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1.
Proc Natl Acad Sci U S A ; 121(39): e2404395121, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39292743

RESUMO

Adult central nervous system (CNS) neurons down-regulate growth programs after injury, leading to persistent regeneration failure. Coordinated lipids metabolism is required to synthesize membrane components during axon regeneration. However, lipids also function as cell signaling molecules. Whether lipid signaling contributes to axon regeneration remains unclear. In this study, we showed that lipin1 orchestrates mechanistic target of rapamycin (mTOR) and STAT3 signaling pathways to determine axon regeneration. We established an mTOR-lipin1-phosphatidic acid/lysophosphatidic acid-mTOR loop that acts as a positive feedback inhibitory signaling, contributing to the persistent suppression of CNS axon regeneration following injury. In addition, lipin1 knockdown (KD) enhances corticospinal tract (CST) sprouting after unilateral pyramidotomy and promotes CST regeneration following complete spinal cord injury (SCI). Furthermore, lipin1 KD enhances sensory axon regeneration after SCI. Overall, our research reveals that lipin1 functions as a central regulator to coordinate mTOR and STAT3 signaling pathways in the CNS neurons and highlights the potential of lipin1 as a promising therapeutic target for promoting the regeneration of motor and sensory axons after SCI.


Assuntos
Axônios , Neurônios Motores , Regeneração Nervosa , Fosfatidato Fosfatase , Fator de Transcrição STAT3 , Transdução de Sinais , Traumatismos da Medula Espinal , Serina-Treonina Quinases TOR , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/genética , Animais , Axônios/metabolismo , Axônios/fisiologia , Regeneração Nervosa/fisiologia , Fator de Transcrição STAT3/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fosfatidato Fosfatase/metabolismo , Fosfatidato Fosfatase/genética , Neurônios Motores/metabolismo , Neurônios Motores/fisiologia , Camundongos , Ácidos Fosfatídicos/metabolismo , Células Receptoras Sensoriais/metabolismo , Feminino , Tratos Piramidais/metabolismo , Tratos Piramidais/patologia
2.
Haematologica ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961734

RESUMO

Generation of mammalian red blood cells requires the expulsion of polarized nuclei late in terminal erythroid differentiation. However, the mechanisms by which spherical erythroblasts determine the direction of nuclear polarization and maintain asymmetry during nuclear expulsion are poorly understood. Given the analogy of erythroblast enucleation to asymmetric cell division and the key role of Aurora kinases in mitosis, we sought to investigate the function of Aurora kinases in erythroblast enucleation. We found that AURKA (Aurora kinase A) is abundantly expressed in orthochromatic erythroblasts. Intriguingly, high-resolution confocal microscopy analyses revealed that AURKA co-localized with the centrosome on the side of the nucleus opposite its membrane contact point during polarization and subsequently translocated to the anterior end of the protrusive nucleus upon nuclear exit. Mechanistically, AURKA regulated centrosome maturation and localization via interaction with i-tubulin to provide polarization orientation for the nucleus. Furthermore, we identified ECT2 (epithelial cell transforming 2), a guanine nucleotide exchange factor, as a new interacting protein and ubiquitination substrate of AURKA. After forming the nuclear protrusion, AURKA translocated to the anterior end of the protrusive nucleus to directly degrade ECT2, which is partly dependent on kinase activity of AURKA. Moreover, knockdown of ECT2 rescued impaired enucleation caused by AURKA inhibition. Our findings have uncovered a previously unrecognized role of Aurora kinases in the establishment of nuclear polarization and eventual nuclear extrusion and provide new mechanistic insights into erythroblast enucleation.

3.
J Chem Phys ; 160(1)2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38180256

RESUMO

To cope with the shuttling of soluble lithium polysulfides in lithium-sulfur batteries, confinement tactics, such as trapping of sulfur within porous carbon structures, have been extensively studied. Although performance has improved a bit, the slow polysulfide conversion inducing fast capacity decay remains a big challenge. Herein, a NiS2/carbon (NiS2/C) composite with NiS2 nanoparticles embedded in a thin layer of carbon over the surface of micro-sized hollow structures has been prepared from Ni-metal-organic frameworks. These unique structures can physically entrap sulfur species and also influence their redox conversion kinetics. By improving the reaction kinetics of polysulfides, the NiS2/carbon@sulfur (NiS2/C@S) composite cathode with a suppressed shuttle effect shows a high columbic efficiency and decent rate performance. An initial capacity of 900 mAh g-1 at the rate of 1 C (1 C = 1675 mA g-1) and a low-capacity decline rate of 0.132% per cycle after 500 cycles are obtained, suggesting that this work provides a rational design of a sulfur cathode.

