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1.
J Cosmet Dermatol ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39014903

RESUMO

BACKGROUND: Aging is a physiological phenomenon in the process of life, and skin aging has a significant impact on human appearance. Therefore, the search for methods to delay skin aging is of great significance for improving the quality of human life. MATERIALS AND METHODS: This study investigated the anti-photoaging effect of Tricholoma matsutake (T) extract composition combined with bakuchiol (B) and ergothioneine (E), and explored its potential mechanism through transcriptome, metabolomics, and network pharmacology. RESULTS: 57 main chemical components are identified from the ethanol extract of T. matsutake (T), including D-carnitine (24.55%), α,α-trehalose (15.56%), DL malic acid (8.99%), D-(-)-quinic acid (7.46%), erucamide (7.04%) and so on. After TBE treatment, inflammation of the mice dorsal skin is significantly minimized. Hematoxylin and eosin (H&E) staining and toluidine blue staining reveal that TBE has an anti-inflammatory effect on the back skin tissue of mice. Masson staining shows that TBE has a repair effect on mice dorsal skin tissue. In addition, the inflammatory factors (IL-1ß, IL-6, TNF-α) in the mice dorsal skin tissues are significantly reduced but collagen (COL-1) is significantly increased. By cellular immunofluorescence assay, TBE is shown to promote PPAR-α expression in cells. Transcriptomics, metabolomics, and network pharmacology have revealed that TBE can regulate exogenous stimuli and cancer-related signaling pathways to prevent skin aging. CONCLUSION: The results suggest that TBE can be a beneficial supplement to natural anti-aging.

2.
Clin Immunol ; 265: 110298, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909972

RESUMO

Prostaglandins (PGs) play a crucial and multifaceted role in various physiological processes such as intercellular signaling, inflammation regulation, neurotransmission, vasodilation, vasoconstriction, and reproductive functions. The diversity and biological significance of these effects are contingent upon the specific types or subtypes of PGs, with each PG playing a crucial role in distinct physiological and pathological processes. Particularly within the immune system, PGs are essential in modulating the function of immune cells and the magnitude and orientation of immune responses. Hence, a comprehensive comprehension of the functions PG signaling pathways in immunosuppressive regulation holds substantial clinical relevance for disease prevention and treatment strategies. The manuscript provides a review of recent developments in PG signaling in immunosuppressive regulation. Furthermore, the potential clinical applications of PGs in immunosuppression are also discussed. While research into the immunosuppressive effects of PGs required further exploration, targeted therapies against their immunosuppressive pathways might open new avenues for disease prevention and treatment.

3.
Neurochem Res ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935224

RESUMO

A ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that exerts antiepileptic effects by attenuating spontaneous recurrent seizures, ameliorating learning and memory impairments, and modulating the gut microbiota composition. However, the role of the gut microbiome in the antiepileptic effects of a KD on temporal lobe epilepsy (TLE) induced by lithium-pilocarpine in adult rats is still unknown. Our study provides evidence demonstrating that a KD effectively mitigates seizure behavior and reduces acute-phase epileptic brain activity and that KD treatment alleviates hippocampal neuronal damage and improves cognitive impairment induced by TLE. We also observed that the beneficial effects of a KD are compromised when the gut microbiota is disrupted through antibiotic administration. Analysis of gut microbiota components via 16S rRNA gene sequencing in fecal samples collected from TLE rats fed either a KD or a normal diet. The Chao1 and ACE indices showed decreased species variety in KD-fed rats compared to TLE rats fed a normal diet. A KD increased the levels of Actinobacteriota, Verrucomicrobiota and Proteobacteria and decreased the level of Bacteroidetes. Interestingly, the abundances of Actinobacteriota and Verrucomicrobiota were positively correlated with learning and memory ability, and the abundance of Proteobacteria was positively correlated with seizure susceptibility. In conclusion, our study revealed the significant antiepileptic and neuroprotective effects of a KD on pilocarpine-induced epilepsy in rats, primarily mediated through the modulation of the gut microbiota. However, whether the gut microbiota mediates the antiseizure effects of a KD still needs to be better elucidated.

