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1.
Biomaterials ; 312: 122707, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39121729

RESUMEN

Polypyrimidine tract-binding protein 1 (PTBP1) regulates numerous alternative splicing events during tumor progression and neurogenesis. Previously, PTBP1 downregulation was reported to convert astrocytes into functional neurons; however, how PTBP1 regulates astrocytic physiology remains unclear. In this study, we revealed that PTBP1 modulated glutamate uptake via ATP1a2, a member of Na+/K+-ATPases, and glutamate transporters in astrocytes. Ptbp1 knockdown altered mitochondrial function and energy metabolism, which involved PTBP1 regulating mitochondrial redox homeostasis via the succinate dehydrogenase (SDH)/Nrf2 pathway. The malfunction of glutamate transporters following Ptbp1 knockdown resulted in enhanced excitatory synaptic transmission in the cortex. Notably, we developed a biomimetic cationic triblock polypeptide system, i.e., polyethylene glycol44-polylysine30-polyleucine10 (PEG44-PLL30-PLLeu10) with astrocytic membrane coating to deliver Ptbp1 siRNA in vitro and in vivo, which approach allowed Ptbp1 siRNA to efficiently cross the blood-brain barrier and target astrocytes in the brain. Collectively, our findings suggest a framework whereby PTBP1 serves as a modulator in glutamate transport machinery, and indicate that biomimetic methodology is a promising route for in vivo siRNA delivery.

2.
J Virol ; : e0063524, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39158346

RESUMEN

Flavivirus infection capitalizes on cellular lipid metabolism to remodel the cellular intima, creating a specialized lipid environment conducive to viral replication, assembly, and release. The Japanese encephalitis virus (JEV), a member of the Flavivirus genus, is responsible for significant morbidity and mortality in both humans and animals. Currently, there are no effective antiviral drugs available to combat JEV infection. In this study, we embarked on a quest to identify anti-JEV compounds within a lipid compound library. Our research led to the discovery of two novel compounds, isobavachalcone (IBC) and corosolic acid (CA), which exhibit dose-dependent inhibition of JEV proliferation. Time-of-addition assays indicated that IBC and CA predominantly target the late stage of the viral replication cycle. Mechanistically, JEV nonstructural proteins 1 and 2A (NS1 and NS2A) impede 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activation by obstructing the liver kinase B1 (LKB1)-AMPK interaction, resulting in decreased p-AMPK expression and a consequent upsurge in lipid synthesis. In contrast, IBC and CA may stimulate AMPK by binding to its active allosteric site, thereby inhibiting lipid synthesis essential for JEV replication and ultimately curtailing viral infection. Most importantly, in vivo experiments demonstrated that IBC and CA protected mice from JEV-induced mortality, significantly reducing viral loads in the brain and mitigating histopathological alterations. Overall, IBC and CA demonstrate significant potential as effective anti-JEV agents by precisely targeting AMPK-associated signaling pathways. These findings open new therapeutic avenues for addressing infections caused by Flaviviruses. IMPORTANCE: This study is the inaugural utilization of a lipid compound library in antiviral drug screening. Two lipid compounds, isobavachalcone (IBC) and corosolic acid (CA), emerged from the screening, exhibiting substantial inhibitory effects on the Japanese encephalitis virus (JEV) proliferation in vitro. In vivo experiments underscored their efficacy, with IBC and CA reducing viral loads in the brain and mitigating JEV-induced histopathological changes, effectively shielding mice from fatal JEV infection. Intriguingly, IBC and CA may activate 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) by binding to its active site, curtailing the synthesis of lipid substances, and thus suppressing JEV proliferation. This indicates AMPK as a potential antiviral target. Remarkably, IBC and CA demonstrated suppression of multiple viruses, including Flaviviruses (JEV and Zika virus), porcine herpesvirus (pseudorabies virus), and coronaviruses (porcine deltacoronavirus and porcine epidemic diarrhea virus), suggesting their potential as broad-spectrum antiviral agents. These findings shed new light on the potential applications of these compounds in antiviral research.