4.
Neuroimage ; 277: 120210, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37311535

RESUMO

Electroencephalography (EEG) and diffuse optical tomography (DOT) are imaging methods which are widely used for neuroimaging. While the temporal resolution of EEG is high, the spatial resolution is typically limited. DOT, on the other hand, has high spatial resolution, but the temporal resolution is inherently limited by the slow hemodynamics it measures. In our previous work, we showed using computer simulations that when using the results of DOT reconstruction as the spatial prior for EEG source reconstruction, high spatio-temporal resolution could be achieved. In this work, we experimentally validate the algorithm by alternatingly flashing two visual stimuli at a speed that is faster than the temporal resolution of DOT. We show that the joint reconstruction using both EEG and DOT clearly resolves the two stimuli temporally, and the spatial confinement is drastically improved in comparison to reconstruction using EEG alone.


Assuntos
Tomografia Óptica , Córtex Visual , Humanos , Eletroencefalografia/métodos , Simulação por Computador , Neuroimagem , Algoritmos , Tomografia Óptica/métodos , Córtex Visual/diagnóstico por imagem , Mapeamento Encefálico/métodos
5.
J Theor Biol ; 572: 111580, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37459953

RESUMO

Cortical spreading depolarization (CSD) is a neuropathological condition involving propagating waves of neuronal silence, and is related to multiple diseases, such as migraine aura, traumatic brain injury (TBI), stroke, and cardiac arrest, as well as poor outcome of patients. While CSDs of different severity share similar roots on the ion exchange level, they can lead to different vascular responses (namely spreading hyperemia and spreading ischemia). In this paper, we propose a mathematical model relating neuronal activities to predict vascular changes as measured with near-infrared spectroscopy (NIRS) and fMRI recordings, and apply it to the extreme case of CSD, where sustained near-complete neuronal depolarization is seen. We utilize three serially connected models (namely, ion exchange, neurovascular coupling, and hemodynamic model) which are described by differential equations. Propagating waves of ion concentrations, as well as the associated vasodynamics and hemodynamics, are simulated by solving these equations. Our proposed model predicts vasodynamics and hemodynamics that agree both qualitatively and quantitatively with experimental literature. Mathematical modeling and simulation offer a powerful tool to help understand the underlying mechanisms of CSD and help interpret the data. In addition, it helps develop novel monitoring techniques prior to data collection. Our simulated results strongly suggest that fMRI is unable to reliably distinguish between spreading hyperemia and spreading ischemia, while NIRS signals are substantially distinct in the two cases.


Assuntos
Depressão Alastrante da Atividade Elétrica Cortical , Hiperemia , Acoplamento Neurovascular , Humanos , Acoplamento Neurovascular/fisiologia , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Hemodinâmica , Neurônios/fisiologia
6.
Molecules ; 28(23)2023 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-38067633

RESUMO

The development of photocatalysts for organic degradation is a hot research topic. In this study, CdZnS was selected as the carrier, and ZIF-8 was combined with it to explore the photocatalytic performance of the composite. In addition, the compound material, CdZnS@ZIF-8, was used as a photocatalyst for the decomposition of methylene blue dye, and the performance of pure CdZnS and pure ZIF-8 was compared. The photocatalytic efficiency of CdZnS@ZIF-8 was significantly higher than that of the other two. In the experimental reaction, the amount of catalyst was 0.04 g, the pH value was 7, the initial concentration of methylene blue aqueous solution was 20 mg/L, and the degradation of methylene blue in 50 mL aqueous solution could reach 99.5% under visible light irradiation for 90 min, showing excellent photocatalytic efficiency in the visible light range. It demonstrated excellent photocatalytic function in the visible light region, and the electron transfer phenomenon at the interface occurred in the het-junction and the separation of the photo-generating electron-hole as an electron acceptor of ZIF-8 further promoted the photocatalytic effect.

7.
Protein Expr Purif ; 175: 105688, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32681953

RESUMO

BST2 is a single-pass type II transmembrane (TM) protein, which has a cytoplasmic domain, a transmembrane domain, and an extracellular domain, each domain is important for biologic function of BST2. BST2 is a host restriction factor that can effectively inhibit retrovirus release. Rhesus monkeys are considered as relevant natural animal models for studying AIDS in humans. In order to recognize rhesus BST2 (RhBST2) protein and detect its function accurately, we prepared a polyclonal antibody (pAb) especially for RhBST2. Meanwhile, we constructed RhBST2 proteins with the addition of an HA-tag at the N-terminus (RhBST2-NHA) or inside of the ectodomain (RhBST2-IHA) to compare the recognition ability of rabbit anti-RhBST2 pAb and anti-HA mAb. The results showed that the anti-HA mAb and rabbit anti-RhBST2 pAb had the same ability to identify RhBST2. RhBST2 demonstrated antiviral activity and the ability to activate NF-κB. Moreover, the N-glycosylation states, cell surface level and intracellular localization of RhBST2 were detected. However, HA tags relatively changed part of the biological function of RhBST2. These results show that the RhBST2 polyclonal antibody is more suitable for analyzing the properties and functions of RhBST2, and the natural domain of RhBST2 is very important for its function.


Assuntos
Anticorpos/imunologia , Antígenos CD , Antivirais , Síndrome da Imunodeficiência Adquirida , Animais , Antígenos CD/biossíntese , Antígenos CD/química , Antígenos CD/imunologia , Antivirais/química , Antivirais/imunologia , Antivirais/metabolismo , Proteínas Ligadas por GPI/biossíntese , Proteínas Ligadas por GPI/química , Proteínas Ligadas por GPI/imunologia , Células HEK293 , HIV-1/imunologia , Humanos , Macaca mulatta , Domínios Proteicos , Coelhos
8.
Sensors (Basel) ; 20(9)2020 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-32375212

RESUMO

The measurement accuracy of the precision instruments that contain rotation joints is influenced significantly by the rotary encoders that are installed in the rotation joints. Apart from the imperfect manufacturing and installation of the rotary encoder, the variations of ambient temperature could cause the angle measurement error of the rotary encoder. According to the characteristics of the 2π periodicity of the angle measurement at the stationary temperature and the complexity of the effects of ambient temperature changes, the method based on the Fourier expansion-back propagation (BP) neural network optimized by genetic algorithm (FE-GABPNN) is proposed to improve the angle measurement accuracy of the rotary encoder. The proposed method, which innovatively integrates the characteristics of Fourier expansion, the BP neural network and genetic algorithm, has good fitting performance. The rotary encoder that is installed in the rotation joint of the articulated coordinate measuring machine (ACMM) is calibrated by using an autocollimator and a regular optical polygon at ambient temperature ranging from 10 to 40 °C. The contrastive analysis is carried out. The experimental results show that the angle measurement errors decrease remarkably, from 110.2″ to 2.7″ after compensation. The mean root mean square error (RMSE) of the residual errors is 0.85″.

9.
J Stroke Cerebrovasc Dis ; 29(4): 104619, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31982305

RESUMO

BACKGROUND: The optimal treatment strategy for residual stenosis in patients with acute intracranial atherosclerotic stenosis related occlusion (ICAS-O) after endovascular treatment (EVT) is unknown. This study aims to evaluate the efficacy and safety of low-dose tirofiban in patients with residual stenosis after EVT due to acute ICAS-O. METHODS: Retrospective analysis of prospectively enrolled consecutive patients with residual stenosis after EVT due to acute ICAS-O from March 2015 to May 2019. Patients were divided into EVT alone group or EVT plus tirofiban group. The primary endpoint was the favorable functional outcome (defined as modified Rankin scale score of 0-2) at 90 days. The secondary endpoints were the proportions of reocclusion of recanalized arteries within 72 hours after EVT, symptomatic intracranial hemorrhage (sICH), any ICH, and mortality at 90 days. Logistic regression for predictors of reocclusion and functional outcomes were performed. RESULTS: A total of 98 patients, 50 treated with tirofiban and 48 without tirofiban, were enrolled in this study. Compared with patients in EVT alone group, patients in EVT plus tirofiban group had higher favorable functional outcome rate, lower mortality, and a lower reocclusion rate (56.3% versus 30.4%; P = .014, 8.3% versus 28.3%; P = .016, and 10.4% versus 32.6%; P = .011, respectively). The rates of any ICH and sICH were similar between the 2 groups. The use of tirofiban was associated with the favorable functional outcome (odds ratio [OR], 3.417; 95% confidence interval [CI], 1.149-10.163; P = .027) and lower reocclusion rate (OR, 0.145; 95% CI, 0.038-0.546; P = .004) on multivariate logistic regression analysis. CONCLUSIONS: In patients with residual stenosis after EVT due to acute ICAS-O, a low-dose of tirofiban is associated with favorable functional outcome and reduced incidence of reocclusion without increasing any ICH and sICH.


Assuntos
Isquemia Encefálica/terapia , Procedimentos Endovasculares , Arteriosclerose Intracraniana/terapia , Inibidores da Agregação Plaquetária/administração & dosagem , Acidente Vascular Cerebral/terapia , Tirofibana/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Isquemia Encefálica/fisiopatologia , Avaliação da Deficiência , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Arteriosclerose Intracraniana/diagnóstico , Arteriosclerose Intracraniana/mortalidade , Arteriosclerose Intracraniana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica , Inibidores da Agregação Plaquetária/efeitos adversos , Recuperação de Função Fisiológica , Recidiva , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Tirofibana/efeitos adversos , Resultado do Tratamento
10.
J Cogn Neurosci ; 31(6): 821-836, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30883289

RESUMO

Although shape perception is primarily considered a function of the ventral visual pathway, previous research has shown that both dorsal and ventral pathways represent shape information. Here, we examine whether the shape-selective electrophysiological signals observed in dorsal cortex are a product of the connectivity to ventral cortex or are independently computed. We conducted multiple EEG studies in which we manipulated the input parameters of the stimuli so as to bias processing to either the dorsal or ventral visual pathway. Participants viewed displays of common objects with shape information parametrically degraded across five levels. We measured shape sensitivity by regressing the amplitude of the evoked signal against the degree of stimulus scrambling. Experiment 1, which included grayscale versions of the stimuli, served as a benchmark establishing the temporal pattern of shape processing during typical object perception. These stimuli evoked broad and sustained patterns of shape sensitivity beginning as early as 50 msec after stimulus onset. In Experiments 2 and 3, we calibrated the stimuli such that visual information was delivered primarily through parvocellular inputs, which mainly project to the ventral pathway, or through koniocellular inputs, which mainly project to the dorsal pathway. In the second and third experiments, shape sensitivity was observed, but in distinct spatio-temporal configurations from each other and from that elicited by grayscale inputs. Of particular interest, in the koniocellular condition, shape selectivity emerged earlier than in the parvocellular condition. These findings support the conclusion of distinct dorsal pathway computations of object shape, independent from the ventral pathway.


Assuntos
Córtex Cerebral/fisiologia , Potenciais Evocados/fisiologia , Percepção de Forma/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Vias Visuais/fisiologia , Adulto , Córtex Cerebral/diagnóstico por imagem , Eletroencefalografia , Feminino , Humanos , Masculino , Fatores de Tempo , Vias Visuais/diagnóstico por imagem , Adulto Jovem
11.
Microb Pathog ; 134: 103568, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31195113

RESUMO

Hand, foot, and mouth disease (HFMD) is a major public health concern, especially among infants and young children. The primary pathogen of HFMD is enterovirus 71 (EV71), whose capsid assembly mechanism including capsid protein processing has been widely studied. However, some of its mechanisms remain unclear, such as the VP0 cleavage. This study aimed to identify the cleavage site of the EV71 VP0 capsid protein and to elucidate the effects of EV71 VP0 cleavage on viral infectivity and assembly. A mass spectrometry analysis indicated that the cleavage site of EV71 VP0 is located between residues Lys69 and Ser70. To analyze the importance of either residue to cleavage, we designed single mutations of Lys69, Ser70 and double mutations respectively and implemented these genomes to encapsulation. The results indicated that Ser70 is more important for VP0 cleavage and EV71 infectivity. In addition, exogenous expression of EV71 protease 2A and 3C was used to verify whether they play roles in VP0 cleavage. Analyses also showed that none of them participate in this process. This study provides novel insights into the mechanisms of EV71 capsid maturation, which may be a potential target to improve the productivity and immunogenicity of EV71 vaccines.


Assuntos
Proteínas do Capsídeo/metabolismo , Enterovirus Humano A/metabolismo , Infecções por Enterovirus/virologia , Clivagem do RNA/fisiologia , Montagem de Vírus , Sequência de Aminoácidos , Anticorpos Antivirais/sangue , Capsídeo/imunologia , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Enterovirus Humano A/genética , Enterovirus Humano A/imunologia , Infecções por Enterovirus/imunologia , Células HEK293 , Humanos , Proteínas Virais/metabolismo , Vacinas Virais
12.
Appl Opt ; 58(21): 5774-5779, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31503880

RESUMO

In this design, we introduced a surface plasmon resonance (SPR) fiber-sensing probe into a column chromatography (CC) system to realize on-line dynamic detection in sample separation. The refractive index of the gel around the probe would be adjusted dynamically by the concentration change of the sample during CC separation. To demonstrate the separation and on-line detection process, bovine serum albumin (BSA) and riboflavin-5-phosphate sodium (FMN-Na) are chosen as the analytes in a Sephadex gel filtration chromatography system. The results show that the apparent reversible shift of the SPR spectrum can characterize the separation process. Specifically, the separated BSA with an outflow time of 8 min can cause a resonance wavelength shift of 15.5 nm, and the FMN-Na with an outflow time of 26 min can cause a shift of 8.4 nm. This on-line dynamic detection of SPR spectra has great potential to save time and simplify the analysis process compared to the complex thin layer chromatography detection steps in traditional manual CC.

13.
Diabetes Res Clin Pract ; 209: 111585, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38364910

RESUMO

AIMS: This study explores the link between Vitamin D deficiency (VDD) and diabetic peripheral neuropathy (DPN) in elderly type 2 diabetes mellitus (T2DM) patients. METHODS: Involving 257 elderly T2DM patients, the study utilized propensity score matching to balance age, sex, and diabetes duration. VDD was defined as serum 25-hydroxyvitamin D [25(OH)D] levels below 20 ng/ml. Large nerve fiber lesions were evaluated by electromyogram, while small nerve fiber lesions were assessed by measuring skin conductance. RESULTS: DPN patients had notably lower serum 25(OH)D levels than non-DPN patients [15.05 vs. 18.4 ng/ml, P = 0.018]. VDD was identified as an independent risk factor for DPN (odds ratio = 2.488, P = 0.008) in multivariate logistic regression analysis. Spearman's correlation showed negative correlations between serum 25(OH)D levels and specific nerve latencies, and positive correlations with specific nerve velocities and amplitudes. The VDD group exhibited longer median sensory nerve latencies and motor evoked potential latencies compared to the vitamin D-sufficient group. Further, VDD is associated with the prolongation of the median motor nerve latency (odds ratio = 1.362, P = 0.038). CONCLUSIONS: VDD is independently associated with a higher risk of DPN. VDD may promote the development of DPN by affecting large nerve fibers.


Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Deficiência de Vitamina D , Humanos , Idoso , Deficiência de Vitamina D/complicações , Fatores de Risco , Vitamina D , Fibras Nervosas
14.
Commun Biol ; 7(1): 1076, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223260

RESUMO

Temporal interference (TI) stimulation is a popular non-invasive neurostimulation technique that utilizes the following salient neural behavior: pure sinusoid (generated in off-target brain regions) appears to cause no stimulation, whereas modulated sinusoid (generated in target brain regions) does. To understand its effects and mechanisms, we examine responses of different cell types, excitatory pyramidal (Pyr) and inhibitory parvalbumin-expressing (PV) neurons, to pure and modulated sinusoids, in intact network as well as in isolation. In intact network, we present data showing that PV neurons are much less likely than Pyr neurons to exhibit TI stimulation. Remarkably, in isolation, our data shows that almost all Pyr neurons stop exhibiting TI stimulation. We conclude that TI stimulation is largely a network phenomenon. Indeed, PV neurons actively inhibit Pyr neurons in the off-target regions due to pure sinusoids (in off-target regions) generating much higher PV firing rates than modulated sinusoids in the target regions. Additionally, we use computational studies to support and extend our experimental observations.


Assuntos
Neurônios , Animais , Camundongos , Neurônios/fisiologia , Potenciais de Ação , Células Piramidais/fisiologia , Córtex Cerebral/fisiologia , Parvalbuminas/metabolismo , Masculino , Modelos Neurológicos
15.
Biomed Opt Express ; 15(8): 4859-4876, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39347003

RESUMO

Diffuse optical tomography (DOT) enhances the localization accuracy of neural activity measured with electroencephalography (EEG) while preserving EEG's high temporal resolution. However, the spatial resolution of reconstructed activity diminishes for deeper neural sources. In this study, we analyzed DOT-enhanced EEG localization of neural sources modeled at depths ranging from 11-25 mm in simulations. Our findings reveal systematic biases in reconstructed depth related to DOT channel length. To address this, we developed a data-informed method for selecting DOT channels to improve the spatial accuracy of DOT-enhanced EEG reconstruction. Using our method, the average absolute reconstruction depth errors of DOT reconstruction across all depths are 0.9 ± 0.6 mm, 1.2 ± 0.9 mm, and 1.2 ± 1.1 mm under noiseless, low-level noise, and high-level noise conditions, respectively. In comparison, using fixed channel lengths resulted in errors of 2.6 ± 1.5 mm, 5.0 ± 2.6 mm, and 7.3 ± 4.5 mm under the same conditions. Consequently, our method improved the depth accuracy of DOT reconstructions and facilitated the use of more accurate spatial priors for EEG reconstructions, enhancing the overall precision of the technique.

16.
Biomolecules ; 14(5)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38785988

RESUMO

Peptides possessing antihypertensive attributes via inhibiting the angiotensin-converting enzyme (ACE) were derived through the enzymatic degradation of Trichiurus lepturus (ribbonfish) using alkaline protease. The resulting mixture underwent filtration using centrifugation, ultrafiltration tubes, and Sephadex G-25 gels. Peptides exhibiting ACE-inhibitory properties and DPPH free-radical-scavenging abilities were isolated and subsequently purified via LC/MS-MS, leading to the identification of over 100 peptide components. In silico screening yielded five ACE inhibitory peptides: FAGDDAPR, QGPIGPR, IFPRNPP, AGFAGDDAPR, and GPTGPAGPR. Among these, IFPRNPP and AGFAGDDAPR were found to be allergenic, while FAGDDAPRR, QGPIGPR, and GPTGPAGP showed good ACE-inhibitory effects. IC50 values for the latter peptides were obtained from HUVEC cells: FAGDDAPRR (IC50 = 262.98 µM), QGPIGPR (IC50 = 81.09 µM), and GPTGPAGP (IC50 = 168.11 µM). Peptide constituents derived from ribbonfish proteins effectively modulated ACE activity, thus underscoring their therapeutic potential. Molecular docking and modeling corroborated these findings, emphasizing the utility of functional foods as a promising avenue for the treatment and prevention of hypertension, with potential ancillary health benefits and applications as substitutes for synthetic drugs.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Células Endoteliais da Veia Umbilical Humana , Peptídeos , Peptidil Dipeptidase A , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/química , Anti-Hipertensivos/isolamento & purificação , Animais , Humanos , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Peptidil Dipeptidase A/metabolismo , Peptidil Dipeptidase A/química , Simulação de Acoplamento Molecular , Perciformes/metabolismo
17.
Clin Rheumatol ; 43(2): 645-655, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38097864

RESUMO

OBJECTIVE: The semaphorins are membrane or secreted proteins first identified in neural development. Semaphorin 4D (Sema4D) is the first family member found to have immune properties. We evaluated the potential of Sema4D as a marker for rheumatoid arthritis (RA) disease activity, singly and in combination with other known biomarkers including rheumatoid factor (RF) and C-reactive protein (CRP). METHODS: Three hundred and eleven RA patients were enrolled. The patients were divided into three groups based on their disease activity in 28 joints (DAS28): mild, moderate, and severe. The healthy group included 40 healthy individuals. SerumSema4D was measured by quantitative ELISA and the specificity and sensitivity of biomarkers were evaluated by generating a receiver operating characteristic (ROC) curve to analyze their diagnostic accuracy. RESULTS: Serum Sema4D levels in the moderate and severe RA groups were elevated significantly above those of the controls (P < 0.01), while levels in the mild RA and control groups did not differ significantly (P > 0.05). The Sema4D cutoff threshold was 15.7 ng/ml when the DAS28 was applied as a reference. Compared to the erythrocyte sedimentation rate (ESR and CRP, Sema4D had the highest specificity (96.8%) and area under the curve (0.80) for diagnosing RA activity. The highest specificity (100%) for the biomarker combinations was obtained when Sema4D was combined with CRP and anti-CCP, the combination of the Sema4D combined with ESR and anti-CCP had the highest sensitivity (99.35%). According to this result, a new model for jointly calculating RA activity of Sema4D,anti-CCP and CRP was constructed. Meanwhile another model is established by using the method of multivariate analysis.Model comparison results showed the the multiple regression algorithm method fitted the patients' disease activity better. CONCLUSION: The serum Sema 4D level effectively reflects moderate to severe RA activity. Sema4D levels can be used together with conventional RA biomarkers to increase the diagnostic power of RA activity. The multiple regression algorithm method is promising in disease activity calculation.