4.
Zhongguo Zhong Yao Za Zhi ; 49(3): 728-734, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621876

RESUMO

Mesona chinensis is a common medicinal and edible plant in the Lingnan region of China, which has extensive pharmacological activity. However, the study of its chemical constituents is not sufficient. In this study, a variety of modern chromatographic separation techniques were used to isolate two compounds from 95% ethanol extract of the grass parts of M. chinensis. Their absolute configurations were determined by ultraviolet spectroscopy(UV), infrared spectroscopy(IR), high resolution mass spectrometry(HR-ESI-MS), 1D and 2D nuclear magnetic resonance(1D NMR and 2D NMR), and single-crystal X-ray diffraction(SC-XRD). Specifically, they were two new benzoyl-sesquiterpenes and named mesonanol A and mesonanol B, respectively. The results of the pharmacological activity evaluation showed that neither of the two new compounds showed obvious antiviral and anti-inflammatory activities.


Assuntos
Lamiaceae , Sesquiterpenos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Espectrofotometria Infravermelho , Estrutura Molecular
5.
Food Sci Nutr ; 11(12): 8027-8034, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38107136

RESUMO

Phase angle and vitamin D can reflect the state of the body cells, and the two may interact with each other. Therefore, this study was conducted to find out the relationship between PA and vitamin D. Taking women in early pregnancy as our study subjects, we found that PA had a positive effect on vitamin D levels. Body composition phase angle, as a noninvasive, easy-to-operate, and easy-to-monitor indicator, can be used an early screening index for vitamin D nutrition levels in early pregnancy, and the cutoff value was 4.95°.

6.
Epigenetics ; 18(1): 2211362, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37196184

RESUMO

Histones are subjected to extensive covalent modifications that affect inter-nucleosomal interactions as well as alter chromatin structure and DNA accessibility. Through switching the corresponding histone modifications, the level of transcription and diverse downstream biological processes can be regulated. Although animal systems are widely used in studying histone modifications, the signalling processes that occur outside the nucleus prior to histone modifications have not been well understood due to the limitations including non viable mutants, partial lethality, and infertility of survivors. Here, we review the benefits of using Arabidopsis thaliana as the model organism to study histone modifications and their upstream regulations. Similarities among histones and key histone modifiers such as the Polycomb group (PcG) and Trithorax group (TrxG) in Drosophila, Human, and Arabidopsis are examined. Furthermore, prolonged cold-induced vernalization system has been well-studied and revealed the relationship between the controllable environment input (duration of vernalization), its chromatin modifications of FLOWERING LOCUS C (FLC), following gene expression, and the corresponding phenotypes. Such evidence suggests that research on Arabidopsis can bring insights into incomplete signalling pathways outside of the histone box, which can be achieved through viable reverse genetic screenings based on the phenotypes instead of direct monitoring of histone modifications among individual mutants. The potential upstream regulators in Arabidopsis can provide cues or directions for animal research based on the similarities between them.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Humanos , Arabidopsis/genética , Histonas/genética , Histonas/metabolismo , Cromatina/genética , Cromatina/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Código das Histonas , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Metilação de DNA , Regulação da Expressão Gênica de Plantas , Flores/genética , Flores/metabolismo
7.
MicroPubl Biol ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37193546

RESUMO

In the early 20th century, Calvin Bridges and Thomas Morgan identified a number of spontaneous mutations that displayed visible phenotypes in adult flies and subsequent analysis of these mutations over the past century have provided fundamental insights into subdisciplines of biology such as genetics, developmental, and cell biology. One of the mutations they identified in 1915 was named tilt ( tt ) and was described by Bridges and Morgan as having two visible phenotype characteristics in the wing. The wings were "held out at a wider angle from the body" and had a break in wing vein L3. Subsequent analysis of the tilt phenotype identified another phenotype: the wings were missing a varying number of campaniform sensilla on L3. Though Bridges and Morgan provided an ink drawing of the wing posture phenotype, only the vein and campaniform sensilla loss images have been published. Here we confirm and document the tilt phenotypes that have been previously described. We also show the penetrance of these phenotypes: the vein break and the distinct outward wing posture have decreased since its discovery.