3.
Cell Mol Life Sci ; 81(1): 232, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38780644

RESUMEN

Ubiquitin-proteasome system dysfunction triggers α-synuclein aggregation, a hallmark of neurodegenerative diseases, such as Parkinson's disease (PD). However, the crosstalk between deubiquitinating enzyme (DUBs) and α-synuclein pathology remains unclear. In this study, we observed a decrease in the level of ubiquitin-specific protease 14 (USP14), a DUB, in the cerebrospinal fluid (CSF) of PD patients, particularly females. Moreover, CSF USP14 exhibited a dual correlation with α-synuclein in male and female PD patients. To investigate the impact of USP14 deficiency, we crossed USP14 heterozygous mouse (USP14+/-) with transgenic A53T PD mouse (A53T-Tg) or injected adeno-associated virus (AAV) carrying human α-synuclein (AAV-hα-Syn) in USP14+/- mice. We found that Usp14 deficiency improved the behavioral abnormities and pathological α-synuclein deposition in female A53T-Tg or AAV-hα-Syn mice. Additionally, Usp14 inactivation attenuates the pro-inflammatory response in female AAV-hα-Syn mice, whereas Usp14 inactivation demonstrated opposite effects in male AAV-hα-Syn mice. Mechanistically, the heterodimeric protein S100A8/A9 may be the downstream target of Usp14 deficiency in female mouse models of α-synucleinopathies. Furthermore, upregulated S100A8/A9 was responsible for α-synuclein degradation by autophagy and the suppression of the pro-inflammatory response in microglia after Usp14 knockdown. Consequently, our study suggests that USP14 could serve as a novel therapeutic target in PD.


Asunto(s)
Calgranulina A , Calgranulina B , Ratones Transgénicos , Enfermedad de Parkinson , Ubiquitina Tiolesterasa , alfa-Sinucleína , alfa-Sinucleína/metabolismo , alfa-Sinucleína/genética , Animales , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/patología , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/deficiencia , Humanos , Ratones , Femenino , Masculino , Calgranulina B/metabolismo , Calgranulina B/genética , Calgranulina A/metabolismo , Calgranulina A/genética , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL
4.
Nanoscale Adv ; 6(6): 1781-1789, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38482037

RESUMEN

Photocatalytic nitrogen (N2) reduction to ammonia (NH3), adopting H2O as the electron source, suffers from low efficiency owing to the sluggish kinetics of N2 reduction and the requirement of a substantial thermodynamic driving force. Herein, we present a straightforward approach for the construction of an S-scheme heterojunction of BiVO4/VS-MoS2 to successfully achieve photocatalytic N2 fixation, which is manufactured by coupling an N2-activation component (VS-MoS2 nanosheet) and water-oxidation module (BiVO4 nanocrystal) through electrostatic self-assembly. The VS-MoS2 nanosheet, enriched with sulfur vacancies, plays a pivotal role in facilitating N2 adsorption and activation. Additionally, the construction of the S-scheme heterojunction enhances the driving force for water oxidation and improves charge separation. Under simulated sunlight irradiation (100 mW cm-2), BiVO4/VS-MoS2 exhibits efficient photocatalytic N2 reduction activity with H2O as the proton source, yielding NH3 at a rate of 132.8 µmol g-1 h-1, nearly 7 times higher than that of pure VS-MoS2. This study serves as a noteworthy example of efficient N2 reduction to NH3 under mild conditions.

5.
ACS Omega ; 9(6): 7269, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38371812

RESUMEN

[This corrects the article DOI: 10.1021/acsomega.3c04101.].

