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1.
Small ; 20(12): e2306991, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37939298

RESUMEN

The shuttle effect, which causes the loss of active sulfur, passivation of lithium anode, and leads to severe capacity attenuation, is currently the main bottleneck for lithium-sulfur batteries. Recent studies have disclosed that molybdenum compounds possess exceptional advantages as a polar substrate to immobilize and catalyze lithium polysulfide such as high conductivity and strong sulfiphilicity. However, these materials show incomplete contact with sulfur/polysulfides, which causes uneven redox conversion of sulfur and results in poor rate performance. Herein, a new type of 2D nano-channeled molybdenum compounds (2D-MoNx) via the 2D organic-polyoxometalate superstructure for accelerating interfacial polysulfide catalysis toward high-performance lithium-sulfur batteries is reported. The 2D-MoNx shows well-interlinked nano-channels, which increase the reactive interface and contact surface with polysulfides. Therefore, the battery equipped with 2D-MoNx displays a high discharge capacity of 912.7 mAh g-1 at 1 C and the highest capacity retention of 523.7 mAh g-1 after 300 cycles. Even at the rate of 2 C, the capacity retention can be maintained at 526.6 mAh g-1 after 300 cycles. This innovative nano-channel and interfacial design of 2D-MoNx provides new nanostructures to optimize the sulfur redox chemistry and eliminate the shuttle effect of polysulfides.

2.
Mol Psychiatry ; 28(5): 2107-2121, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36754983

RESUMEN

Psychosis is an abnormal mental condition that can cause patients to lose contact with reality. It is a common symptom of schizophrenia, bipolar disorder, sleep deprivation, and other mental disorders. Clinically, antipsychotic medications, such as olanzapine and clozapine, are very effective in treatment for psychosis. To investigate the neural circuit mechanism that is affected by antipsychotics and identify more selective therapeutic targets, we employed a strategy by using these effective antipsychotics to identify antipsychotic neural substrates. We observed that local injection of antipsychotics into the ventral tegmental area (VTA) could reverse the sensorimotor gating defects induced by MK-801 injection in mice. Using in vivo fiber photometry, electrophysiological techniques, and chemogenetics, we found that antipsychotics could activate VTA gamma-aminobutyric acid (GABA) neurons by blocking GABAA receptors. Moreover, we found that the VTAGABA nucleus accumbens (NAc) projection was crucially involved in such antipsychotic effects. In summary, our study identifies a novel therapeutic target for the treatment of psychosis and underscores the utility of a 'bedside-to-bench' approach for identifying neural circuits that influence psychotic disorders.

3.
Int J Mol Sci ; 25(11)2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38892414

RESUMEN

Berberine (BBR) is used to treat cancer, inflammatory conditions, and so on. But the side effects of BBR causing constipation should not be ignored. In clinical application, the combination of Amomum villosum Lour. (AVL) and BBR can relieve it. However, the effective ingredients and molecular mechanism of AVL in relieving constipation are not clear. A small intestine propulsion experiment was conducted in constipated mice to screen active ingredients of AVL. We further confirmed the molecular mechanism of action of the active ingredient on BBR-induced constipation. Quercetin (QR) was found to be the effective ingredient of AVL in terms of relieving constipation. QR can efficiently regulate the microbiota in mice suffering from constipation. Moreover, QR significantly raised the levels of substance P and motilin while lowering those of 5-hydroxytryptamine and vasoactive intestinal peptide; furthermore, it also increased the protein expression levels of calmodulin, myosin light-chain kinase, and myosin light chain. The use of QR in combination with BBR has an adverse effect-reducing efficacy. The study provides new ideas and possibilities for the treatment of constipation induced by BBR.


