RESUMO
The concept of ferroptosis inhibition has gained growing recognition as a promising therapeutic strategy for addressing a wide range of diseases. Here, we present the discovery of four series of ortho-aminophenol derivatives as potential ferroptosis inhibitors beginning with the endogenous substance 3-hydroxyanthranilic acid (3-HA) by employing quantum chemistry techniques, in vitro and in vivo assays. Our findings reveal that these ortho-aminophenol derivatives exhibit unique intra-H bond interactions, compelling ortho-amines to achieve enhanced alignment with the aromatic π-system, thereby expanding their activity. Notably, compounds from all four series display remarkable activity against RSL3-induced ferroptosis, showcasing an activity 100 times more than that of 3-HA. Furthermore, these compounds also demonstrate robust in vivo efficacy in protecting mice from kidney ischemia-reperfusion injury and acetaminophen-induced hepatotoxicity. In summary, we provide four distinct series of active scaffolds that significantly expand the chemical space of ferroptosis inhibitors, serving as valuable insights for future structural modifications.
Assuntos
Aminofenóis , Ferroptose , Peroxidação de Lipídeos , Animais , Aminofenóis/farmacologia , Aminofenóis/química , Ferroptose/efeitos dos fármacos , Camundongos , Peroxidação de Lipídeos/efeitos dos fármacos , Humanos , Relação Estrutura-Atividade , Acetaminofen/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Masculino , Descoberta de Drogas , Camundongos Endogâmicos C57BLRESUMO
In the context of global warming, there is a substantial demand for accurate and cost-effective assessment and comprehensive understanding of forest above-ground biomass (AGB) dynamics. The timeliness and low cost of optical remote sensing data enable the mapping of large-scale forest AGB dynamics. However, mapping forest AGB with optical remote sensing data presents challenges primarily due to data uncertainty and the complex nature of the forest environment. Previous studies have demonstrated the potential of meteorological data in enhancing forest AGB mapping. To accurately capture the dynamics of forest AGB, we initially acquired Landsat datasets, digital elevation model (DEM), and meteorological datasets (temperature, humidity, and precipitation) from 2010 to 2020 in Changsha-Zhuzhou-Xiangtan urban agglomeration (CZT) located in Hunan Province, China. Spectral variables (SVs), including spectral bands and vegetation indices, were extracted from Landsat images, while meteorological variables (MVs) were derived from the monthly meteorological data using the Savitzky-Golay (S-G) filtering algorithm. Additionally, terrain variables (TVs) were also extracted from the DEM data. Three modelling models, multiple linear regression (MLR), K nearest neighbor (KNN) and random forest (RF), were developed for mapping the dynamics of forest AGB in CZT. The result revealed that MVs have the potential to improve forest AGB mapping. Integration of MVs into the models resulted in a significant reduction in root mean square error (RMSE) ranging from 32.85 % to 19.25 % compared to utilizing only SVs. However, minimal improvement was observed with the inclusion of TVs due to negligible topographic relief within the study area. An upward trend of forest AGB in CZT was observed during this period, which can be attributed to the effective implementation of government environmental protection policies. It is confirmed that the meteorological data has significant contribution to forest AGB mapping, thereby endorsing advancements in forest resource monitoring and management programs.