6.
ACS Omega ; 9(1): 252-263, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38222523

RESUMEN

Supercritical cyclohexane (SC-cyclohexane) shows significant advantages in mild operating conditions and the modulation of product distribution. To gain insights into the upgrading process of heavy oil in SC-cyclohexane, the dissolution process of polycyclic aromatic hydrocarbons (PAHs) contained in heavy oil was simulated based on molecular dynamics with the use of naphthalene, benzopyrene, and mixtures of naphthalene and benzopyrene as the model compounds. As indicated by the radial distribution function results, in SC-cyclohexane exhibiting low density, cyclohexane formed a solvent shell around PAHs such that the local concentration was reduced and the aggregation of PAHs was inhibited. The results of the solvation free energy suggested that van der Waals forces between PAHs and cyclohexane were mainly dominant. As revealed by the dissolution process of the model compounds in SC-cyclohexane, a low density and a suitable temperature contributed to the solubilization of PAHs. An appropriate temperature and a low density can be selected for the upgrading reaction to limit coke formation.

7.
Mol Med Rep ; 29(1)2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38038164

RESUMEN

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the ß­actin control western blotting data shown in Fig. 3D on p. 1893 were very similar to the contol data shown in Fig. 4A on p. 1894; furthermore, the data shown for the MMP­9 and the INOS protein bands in Fig. 4C were remarkably similar to the data shown for the IL­1ß and IL­6 proteins, respectively, albeit the backgrounds surrounding the bands were different. Moreover, various of the western blotting data shown in these figures were strikingly similar to data that had already been published in different form in other articles written by (largely) different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, and due to the number of apparent duplications of strikingly similar data between Figs. 3 and 4, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 7: 1889­1895, 2013; DOI: 10.3892/mmr.2013.1444].

8.
Exploration (Beijing) ; 3(3): 20220160, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37933376

RESUMEN

Contactin-associated protein-like 4 (Cntnap4) is critical for GABAergic transmission in the brain. Impaired Cntnap4 function is implicated in neurological disorders, such as autism; however, the role of Cntnap4 on memory processing is poorly understood. Here, we demonstrate that hippocampal Cntnap4 deficiency in female mice manifests as impaired cognitive function and synaptic plasticity. The underlying mechanisms may involve effects on the pro-inflammatory response resulting in dysfunctional GABAergic transmission and activated tryptophan metabolism. To efficiently and accurately inhibit the pro-inflammatory reaction, we established a biomimetic microglial nanoparticle strategy to deliver FDA-approved PLX3397 (termed MNPs@PLX). We show MNPs@PLX successfully penetrates the blood brain barrier and facilitates microglial-targeted delivery of PLX3397. Furthermore, MNPs@PLX attenuates cognitive decline, dysfunctional synaptic plasticity, and pro-inflammatory response in female heterozygous Cntnap4 knockout mice. Together, our findings show loss of Cntnap4 causes pro-inflammatory cognitive decline that is effectively prevented by supplementation with microglia-specific inhibitors; thus validating the targeting of microglial function as a therapeutic intervention in neurocognitive disorders.

9.
Clinics (Sao Paulo) ; 78: 100215, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37196588

RESUMEN

BACKGROUND: Acute Respiratory Distress syndrome (ARDS) is a common complication of Acute Pancreatitis (AP) and is associated with high mortality. This study used Machine Learning (ML) to predict ARDS in patients with AP at admission. METHODS: The authors retrospectively analyzed the data from patients with AP from January 2017 to August 2022. Clinical and laboratory parameters with significant differences between patients with and without ARDS were screened by univariate analysis. Then, Support Vector Machine (SVM), Ensembles of Decision Trees (EDTs), Bayesian Classifier (BC), and nomogram models were constructed and optimized after feature screening based on these parameters. Five-fold cross-validation was used to train each model. A test set was used to evaluate the predictive performance of the four models. RESULTS: A total of 83 (18.04%) of 460 patients with AP developed ARDS. Thirty-one features with significant differences between the groups with and without ARDS in the training set were used for modeling. The Partial Pressure of Oxygen (PaO2), C-reactive protein, procalcitonin, lactic acid, Ca2+, the neutrophil:lymphocyte ratio, white blood cell count, and amylase were identified as the optimal subset of features. The BC algorithm had the best predictive performance with the highest AUC value (0.891) than SVM (0.870), EDTs (0.813), and the nomogram (0.874) in the test set. The EDT algorithm achieved the highest accuracy (0.891), precision (0.800), and F1 score (0.615), but the lowest FDR (0.200) and the second-highest NPV (0.902). CONCLUSIONS: A predictive model of ARDS complicated by AP was successfully developed based on ML. Predictive performance was evaluated by a test set, for which BC showed superior predictive performance and EDTs could be a more promising prediction tool for larger samples.


Asunto(s)
Pancreatitis , Síndrome de Dificultad Respiratoria , Humanos , Pancreatitis/complicaciones , Pancreatitis/diagnóstico , Estudios Retrospectivos , Enfermedad Aguda , Teorema de Bayes , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/etiología , Aprendizaje Automático
10.
Cell Mol Life Sci ; 80(6): 155, 2023 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-37204481

RESUMEN

Parkinson's disease (PD) is a progressive movement disorder characterized by dopaminergic (DA) neuron degeneration and the existence of Lewy bodies formed by misfolded α-synuclein. Emerging evidence supports the benefits of dietary interventions in PD due to their safety and practicality. Previously, dietary intake of α-ketoglutarate (AKG) was proved to extend the lifespan of various species and protect mice from frailty. However, the mechanism of dietary AKG's effects in PD remains undetermined. In the present study, we report that an AKG-based diet significantly ameliorated α-synuclein pathology, and rescued DA neuron degeneration and impaired DA synapses in adeno-associated virus (AAV)-loaded human α-synuclein mice and transgenic A53T α-synuclein (A53T α-Syn) mice. Moreover, AKG diet increased nigral docosahexaenoic acid (DHA) levels and DHA supplementation reproduced the anti-α-synuclein effects in the PD mouse model. Our study reveals that AKG and DHA induced microglia to phagocytose and degrade α-synuclein via promoting C1q and suppressed pro-inflammatory reactions. Furthermore, results indicate that modulating gut polyunsaturated fatty acid metabolism and microbiota Lachnospiraceae_NK4A136_group in the gut-brain axis may underlie AKG's benefits in treating α-synucleinopathy in mice. Together, our findings propose that dietary intake of AKG is a feasible and promising therapeutic approach for PD.


Asunto(s)
Enfermedad de Parkinson , Sinucleinopatías , Ratones , Animales , Humanos , Enfermedad de Parkinson/patología , Ácidos Cetoglutáricos/farmacología , Ratones Transgénicos , Degeneración Nerviosa/patología , Dopamina , Ingestión de Alimentos , Modelos Animales de Enfermedad
11.
Cell Death Dis ; 14(4): 285, 2023 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-37087484

RESUMEN

Parkinson's disease (PD) is the most common progressive neurodegenerative movement disorder, which is characterized by dopaminergic (DA) neuron death and the aggregation of neurotoxic α-synuclein. Cntnap4, a risk gene of autism, has been implicated to participate in PD pathogenesis. Here we showed Cntnap4 lacking exacerbates α-synuclein pathology, nigrostriatal DA neuron degeneration and motor impairment, induced by injection of adeno-associated viral vector (AAV)-mediated human α-synuclein overexpression (AAV-hα-Syn). This scenario was further validated in A53T α-synuclein transgenic mice injected with AAV-Cntnap4 shRNA. Mechanistically, α-synuclein derived from damaged DA neuron stimulates astrocytes to release complement C3, activating microglial C3a receptor (C3aR), which in turn triggers microglia to secrete complement C1q and pro-inflammatory cytokines. Thus, the astrocyte-microglia crosstalk further drives DA neuron death and motor dysfunction in PD. Furthermore, we showed that in vivo depletion of microglia and microglial targeted delivery of a novel C3aR antagonist (SB290157) rescue the aggravated α-synuclein pathology resulting from Cntnap4 lacking. Together, our results indicate that Cntnap4 plays a key role in α-synuclein pathogenesis by regulating glial crosstalk and may be a potential target for PD treatment.


Asunto(s)
Proteínas de la Membrana , Degeneración Nerviosa , Proteínas del Tejido Nervioso , Enfermedad de Parkinson , Ratones Transgénicos , Animales , Ratones , Humanos , Masculino , Ratones Endogámicos C57BL , alfa-Sinucleína/genética , Proteínas de la Membrana/genética , Proteínas del Tejido Nervioso/genética , Complemento C3/metabolismo , Receptores de Complemento/metabolismo , Neuronas Dopaminérgicas/metabolismo , Astrocitos/metabolismo , Degeneración Nerviosa/patología , Microglía/metabolismo , Enfermedad de Parkinson/fisiopatología , Ferroptosis , Mitocondrias , Inflamación
12.
Vaccines (Basel) ; 11(3)2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36992248

RESUMEN

Goose astrovirus (GAstV) was classified into GAstV-1 and GAstV-2, and both caused gosling viral gout. Recently, there has been no effective commercial vaccine to control the infection. It is important to establish serological methods to distinguish between the two genotypes. In this study, we reported the development and application of two indirect enzyme-linked immunosorbent assays (ELISAs) using the GAstV-1 virus and a recombinant GAstV-2 capsid protein as specific antigens to detect antibodies against GAstV-1 and GAstV-2, respectively. The optimal coating antigen concentration of indirect GAstV-1-ELISA and GAstV-2-Cap-ELISA was 1.2 µg/well and 125 ng/well, respectively. In addition, the antigen coating temperature and time, sera dilution and reaction time, and the dilution and reaction time of HRP-conjugated secondary antibody were optimized. The cut-off values were 0.315 and 0.305, and the analytical sensitivity was 1:6400 and 1:3200 for indirect GAstV-1-ELISA and GAstV-2-Cap-ELISA, respectively. The assays were able to differentiate specific sera against GAstVs, TUMV, GPV, and H9N2-AIV. The intra- and inter-plate variabilities of indirect ELISAs were less than 10%. The coincidence rate of positive sera was higher than 90%. The indirect ELISAs were further applied to test 595 goose serum samples. The results showed that the detection rates were 33.3% and 71.4% in GAstV-1-ELISA and GAstV-2-Cap-ELISA, respectively, and the co-detection rate was 31.1%, which indicates that the seroprevalence rate of GAstv-2 was higher than that of GastV-1, and the co-infection existed between GAstV-1 and GAstV-2. In summary, the developed GAstV-1-ELISA and GAstV-2-Cap-ELISA have high specificity, sensitivity, and reproducibility and can be used in the clinical detection of the antibody against GAstV-1 and GAstV-2.

13.
Adv Sci (Weinh) ; 10(12): e2300180, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36799538

RESUMEN

Neuroinflammation, for which microglia are the predominant contributors, is a significant risk factor for cognitive dysfunction. Riboflavin (also known as vitamin B2) ameliorates cognitive impairment via anti-oxidative stress and anti-inflammation properties; however, the underlying mechanisms linking riboflavin metabolism and microglial function in cognitive impairment remain unclear. Here, it is demonstrated that riboflavin kinase (RFK), a critical enzyme in riboflavin metabolism, is specifically expressed in microglia. An intermediate product of riboflavin, flavin mononucleotide (FMN), inhibited RFK expression via regulation of lysine-specific methyltransferase 2B (KMT2B). FMN supplementation attenuated the pro-inflammatory TNFR1/NF-κB signaling pathway, and this effect is abolished by KMT2B overexpression. To improve the limited anti-inflammatory efficiency of free FMN, a biomimetic microglial nanoparticle strategy (designated as MNPs@FMN) is established, which penetrated the blood brain barrier with enhanced microglial-targeted delivery efficiency. Notably, MNPs@FMN ameliorated cognitive impairment and dysfunctional synaptic plasticity in a lipopolysaccharide-induced inflammatory mouse model and in a 5xFAD mouse model of Alzheimer's disease. Taken together, biomimetic microglial delivery of FMN may serve as a potential therapeutic approach for inflammation-dependent cognitive decline.