Asunto(s)
Berberina , Estreñimiento , Microbioma Gastrointestinal , Quercetina , Animales , Berberina/farmacología , Berberina/uso terapéutico , Quercetina/farmacología , Estreñimiento/tratamiento farmacológico , Estreñimiento/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Masculino , Modelos Animales de Enfermedad , Motilina/metabolismo
4.
Entropy (Basel) ; 26(3)2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38539751

RESUMEN

Efficient flotation beneficiation heavily relies on accurate flotation condition recognition based on monitored froth video. However, the recognition accuracy is hindered by limitations of extracting temporal features from froth videos and establishing correlations between complex multi-modal high-order data. To address the difficulties of inadequate temporal feature extraction, inaccurate online condition detection, and inefficient flotation process operation, this paper proposes a novel flotation condition recognition method named the multi-modal temporal hypergraph neural network (MTHGNN) to extract and fuse multi-modal temporal features. To extract abundant dynamic texture features from froth images, the MTHGNN employs an enhanced version of the local binary pattern algorithm from three orthogonal planes (LBP-TOP) and incorporates additional features from the three-dimensional space as supplements. Furthermore, a novel multi-view temporal feature aggregation network (MVResNet) is introduced to extract temporal aggregation features from the froth image sequence. By constructing a temporal multi-modal hypergraph neural network, we encode complex high-order temporal features, establish robust associations between data structures, and flexibly model the features of froth image sequence, thus enabling accurate flotation condition identification through the fusion of multi-modal temporal features. The experimental results validate the effectiveness of the proposed method for flotation condition recognition, providing a foundation for optimizing flotation operations.

5.
Artículo en Inglés | MEDLINE | ID: mdl-37963065

RESUMEN

OBJECTIVE: To investigate the pathogenic role and underlying mechanisms of lncRNAs in antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). METHODS:: RNA-sequencing (RNA-seq) was applied to screen the expression profile of lncRNAs in peripheral leukocytes from 5 AAV patients and 5 healthy controls (HC). Candidate lncRNAs were preliminarily verified in peripheral leukocytes from 46 AAV patients and 35 HC by qRT-PCR. Then, the identified LINC02193 was further validated in peripheral neutrophils from 67 AAV patients, 45 HC and 64 disease controls. Correlation between LINC02193 levels and disease activity was analyzed. Then, a loss-of-function study was conducted to investigate the role of LINC02193 in neutrophils activation. Furthermore, bioinformatics analysis, dual luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to explore the mechanism of LINC02193 regulating neutrophils activation. RESULTS: A total of 467 upregulated and 412 downregulated lncRNAs were identified in AAV patients. From top 5 upregulated lncRNAs, an elevation of LINC02193 was validated in a larger sample of AAV patients, and positively correlated with disease activity. Knockdown of LINC02193 inhibited ROS and NO production, NETs release and adhesion to endothelial cells of differentiated human promyelocytic leukaemia HL­60 cells (dHL-60), whereas overexpression of ICAM1 counteracted these effects. Mechanistic analysis demonstrated that LINC02193 acted as a miR-485-5p sponge to relieve the repressive effect of miR-485-5p on ICAM1, thus promoting ICAM1 expression. CONCLUSION: LINC02193, a novel lncRNA identified in AAV could function as competing endogenous RNAs (ceRNA) for miR-485-5p to promote ICAM1 expression and neutrophils activation, suggesting its potential as a therapeutic target of AAV.

6.
Opt Express ; 31(25): 42240-42254, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38087602

RESUMEN

Non-line-of-sight (NLOS) imaging can visualize a remote object out of the direct line of sight and can potentially be used in endoscopy, unmanned vehicles, and robotic vision. In an NLOS imaging system, multiple diffusive reflections of light usually induce large optical attenuation, and therefore, a sensitive and efficient photodetector, or, their array, is required. Limited by the spectral sensitivity of the light sensors, up to now, most of the NLOS imaging experiments are performed in the visible bands, and a few at the near-infrared, 1550 nm. Here, to break this spectral limitation, we demonstrate a proof-of-principle NLOS imaging system using a fractal superconducting nanowire single-photon detector, which exhibits intrinsic single-photon sensitivity over an ultra-broad spectral range. We showcase NLOS imaging at 1560- and 1997-nm two wavelengths, both technologically important for specific applications. We develop a de-noising algorithm and combine it with the light-cone-transform algorithm to reconstruct the shape of the hidden objects with significantly enhanced signal-to-noise ratios. We believe that the joint advancement of the hardware and the algorithm presented in this paper could further expand the application spaces of the NLOS imaging systems.