RESUMO
BACKGROUND: Academic procrastination is especially prevalent among nursing students in higher vocational colleges and it is considered an important factor of poor academic performance. However, existing research mainly focused on the overall level of academic procrastination, and little is known about the individual heterogeneity of academic procrastination among nursing students in higher vocational colleges. Thus, the aim of this study was to clarify the subgroups and factors of academic procrastination among nursing students in higher vocational college and explore academic procrastination networks of the latent subgroups. METHODS: A cross-sectional study with online survey. 1369 nursing students in one higher vocational college were recruited using convenience sampling. Participants completed electronic questionnaires that collected demographic and academic characteristics, perceived stress, and academic procrastination. Latent profile analysis, multinomial logistic regression analysis, and network analysis were performed to analyze the data. RESULTS: Three latent profiles of academic procrastination were identified: low (32.4 %), medium (53.3 %), and high (14.3 %). Higher vocational college nursing students who have reset an exam, low professional identity, and perceived more stress are more likely to have higher academic procrastination than other profiles. Network analysis showed that academic procrastination networks structure of the three latent profiles had distinct central components. For the low academic procrastination group, AP11 ("I make study plans, but I often fail to stick to them") and AP12 ("If there is no external pressure, I tend to postpone assignments or reports with deadlines") were the core components. For the medium academic procrastination group, AP17 ("I always wait until I can't postpone my academic tasks any longer before starting them") and AP16 ("I always tend to postpone on assignments or other academic tasks") were the central components. For the high academic procrastination group, AP16 and AP7 ("When studying in my dorm room, I often stop to do other things") were the essential components. CONCLUSIONS: There is heterogeneity in higher vocational college nursing students' academic procrastination that can be classified into three latent profiles. The examined factors of academic procrastination and identified the central components of academic procrastination networks of the three latent profiles help nurse educators tailor targeted interventions.
Assuntos
Procrastinação , Estudantes de Enfermagem , Humanos , Feminino , Masculino , Estudantes de Enfermagem/psicologia , Estudos Transversais , Adulto Jovem , Adulto , Universidades , Inquéritos e Questionários , Estresse Psicológico/psicologiaRESUMO
OBJECTIVE: This work aimed to investigate the role of rhythm gene PER1 in mediating granulosa cell ferroptosis and lipid metabolism of polycystic ovary syndrome (PCOS). METHODS: We injected dehydroepiandrosterone and Ferrostatin-1 (Fer-1) into mice to explore the mechanism of ferroptosis in PCOS. The effect of PER1 on ferroptosis-like changes in granulosa cells was explored by overexpression of PER1 plasmid transfection and Fer-1 treatment. RESULTS: We found that Fer-1 ameliorated the characteristic polycystic ovary morphology, suppressed ferroptosis in the PCOS mice. PER1 and ALOX15 were highly expressed in PCOS, whereas SREBF2 was lowly expressed. Overexpression of PER1 decreased granulosa cell viability and inhibited proliferation. Meanwhile, overexpression of PER1 increased lipid reactive oxygen species, 4-Hydroxynonenal (4-HNE), Malondialdehyde (MDA), total Fe, and Fe2+ levels in granulosa cells and decreased Glutathione (GSH) content. Fer-1, SREBF2 overexpression, or ALOX15 silencing treatment reversed the effects of PER1 overexpression on granulosa cells. PER1 binds to the SREBF2 promoter and represses SREBF2 transcription. SREBF2 binds to the ALOX15 promoter and represses ALOX15 transcription. Correlation analysis of clinical trials showed that PER1 was positively correlated with total cholesterol, low-density lipoprotein cholesterol, luteinizing hormone, testosterone, 4-HNE, MDA, total Fe, Fe2+, and ALOX15. In contrast, PER1 was negatively correlated with SREBF2, high-density lipoprotein cholesterol, follicle-stimulating hormone, progesterone, and GSH. CONCLUSION: This study demonstrates that the rhythm gene PER1 promotes ferroptosis and dysfunctional lipid metabolism in granulosa cells in PCOS by inhibiting SREBF2/ALOX15 signaling.