8.
Methods Mol Biol ; 2665: 95-111, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37166596

RESUMO

Vital biochemical reactions including photosynthesis to respiration require iron, which should be tightly regulated. Although increasing evidence reveals the importance of epigenetic regulation in gene expression and signaling, the role of histone modifications and chromatin remodeling in plant iron homeostasis is not well understood. In this study, we surveyed publicly available ChIP-seq datasets of Arabidopsis wild-type and mutants defective in key enzymes of histone modification and chromatin remodeling and compared the deposition of epigenetic marks on loci of genes involved in iron regulation. Based on the analysis, we compiled a comprehensive list of iron homeostasis genes with differential enrichment of various histone modifications. This report will provide a resource for future studies to investigate epigenetic regulatory mechanisms of iron homeostasis in plants.


Assuntos
Arabidopsis , Sequenciamento de Cromatina por Imunoprecipitação , Epigênese Genética , Arabidopsis/genética , Arabidopsis/metabolismo , Ferro/metabolismo , Cromatina/genética , Cromatina/metabolismo , Homeostase/genética
9.
Clin Genitourin Cancer ; 21(2): e78-e91, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36127253

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common and lethal cancer of the adult kidney. ADAP2 is a GTPase-activating protein was upregulated in clear cell renal cell carcinoma. The role of ADAP2 in ccRCC progression is unknown. METHODS: ADAP2 expression in ccRCC cell lines and tissues was examined via real-time PCR, Western blot and IHC. MTS, colony formation and transwell assay to explore the role of ADAP2 in ccRCC. ADAP2 in growth and metastasis of ccRCC were evaluated in vivo through ccRCC xenograft tumor growth, lung metastatic mice model. The prognostic role of ADAP2 was evaluated by survival analysis. RESULTS: ADAP2 mRNA was expressed at significantly higher levels in 23 pairs of ccRCC tissues than in normal kidney tissues (P < 0.01). Immunohistochemical analysis of 298 ccRCC tissues revealed elevated ADAP2 expression as an independent unfavorable prognostic factor for the overall survival (P = 0.0042) and progression-free survival (P = 0.0232) of patients. The KaplanMeier survival curve showed that patients with a higher expression of ADAP2 showed a significantly lower overall survival rate and disease-free survival rate. Moreover, high expression of ADAP2 at the mRNA level was associated with a worse prognosis for overall survival (P = 0.0083) in The Cancer Genome Atlas (TCGA) cohort. In vivo and in vitro functional study showed that overexpression of ADAP2 promotes ccRCC cell proliferation and metastasis ability, whereas knockdown of ADAP2 inhibited cell proliferation, colony formation, migration and invasion. CONCLUSION: ADAP2 is a novel prognostic marker and could promotes tumor progression in ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Adulto , Animais , Humanos , Camundongos , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Rim/patologia , Neoplasias Renais/patologia , Prognóstico , RNA Mensageiro/genética
10.
Sensors (Basel) ; 22(14)2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35891134

RESUMO

In indoor low-texture environments, the point feature-based visual SLAM system has poor robustness and low trajectory accuracy. Therefore, we propose a visual inertial SLAM algorithm based on point-line feature fusion. Firstly, in order to improve the quality of the extracted line segment, a line segment extraction algorithm with adaptive threshold value is proposed. By constructing the adjacent matrix of the line segment and judging the direction of the line segment, it can decide whether to merge or eliminate other line segments. At the same time, geometric constraint line feature matching is considered to improve the efficiency of processing line features. Compared with the traditional algorithm, the processing efficiency of our proposed method is greatly improved. Then, point, line, and inertial data are effectively fused in a sliding window to achieve high-accuracy pose estimation. Finally, experiments on the EuRoC dataset show that the proposed PLI-VINS performs better than the traditional visual inertial SLAM system using point features and point line features.


Assuntos
Algoritmos
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(3): 836-843, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35680814

RESUMO

OBJECTIVE: To analysis the specific protein markers of essential thrombocythemia (ET) based on proteomics technology, to explore and verify the differential protein related to platelet activation. METHODS: Blood samples were obtained from ET patients and healthy people and a certain protein mass spectrometry was detected using label-free quantitative technology. The proteins relative abundance increased or down-regulated by 1.3 times in the disease group compared with the control group, and the protein abundance in the two groups t test P<0.05 were defined as differential proteins. Bioinformatics analysis of the differential proteins was performed using GO and KEGG. The difference in the average protein abundance between the two groups was analyzed by t test and P<0.05 was considered statistically significant. Differential proteins were selected for verification by parallel reaction monitoring (PRM) technology. RESULTS: A total of 140 differential proteins were found, of which 72 were up-regulated and 68 were down-regulated. KEGG enrichment showed that the differential protein expression was related to the platelet activation pathway. The differential proteins related to platelet activation were GPV, COL1A2, GP1bα, COL1A1 and GPVI. Among them, the expressions of GPV, GP1bα and GPVI were up-regulated, and the expressions of COL1A2 and COL1A1 were down-regulated. PRM verification of COL1A1, GP1bα, GPVI and GPV was consistent with LFP proteomics testing. CONCLUSION: Differential proteins in ET patients are related to platelet activation pathway activation.Differential proteins such as GPV, GPVI, COL1A1 and GP1bα can be used as new targets related to ET platelet activation.


Assuntos
Trombocitemia Essencial , Plaquetas/metabolismo , Humanos , Ativação Plaquetária , Glicoproteínas da Membrana de Plaquetas/metabolismo , Tecnologia
12.
Fish Shellfish Immunol ; 127: 155-165, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35716969

RESUMO

The reduction of fishmeal in aquafeeds has been the concern of researchers. Replacing fishmeal with plant proteins affects intestinal function and inflammation, but the interaction between the intestinal responses and gut microbiota remains unclear. In this study, juvenile channel catfish (Ictalurus punctatus) was fed with four diets in which enzymatic rice protein (RP) replaced fishmeal at levels of 0 (FM), 2.5% (RP2.5), 5.0% (RP5.0), and 7.5% (RP7.5) for 8 weeks to solve the problem mentioned above. Quantification of intestinal morphology showed that 2.5% or 5.0% RP significantly increased villus length and goblet cell number, accompanied by higher activities of intestinal trypsin, alkaline phosphatase (AKP), and Na+/K+-ATPase (NKA) in RP2.5 group (P < 0.05). In contrast, 7.5% RP slightly damaged the intestinal mucosa and significantly reduced the activities of amylase, AKP, and NKA, as well as decreased serum complement 4 (C4) and immunoglobulin M (IgM). Noteworthy, RT-qPCR showed that 2.5% RP significantly down-regulated intestinal mRNA expression level of il8, while up-regulated mif, tlr4, tlr7, tgfß3, and cldn2. In contrast, 7.5% RP up-regulated the mRNA expression levels of il1ß, il8, and mif, while down-regulated cldn3d. Analysis of gut microbiota showed that 2.5% RP increased the relative abundance of Bacteroidetes and significantly activated potential functions of gut microbiota involved in carbohydrate metabolism. The 7.5% RP increased the diversity of the gut microbiota, accompanied by a significant increase in the relative abundance of conditionally pathogenic bacteria such as Vibrio, Serratia, and Aeromonas (classified as Proteobacteria). Notably, Vibrio was the biomarker species with the greatest difference between the FM and RP7.5 groups (genus level). Correlation analysis indicated that Vibrio may affect immunity through the C4 pathway and further lead to gut inflammation and digestive impairment. Taken above, these results indicated that RP could affect intestinal morphology, digestion, and inflammation, and interact with the composition and potential function of gut microbiota. The low RP supplement (2.5%) improved intestinal morphology and digestion, while high supplement (7.5%) disrupted gut microbiota homeostasis, resulting in damage to intestinal mucosa and inflammatory response.


Assuntos
Microbioma Gastrointestinal , Ictaluridae , Oryza , Ração Animal/análise , Animais , Dieta/veterinária , Proteínas Alimentares , Digestão , Ictaluridae/genética , Inflamação/veterinária , Interleucina-8 , RNA Mensageiro
13.
Front Neurol ; 13: 843975, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493838

RESUMO

Background: Dravet syndrome (DS) is a refractory developmental and epileptic encephalopathy (EE) with a variety of comorbidities, including cognitive impairment, autism-like behavior, speech dysfunction, and ataxia, which can seriously affect the quality of life of patients and impose a great burden on society and their families. Currently, the pharmacological therapy is patient dependent and may work or not. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), responsive neurostimulation (RNS), and chronic subthreshold cortical stimulation (CSCS), have become common adjuvant therapies for neurological diseases, but their efficacy in the treatment of DS is unknown. Methods: We searched Web of Science, PubMed, and SpringerLink for all published cases related to the neuromodulation techniques of DS until January 15, 2022. The systematic review was supplemented with relevant articles from the references. The results reported by each study were summarized narratively. Results: The Web of science, PubMed and SpringerLink search yielded 258 items. A total of 16 studies published between 2016 and 2021 met the final inclusion criteria. Overall, 16 articles (109 cases) were included in this study, among which fifteen (107 patients) were involved VNS, and one (2 patients) was involved DBS. After VNS implantation, seizures were reduced to ≥50% in 60 cases (56%), seizure free were found in 8 cases (7.5%). Only two DS patients received DBS treatment, and the initial outcomes of DBS implantation were unsatisfactory. The seizures significantly improved over time for both DBS patients after the addition of antiepileptic drugs. Conclusion: More than half of the DS patients benefited from VNS, and VNS may be effective in the treatment of DS. However, it is important to note that VNS does not guarantee improvement of seizures, and there is a risk of infection and subsequent device failure. Although DBS is a safe and effective strategy for the treatment of refractory epilepsy, the role of DBS in DS needs further study, as the sample size was small. Thus far, there is no strong evidence for the role of DBS in DS.

14.
Ecotoxicol Environ Saf ; 233: 113318, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35182799

RESUMO

Carboxin is a heterocyclic systemic fungicide, mainly used to prevent and control grain smut and wheat rust. Although its mammalian toxicity has been reported, its toxicity to acute exposure to aquatic animals is unknown. In our study, we used zebrafish as aquatic organisms to study Carboxin toxicity. Carboxin can cause developmental toxicity and cardiotoxicity in zebrafish embryos. Histopathological staining of cardiac sections reveals structural changes in zebrafish hearts, and fluorescence quantitative PCR results shows the heart developmental genes mRNA expression levels were disrupted significantly. Besides, carboxin can also cause oxidative stress and reactive oxygen species (ROS) accumulation in zebrafish embryos. The accumulation of ROS causes mitochondrial damage, which is where ATP energy is produced. So ATPase activities and gene expression level were measured and significantly decreased after exposure to carboxin. From the confocal images, the number of blood cells in the heart were decreased significantly after carboxin exposure. Besides, Carboxin exposure can inhibit myocardial cell proliferation. These are all causes to the heart failure, eventually leading to embryos death.


Assuntos
Cardiotoxicidade , Peixe-Zebra , Animais , Carboxina/metabolismo , Cardiotoxicidade/metabolismo , Embrião não Mamífero/metabolismo , Estresse Oxidativo , Peixe-Zebra/metabolismo
15.
Antioxidants (Basel) ; 10(11)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34829560

RESUMO

Dietary lipids provide energy for growth and development and provide fatty acids necessary for normal structure and biological function. However, oxidized lipids cause oxidative stress and intestinal damage. An 8-week feeding trial with fresh fish oil (FFO, control group), oxidized fish oil (OFO), and taurine-supplemented diets (OFOT, OFO + 0.2% of taurine) was conducted to evaluate the protective effect of taurine on oxidized fish-oil-induced liver oxidative stress and intestine impairment in juvenile Ictaluruspunctatus. The results showed that (1) Growth performance was significantly lower in fish fed OFO than in those fed other diets, whereas the opposite occurred in the hepatosomatic index. (2) OFO-feeding significantly increased lipid deposition compared with the FFO group. The addition of taurine ameliorated the OFO-induced increase in lipid vacuolization in the liver, significantly upregulated lpl mRNA expression, and downregulated fas and srebp1 mRNA expression. (3) OFO-feeding significantly reduced oxidative damage of liver. Compared with the OFO group, the OFOT group remarkably upregulated antioxidant enzyme mRNA expression through the Nrf2-Keap1 signaling pathway based on the transcriptional expression. (4) OFO diets induced intestinal physical and immune barrier damage. Compared with the OFO group, OFOT diets remarkably downregulated il-1ß, il-6, tnf-α, and il-8 mRNA expression and upregulated tgf-ß mRNA expression through the NF-κB signaling pathway. Besides, the addition of taurine to OFO diets significantly upregulated zo-2 and zo-1 mRNA expression, and downregulated claudin-15 and claudin-12 mRNA expression. In conclusion, oxidized-fish-oil diets can cause negative physiological health effects in Ictaluruspunctatus, while adding taurine can increase growth and antioxidant ability, reduce lipid deposition, and improve intestinal health.

16.
J Virol ; 95(20): e0120521, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34379500

RESUMO

The fusion glycoprotein (F) is essential for respiratory syncytial virus (RSV) entry and has become an attractive target for anti-RSV drug development. Despite the promising prospect of RSV F inhibitors, issues of drug resistance remain challenging. In this study, we established a dual-luciferase protocol for RSV fusion inhibitor discovery. A small-molecule inhibitor, salvianolic acid R (LF-6), was identified to inhibit virus-cell and cell-cell fusion mediated by the RSV F protein. Sequence analysis of the resultant resistant viruses identified a K394R mutation in the viral F protein. The K394R mutant virus also conferred cross-resistance to multiple RSV fusion inhibitors, including several inhibitors undergoing clinical trials. Our study further showed that K394R mutation not only increased the triggering rate of F protein in prefusion conformation but also enhanced the fusion activity of F protein, both of which were positively correlated with resistance to fusion inhibitors. Moreover, the K394R mutation also showed cooperative effects with other escape mutations to increase the fusion activity of F protein. By substitution of K394 into different amino acids, we found that K394R or K394H substitution resulted in hyperfusiogenic F proteins, whereas F variants with other substitutions exhibited less fusion activity. Both K394R and K394H in F protein exhibited cross-resistance to RSV fusion inhibitors. Collectively, these findings reveal a positive correlation between the membrane fusion activity of F protein and the resistance of corresponding inhibitors. All of the results demonstrate that K394R in F protein confers cross-resistance to fusion inhibitors through destabilizing F protein and increasing its membrane fusion activity. IMPORTANCE Respiratory syncytial virus (RSV) causes serious respiratory tract disease in children and the elderly. Therapeutics against RSV infection are urgently needed. This study reports the discovery of a small-molecule inhibitor of RSV fusion glycoprotein by using a dual-luciferase protocol. The escape mutation (K394R) of this compound also confers cross-resistance to multiple RSV fusion inhibitors that have been reported previously, including two candidates currently in clinical development. The combination of K394R with other escape mutations can increase the resistance of F protein to these inhibitors through destabilizing F protein and enhancing the membrane fusion activity of F protein. By amino acid deletion or substitution, we found that a positively charged residue at the 394th site is crucial for the fusion ability of F protein, as well as for the cross-resistance against RSV fusion inhibitors. These results reveal the mechanism of cross-resistance conferred by the K394R mutation and the possible cross-resistance risk of RSV fusion inhibitors.


Assuntos
Vírus Sinciciais Respiratórios/genética , Proteínas Virais de Fusão/genética , Anticorpos Neutralizantes/genética , Anticorpos Antivirais/genética , China , Células HEK293 , Células Hep G2 , Humanos , Mutação/genética , Infecções por Vírus Respiratório Sincicial/genética , Vírus Sincicial Respiratório Humano/genética
17.
Ecotoxicol Environ Saf ; 224: 112696, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34455182

RESUMO

Benoxacor (BN) is a highly effective antidote of dichloroacetamide herbicides generally used to protect crops from herbicidal damage. As a commonly used agrochemical, this herbicide antidote is continuously discharged in watercourses thus causing toxicity to aquatic organisms, and ultimately leading to contamination of the food chain. To date, its potential toxicity to the cardiac development of aquatic organisms has not been evaluated. In the present study, we have selected the zebrafish as a model to study the impact of BN on embryonic developmental and cardiac toxicity. The zebrafish embryos were exposed in 0.5, 1.0 and 2.0 mg/L BN from 5.5 to 72 h post-fertilization (hpf). The results indicated that the exposure to BN led to increased mortality and diminished heart and hatching rates in the embryos. BN exposure also brought pericardial edema (PE) and linear stretching of heart. Besides, exposure to BN induced an excessive accumulation of reactive oxygen species (ROS) in the zebrafish embryos and abnormal activities of the antioxidant enzymes, including catalase (CAT) and malondialdehyde (MDA). Moreover, exposure to BN caused serious cardiac toxicity of the embryos, accompanied by abnormality of heart development- and apoptosis-related genes. Surprisingly, astaxanthin (ASTA), as a common antioxidant, was found to be able to partially rescue the cardiac toxicity caused by BN, which indicated that ROS are probably the major reason for the resulting cardiotoxicity in zebrafish embryos. Our results suggest the need for a comprehensive safety evaluation of the regular consumption of benoxacor, which provides scientific basis for the development of health standards and assessment of potential risk in aquatic organisms or even human.

18.
Environ Pollut ; 274: 116539, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33549839

RESUMO

Bifenazate is a novel acaricide for selective foliar spraying and is widely used to control mites in agricultural production. However, its toxicity to aquatic organisms is unknown. Here, a zebrafish model was used to study bifenazate toxicity to aquatic organisms. Exposure to bifenazate was found to cause severe cardiotoxicity in zebrafish embryos, along with disorders in the gene expression related to heart development. Bifenazate also caused oxidative stress. Cardiotoxicity caused by bifenazate was partially rescued by astaxanthin (an antioxidant), accompanied by cardiac genes and oxidative stress-related indicators becoming normalized. Our results showed that exposure to bifenazate can significantly change the ATPase activity and gene expression levels of the calcium signaling pathway. These led to heart failure, in which the blood accumulated outside the heart without entering it, eventually leading to death. The results indicated that bifenazate exposure caused cardiotoxicity in zebrafish embryos through the induction of oxidative stress and inhibition of the calcium signaling pathway.


Assuntos
Cardiotoxicidade , Peixe-Zebra , Animais , Carbamatos/metabolismo , Cardiotoxicidade/metabolismo , Embrião não Mamífero/metabolismo , Hidrazinas , Estresse Oxidativo
19.
IEEE Trans Image Process ; 30: 2313-2324, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33481707

RESUMO

3D spatial information is known to be beneficial to the semantic segmentation task. Most existing methods take 3D spatial data as an additional input, leading to a two-stream segmentation network that processes RGB and 3D spatial information separately. This solution greatly increases the inference time and severely limits its scope for real-time applications. To solve this problem, we propose Spatial information guided Convolution (S-Conv), which allows efficient RGB feature and 3D spatial information integration. S-Conv is competent to infer the sampling offset of the convolution kernel guided by the 3D spatial information, helping the convolutional layer adjust the receptive field and adapt to geometric transformations. S-Conv also incorporates geometric information into the feature learning process by generating spatially adaptive convolutional weights. The capability of perceiving geometry is largely enhanced without much affecting the amount of parameters and computational cost. Based on S-Conv, we further design a semantic segmentation network, called Spatial information Guided convolutional Network (SGNet), resulting in real-time inference and state-of-the-art performance on NYUDv2 and SUNRGBD datasets.

20.
Environ Pollut ; 265(Pt A): 114775, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32504889

RESUMO

Oxadiazon-Butachlor (OB) is a widely used herbicide for controlling most annual weeds in rice fields. However, its potential toxicity in aquatic organisms has not been evaluated so far. We used the zebrafish embryo model to assess the toxicity of OB, and found that it affected early cardiac development and caused extensive cardiac damage. Mechanistically, OB significantly increased oxidative stress in the embryos by inhibiting antioxidant enzymes that resulted in excessive production of reactive oxygen species (ROS), eventually leading to cardiomyocyte apoptosis. In addition, OB also inhibited the WNT signaling pathway and downregulated its target genes includinglef1, axin2 and ß-catenin. Reactivation of this pathway by the Wnt activator BML-284 and the antioxidant astaxanthin rescued the embryos form the cardiotoxic effects of OB, indicating that oxidative stress, and inhibition of WNT target genes are the mechanistic basis of OB-induced damage in zebrafish. Our study shows that OB exposure causes cardiotoxicity in zebrafish embryos and may be potentially toxic to other aquatic life and even humans.


Assuntos
Cardiotoxicidade , Peixe-Zebra , Acetanilidas , Animais , Embrião não Mamífero , Oxidiazóis , Estresse Oxidativo
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