7.
Opt Lett ; 48(2): 415-418, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36638471

RESUMEN

We demonstrate a fiber-coupled fractal superconducting nanowire single-photon detector (SNSPD) system with minimum polarization dependence of detection efficiency. Its system detection efficiency (SDE) was maximized at the wavelength of 1540 nm, which was measured to be 91 ± 4%; furthermore, we observed the second local maximum of SDE at the wavelength of 520 nm, which was measured to be 61 ± 2%. This dual-band feature of SDE was due to the enhancement of the optical absorptance by two longitudinal resonance modes of the micro-cavity. By using high SDE with minimum polarization dependence in these two bands, we implemented a hybrid LIDAR for imaging the remote objects in free space and under water.

8.
Exp Cell Res ; 417(2): 113221, 2022 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-35623419

RESUMEN

Subretinal fibrosis causes local damage to the retina and irreversible vision loss, as the final stage of neovascular age-related macular degeneration (nAMD). More recently, the endothelial-to-mesenchymal transition (EndoMT) has been considered one of the most significant sources of myofibroblasts in subretinal fibrosis, though the underpinning molecular mechanisms remain unclear. In this study, a series of experiments were performed to test the hypothesis that Yes-associated protein (YAP) may be involved in EndoMT and subretinal fibrosis. We demonstrated that transforming growth factor (TGF)-ß2 stimulation induces YAP dephosphorylation (activated) and nuclear transcription in human umbilical vein endothelial cells (HUVECs) by increasing reactive oxygen species (ROS) levels. Moreover, TGF-ß2-mediated EndoMT and proinflammatory cytokine production in HUVECs were reduced by ROS clearance or YAP knockdown. Furthermore, the severity of subretinal fibrosis was markedly relieved by intravitreal administration of a small interfering RNA targeting YAP in the mouse laser-induced choroidal neovascularization (CNV) model. Our findings provide novel insights into a previously unknown effect of YAP on the EndoMT process and reveal YAP as a potential target for suppressing CNV-related subretinal fibrosis and protect vision.


Asunto(s)
Neovascularización Coroidal , Animales , Neovascularización Coroidal/genética , Modelos Animales de Enfermedad , Fibrosis , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Inflamación/complicaciones , Ratones , Ratones Endogámicos C57BL , Especies Reactivas de Oxígeno
9.
Bioorg Chem ; 138: 106594, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37186998

RESUMEN

The selective inhibition of PI3Kδ is a potential therapeutic strategy for the treatment of hematologic malignancies. Herein, we report a series of compounds bearing amino acid fragments as potent and selective PI3Kδ inhibitors. Among them, compound A10 exhibited sub-nanomolar PI3Kδ potency. In cellular assays, A10 achieved strong antiproliferation against SU-DHL-6 cells, and caused cell cycle arrest, and induced apoptosis in SU-DHL-6 cells. The docking study showed that A10 tightly bound to PI3Kδ protein with a planar-shaped conformation. Collectively, compound A10 represented a promising potent and selective PI3Kδ inhibitor bearing amino acid fragement albeit with moderate selectivity over PI3Kγ but superior selectivity against PI3Kα and ß. This study suggested that using the amino acid fragments instead of the pyrrolidine ring is new strategy for design of potent PI3Kδ inhibitors.


Asunto(s)
Aminoácidos , Inhibidores de Proteínas Quinasas , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad , Línea Celular Tumoral , Aminoácidos/farmacología , Proliferación Celular
10.
Neoplasma ; 70(2): 216-228, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36964721

RESUMEN

Ovarian cancer (OC) is one of the most prevalent malignant tumors affecting women's life and health. Since OC has a poor prognosis due to extensive metastasis, there is a need to explore a new mechanism of OC metastasis. microRNAs (miRs) are single-stranded, non-coding RNAs. miR-9 has been reported to promote cancer and may provide a new strategy for OC diagnosis. The purpose of this study was to examine the function and underlying mechanism of miR-9 in OC. RT-qPCR was used to assess miR-9 expression levels. Transwell assays were used to determine the number of migrating and invading OC cells. The protein expression levels of the PI3K/AKT/mTOR/GSK3ß signaling pathway were examined using western blotting. The results informed that, when compared to normal ovarian tissues, miR-9 was remarkably expressed in OC tissues, and hypoxia might lead to overexpression of miR-9-5p while inhibiting miR-9 notably suppressed the migrating and invading cell numbers in OC cells. In vivo, miR-9-5p knockdown inhibited tumor growth in a subcutaneous nude mice model of SKOV3 cells. Our findings suggest that miR-9 could be an underlying oncogene in OC, opening up new avenues for OC diagnosis and treatment of OC by targeting miR-9.