Asunto(s)
Disfunción Cognitiva , Microglía , Ratones , Animales , Microglía/metabolismo , Enfermedades Neuroinflamatorias , Biomimética , Riboflavina/farmacología , Riboflavina/metabolismo , Disfunción Cognitiva/tratamiento farmacológico
14.
HGG Adv ; 4(1): 100160, 2023 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-36483158

RESUMEN

We investigated the awareness, perceived usefulness, and use of genetic testing among Hispanic and Latino individuals. Annual follow-up surveys for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from 2019 to April 2020 assessed participants' level of awareness and use of genetic tests to determine disease risks, likelihood of passing disease to children, disease treatment, or drug selection. They also were asked to rate the usefulness of the tests for managing a person's health on a 1 (not at all useful) to 10 (extremely useful) scale. There were 5,769 HCHS/SOL participants who completed at least one survey question. Of the target population, 55.2% was aware of at least one type of genetic test. Awareness varied between HCHS/SOL enrollment sites and was higher among individuals who had higher educational attainment and had higher incomes. Only 3.3% of the target population reported receiving one or more of the tests described. HCHS/SOL individuals rated the usefulness as 8.4, on average, with lower scores observed among U.S.-born individuals compared to individuals born outside the United States, with differences by HCHS/SOL enrollment sites. In conclusion, while awareness of genetic testing among Hispanic and Latino individuals varies by location, education, and income, perceptions about its usefulness are high while experiences with testing are rare. Results identify groups and locations that may benefit from greater outreach about the capabilities of genetic testing and precision medicine.


Asunto(s)
Pruebas Genéticas , Hispánicos o Latinos , Salud Pública , Humanos , Hispánicos o Latinos/genética , Renta , Factores de Riesgo , Estados Unidos/epidemiología , Conocimientos, Actitudes y Práctica en Salud
15.
Clinics ; 78: 100215, 2023. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1447984

RESUMEN

Abstract Background Acute Respiratory Distress syndrome (ARDS) is a common complication of Acute Pancreatitis (AP) and is associated with high mortality. This study used Machine Learning (ML) to predict ARDS in patients with AP at admission. Methods The authors retrospectively analyzed the data from patients with AP from January 2017 to August 2022. Clinical and laboratory parameters with significant differences between patients with and without ARDS were screened by univariate analysis. Then, Support Vector Machine (SVM), Ensembles of Decision Trees (EDTs), Bayesian Classifier (BC), and nomogram models were constructed and optimized after feature screening based on these parameters. Five-fold cross-validation was used to train each model. A test set was used to evaluate the predictive performance of the four models. Results A total of 83 (18.04%) of 460 patients with AP developed ARDS. Thirty-one features with significant differences between the groups with and without ARDS in the training set were used for modeling. The Partial Pressure of Oxygen (PaO2), C-reactive protein, procalcitonin, lactic acid, Ca2+, the neutrophil:lymphocyte ratio, white blood cell count, and amylase were identified as the optimal subset of features. The BC algorithm had the best predictive performance with the highest AUC value (0.891) than SVM (0.870), EDTs (0.813), and the nomogram (0.874) in the test set. The EDT algorithm achieved the highest accuracy (0.891), precision (0.800), and F1 score (0.615), but the lowest FDR (0.200) and the second-highest NPV (0.902). Conclusions A predictive model of ARDS complicated by AP was successfully developed based on ML. Predictive performance was evaluated by a test set, for which BC showed superior predictive performance and EDTs could be a more promising prediction tool for larger samples.

16.
Vaccines (Basel) ; 10(12)2022 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-36560500

RESUMEN

Goose astrovirus (GAstV) leads to viscera and joints urate deposition in 1- to 20-day-old goslings, with a mortality rate of up to 50%, posing a severe threat to entire colonies; however, there is no efficient prevention and control method for GAstV infection. This study describes a prophylactic anti-GAstV strategy based on the specific immunoglobulin Y (IgY) from egg yolk. The specific IgY was produced by 22-week-old laying hens intramuscularly immunized with the inactivated GAstV three consecutive times, with 2-week intervals. The egg yolk was collected weekly after the immunization and the anti-GAstV IgY titer was monitored using an agar gel immune diffusion assay (AGID). The results revealed that the AGID titer began to increase on day 7, reached a peak on day 49, and remained at a high level until day 77 after the first immunization. The specific IgY was prepared from the combinations of egg yolk from day 49 to day 77 through PEG-6000 precipitation. Animal experiments were conducted to evaluate the effects of prevention and treatment. The result of the minimum prophylactic dose of the IgY showed that the protection rate was 90.9% when 2.5 mg was administrated. Results of the prevention and the treatment experiments showed prevention and cure rates of over 80% when yolk antibody was administered in the early stages of the GAstV infection. These results suggested that the specific IgY obtained from immunized hens with the inactivated GAstV could be a novel strategy for preventing and treating GAstV infection.

17.
EBioMedicine ; 86: 104323, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36395738

RESUMEN

BACKGROUND: Autism spectrum disorder (ASD) is a common neurodevelopmental disease, characterized by deficits in social communication, restricted and repetitive behaviours, and impaired fear memory processing. Severe gastrointestinal dysfunction and altered gut microbiome have been reported in ASD patients and animal models. Contactin associated protein-like 4 (CNTNAP4) has been suggested to be a novel risk gene, though its role in ASD remains unelucidated. METHODS: Cntnap4-/- mice were generated to explore its role in ASD-related behavioural abnormalities. Electrophysiological recording was employed to examine GABAergic transmission in the basolateral amygdala (BLA) and prefrontal cortex. RNA-sequencing was performed to assess underlying mechanisms. 16S rDNA analysis was performed to explore changes in faecal microbial composition. Male Cntnap4-/- mice were fed with Lactobacillus reuteri (L. reuteri) or faecal microbiota to evaluate the effects of microbiota supplementation on the impaired fear conditioning mediated by Cntnap4 deficiency. FINDINGS: Male Cntnap4-/- mice manifested deficiency in social behaviours and tone-cue fear conditioning. Notably, reduced GABAergic transmission and GABA receptor expression were found in the BLA but not the prefrontal cortex. In addition, gut Lactobacillus were less abundant in male Cntnap4-/- mice, and L. reuteri treatment or faecal microbiota transplantation rescued abnormal tone-cued fear memory and improved local GABAergic transmission in the BLA of male Cntnap4-/- mice. INTERPRETATION: Cntnap4 shapes GABAergic transmission of amygdala and fear conditioning, and microbial intervention represents a promising therapy in ASD intervention. FUNDING: National Natural Science Foundation of China, Science and Technology Planning Project of Guangzhou, Guangzhou Medical University, and China Postdoctoral Science Foundation.


Asunto(s)
Trastorno del Espectro Autista , Limosilactobacillus reuteri , Animales , Masculino , Ratones , Amígdala del Cerebelo/metabolismo , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/microbiología , Miedo/fisiología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones Noqueados , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Modelos Animales de Enfermedad , Trasplante de Microbiota Fecal , Memoria/fisiología
18.
PLoS One ; 17(10): e0276272, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36251726

RESUMEN

With the advancement of urbanization and the expansion of urban areas, NIMBY (not in my back yard) environmental public facilities are increasing day by day. It is meaningful to incorporate public participation into the regulatory process for the existing pollution NIMBY facility enterprises. Through the establishment of the tripartite game model of local government, polluting NIMBY facility enterprises and the public, the evolution stability analysis and simulation analysis of their strategies are carried out, and the Pareto optimal solution is obtained. The results show that: The strategy choices of the players of the three-party game are different under different stability conditions. The system can be broken out of the bad state by increasing government punishment, local governments strictly controlling the potential profits, the potential losses of polluting enterprises not rebuilding, the long-term public benefits and reducing the cost of public participation, etc., and the three-party common governance mode can be formed. The strategy evolution speed of a player in a three-party game is affected by his own strategy choice proportion and the strategy choice proportion of the other two players, but no matter how the strategy choice proportion of the player in a three-party game changes, it will not change the final game result. On the basis of comprehensive analysis, a series of relevant suggestions are put forward from the three aspects of government, enterprises and the public, so as to provide certain reference for the design of the public participation system of polluting NIMBY facilities.


Asunto(s)
Participación de la Comunidad , Contaminación Ambiental , China , Teoría del Juego , Gobierno , Vivienda , Humanos , Castigo
19.
Front Plant Sci ; 13: 921310, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36204071

RESUMEN

Astragalus variabilis is a locoweed of northwest China that can seriously impede livestock development. However, it also plays various ecological roles, such as wind protection and sand fixation. Here, we used an optimized MaxEnt model to predict the distribution of suitable habitat of A. variabilis under current (1970-2000) conditions and future (2021-2080) climate change scenarios based on recent occurrence records. The most important environmental variables (suitability ranges in parentheses) affecting the distribution of A. variabilis were average maximum temperature of February (-2.12-5.34°C), followed by total precipitation of June (2.06-37.33 mm), and topsoil organic carbon (0.36-0.69%). The habitat suitability of A. variabilis was significantly correlated with the frequency of livestock poisoning (p < 0.05). Under current climate conditions, the suitable environment of A. variabilis was distributed in central and western Inner Mongolia, Ningxia, central and northwestern Gansu, central and northwestern Qinghai, and the four basins around the Tianshan Mountains in Xinjiang. Under future climate conditions, the suitable habitat of A. variabilis shifted to higher latitudes and altitudes. No previous studies have used niche models to predict the suitable environment of this species nor analyzed the relationship between the habitat suitability of poisonous plants and the frequency of animal poisoning. Our findings provide new insights that will aid the prevention of livestock animal poisoning and the control of poisonous plants, promote the development of the livestock husbandry industry, and provide basic information that will facilitate the maintenance of the ecological balance of grassland ecosystems.

20.
PLoS One ; 17(7): e0271120, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35819931

RESUMEN

In recent years, NIMBY(Not In My Backyard) conflicts gradually become hot and difficult in the international community governance, people have realized that the government and people on both sides of the emotional factors have great influences on the results of the conflicts, especially to study the effects of emotion on the evolution of conflicts in China, this article from the following several aspects. First of all, a game model under the influences of emotion is constructed by using Range Dependent Expected Utility(RDEU) theory and emotional function. Secondly, the Jacobian matrix is utilized to analyze the stability of the equilibrium point for the model constructed above. Next, numerical simulation is used to analyze the evolution trend of discrete emotions. The evolutionary results show that when one party holds an optimistic mood, equilibrium evolves to a relatively optimal state; while when one party holds a pessimistic mood, the more pessimistic the party is, the more likely it is to cause NIMBY conflicts. Compared with the people's sentiments, the government's moods have a greater impact on the evolutionary consequences. Finally, depending on the conclusions of the evolutionary analysis, some suggestions on the governance of NIMBY conflicts are put forward.


Asunto(s)
Gobierno , Vivienda , China , Humanos
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