Assuntos
Ferroptose , Células da Granulosa , Metabolismo dos Lipídeos , Síndrome do Ovário Policístico , Animais , Feminino , Humanos , Camundongos , Araquidonato 12-Lipoxigenase , Araquidonato 15-Lipoxigenase/metabolismo , Araquidonato 15-Lipoxigenase/genética , Cicloexilaminas/farmacologia , Desidroepiandrosterona/metabolismo , Ferroptose/genética , Células da Granulosa/metabolismo , Células da Granulosa/patologia , Metabolismo dos Lipídeos/genética , Fenilenodiaminas/farmacologia , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
Background: Oxidative stress has been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). To develop novel antioxidant drugs, it is necessary to explore the key regulatory molecules involved in oxidative stress in PCOS. Plasma YKL-40 levels are elevated in patients with PCOS; however, its role remains unclear. Methods: The follicular fluids of 20 women with PCOS and 12 control subjects with normal ovarian function were collected, and YKL-40 in follicular fluids was measured by enzyme-linked immunosorbent assay. A letrozole-induced PCOS rat model was established and the expression level of YKL-40 in the ovaries was detected by immunohistochemistry. KGN cells were treated with H2O2 to generate an ovarian granulosa cell (OGC) model of oxidative stress. The siRNA was transfected into the cells for knockdown. The effect of YKL-40 knockdown on H2O2-treated KGN cells was evaluated by measuring proliferation, apoptosis, activities of T-SOD, GSH-Px, and CAT, levels of MDA, IL-1ß, IL-6, IL-8, and TNF-α, and the PI3K/AKT/NF-κB signaling pathway. Results: YKL-40 levels were elevated in the follicular fluids of women with PCOS compared with control subjects with normal ovarian function. The expression level of YKL-40 in the ovaries of rats with PCOS is obviously higher than that in the ovaries of the control group rats. H2O2 treatment enhanced YKL-40 mRNA expression and protein secretion. YKL-40 knockdown enhanced cell proliferation and antioxidant capacity while decreasing apoptosis and inflammatory factor levels in KGN cells following H2O2 treatment. The knockdown activated the PI3K/AKT signaling pathway and suppressed NF-κB nuclear translocation from the cytoplasm. Conclusion: YKL-40 levels were elevated in the follicular fluids of women with PCOS and the ovaries of rats with PCOS. YKL-40 expression can be induced by oxidative stress, and YKL-40 knockdown can decrease oxidative stress damage in OGCs.
Assuntos
Proteína 1 Semelhante à Quitinase-3 , Líquido Folicular , Células da Granulosa , Estresse Oxidativo , Síndrome do Ovário Policístico , Transdução de Sinais , Adulto , Animais , Feminino , Humanos , Ratos , Apoptose , Proliferação de Células , Proteína 1 Semelhante à Quitinase-3/metabolismo , Proteína 1 Semelhante à Quitinase-3/genética , Modelos Animais de Doenças , Líquido Folicular/metabolismo , Técnicas de Silenciamento de Genes , Células da Granulosa/metabolismo , Peróxido de Hidrogênio/metabolismo , NF-kappa B/metabolismo , Ovário/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/genética , Ratos Sprague-DawleyRESUMO
Phytophthora capsici, a destructive fungal pathogen, poses a severe threat to pepper (Capsicum annuum L.) crops worldwide, causing blights that can result in substantial yield losses. Traditional control methods often come with environmental concerns or entail substantial time investments. In this research, we investigate an alternative approach involving ferrous sulfate (FeSO4) application to combat P. capsici and promote pepper growth. We found that FeSO4 effectively inhibits the growth of P. capsici in a dose-dependent manner, disrupting mycelial development and diminishing pathogenicity. Importantly, FeSO4 treatment enhances the biomass and resistance of pepper plants, mitigating P. capsici-induced damage. Microbiome analysis demonstrates that FeSO4 significantly influences soil microbial communities, particularly fungi, within the pepper root. Metabolomics data reveal extensive alterations in the redox metabolic processes of P. capsici under FeSO4 treatment, leading to compromised cell membrane permeability and oxidative stress in the pathogen. Our study presents FeSO4 as a promising and cost-effective solution for controlling P. capsici in pepper cultivation while simultaneously promoting plant growth. These findings contribute to a deeper understanding of the intricate interactions between iron, pathogen control, and plant health, offering a potential tool for sustainable pepper production.
RESUMO
Objective This study aimed to establish a pre-metastatic niche mouse model utilizing luciferase-labeled Lewis (Luc-Lewis) lung cancer cells and to assess the efficacy of this model employing both qualitative and quantitative methods. Methods C57BL/6 mice were categorized into two groups: a normal control group and a model group, each containing 15 individual mice. The pre-metastatic niche model was established via tail vein injection of Luc-Lewis lung cancer cells. Body mass were measured daily for all groups. Tumor fluorescence signals within the mice were detected using a high-throughput enzyme marker instrument. Lung tissue specimens were harvested to evaluate metastatic progression. HE staining was used to assess histopathological changes. Real-time quantitative PCR and Western blot analysis were used to detect the mRNA and protein expression of lysyl oxidase (LOX), matrix metalloproteinase 9 (MMP9), versican (VCAN), and fibronectin (FN), which are the specific markers for the formation of the microenvironment of lung tissues before metastasis. Results Significant declines in body mass and observable lethargy were noted in the model group when compared to the control group. Distinct fluorescence signals were observed in the lung tissue of the model group, demonstrating a positive correlation with the duration of model establishment. By day 14, elevated mRNA and protein expression levels of LOX, MMP9, VCAN, and FN were significantly evident. In addition, histopathological evaluations revealed augmented interstitial thickness, alveolar atrophy and significant inflammatory cell infiltration within the lung tissues of the model group. By the 21st day, metastatic lesions manifested in the lung tissues of the model group, suggesting an approximate pre-metastatic niche maturation timeline of 14 days. Conclusion A pre-metastatic niche mouse model for Lewis lung cancer is successfully established.
Assuntos
Carcinoma Pulmonar de Lewis , Neoplasias Pulmonares , Camundongos , Animais , Neoplasias Pulmonares/patologia , Metaloproteinase 9 da Matriz , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , RNA Mensageiro , Microambiente TumoralRESUMO
Objective: Jining Grey Goat is a local Chinese goat breed that is well known for its high fertility and excellent meat quality but shows low meat production performance. Numerous studies have focused on revealing the genetic mechanism of its high fertility, but its highlighting meat quality and muscle growth mechanism still need to be studied. Methods: In this research, an integrative analysis of the genomics and transcriptomics of Jining Grey goats compared with Boer goats was performed to identify candidate genes and pathways related to the mechanisms of meat quality and muscle development. Results: Our results overlap among five genes (ABHD2, FN1, PGM2L1, PRKAG3, RAVER2) and detected a set of candidate genes associated with fatty acid metabolism (PRKAG3, HADHB, FASN, ACADM), amino acid metabolism (KMT2C, PLOD3, NSD2, SETDB1, STT3B, MAN1A2, BCKDHB, NAT8L, P4HA3) and muscle development (MSTN, PPARGC1A, ANKRD2). Several pathways have also been detected, such as the FoxO signaling pathway and Apelin signaling pathway that play roles in lipid metabolism, lysine degradation, N-glycan biosynthesis, valine, leucine and isoleucine degradation that involving with amino acid metabolism. Conclusion: The comparative genomic and transcriptomic analysis of Jining Grey Goat and Boer Goat revealed the mechanisms underlying the meat quality and meat productive performance of goats. These results provide valuable information for future breeding in goats.
RESUMO
Eleven alkaloids, including five previously undescribed indolizidine alkaloids (1, 2a, 2b, 3a, and 3b) and four new pyrrolidine alkaloids (5-8), were isolated from the roots of Anisodus tanguticus. Of these, two new pairs of enantiomeric alkaloids (2a/2b and 3a/3b) are the first examples of alkaloids containing both indolizidine and pyrrolidine structural fragments. The one-carbon bridge connections with two pyrrolidine rings (6) or with a pyrrolidine ring and a pyridine ring (8) are the first reported from nature. Extensive spectroscopic techniques were used to elucidate their structures, and NMR and ECD calculations were used to determine the absolute configurations. The viability of human umbilical vein endothelial cells (HUVECs) was inhibited by compounds 2a, 2b, 3a, 4b, and 5, and compound 2b exhibited a potential anti-angiogenic effect by inhibiting the proliferation, migration, and tube formation of HUVECs. A chorioallantoic membrane assay also demonstrated the anti-angiogenic activity of 2b. In addition, compounds 2a, 2b, 3a, and 4b exhibited moderate cytotoxicity against A2780 cells.
RESUMO
Forest stand structure (the characteristics and interrelationships of live trees) and site conditions (the physical and environmental characteristics of a specific location) have been linked to forest regeneration, nutrient cycling, wildlife habitat, and climate regulation. While the effects of stand structure (i.e., spatial and non-spatial) and site conditions on the single function of Cunninghamia lanceolata and Phoebe bournei (CLPB) mixed forest have been studied in previous studies, the relative importance of stand structure and site conditions in terms of productivity, species diversity, and carbon sequestration remains unresolved. In this study, a structural equation model (SEM) was adopted to analyze the relative importance of stand structure and site conditions for the forest productivity, species diversity, and carbon sequestration of CLPB mixed forest in Jindong Forestry in Hunan Province. Our research demonstrates that site conditions have a greater influence on forest functions than stand structure, and that non-spatial structures have a greater overall impact on forest functions than spatial structures. Specifically, the intensity of the influence of site conditions and non-spatial structure on functions is greatest for productivity, followed by carbon sequestration and species diversity. In contrast, the intensity of the influence of spatial structure on functions is greatest for carbon sequestration, followed by species diversity and productivity. These findings provide valuable insights for the management of CLPB mixed forest in Jindong Forestry and have significant reference value for the close-to-natural forest management (CTNFM) of pure Cunninghamia lanceolata forests.
RESUMO
Bitter gourd (Momordica charantia L.) is a significant vegetable. Although it has a special bitter taste, it is still popular with the public. The industrialization of bitter gourd could be hampered by a lack of genetic resources. The bitter gourd's mitochondrial and chloroplast genomes have not been extensively studied. In the present study, the mitochondrial genome of bitter gourd was sequenced and assembled, and its substructure was investigated. The mitochondrial genome of bitter gourd is 331,440 bp with 24 unique core genes, 16 variable genes, 3 rRNAs, and 23 tRNAs. We identified 134 SSRs and 15 tandem repeats in the entire mitochondrial genome of bitter gourd. Moreover, 402 pairs of repeats with a length greater than or equal to 30 were observed in total. The longest palindromic repeat was 523 bp, and the longest forward repeat was 342 bp. We found 20 homologous DNA fragments in bitter gourd, and the summary insert length was 19,427 bp, accounting for 5.86% of the mitochondrial genome. We predicted a total of 447 potential RNA editing sites in 39 unique PCGs and also discovered that the ccmFN gene has been edited the most often, at 38 times. This study provides a basis for a better understanding and analysis of differences in the evolution and inheritance patterns of cucurbit mitochondrial genomes.
RESUMO
AIM: This study aimed to evaluate the effectiveness of melatonin in treating insomnia in children with autism spectrum disorder (ASD). METHODS: Comprehensive searches were conducted in the PubMed, EMBASE, and Web of Science databases from their inception to April 20, 2022. Data were extracted and assessed for quality by two researchers. Statistical analysis was performed using the Stata 15.0 software. RESULTS: Four studies including 238 patients were included. The results showed that compared with the control group, melatonin could shorten the sleep-onset latency (standardized mean difference [SMD] = - 1.34, 95% CI: -2.19 to -0.48), reduce the number of awakenings (SMD = -2.35, 95% CI: -4.62 to -0.08), and prolong the total sleep time (SMD = 1.42, 95% CI: 0.5-2.33) in children with ASD. CONCLUSION: Melatonin has a certain effect on relieving sleep disturbances in children with ASD, which can shorten sleep latency, reduce the number of awakenings, and prolong total sleep time. Larger studies are required to verify this hypothesis.
Assuntos
Transtorno do Espectro Autista , Melatonina , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Humanos , Criança , Melatonina/uso terapêutico , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Duração do SonoRESUMO
As a common malignant tumor, the morbidity and mortality of lung cancer have been rising in recent years. The concept of "premetastatic niche" may lead to a revolutionary change in antitumor metastasis therapeutic strategies. Traditional Chinese medicine with multitargets and lower poisonous agents may be a potentially effective means to intervene in the "premetastatic niche (PMN)" to prevent and treat tumor metastasis. Astragalus polysaccharide (APS) is a substance with strong immune activity in Astragalus membranaceus that has excellent biological activities such as immunomodulation, anti-inflammatory, and antitumor. In this study, we constructed a tumor lung metastasis animal model to explore the intervention mechanism of APS on the premetastatic niche. We found that APS inhibited the formation of the lung premetastatic niche and inhibited the recruitment of myeloid-derived suppressor cells (MDSCs) in the lung. Mechanistically, we showed that the proteins and gene expression of S1PR1, STAT3, and p-STAT3 in the S1PR1/STAT3 signaling pathway were suppressed by APS. In line with the above findings, our results confirmed that APS may inhibit the accumulation of MDSCs in the premetastatic niche through the intervention of the S1PR1-STAT3 signaling pathway to achieve the antitumor effect.
RESUMO
OBJECTIVE: To invest the correlation of sperm high DNA stainability (HDS) with sperm DNA fragmentation index (DFI) and sperm abnormalities and its influence on in vitro fertilization (IVF) in male infertility patients, and assess the clinical value of HDS. METHODS: Using flow cytometry-assisted sperm chromatin structure assay (SCSA), we examined sperm HDS and sperm DFI in 322 male infertility patients undergoing IVF due to female fallopian tube factors only. Based on sperm HDS, we divided the patients into five groups and compared the semen routine parameters, percentage of morphologically abnormal sperm (MAS), sperm DFI, rates of fertilization, cleavage and high-quality embryos, and pregnancy outcomes among different HDS groups. RESULTS: Among the 322 male infertility patients, 119 (36.96%) were found with a sperm HDS of 0 ï¼ <5%, 117 (36.34%) of 5% ï¼ <10%, 50 (15.53%) of 10% ï¼ <15%, 23 (7.14%) of 15% ï¼ <20%, and 13 (4.03%) of ≥20%. Sperm concentration, motility and progressive motility were decreased with the increase of sperm HDS, but with no statistically significant difference (P > 0.05), so were the rates of fertilization, high-quality embryos and pregnancy (P > 0.05). Sperm DFI and sperm abnormality were correlated positively with sperm HDS (r = 0.236, r = 0.203). The rate of early abortion was remarkably increased in those with sperm HDS greater than 10%. CONCLUSION: Sperm HDS may be a risk indicator of sperm DFI and sperm abnormality, and can be used as a predictive indicator of early abortion in IVF.
Assuntos
Infertilidade Masculina , Sêmen , Gravidez , Masculino , Humanos , Feminino , Fertilização in vitro , Espermatozoides , DNARESUMO
Objective: To analyse the factors influencing clinical pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in older women, and to establish a risk prediction model. Methods: A total of 425 patients receiving IVF/ICSI from March 2018 to March 2020 were divided into pregnancy group (n=194) and non-pregnancy group (n=231). The factors affecting the outcomes of IVF/ICSI were explored by univariate and multivariate logistic regression analyses. A nomogram prediction model was constructed. Results: The two groups had significantly different age, body mass index, dysmenorrhea, parity, times of full-term births, history of cesarean section, basal follicle stimulating hormone, basal antral follicle count (AFC), number of high-quality embryos, and basal estradiol, luteinizing hormone and endometrial thickness on the day of human chorionic gonadotropin (HCG) administration (P<0.05). Age ≥40 years old, dysmenorrhea, history of cesarean section, basal AFC<9, number of high-quality embryos <4, and endometrial thickness on the day of HCG administration <11 mm led to IVF/ICSI failure. The established model exhibited high calibration and discrimination degrees in predicting the outcome of IVF/ICSI. Conclusion: The risk prediction model for the pregnancy outcome of IVF/ICSI in older women helps evaluate the fertility probability and risk, providing references for formulating reasonable assisted reproduction plans.
Assuntos
Resultado da Gravidez , Injeções de Esperma Intracitoplásmicas , Gravidez , Humanos , Masculino , Feminino , Idoso , Adulto , Resultado da Gravidez/epidemiologia , Cesárea , Dismenorreia , Sêmen , Fertilização in vitro , Gonadotropina Coriônica , Taxa de Gravidez , Estudos RetrospectivosRESUMO
Although a few studies have elucidated the creation of bitter gourd mutants, the suitable concentration and duration of ethyl methanesulfonate (EMS) mutagenesis have not been determined. In this study, mutant collection was conducted to create new germplasms and widen genetic diversity. By employing the seeds of the inbred line Y52 as the mutagenic material, EMS as the mutagen, and the suitable mutagenic conditions for bitter gourd seeds (EMS concentration 0.2%, mutagenic time 10 h), we mutated 10,000 seeds and acquired 3223 independent M1 lines. For the randomly selected 1000 M2 lines, 199 M2 lines with visible phenotypes were found, and 167 M2 lines were mutants of fruit shape, size, and tubercles. Furthermore, fourteen dwarf, eleven leaf color, five leaf shape, and eight meristem defect mutants were discovered in this mutant collection. In addition, three lines of 1253, 2284, and 3269 represented recessive mutants crossed with Y52. Furthermore, the yellow leaf lines of 2284 and 3269 were not mutated at the same gene locus. This study constructed a mutant collection through innovative new germplasms and provided valuable resources for bitter gourd breeding and functional gene research.
RESUMO
Normally, forest quality (FQ) and site quality (SQ) play an important role in evaluating actual and potential forest productivity. Traditionally, these assessment indices (FQ and SQ) are mainly based on forest parameters extracted from ground measurement (forest height, age, density, forest stem volume (FSV), and DBH), which is labor-intensive and difficult to access in certain remote forest areas. Recently, remote sensing images combined with a small number of samples were gradually applied to map forest parameters because of the various advantages of remote sensing technology, such as low cost, spatial coverage, and high efficiency. However, FQ and SQ related to forest parameters are rarely estimated using remote sensing images and machine learning models. In this study, the Sentinel images and ground samples of planted Chinese fir forest located in the ecological "green-core" area of Changzhutan urban cluster, were initially employed to explore the feasibility of mapping the FQ and SQ. And then, four types of alternative variables (backscattering coefficients (VV and VH), multi-spectral bands, vegetation indices, and texture characteristics) were extracted from Sentinel-1A and Sentinel-2A images, respectively. After selecting variables using a stepwise regression model, three machine learning models (SVR, RF, and KNN) were employed to estimate various forest parameters. Finally, the FQ of the study region was directly mapped by the weights sum of related factors extracted by the factor analysis method, and the SQ was also extracted using mapped forest height and age. The results illustrated that the accuracy of estimated forest parameters (DBH, H, and Age) was significantly higher than FSV, FCC, and Age and the largest and smallest rRMSEs were observed from FSV (0.38~0.40) and forest height (0.20~0.21), respectively. Using mapped forest parameters, it also resulted that the rRMSEs of estimated FQ and SQ were 0.19 and 0.15, respectively. Furthermore, after normalization and grading, the grades of forest quality were mainly concentrated in grades I, II, and III in the study region. Though the accuracy of mapping FQ and SQ is limited by the saturation phenomenon, it is significantly proved that using machine learning models and Sentinel images has great potential to indirectly map FQ and SQ.
RESUMO
OBJECTIVE: Luxi Black Head sheep (LBH) is the first crossbreed specialized for meat production and was developed by crossbreeding Black Head Dorper sheep (DP) and Small Tailed Han sheep (STH) in the farming areas of northern China. Research on the genomic variations and selection signatures of LBH caused by continuous artificial selection is of great significance for identifying the genetic mechanisms of important traits of sheep and for the continuous breeding of LBH. METHODS: We explored the genetic relationships of LBH, DP, and several Mongolian sheep breeds by constructing phylogenetic tree, principal component analysis and linkage disequilibrium analysis. In addition, we analysed 29 whole genomes of sheep. The genomewide selection signatures have been scanned with four methods heterozygosity (HP), fixation index (FST), cross-population extended haplotype homozygosity (XP-EHH) and the nucleotide diversity (θπ) ratio. RESULTS: The genetic relationships analysis showed that LBH appeared to be an independent cluster closer to DP. The candidate signatures of positive selection in sheep genome revealed candidate genes for developmental process (HoxA gene cluster, BCL2L11, TSHR), immunity (CXCL6, CXCL1, SKAP2, PTK6, MST1R), growth (PDGFD, FGF18, SRF, SOCS2), and reproduction (BCAS3, TRIM24, ASTL, FNDC3A). Moreover, two signalling pathways closely related to reproduction, the thyroid hormone signalling pathway and the oxytocin signalling pathway, were detected. CONCLUSION: The selective sweep analysis of LBH genome revealed candidate genes and signalling pathways associated with developmental process, immunity, growth, and reproduction. Our findings provide a valuable resource for sheep breeding and insight into the mechanisms of artificial selection.
RESUMO
BACKGROUND: Hepatocellular damage has been reported for the antimalarial piperaquine (PQ) in the clinic after cumulative doses. OBJECTIVES: The role of metabolism in PQ toxicity was evaluated, and the mechanism mediating PQ hepatotoxicity was investigated. METHODS: The toxicity of PQ and its major metabolite (PQ N-oxide; M1) in mice was evaluated in terms of serum biochemical parameters. The role of metabolism in PQ toxicity was investigated in mice pretreated with an inhibitor of CYP450 (ABT) and/or FMO enzyme (MMI). The dose-dependent pharmacokinetics of PQ and M1 were studied in mice. Histopathological examination was performed to reveal the mechanism mediating PQ hepatotoxicity. RESULTS: Serum biochemical levels (ALT and BUN) increased significantly (P < 0.05) in mice after three-day oral doses of PQ (> 200 mg/kg/day), indicating hepatotoxicity and nephrotoxicity of PQ at a high dose. Weaker toxicity was observed for M1. Pretreatment with ABT and/or MMI did not increase PQ toxicity. PQ and M1 showed linear pharmacokinetics in mice after a single oral dose, and multiple oral doses led to their cumulative exposures. Histopathological examination showed that a high dose of PQ (> 200 mg/kg/day for three days) could induce hepatocyte apoptosis. The mRNA levels of targets in NF-κB and p53 pathways could be up-regulated by 2-30-fold in mice by PQ or M1. CONCLUSION: PQ metabolism led to detoxification of PQ, but there was a low possibility of altered toxicity induced by metabolism inhibition. The hepatotoxicity of PQ and its N-oxidation metabolite was partly mediated by NF-κB inflammatory pathway and p53 apoptosis pathway.
Assuntos
Artemisininas , Doença Hepática Induzida por Substâncias e Drogas , Inativação Metabólica , Nefropatias , Piperazinas , Quinolinas , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacocinética , Antimaláricos/administração & dosagem , Antimaláricos/farmacocinética , Antimaláricos/toxicidade , Artemisininas/administração & dosagem , Artemisininas/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/toxicidade , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Redes e Vias Metabólicas , Camundongos , NF-kappa B/metabolismo , Piperazinas/administração & dosagem , Piperazinas/farmacocinética , Piperazinas/toxicidade , Quinolinas/administração & dosagem , Quinolinas/farmacocinética , Quinolinas/toxicidade , Proteína Supressora de Tumor p53/metabolismoRESUMO
The Solanaceae plants distributed in China belong to 105 species and 35 varietas of 24 genera. Some medicinal plants of Solanaceae are rich in tropane alkaloids(TAs), which have significant pharmacological activities. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, pharmacological activities, and biosynthetic pathways of TAs in Solanaceous plants were summarized. Besides, the phylogeny of medicinal plants belonging to Solanaceae was visualized by network diagram. Fourteen genera of Solanaceae plants in China contain TAs and have medical records. TAs mainly exist in Datura, Anisodus, Atropa, Physochlaina, and Hyoscyamus. The TAs-containing species were mainly concentrated in Southwest China, and the content of TAs was closely related to plant distribution area and altitude. The Solanaceae plants containing TAs mainly have antispasmodic, analgesic, antiasthmatic, and antitussive effects. Modern pharmacological studies have proved the central sedative, pupil dilating, glandular secretion-inhibiting, and anti-asthma activities of TAs. These pharmacological activities provide a reasonable explanation for the traditional therapeutic efficacy of tropane drugs. In this paper, the geographical distribution, chemical components, traditional therapeutic effect, and modern pharmacological activities of TAs-containing species in Solanaceae were analyzed for the first time. Based on these data, the genetic relationship of TAs-containing Solanaceae species was preliminarily discussed, which provided a scientific basis for the basic research on TAs-containing solanaceous species and was of great significance for the development of natural medicinal plant resources containing TAs.