Asunto(s)
MicroARNs , Neoplasias Ováricas , Humanos , Animales , Ratones , Femenino , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones Desnudos , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Proliferación Celular , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias Ováricas/patología , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Línea Celular Tumoral , Movimiento Celular
11.
Ecotoxicol Environ Saf ; 262: 115319, 2023 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-37542982

RESUMEN

Ultraviolet B (UV-B, 280-320 nm) radiation is a major environmental stressor for aquatic organisms on Earth's surface. Its effects on biological systems are well known, but the mechanisms by which organisms respond and adapt to UV-B radiation are still being explored. In this study, we investigated the effects of UV-B radiation on the monogonont rotifer Brachionus asplanchnoidis, focusing on physiological parameters, antioxidant systems, DNA damage, and DNA repair-related molecular mechanism. Our results showed that the LD50 was at 28.53 kJ/m2, indicating strong tolerance to UV-B. However, UV-B radiation caused adverse effects on growth and reproduction, with shortened reproductive period and longevity, decreased fecundity and hatchability, and inhibition of population growth. Biochemical analyses revealed severe oxidative damage and lipid peroxidation, with increased ROS and MDA levels. Activities of antioxidant enzymes were highly induced at low doses but decreased at high doses. DNA damage also occurred in UV-B-exposed rotifers. Furthermore, selected DNA repair-related genes were up-regulated in a dose-dependent manner. These findings provide a comprehensive understanding of the effects of UV-B radiation on rotifers and highlight the importance of considering both ecological and molecular responses in assessing the impact of UV-B radiation on aquatic organisms.

12.
Chem Biodivers ; 20(8): e202300578, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37458474

RESUMEN

The rhizoma of Anemarrhenae asphodeloides has a long history of hypoglycemic use in Chinese traditional medicine. In this article, 400 µmol/L H2 O2 induced normal INS-1 pancreatic beta cells to establish experimental model of oxidative damage. Quercetin was used as a positive drug, and mangiferin and its ethanolic extract were selected as therapeutic agents in an oxidative damage model to evaluate the ameliorative effect of the active ingredients of Anemarrhenae asphodeloides rhizoma on oxidative damage in INS-1 pancreatic ß-cells. Building a qualitative analysis method of membrane phospholipids of INS-1 pancreatic beta cells and identified 82 phospholipids based on the UPLC/Q-TOF MS technology, which could provide a database for further statistics analysis. OPLS-DA was used to screen the phospholipid biomarkers from the raw data. Exploring the biological significances of these biomarkers, and discussing the toxic effect of the effective components of Anemarrhena asphodeloides rhizoma, on oxidatively damaged INS-1 pancreatic beta cell.


Asunto(s)
Anemarrhena , Medicamentos Herbarios Chinos , Células Secretoras de Insulina , Cromatografía Líquida de Alta Presión/métodos , Rizoma , Medicamentos Herbarios Chinos/farmacología
13.
Chem Biodivers ; 20(8): e202300754, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37401658

RESUMEN

Magnolol and Honokiol are the primary active components that have been identified and extracted from Magnolia officinalis, and several investigations have demonstrated that they have significant pharmacological effects. Despite their therapeutic benefits for a wide range of illnesses, research on and the implementation of these compounds have been hindered by their poor water solubility and low bioavailability. Researchers are continually using chemical methods to alter their structures to make them more effective in treating and preventing diseases. Researchers are also continuously developing derivative drugs with high efficacy and few adverse effects. This article summarizes and analyzes derivatives with significant biological activities reported in recent research obtained by structural modification. The modification sites have mainly focused on the phenolic hydroxy groups, benzene rings, and diene bonds. Changes to the allyl bisphenol structure will result in unexpected benefits, including high activity, low toxicity, and good bioavailability. Furthermore, alongside earlier experimental research in our laboratory, the structure-activity relationships of magnolol and honokiol were preliminarily summarized, providing experimental evidence for improving their development and utilization.


Asunto(s)
Lignanos , Magnolia , Lignanos/farmacología , Lignanos/química , Compuestos de Bifenilo/química , Relación Estructura-Actividad , Magnolia/química
14.
Mikrochim Acta ; 190(4): 150, 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36952134

RESUMEN

For practical analysis and simultaneous detection of arbutin (AR) and hydrochinone (HQ) in cosmetics, an electrochemical sensor has been designed based on nitrogen and sulfur co-doped Fe-Ni alloy (N,S-FeNi3/C) nanoparticles. The N,S-FeNi3/C has been prepared for the first time via hydrothermal synthesis and high-temperature carbonization. N,S-FeNi3/C not only improves the charge transfer to the surface, but also provides rich active sites and fast ion diffusion rates owing to the iron and nickel bimetallic materials. In addition, the d-band structure of transition metals (nickel and iron) introduced by the N and S atoms exhibits an electronic structure similar to that of noble metal catalysts, thus enhancing electrocatalytic activity and increasing conductivity. Additionally, the double doping of S and N atoms significantly increases the active sites of carbon atoms; thus, N-S-FeNi3/C exhibits excellent electrochemical catalytic activity for the oxidation of AR and HQ. Further, the N,S-FeNi3/C sensor is used for the simultaneous determination of HQ and AR by square-wave pulse voltammetry. Distinct oxidation peaks of HQ and AR are observed at potentials of +0.028 V and +0.352 V (vs. SCE). The electrical signal increases linearly in the HQ concentration ranges of 0.1-100 µM and 0.05-70 µM for the simultaneous determination of AR and HQ with a detection limit as low as 0.0476 and 0.0135 µM (S/N = 3), respectively. Thus, rapid and accurate detection of AR and HQ in spiked cosmetics is successfully achieved, with a recovery ranging from 96.4 to 104.2%, and the relative standard deviation is lower than 3.8-4.0%.

15.
Int J Mol Sci ; 24(13)2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37446006

RESUMEN

The pathogenesis of ulcerative colitis (UC) is associated with inflammation, oxidative stress, and gut microbiota imbalance. Although most researchers have demonstrated the antioxidant bioactivity of the phenolic compounds in plants, their UC-curing ability and underlying mechanisms still need to be further and adequately explored. Herein, we studied the antioxidation-structure relationship of several common polyphenols in plants including gallic acid, proanthocyanidin, ellagic acid, and tannic acid. Furthermore, the in vivo effects of the plant polyphenols on C57BL/6 mice with dextran-sulfate-sodium-induced UC were evaluated and the action mechanisms were explored. Moreover, the interplay of several mechanisms was determined. The higher the number of phenolic hydroxyl groups, the stronger the antioxidant activity. All polyphenols markedly ameliorated the symptoms and pathological progression of UC in mice. Furthermore, inflammatory cytokine levels were decreased and the intestinal barrier was repaired. The process was regulated by the antioxidant-signaling pathway of nuclear-erythroid 2-related factor 2. Moreover, the diversity of the intestinal microbiota, Firmicutes-to-Bacteroides ratio, and relative abundance of beneficial bacteria were increased. An interplay was observed between microbiota regulation and oxidative stress, immunity, and inflammatory response. Furthermore, intestinal barrier repair was found to be correlated with inflammatory responses. Our study results can form a basis for comprehensively developing plant-polyphenol-related medicinal products.


Asunto(s)
Colitis Ulcerosa , Microbiota , Animales , Ratones , Ratones Endogámicos C57BL , Antioxidantes/farmacología , Polifenoles/farmacología , Polifenoles/uso terapéutico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Fenoles
16.
Molecules ; 28(9)2023 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-37175163

RESUMEN

Based on the principle of molecular splicing and theory of traditional Chinese medicine pairs, a new multi-active compound (HM475) was synthesized by connecting metformin with honokiol, and its structure was characterized, which not only reduced the toxicity of raw materials, but also maintained the original activity, and had a certain significance in research and innovation. At the same time, quality control and preliminary activity evaluation were carried out, and the effect of HM475 on neuroinflammation was further explored, which provided a new idea for drug development of neurodegenerative diseases.


Asunto(s)
Medicamentos Herbarios Chinos , Lignanos , Medicina Tradicional China , Control de Calidad , Compuestos de Bifenilo , Desarrollo de Medicamentos , Lignanos/farmacología
17.
Int Ophthalmol ; 43(10): 3831-3839, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37561250

RESUMEN

PURPOSE: To investigate the neuroprotective effect of idebenone against hydrogen peroxide (H2O2)-induced oxidative damage in retinal ganglion cells-5 (RGC-5 cells). METHODS: RGC-5 cells were pre-treated with various idebenone concentrations (5, 10, and 20 µM) for 12 h and were then subjected to 300 µM H2O2 for a further 12 h. Apoptosis in RGC-5 was measured by flow cytometry. The changes of mitochondrial membrane potential (MMP) were detected by JC-1 staining. Autophagy in RGC-5 cells was observed by transmission electron microscopy. Western blots were used to measure the expression of autophagy-related protein light chain 3 (LC3), Beclin-1, and the release of Cytochrome c (Cyt-c). RESULTS: Flow cytometry showed that the apoptosis rates in the normal control group, H2O2 group, and idebenone groups were 6.48 ± 0.55%, 27.3 ± 0.51%, 22.8 ± 0.52%, 15.45 ± 0.81%, and 12.59 ± 0.58%, respectively (F = 559.7, P < 0.0001). After incubation with H2O2, the number of autophagosomes increased significantly, whereas it was decreased in the idebenone groups. After incubation of RGC-5 cells with H2O2, MMP levels were significantly decreased, while idebenone could prevent the decrease in MMP levels. Compared with that in the normal control group, LC3 II/I, the expression levels of Beclin-1 and Cyt-c were increased significantly in the H2O2 group (P < 0.05). Compared with that in the H2O2 group, LC3 II/I, the expression of Beclin-1 and Cyt-c was significantly decreased in idebenone groups (P < 0.05). CONCLUSIONS: Idebenone protects RGC-5 cells against H2O2-induced oxidative damage by reducing mitochondrial damage and autophagic activity.


Asunto(s)
Fármacos Neuroprotectores , Humanos , Fármacos Neuroprotectores/farmacología , Peróxido de Hidrógeno/toxicidad , Peróxido de Hidrógeno/metabolismo , Beclina-1/farmacología , Células Ganglionares de la Retina , Estrés Oxidativo , Supervivencia Celular
18.
Angew Chem Int Ed Engl ; 62(20): e202302436, 2023 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-36916443

RESUMEN

Enzyme immobilization has been demonstrated to be a favorable protocol for promoting the industrialization of bioactive molecules, but still with formidable challenge. Addressing this challenge, we create a dynamic defect generation strategy for enzyme immobilization by using the dissociation equilibrium of metal-organic frameworks (MOFs) mediated by enzymes. Enzymes can act as "macro ligands" to generate competitive coordination against original ligands, along with the release of metal clusters of MOFs to generate defects, hence promoting the gradual transport of enzymes from the surface to inside. Various enzymes can be efficiently immobilized in MOFs to afford composites with good enzymatic activities, protective performances and exceptional reusabilities. Moreover, multienzyme bioreactors capable of efficient cascade reactions can also be generated. This study provides new opportunities to construct highly efficient biocatalysts incorporating different types of enzymes.


Asunto(s)
Estructuras Metalorgánicas , Ligandos , Hidrólisis , Enzimas Inmovilizadas , Catálisis
19.
J Neuroinflammation ; 19(1): 140, 2022 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-35690819

RESUMEN

BACKGROUND: Anti-IgLON5 disease is a rare neurological disorder associated with autoantibodies against the neuronal cell adhesion protein, IgLON5. Cellular investigations with human IgLON5 antibodies have suggested an antibody-mediated pathogenesis, but whether human IgLON5 autoantibodies can induce disease symptoms in mice is yet to be shown. Moreover, the effects of anti-IgLON5 autoantibodies on neurons and the precise molecular mechanisms in vivo remain controversial. METHODS: We investigated the effects of anti-IgLON5 antibodies in vivo and evaluated their long-term effects. We used two independent passive-transfer animal models and evaluated the effects of the antibodies on mouse behaviors at different time points from day 1 until day 30 after IgG infusion. A wide range of behaviors, including tests of locomotion, coordination, memory, anxiety, depression and social interactions were established. At termination, brain tissue was analyzed for human IgG, neuronal markers, glial markers, synaptic markers and RNA sequencing. RESULTS: These experiments showed that patient's anti-IgLON5 antibodies induced progressive and irreversible behavioral deficits in vivo. Notably, cognitive abnormality was supported by impaired average gamma power in the CA1 during novel object recognition testing. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies in the hippocampus of anti-IgLON5 IgG-injected mice, which persisted 30 days after the injection of patient's antibodies was stopped. Microglial and astrocyte density was increased in the hippocampus of anti-IgLON5 IgG-injected mice at Day 30. Whole-cell voltage clamp recordings proved that anti-IgLON5 antibodies affected synaptic homeostasis. Further western blot investigation of synaptic proteins revealed a reduction of presynaptic (synaptophysin) and post-synaptic (PSD95 and NMDAR1) expression in anti-IgLON5 IgG-injected mice. CONCLUSIONS: Overall, our findings indicated an irreversible effect of anti-IgLON5 antibodies and supported the pathogenicity of these antibodies in vivo.


Asunto(s)
Moléculas de Adhesión Celular Neuronal , Enfermedades del Sistema Nervioso , Animales , Autoanticuerpos , Moléculas de Adhesión Celular Neuronal/metabolismo , Inmunoglobulina G/farmacología , Ratones , Enfermedades del Sistema Nervioso/patología , Neuronas
20.
Reproduction ; 164(1): 1-8, 2022 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-35521903

RESUMEN

In Brief: Polycystic ovary syndrome (PCOS) is a common cause of anovulatory infertility in women. This study identified changes in free fatty acids profiles in the follicular fluid that may lead to better diagnosis and management of infertility in PCOS women. Abstract: Polycystic ovary syndrome (PCOS) is a heterogeneous disease characterized by various endocrine/metabolic disorders and impaired reproductive potential. Alterations in oocyte competence are considered potentially causative factors for infertility in PCOS women and analyzing the composition of follicular fluid in these patients may help to identify which changes have the potential to alter oocyte quality. In this study, free fatty acid metabolic signatures in follicular fluid were performed to identify changes that may impact oocyte competence in non-obese PCOS women. Sixty-four non-obese women (32 with PCOS and 32 age- and BMI-matched controls) undergoing in vitro fertilization were recruited. Embryo quality was morphologically assessed. Free fatty acid metabolic profiling in follicular fluid was performed using gas/liquid chromatography-mass spectrometry. Principal component analysis and orthogonal partial least squares-discriminant analysis models were further constructed. Nine free fatty acids and 24 eicosanoids were identified and several eicosanoids synthesized by the cyclooxygenase pathway were significantly elevated in PCOS patients compared to controls. The combination of PGE2, PGF2α, PGJ2, and TXB2 had an area under the curve of 0.867 (0.775-0.960) for PCOS discrimination. Furthermore, follicular fluid levels of PGE2 and PGJ2 were negatively correlated with high-quality embryo rate in PCOS patients (P < 0.05). Metabolomic analysis revealed that follicular fluid lipidomic profiles undergo changes in non-obese PCOS women, which suggests that identifying changes in important metabolic signatures may give us a better understanding of the pathogenesis of PCOS. Furthermore, elevated PGE2 and PGJ2 concentrations may contribute to impaired oocyte competence in non-obese PCOS patients.


Asunto(s)
Infertilidad Femenina , Síndrome del Ovario Poliquístico , Dinoprostona/metabolismo , Ácidos Grasos no Esterificados , Femenino , Líquido Folicular/metabolismo , Humanos , Infertilidad Femenina/metabolismo , Oocitos/metabolismo , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/metabolismo
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