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35675756

RESUMO

Enantiomeric series of C-4 hydroxymethyl depleted DAB and LAB derivatives (trans, trans-2-C-aryl-3,4-dihydroxypyrrolidines), designed as ß-glucosidase inhibitors by molecular docking calculations, have been synthesized in 2 steps from l- and d-tartaric acid derived enantiomeric cyclic nitrones 29L and 29D, respectively. Both series of C-4 hydroxymethyl depleted DAB and LAB derivatives 28Da-e and 28La-e, which are structurally trans, trans-2-C-aryl-3,4-dihydroxypyrrolidines, were potent and selective human lysosome acid ß-glucosidase (GCase) inhibitors, of which 28Dd and 28Ld with C-4 biphenyls showed the highest potency relative to other compounds of the same series. The work provided a series of pyrrolidine-type potent and selective GCase inhibitors with minimal hydroxyl substitutions and synthetic procedures. Structure-activity relationship study revealed not only the rationality of hydrophobic and aromatic properties of the binding sites in GCase, but also the great potential of pyrrolidine family in development of new GCase inhibitors with minimized undesirable side effects. The results indicate a strategy for the development of drugs for the treatment of related diseases targeting acid ß-glucosidase, such as Gaucher disease and Parkinson's disease.


Assuntos
Doença de Gaucher , Inibidores Enzimáticos/química , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase , Humanos , Simulação de Acoplamento Molecular , Pirrolidinas/farmacologia , Pirrolidinas/uso terapêutico , beta-Glucosidase
19.
J Org Chem ; 87(11): 7291-7307, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35584209

RESUMO

C-7-fluorinated derivatives of two important polyhydroxylated pyrrolizidines, casuarine and australine, were synthesized with organocatalytic stereoselective α-fluorination of aldehydes as the key step. The strategy is extensively applicable to some synthetically challenging fluorinated iminosugars and carbohydrates. The docking studies indicated that the potent inhibitions of trehalase and amyloglucosidase by the fluorinated polyhydroxylated pyrrolizidines are due to the interaction modes dominated by fluorine atoms in these iminosugars with the amino acids' residues of the corresponding enzymes. Steady interactions were established between the C-7 fluoride and a hydrophobic pocket in amyloglucosidase by untypical anion-π interactions. These unexpected docking modes and related structure-activity relationship studies emphasize the value of fluorination in the design of polyhydroxylated pyrrolizidine glycosidase inhibitors.


Assuntos
Glucana 1,4-alfa-Glucosidase , Glicosídeo Hidrolases , Alcaloides , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Pirróis , Alcaloides de Pirrolizidina
20.
Biomed Opt Express ; 13(4): 1834-1854, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35519239

RESUMO

In this study, we demonstrate a sparsity-regularized, complex, blind deconvolution method for removing sidelobe artefacts and stochastic noise from optical coherence tomography (OCT) images. Our method estimates the complex scattering amplitude of tissue on a line-by-line basis by estimating and deconvolving the complex, one-dimensional axial point spread function (PSF) from measured OCT A-line data. We also present a strategy for employing a sparsity weighting mask to mitigate the loss of speckle brightness within tissue-containing regions caused by the sparse deconvolution. Qualitative and quantitative analyses show that this approach suppresses sidelobe artefacts and background noise better than traditional spectral reshaping techniques, with negligible loss of tissue structure. The technique is particularly useful for emerging OCT applications where OCT images contain strong specular reflections at air-tissue boundaries that create large sidelobe artefacts.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA