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1.
Appl Microbiol Biotechnol ; 108(1): 384, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896287

RESUMEN

Bacteriocins have the potential to effectively improve food-borne infections or gastrointestinal diseases and hold promise as viable alternatives to antibiotics. This study aimed to explore the antibacterial activity of three bacteriocins (nisin, enterocin Gr17, and plantaricin RX-8) and their ability to attenuate intestinal barrier dysfunction and inflammatory responses induced by Listeria monocytogenes, respectively. Bacteriocins have shown excellent antibacterial activity against L. monocytogenes without causing any cytotoxicity. Bacteriocins inhibited the adhesion and invasion of L. monocytogenes on Caco-2 cells, lactate dehydrogenase (LDH), trans-epithelial electrical resistance (TEER), and cell migration showed that bacteriocin improved the permeability of Caco-2 cells. These results were attributed to the promotion of tight junction proteins (TJP) assembly, specifically zonula occludens-1 (ZO-1), occludin, and claudin-1. Furthermore, bacteriocins could alleviate inflammation by inhibiting the mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways and reducing the secretion of interleukin-6 (IL-6), interleukin-1 ß (IL-1ß) and tumor necrosis factor α (TNF-α). Among three bacteriocins, plantaricin RX-8 showed the best antibacterial activity against L. monocytogenes and the most pronounced protective effect on the intestinal barrier due to its unique structure. Based on our findings, we hypothesized that bacteriocins may inhibit the adhesion and invasion of L. monocytogenes by competing adhesion sites. Moreover, they may further enhance intestinal barrier function by inhibiting the expression of L. monocytogenes virulence factors, increasing the expression of TJP and decreasing the secretion of inflammatory factors. Therefore, bacteriocins will hopefully be an effective alternative to antibiotics, and this study provides valuable insights into food safety concerns. KEY POINTS: • Bacteriocins show excellent antibacterial activity against L. monocytogenes • Bacteriocins improve intestinal barrier damage and inflammatory response • Plantaricin RX-8 has the best protective effect on Caco-2 cells damage.


Asunto(s)
Antibacterianos , Bacteriocinas , Listeria monocytogenes , Listeria monocytogenes/efectos de los fármacos , Bacteriocinas/farmacología , Humanos , Células CACO-2 , Antibacterianos/farmacología , Inflamación , FN-kappa B/metabolismo , Adhesión Bacteriana/efectos de los fármacos , Proteínas de Uniones Estrechas/metabolismo , Citocinas/metabolismo , Listeriosis/microbiología , Listeriosis/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos
2.
Heliyon ; 10(8): e29712, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38681606

RESUMEN

This study employs Latent Dirichlet Allocation (LDA) topic modelling methodology to analyze documents related to renewable energy laws and policies at the central level in China. The objective is to investigate the development and evolution of renewable energy policies in China and to gain insights into the national-level attitudes towards renewable energy development. The study consists of two phases: initially, renewable energy policy documents undergo keyword analysis using word clouds and keyword co-occurrence network analysis to elucidate the focal areas and their interconnections within the legal and policy texts. Subsequently, after determining the optimal number of topics for modelling based on topic perplexity and consistency results, the text undergoes data cleaning to isolate words with practical significance. These words are then incorporated into the LDA topic model to analyze the distribution and content of potential topics within the policies. Lastly, by linearly segmenting the time frame, changes in topic intensity over time are visually examined using heat maps. The findings indicate that energy policies have consistently prioritized "development" and emphasized the significance of "new energy" in renewable energy policies. Moreover, as renewable energy has progressed, governments and policymakers have come to acknowledge the importance of comprehensive energy planning, transitioning to clean energy sources, and regulating the electricity market. This growing awareness has led to efforts to strengthen policy and regulatory measures to foster renewable energy's sustainable development and utilization. In summary, this study highlights the effectiveness of the LDA topic model in analyzing renewable energy policies, advancing its adoption and furthering research in the field.

3.
Food Funct ; 15(9): 5012-5025, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38618675

RESUMEN

Punicic acid (PA), mainly found in pomegranate seed oil (PSO), has attracted increasing attention due to its potential to mitigate obesity. The regulation of intestinal microflora was identified as a crucial factor and an effective strategy to reverse obesity-related hyperlipidemia and non-alcoholic fatty liver disease (NAFLD). To assess the impact of PSO on hyperlipidemia related to obesity, we investigated the hepatic lipid status and gut microbiota regulation in mice over 13 weeks of feeding a high-fructose high-fat diet (HFHFD). Serum lipid markers, including TG, TC and LDL-C, were markedly reduced in hyperlipidemic mice. PSO supplementation reduced hepatic lipid accumulation and steatosis, inhibited the expression of pro-inflammatory mediators (including IL-6 and IL-1ß), and restored the normal levels of the anti-inflammatory cytokine IL-10. In addition, PSO also alleviated oxidative stress and increased T-AOC and SOD activities, as well as GSH levels, while reducing the MDA content in the liver of HFHFD-fed mice. The activation of TLR4/MyD88/NF-κB and TLR4/IL-22/STAT3 signaling pathways in the liver due to the HFHFD was also evidently inhibited by PSO. Furthermore, supplementation of PSO ameliorated the HFHFD-induced dysbiosis of intestinal microflora, resulting in a markedly increased proportion of Muribaculaceae, a decreased ratio of Blautia, and elevated levels of microbiota-derived short-chain fatty acids (SCFAs). Moreover, the expression of tight junction proteins correlated with intestinal barrier function was notably restored in the colon. The collected results indicate that PSO may be an effective nutraceutical ingredient for attenuating lipid metabolic disorders.


Asunto(s)
Microbioma Gastrointestinal , Hiperlipidemias , Ácidos Linolénicos , Lipopolisacáridos , Ratones Endogámicos C57BL , Obesidad , Transducción de Señal , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Hiperlipidemias/tratamiento farmacológico , Masculino , Transducción de Señal/efectos de los fármacos , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Ácidos Linolénicos/farmacología , Dieta Alta en Grasa , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Granada (Fruta)/química , Hígado/metabolismo , Hígado/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos
4.
J Ethnopharmacol ; 328: 117974, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38467317

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication is one of the leading causes of coma. A well-regarded Chinese herbal formula, known as An-Gong-Niu-Huang-Wan (AGNHW), has garnered recognition for its efficacy in treating various brain disorders associated with impaired consciousness, including acute alcohol-induced coma. Despite its clinical effectiveness, the scientific community lacks comprehensive research on the mechanistic aspects of AGNHW's impact on the electroencephalogram (EEG) patterns observed during alcohol-induced coma. Gaining a deeper understanding of AGNHW's mechanism of action in relation to EEG characteristics would hold immense importance, serving as a solid foundation for further advancing its clinical therapeutic application. AIM OF THE STUDY: The study sought to investigate the impact of AGNHW on EEG activity and sleep EEG patterns in rats with alcoholic-induced coma. MATERIALS AND METHODS: A rat model of alcohol-induced coma was used to examine the effects of AGNHW on EEG patterns. Male Sprague-Dawley rats were intraperitoneally injected with 32% ethanol to induce a coma, followed by treatment with AGNHW. Wireless electrodes were implanted in the cortex of the rats to obtain EEG signals. Our analysis focused on evaluating alterations in the Rat Coma Scale (RCS), as well as assessing changes in the frequency and distribution of EEG patterns, sleep rhythms, and body temperature subsequent to AGNHW treatment. RESULTS: The study found a significant increase in the δ-band power ratio, as well as a decrease in RCS scores and ß-band power ratio after modeling. AGNHW treatment significantly reduced the δ-band power ratio and increased the ß-band power ratio compared to naloxone, suggesting its superior arousal effects. The results also revealed a decrease in the time proportion of WAKE and REM EEG patterns after modeling, accompanied by a significant increase in the time proportion of NREM EEG patterns. Both naloxone and AGNHW effectively counteracted the disordered sleep EEG patterns. Additionally, AGNHW was more effective than naloxone in improving hypothermia caused by acute alcohol poisoning in rats. CONCLUSION: Our study provides evidence for the arousal effects of AGNHW in alcohol-induced coma rats. It also suggests a potential role for AGNHW in regulating post-comatose sleep rhythm disorders.


Asunto(s)
Intoxicación Alcohólica , Coma , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Coma/inducido químicamente , Coma/tratamiento farmacológico , Electroencefalografía , Nivel de Alerta/fisiología , Sueño , Naloxona/farmacología
5.
Int J Biol Macromol ; 254(Pt 2): 127844, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37923032

RESUMEN

To address the challenges posed by spilled oil and oily wastewater, the development of clean oil-adsorption materials is crucial. However, traditional oil-adsorption materials suffer from the issue of secondary pollution. Herein, fully biodegradable nanofibrillated poly(butylene succinate)/poly(lactic acid) (PBS/PLA) foams with outstanding selective oil-adsorption performance were successfully fabricated via an eco-friendly supercritical CO2 foaming technology. The PBS/PLA composites, featuring nanofibrils with a diameter of approximately 100 nm, were prepared through a hot-stretching method subsequent to extrusion. Substantial improvements were observed in the crystallization rate and rheological properties of the fibrillated PBS/PLA composites. Furthermore, PLA nanofibrils enhanced foamability of the composite, achieving an impressive expansion ratio of up to 38.0, resulting in an outstanding oil-absorption performance (19.2-50.4 g/g) of the F-1 %-95 foam. Additionally, 20 adsorption-desorption cycles illustrated the prepared F-1 %-95 foam displayed recyclable oil-absorption characteristics. This work provides an eco-friendly strategy for preparing fully biodegradable foams intended for application as oil-adsorption materials.


Asunto(s)
Poliésteres , Temperatura , Poliésteres/química , Fenómenos Químicos , Cristalización
6.
Autophagy ; 20(3): 590-613, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37908119

RESUMEN

Although microglial activation is induced by an increase in chemokines, the role of mitophagy in this process remains unclear. This study aimed to elucidate the role of microglial mitophagy in CKLF/CKLF1 (chemokine-like factor 1)-induced microglial activation and neuroinflammation, as well as the underlying molecular mechanisms following CKLF treatment. This study determined that CKLF, an inducible chemokine in the brain, leads to an increase in mitophagy markers, such as DNM1L, PINK1 (PTEN induced putative kinase 1), PRKN, and OPTN, along with a simultaneous increase in autophagosome formation, as evidenced by elevated levels of BECN1 and MAP1LC3B (microtubule-associated protein 1 light chain 3 beta)-II. However, SQSTM1, a substrate of autophagy, was also accumulated by CKLF treatment, suggesting that mitophagy flux was reduced and mitophagosomes accumulated. These findings were confirmed by transmission electron microscopy and confocal microscopy. The defective mitophagy observed in our study was caused by impaired lysosomal function, including mitophagosome-lysosome fusion, lysosome generation, and acidification, resulting in the accumulation of damaged mitochondria in microglial cells. Further analysis revealed that pharmacological blocking or gene-silencing of mitophagy inhibited CKLF-mediated microglial activation, as evidenced by the expression of the microglial marker AIF1 (allograft inflammatory factor 1) and the mRNA of proinflammatory cytokines (Tnf and Il6). Ultimately, defective mitophagy induced by CKLF results in microglial activation, as observed in the brains of adult mice. In summary, CKLF induces defective mitophagy, microglial activation, and inflammation, providing a potential approach for treating neuroinflammatory diseases.Abbreviation: 3-MA: 3-methyladenine; AIF1: allograft inflammatory factor 1; ANOVA: analysis of variance; BAF: bafilomycin A1; BSA: bovine serum albumin; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; CKLF/CKLF1: chemokine-like factor 1; CNS: central nervous system; DMEM: Dulbecco's Modified Eagle Medium; DNM1L: dynamin 1 like; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescence protein; IRF3: interferon regulatory factor 3; IgG: immunoglobulin G; LAMP1: lysosomal-associated membrane protein 1; LAPTM4A: lysosomal-associated protein transmembrane 4A; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; Mdivi-1: mitochondrial division inhibitor 1; mRFP: monomeric red fluorescent protein; mtDNA: mitochondrial DNA; MTORC1: mechanistic target of rapamycin kinase complex 1; OPTN: optineurin; PBS: phosphate-buffered saline; PCR: polymerase chain reaction; PINK1: PTEN induced putative kinase 1; PLL: poly-L-lysine; PRKN: parkin RBR E3 ubiquitin protein ligase; qPCR: quantitative polymerase chain reaction; ROS: reactive oxygen species; SQSTM1: sequestosome 1; TBK1: TANK-binding kinase 1; TFEB: transcription factor EB; VDAC: voltage-dependent anion channel.


Asunto(s)
Enfermedades Mitocondriales , Mitofagia , Ratones , Animales , Mitofagia/genética , Autofagia , Proteína Sequestosoma-1/metabolismo , Microglía/metabolismo , ADN Mitocondrial/metabolismo , Enfermedades Mitocondriales/metabolismo , Proteínas Asociadas a Microtúbulos/metabolismo , Quimiocinas/metabolismo
7.
Artículo en Inglés | MEDLINE | ID: mdl-38032835

RESUMEN

Achieving a high-strength piezoresistive foam with high sensitivity and a large workable range remains a major challenge. To realize these goals, we developed a facile, novel, and eco-friendly strategy for constructing segregated microcellular structures fabricated using coating, heat compression molding, and supercritical CO2 (ScCO2) foaming. The segregated poly(ether block amide) (PEBA)/carbon nanostructure (CNS) composites were fabricated via compression molding. This effectively improved the foamability and cell morphology of PEBA/CNS composites. Moreover, compared with the randomly distributed structure, the segregated structure also endowed the foams with better conductivity and sensing capability. Subsequently, the ScCO2 foaming was employed to fabricate segregated PEBA/CNS composite foams. The foaming gave composites a large compressibility and reduced their percolation threshold. Under 1 wt % CNS loading, via tuning the expansion ratio of foam from ∼2.1 to 4.1, the compression stress at 50% compression strain of foam varied from ∼3.3 to 0.5 MPa, and the conductivity changed from 4.89 × 10-3 to 1.93 × 10-6 s/m, implying a tunable conductivity. Additionally, the adjustable conductivity enabled the sensitivity of segregated composite foams to be regulated. The segregated PEBA/CNS foam (FCNS1-4.1) exhibited a good combination of high sensitivity (GF = 3.5), large work range (80% strain), and high compression strength (∼0.5 MPa at 50% strain) as well as a stable, reproducible, and durable sensing response under a low CNS content (∼0.11 vol %). Furthermore, the ΔI/I0 of FCNS1-4.1 (75.6% porosity) reached a high value of ∼810 and exhibited an ultrahigh sensitivity of ∼3706 (ΔI/I0ε) from 60 to 80% strain. Moreover, the foam sensor could be used as a sensing function sole for monitoring diverse human motions. Therefore, the segregated PEBA/CNS composite foams with outstanding piezoresistive performances show promising potential applications in monitoring human motions as wearable electronics and provides a new design strategy for a new generation of foam sensors with high performance.

8.
Invest Ophthalmol Vis Sci ; 64(12): 43, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37773501

RESUMEN

Purpose: The neuroregulatory center of intraocular pressure (IOP) is located in the hypothalamus. An efferent neural pathway exists between the hypothalamic nuclei and the autonomic nerve endings in the anterior chamber of the eye. This study was designed to investigate whether the paraventricular hypothalamic nucleus (PVH) regulates IOP as the other nuclei do. Methods: Optogenetic manipulation of PVH neurons was used in this study. Light stimulation was applied via an optical fiber embedded over the PVH to activate projection neurons after AAV2/9-CaMKIIα-hChR2-mCherry was injected into the right PVH of C57BL/6J mice. The same methods were used to inhibit projection neurons after AAV2/9-CaMKIIα-eNpHR3.0-mCherry was injected into the bilateral PVH of C57BL/6J mice. AAV2/9-EF1α-DIO-hChR2-mCherry was injected into the right PVH of Vglut2-Cre mice to elucidate the effect of glutamatergic neuron-specific activation. IOP was measured before and after light manipulation. Associated nuclei activation was clarified by c-Fos immunohistochemical staining. Only mice with accurate viral expression and fiber embedding were included in the statistical analysis. Results: Activation of projection neurons in the right PVH induced significant bilateral IOP elevation (n = 11, P < 0.001); the ipsilateral IOP increased more noticeably (n = 11, P < 0.05); Bilateral inhibition of PVH projection neurons did not significantly influence IOP (n = 5, P > 0.05). Specific activation of glutamatergic neurons among PVH projection neurons also induced IOP elevation in both eyes (n = 5, P < 0.001). The dorsomedial hypothalamic nucleus, ventromedial hypothalamic nucleus, locus coeruleus and basolateral amygdaloid nucleus responded to light stimulation of PVH in AAV-ChR2 mice. Conclusions: The PVH may play a role in IOP upregulation via glutamatergic neurons.


Asunto(s)
Presión Intraocular , Núcleo Hipotalámico Paraventricular , Ratones , Animales , Núcleo Hipotalámico Paraventricular/metabolismo , Ratones Endogámicos C57BL , Neuronas/metabolismo , Vías Nerviosas/fisiología
9.
Cell Rep ; 42(7): 112674, 2023 07 25.
Artículo en Inglés | MEDLINE | ID: mdl-37352098

RESUMEN

Everyday episodic memories involve linking together related events that are temporally separated. However, the mechanisms of forming this temporal association have remained unclear. Here, using astrocyte-specific manipulations, we show that potentiating astrocyte Ca2+ signaling in the hippocampal cornu ammonis 1 (CA1) enhances the strength of such temporal association, in parallel with long-term potentiation (LTP) enhancement of temporoammonic pathway to CA1, whereas attenuation of astrocyte Ca2+ signaling has the opposite effect. Moreover, we identify that these effects are mediated by astrocytic α4 subunit-containing nicotinic acetylcholine receptors (α4-nAChRs) via mechanisms involving NMDAR co-agonist supply. Finally, astrocytic α4-nAChRs underlie the cognitive enhancer nicotine's physiological effects. Together, these findings highlight the importance of astrocyte Ca2+ signaling in cognitive behavior and reveal a mechanism in governing the temporal association of episodic memory formation that operates through α4-nAChRs on hippocampal astrocytes.


Asunto(s)
Nicotina , Receptores Nicotínicos , Nicotina/farmacología , Nicotina/metabolismo , Agonistas Nicotínicos/metabolismo , Astrocitos/metabolismo , Hipocampo/metabolismo , Receptores Nicotínicos/metabolismo , Potenciación a Largo Plazo/fisiología
10.
Nat Commun ; 14(1): 3792, 2023 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-37365155

RESUMEN

Viral tracers that enable efficient retrograde labeling of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Currently, some recombinant adeno-associated viruses (rAAVs) based on capsid engineering are widely used for retrograde tracing, but display undesirable brain area selectivity due to inefficient retrograde transduction in certain neural connections. Here we developed an easily editable toolkit to produce high titer AAV11 and demonstrated that it exhibits potent and stringent retrograde labeling of projection neurons in adult male wild-type or Cre transgenic mice. AAV11 can function as a powerful retrograde viral tracer complementary to AAV2-retro in multiple neural connections. In combination with fiber photometry, AAV11 can be used to monitor neuronal activities in the functional network by retrograde delivering calcium-sensitive indicator under the control of a neuron-specific promoter or the Cre-lox system. Furthermore, we showed that GfaABC1D promoter embedding AAV11 is superior to AAV8 and AAV5 in astrocytic tropism in vivo, combined with bidirectional multi-vector axoastrocytic labeling, AAV11 can be used to study neuron-astrocyte connection. Finally, we showed that AAV11 allows for analyzing circuit connectivity difference in the brains of the Alzheimer's disease and control mice. These properties make AAV11 a promising tool for mapping and manipulating neural circuits and for gene therapy of some neurological and neurodegenerative disorders.


Asunto(s)
Astrocitos , Neuronas , Ratones , Masculino , Animales , Ratones Transgénicos , Interneuronas , Encéfalo , Dependovirus/genética , Vectores Genéticos/genética
11.
Acta Pharmacol Sin ; 44(10): 1935-1947, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37198412

RESUMEN

Chemokine receptor 5 (CCR5) is one of the main co-receptors of HIV-1, and has been found to be a potential therapeutic target for stroke. Maraviroc is a classic CCR5 antagonist, which is undergoing clinical trials against stroke. As maraviroc shows poor blood-brain barrier (BBB) permeability, it is of interest to find novel CCR5 antagonists suitable for neurological medication. In this study we characterized the therapeutic potential of a novel CCR5 antagonist A14 in treating ischemic stroke mice. A14 was discovered in screening millions compounds in the Chemdiv library based on the molecular docking diagram of CCR5 and maraviroc. We found that A14 dose-dependently inhibited the CCR5 activity with an IC50 value of 4.29 µM. Pharmacodynamic studies showed that A14 treatment exerted protective effects against neuronal ischemic injury both in vitro and vivo. In a SH-SY5Y cell line overexpressing CCR5, A14 (0.1, 1 µM) significantly alleviated OGD/R-induced cell injury. We found that the expression of CCR5 and its ligand CKLF1 was significantly upregulated during both acute and recovery period in focal cortical stroke mice; oral administration of A14 (20 mg·kg-1·d-1, for 1 week) produced sustained protective effect against motor impairment. A14 treatment had earlier onset time, lower onset dosage and much better BBB permeability compared to maraviroc. MRI analysis also showed that A14 treatment significantly reduced the infarction volume after 1 week of treatment. We further revealed that A14 treatment blocked the protein-protein interaction between CCR5 and CKLF1, increasing the activity of CREB signaling pathway in neurons, thereby improving axonal sprouting and synaptic density after stroke. In addition, A14 treatment remarkably inhibited the reactive proliferation of glial cells after stroke and reduced the infiltration of peripheral immune cells. These results demonstrate that A14 is a promising novel CCR5 antagonist for promoting neuronal repair after ischemic stroke. A14 blocked the protein-protein interaction between CKLF1 and CCR5 after stroke by binding with CCR5 stably, improved the infarct area and promoted motor recovery through reversing the CREB/pCREB signaling which was inhibited by activated CCR5 Gαi pathway, and benefited to the dendritic spines and axons sprouting.


Asunto(s)
Antagonistas de los Receptores CCR5 , Accidente Cerebrovascular Isquémico , Neuroblastoma , Accidente Cerebrovascular , Animales , Humanos , Ratones , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Maraviroc/uso terapéutico , Maraviroc/farmacología , Simulación del Acoplamiento Molecular , Receptores CCR5/metabolismo , Accidente Cerebrovascular/tratamiento farmacológico , Antagonistas de los Receptores CCR5/química , Antagonistas de los Receptores CCR5/farmacología
12.
J Neuroinflammation ; 20(1): 97, 2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37098609

RESUMEN

Ischemic stroke is characterized by the presence of reactive microglia. However, its precise involvement in stroke etiology is still unknown. We used metabolic profiling and showed that chemokine like factor 1 (CKLF1) causes acute microglial inflammation and metabolic reprogramming from oxidative phosphorylation to glycolysis, which was reliant on the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR)-hypoxia inducible factor 1α (HIF-1α) signaling pathway. Once activated, microglia enter a chronic tolerant state as a result of widespread energy metabolism abnormalities, which reduces immunological responses, including cytokine release and phagocytosis. Metabolically dysfunctional microglia were also found in mice using genome-wide RNA sequencing after chronic administration of CKLF1, and there was a decrease in the inflammatory response. Finally, we showed that the loss of CKLF1 reversed the defective immune response of microglia, as indicated by the maintenance its phagocytosis to neutrophils, thereby mitigating the long-term outcomes of ischemic stroke. Overall, CKLF1 plays a crucial role in the relationship between microglial metabolic status and immune function in stroke, which prepares a potential therapeutic strategy for ischemic stroke.


Asunto(s)
Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Ratones , Citocinas/metabolismo , Tolerancia Inmunológica , Accidente Cerebrovascular Isquémico/metabolismo , Mamíferos/metabolismo , Microglía/metabolismo , Accidente Cerebrovascular/metabolismo
13.
Front Public Health ; 11: 1044525, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36908475

RESUMEN

Introduction: In light of the potential problems of missed diagnosis and misdiagnosis in the diagnosis of spinal diseases caused by experience differences and fatigue, this paper investigates the use of artificial intelligence technology for auxiliary diagnosis of spinal diseases. Methods: The LableImg tool was used to label the MRIs of 604 patients by clinically experienced doctors. Then, in order to select an appropriate object detection algorithm, deep transfer learning models of YOLOv3, YOLOv5, and PP-YOLOv2 were created and trained on the Baidu PaddlePaddle framework. The experimental results showed that the PP-YOLOv2 model achieved a 90.08% overall accuracy in the diagnosis of normal, IVD bulges and spondylolisthesis, which were 27.5 and 3.9% higher than YOLOv3 and YOLOv5, respectively. Finally, a visualization of the intelligent spine assistant diagnostic software based on the PP-YOLOv2 model was created and the software was made available to the doctors in the spine and osteopathic surgery at Guilin People's Hospital. Results and discussion: This software automatically provides auxiliary diagnoses in 14.5 s on a standard computer, is much faster than doctors in diagnosing human spines, which typically take 10 min, and its accuracy of 98% can be compared to that of experienced doctors in the comparison of various diagnostic methods. It significantly improves doctors' working efficiency, reduces the phenomenon of missed diagnoses and misdiagnoses, and demonstrates the efficacy of the developed intelligent spinal auxiliary diagnosis software.


Asunto(s)
Aprendizaje Profundo , Enfermedades de la Columna Vertebral , Humanos , Inteligencia Artificial , Imagen por Resonancia Magnética/métodos , Columna Vertebral
14.
Neural Regen Res ; 18(8): 1827-1833, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36751812

RESUMEN

Analyzing the structure and function of the brain's neural network is critical for identifying the working principles of the brain and the mechanisms of brain diseases. Recombinant rabies viral vectors allow for the retrograde labeling of projection neurons and cell type-specific trans-monosynaptic tracing, making these vectors powerful candidates for the dissection of synaptic inputs. Although several attenuated rabies viral vectors have been developed, their application in studies of functional networks is hindered by the long preparation cycle and low yield of these vectors. To overcome these limitations, we developed an improved production system for the rapid rescue and preparation of a high-titer CVS-N2c-ΔG virus. Our results showed that the new CVS-N2c-ΔG-based toolkit performed remarkably: (1) N2cG-coated CVS-N2c-ΔG allowed for efficient retrograde access to projection neurons that were unaddressed by rAAV9-Retro, and the efficiency was six times higher than that of rAAV9-Retro; (2) the trans-monosynaptic efficiency of oG-mediated CVS-N2c-ΔG was 2-3 times higher than that of oG-mediated SAD-B19-ΔG; (3) CVS-N2c-ΔG could delivery modified genes for neural activity monitoring, and the time window during which this was maintained was 3 weeks; and (4) CVS-N2c-ΔG could express sufficient recombinases for efficient transgene recombination. These findings demonstrate that new CVS-N2c-ΔG-based toolkit may serve as a versatile tool for structural and functional studies of neural circuits.

15.
Carbohydr Polym ; 302: 120419, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36604081

RESUMEN

In this work, an innovative PLA/CNF nanocomposite foam with a bimodal cell structure is prepared by a simple one-step depressurization foaming process using only supercritical carbon dioxide (ScCO2) as the foaming agent. Only at a specific foaming temperature, PLA/CNF nanocomposites foam with a bimodal cell structure could be obtained. According to the different crystallization kinetics and nucleation efficiency of samples, it was inferred that the crystallization rate and phase interface would affect the cell structure. The prepared PLA/CNF nanocomposite foam with a bimodal cell structure had an expansion ratio as high as 20 times and thermal conductivity of 0.041 w m-1 k-1, which exhibited low density and excellent thermal-insulation property. Meanwhile, the PLA/CNF nanocomposite foam exhibited excellent compression performance due to the presence of CNFs, which showed promising application in packaging and construction materials.


Asunto(s)
Celulosa , Nanocompuestos , Celulosa/química , Poliésteres/química , Presión , Ácido Láctico , Nanocompuestos/química
16.
Nat Prod Res ; 37(10): 1662-1667, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-35875993

RESUMEN

Callicarpa kwangtungensis (C. Kw), C. macrophylla (C. Ma), C. nudiflora (C. Nu), C. formosana (C. Fo), and C. kochiana (C. Ko) were medicinal plant resource in China. In this study, the UPLC/Q-TOF-MS analysis was performed and 151 compounds were identified. PCA analysis metabolic profiles of C. Nu, C. Ko and C. Kw leaves differ significantly from the other two Callicarpa species, while C. Fo and C. Ma share similar chemical constituents. OPLS-DA highlight with an S-plot indicated that there are 14 robust known chemical markers enabling the differentiation between these five Callicarpa plants. C. Ma, C. Nu, and C. Fo leaves extracts treatment effectively reversed the body weight loss, uric acid and creatinine content, hepatic XOD activity, kidney, liver, and ankle tissues injury and inflammation induced by potassium oxonate in hyperuricemia mice. While Ko and C. Kw leaves extracts treatment showed less improvement in hyperuricemia mice.


Asunto(s)
Callicarpa , Hiperuricemia , Plantas Medicinales , Animales , Ratones , Callicarpa/química , Hiperuricemia/tratamiento farmacológico , Inflamación , Metaboloma , Plantas Medicinales/química , Cromatografía Líquida de Alta Presión , Espectrometría de Masas
17.
J Integr Plant Biol ; 65(3): 755-771, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36333887

RESUMEN

Most of the reported P-type pentatricopeptide repeat (PPR) proteins play roles in organelle RNA stabilization and splicing. However, P-type PPRs involved in both RNA splicing and editing have rarely been reported, and their underlying mechanism remains largely unknown. Here, we report a rice floury endosperm22 (flo22) mutant with delayed amyloplast development in endosperm cells. Map-based cloning and complementation tests demonstrated that FLO22 encodes a mitochondrion-localized P-type PPR protein. Mutation of FLO22 resulting in defective trans-splicing of mitochondrial nad1 intron 1 and perhaps causing instability of mature transcripts affected assembly and activity of complex Ⅰ, and mitochondrial morphology and function. RNA-seq analysis showed that expression levels of many genes involved in starch and sucrose metabolism were significantly down-regulated in the flo22 mutant compared with the wild type, whereas genes related to oxidative phosphorylation and the tricarboxylic acid cycle were significantly up-regulated. In addition to involvement in splicing as a P-type PPR protein, we found that FLO22 interacted with DYW3, a DYW-type PPR protein, and they may function synergistically in mitochondrial RNA editing. The present work indicated that FLO22 plays an important role in endosperm development and plant growth by participating in nad1 maturation and multi-site editing of mitochondrial messager RNA.


Asunto(s)
Endospermo , Oryza , ARN Mitocondrial/metabolismo , Endospermo/metabolismo , Oryza/genética , Empalme del ARN , Mitocondrias/metabolismo , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
18.
Int J Mol Sci ; 23(21)2022 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-36361595

RESUMEN

As powerful tools for local gene delivery, adeno-associated viruses (AAVs) are widely used for neural circuit studies and therapeutical purposes. However, most of them have the characteristics of large diffusion range and retrograde labeling, which may result in off-target transduction during in vivo application. Here, in order to achieve precise gene delivery, we screened AAV serotypes that have not been commonly used as gene vectors and found that AAV13 can precisely transduce local neurons in the brain, with a smaller diffusion range than AAV2 and rigorous anterograde labeling. Then, AAV13-based single-viral and dual-viral strategies for sparse labeling of local neurons in the brains of C57BL/6 or Cre transgenic mice were developed. Additionally, through the neurobehavioral test in the ventral tegmental area, we demonstrated that AAV13 was validated for functional monitoring by means of carrying Cre recombinase to drive the expression of Cre-dependent calcium-sensitive indicator. In summary, our study provides AAV13-based toolkits for precise local gene delivery, which can be used for in situ small nuclei targeting, sparse labeling and functional monitoring.


Asunto(s)
Dependovirus , Vectores Genéticos , Animales , Ratones , Ratones Endogámicos C57BL , Dependovirus/metabolismo , Vectores Genéticos/genética , Técnicas de Transferencia de Gen , Ratones Transgénicos , Transducción Genética
19.
Se Pu ; 40(10): 929-936, 2022 Oct.
Artículo en Chino | MEDLINE | ID: mdl-36222256

RESUMEN

Pesticides are used in the agricultural production process to ensure the yield and quality of agricultural products. However, in recent years, environmental pollution issues caused by pesticide residues have sparked widespread concern in society. It is important to develop convenient and efficient approaches to detect and monitor pesticide residues. In this study, targeting benzoylurea insecticides (BUs), polyamidoamine dendrimer-functionalized silica nanocomposite with polydopamine coating (SiO2-PAMAM-PDA) was designed and successfully synthesized. First, monodisperse silica nanoparticles were prepared by the hydrolysis of tetraethyl orthosilicate (TEOS) in mixed solution of ethanol, water and ammonia. The silane coupling agent (3-aminopropyl)triethoxysilane was then employed to introduce amino groups into the silica. Silica with the zeroth generation of polyamidoamine (PAMAM) modification (SiO2-PAMAM-G0) was obtained through Michael addition reaction of methyl acrylate. Ethylenediamine was added to polymerize with methyl acrylate using an amidation reaction to form the first-generation PAMAM (SiO2-PAMAM-G1). Finally, by polymerizing dopamine under alkaline conditions (pH=8.5), the SiO2-PAMAM-G1 was coated with PDA. Thus, the final product named SiO2-PAMAM-PDA was obtained. The composite was characterized using a transmission electron microscope (TEM) and an increase in surface roughness indicated the successful grafting of PDA coating. Dopamine structure contains abundant benzene rings and amino and hydroxyl groups. It could bind with BUs through multiple secondary interactions, such as hydrogen bond and π-π stacking interaction. Therefore, the introduction of PDA could effectively enhance the affinity of the material toward benzoylurea insecticides. The prepared nanocomposites were used as sorbents in a dispersive micro solid-phase extraction approach (D-µ-SPE). The established approach was employed to extract and enrich the BUs in water samples before high-performance liquid chromatography (HPLC) analysis. Diflubenzuron, triflumuron, hexaflumuron, and teflubenzuron were chosen as target analytes. The following was a typical D-µ-SPE procedure. The prepared adsorbents measuring 40 mg were first dispersed in an 8-mL sample solution containing 150 g/L NaCl. The dispersion was assisted by 120-s vortexing to ensure full contact between the SiO2-PAMAM-PDA and the targets. Next, the adsorbents were separated from the liquid phase by 4-min centrifugation (5000 r/min). Thereafter, the adsorbed benzoylureas were eluted using 1 mL acetonitrile as desorption solvent by 120-s vortexing. Separated by centrifugation, the eluate was dried under a mild nitrogen stream. The solid remains were redissolved in 0.1 mL of acetonitrile, filtered by filter membrane (0.22 µm), and then analyzed by HPLC. The experimental conditions in the D-µ-SPE process could have a great impact on the extraction efficiency. Experimental conditions were optimized using a single factor optimization approach to further enhance the extraction recoveries. The optimized conditions included adsorbent amount, extraction time, desorption solvent type, desorption solvent volume, desorption time, and NaCl addition amount. Under the optimal conditions, a linearity range of 10-500 µg/L and limits of detection (LODs, S/N=3) of 1.1-2.1 µg/L were obtained. The extraction recoveries and relative standard deviations (RSDs) of the four BUs were 82.8%-94.1% and 2.1%-8.0%, respectively. The established approach was compared with reported approaches targeting benzoylurea insecticides. It was discovered that this approach consumed less sample, material, organic solvent, and pretreatment time. It provided a more rapid and green choice for the determination of benzoylurea pesticides. To determine the applicability, the proposed approach was applied to analyze the four benzoylurea insecticides in three river water samples. The real water samples were pretreated using the developed approach ahead of instrumental analysis, and no benzoylurea pesticides residue was detected. Next, standard addition experiments were performed under three spiking levels, including 15, 50, and 200 µg/L. The established approach had good accuracy and feasibility with satisfactory recoveries (69.5%-99.4%) and RSDs (0.2%-9.5%).


Asunto(s)
Dendrímeros , Diflubenzurón , Insecticidas , Nanocompuestos , Residuos de Plaguicidas , Acetonitrilos/análisis , Acrilatos , Amoníaco/análisis , Benceno/análisis , Cromatografía Líquida de Alta Presión , Dendrímeros/análisis , Diflubenzurón/análisis , Dopamina/análisis , Etanol/análisis , Etilenodiaminas/análisis , Indoles , Insecticidas/análisis , Nanocompuestos/análisis , Nitrógeno/análisis , Residuos de Plaguicidas/análisis , Poliaminas , Polímeros , Silanos/análisis , Dióxido de Silicio/análisis , Cloruro de Sodio/análisis , Extracción en Fase Sólida , Solventes/análisis , Agua/análisis
20.
J Colloid Interface Sci ; 625: 521-531, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35749847

RESUMEN

Designing earth-abundant and advanced bi-functional oxygen electrodes for efficient oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are extremely urgent but still ambiguous. Thus, metal-semiconductor nanohybrids were developed with functionally integrating ORR-active Ni species, OER-active Fe/Fe3C components, and multifunctional N-doped carbon (NDC) support. Expectantly, the resulted NDC nanocage embedded with Ni-Fe alloy and Fe3C particles, as assembled Mott-Schottky-typed catalyst, delivered a promoted half-wave potential of 0.904 V for ORR and a low overpotential of 315 mV at 10 mA/cm2 for OER both in alkaline media, outperforming those of commercial Pt/C and RuO2 counterparts. Most importantly, the optimized Ni-Fe/Fe3C@NDC sample also afforded a peak power density of 267.5 mW/cm2 with a specific capacity of 773.8 mAh/gZn and excellent durability over 80 h when used as the air electrode in rechargeable Zn-air batteries, superior to the state-of-the-art bi-functional catalysts. Ultraviolet photoelectron spectroscopy revealed that the introduction of Ni into the Fe/Fe3C@NDC component could well manipulate the electronic structure of the designed electrocatalyst, leading to an effective built-in electric field established by the Mott-Schottky heterojunction to expedite the continuous interfacial charge-transfer and thus significantly promote the utilization of electrocatalytic active sites. Therefore, this work provides an avenue for the designing and developing robust and durable Mott-Schottky-typed bi-functional catalysts for promising energy conversion.

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