Assuntos
Antígenos CD , Artrite Reumatoide , Semaforinas , Humanos , Anticorpos Antiproteína Citrulinada , Biomarcadores , Proteína C-Reativa/metabolismo
18.
J Biomed Opt ; 29(Suppl 3): S33310, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39323492

RESUMO

Significance: Near-infrared spectroscopy (NIRS) is a non-invasive optical method that measures changes in hemoglobin concentration and oxygenation. The measured light intensity is susceptible to reduced signal quality due to the presence of melanin. Aim: We quantify the influence of melanin concentration on NIRS measurements taken with a frequency-domain near-infrared spectroscopy system using 690 and 830 nm. Approach: Using a forehead NIRS probe, we measured 35 healthy participants and investigated the correlation between melanin concentration indices, which were determined using a colorimeter, and several key metrics from the NIRS signal. These metrics include signal-to-noise ratio (SNR), two measurements of oxygen saturation (arterial oxygen saturation, SpO 2 , and tissue oxygen saturation, StO 2 ), and optical properties represented by the absorption coefficient ( µ a ) and the reduced scattering coefficient ( µ s ' ). Results: We found a significant negative correlation between the melanin index and the SNR estimated in oxy-hemoglobin signals ( r s = - 0.489 , p = 0.006 ) and SpO 2 levels ( r s = - 0.413 , p = 0.023 ). However, no significant changes were observed in the optical properties and StO 2 ( r s = - 0.146 , p = 0.44 ). Conclusions: We found that estimated SNR and SpO 2 values show a significant decline and dependence on the melanin index, whereas StO 2 and optical properties do not show any correlation with the melanin index.


Assuntos
Melaninas , Razão Sinal-Ruído , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Melaninas/análise , Melaninas/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Masculino , Feminino , Adulto , Adulto Jovem , Saturação de Oxigênio/fisiologia , Oxigênio/metabolismo , Oxiemoglobinas/análise , Oximetria/métodos , Hemoglobinas/análise
19.
Biomed Opt Express ; 15(9): 5009-5024, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39296388

RESUMO

Biosynthesis in bioreactors plays a vital role in many applications, but tools for accurate in situ monitoring of the cells are still lacking. By engineering the cells such that their conditions are reported through fluorescence, it is possible to fill in the gap using fluorescence diffuse optical tomography (fDOT). However, the spatial accuracy of the reconstruction can still be limited, due to e.g. undersampling and inaccurate estimation of the optical properties. Utilizing controlled phantom studies, we use a two-step hybrid approach, where a preliminary fDOT result is first obtained using the classic model-based optimization, and then enhanced using a neural network. We show in this paper using both simulated and phantom experiments that the proposed method can lead to a 8-fold improvement (Intersection over Union) of fluorescence inclusion reconstruction in noisy conditions, at the same speed of conventional neural network-based methods. This is an important step towards our ultimate goal of fDOT monitoring of bioreactors.

20.
Artigo em Inglês | MEDLINE | ID: mdl-37878785

RESUMO

The insufficient cyclic efficiency and poor safety have prohibited the commercial applications of the lithium-metal anode because of its uncontrolled dendrite growth at the surface. A mechanically stable and highly ionic conductive solid electrolyte interphase (SEI) holds great promise to address the issues. Herein, a viable surface engineering approach is proposed for stabilizing the Li anode via a scalable artificial method. The surface of Li metal is functionalized by constructing a mechanically tough and electron-insulating metal-organic framework (MOF) of the MIL-125(Ti) layer. In-situ optical microscopy reveals its crucial role in inhibiting dendritic Li growth. Because of the intrinsic insulativity and highly ordered micropores of MIL-125(Ti), the Li+ ions acquire electrons under the coating layer, resulting in a uniform and dense Li deposition behavior. The symmetric cell of the MOF-modified Li electrode delivers a long life span of 2000 h with an overpotential of less than 20 mV at 0.5 mA cm-2. When paired with the same MOF-derived sulfur cathode, decent cycling retention is available as well. This work demonstrates a feasible strategy for the development of a stable Li-metal anode with alleviative dendritic growth.

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