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BACKGROUND: Central post-stroke pain (CPSP) is an intractable and disabling central neuropathic pain that severely affects patients' lives, well-being, and socialization abilities. However, CPSP has been poorly studied mechanistically and its treatment remains challenging. Here, we used a rat model of CPSP induced by thalamic hemorrhage to investigate its underlying mechanisms and the effect of stellate ganglion block (SGB) on CPSP and emotional comorbidities. METHODS: Thalamic hemorrhage was produced by injecting collagenase IV into the ventral-posterolateral nucleus (VPL) of the right thalamus. The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Behavioral tests were carried out to examine depressive and anxiety-like behaviors including the open field test (OFT), elevated plus maze test (EPMT), novelty-suppressed feeding test (NSFT), and forced swim test (FST). The peri-thalamic lesion tissues were collected for immunofluorescence, western blotting, and enzyme-linked immunosorbent assay (ELISA). Genetic knockdown of thalamic hypoxia-inducible factor-1α (HIF-1α) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) with microinjection of HIF-1α siRNA and NLRP3 siRNA into the VPL of thalamus were performed 3 days before collagenase injection into the same regions. Microinjection of lificiguat (YC-1) and MCC950 into the VPL of thalamus were administrated 30 min before the collagenase injection in order to inhibited HIF-1α and NLRP3 pharmacologically. Repetitive right SGB was performed daily for 5 days and laser speckle contrast imaging (LSCI) was conducted to examine cerebral blood flow. RESULTS: Thalamic hemorrhage caused persistent mechanical allodynia and anxiety- and depression-like behaviors. Accompanying the persistent mechanical allodynia, the expression of HIF-1α and NLRP3, as well as the activities of microglia and astrocytes in the peri-thalamic lesion sites, were significantly increased. Genetic knockdown of thalamic HIF-1α and NLRP3 significantly attenuated mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. Further studies revealed that intra-thalamic injection of YC-1, or MCC950 significantly suppressed the activation of microglia and astrocytes, the release of pro-inflammatory cytokines, the upregulation of malondialdehyde (MDA), and the downregulation of superoxide dismutase (SOD), as well as mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. In addition, repetitive ipsilateral SGB significantly restored the upregulated HIF-1α/NLRP3 signaling and the hyperactivated microglia and astrocytes following thalamic hemorrhage. The enhanced expression of pro-inflammatory cytokines and the oxidative stress in the peri-thalamic lesion sites were also reversed by SGB. Moreover, LSCI showed that repetitive SGB significantly increased cerebral blood flow following thalamic hemorrhage. Most strikingly, SGB not only prevented, but also reversed the development of mechanical allodynia and anxiety- and depression-like behaviors induced by thalamic hemorrhage. However, pharmacological activation of thalamic HIF-1α and NLRP3 with specific agonists significantly eliminated the therapeutic effects of SGB on mechanical allodynia and anxiety- and depression-like behaviors following thalamic hemorrhage. CONCLUSION: This study demonstrated for the first time that SGB could improve CPSP with comorbid anxiety and depression by increasing cerebral blood flow and inhibiting HIF-1α/NLRP3 inflammatory signaling.
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Acidente Vascular Cerebral Hemorrágico , Neuralgia , Acidente Vascular Cerebral , Ratos , Animais , Hiperalgesia/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Acidente Vascular Cerebral Hemorrágico/complicações , Acidente Vascular Cerebral Hemorrágico/patologia , Depressão/etiologia , Depressão/terapia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Gânglio Estrelado/metabolismo , Gânglio Estrelado/patologia , Ratos Sprague-Dawley , Acidente Vascular Cerebral/patologia , Tálamo/metabolismo , Hemorragia Cerebral/patologia , Neuralgia/metabolismo , Ansiedade , Colagenases/metabolismo , Citocinas/metabolismoRESUMO
KEY MESSAGE: Here, we revealed maize prolificacy highly correlated with domestication and identified a causal gene ZmEN1 located in one novel QTL qGEN261 that regulating maize prolificacy by using multiple-mapping methods. The development of maize prolificacy (EN) is crucial for enhancing yield and breeding specialty varieties. To achieve this goal, we employed a genome-wide association study (GWAS) to analyze the genetic architecture of EN in maize. Using 492 inbred lines with a wide range of EN variability, our results demonstrated significant differences in genetic, environmental, and interaction effects. The broad-sense heritability (H2) of EN was 0.60. Through GWAS, we identified 527 significant single nucleotide polymorphisms (SNPs), involved 290 quantitative trait loci (QTL) and 806 genes. Of these SNPs, 18 and 509 were classified as major effect loci and minor loci, respectively. In addition, we performed a bulk segregant analysis (BSA) in an F2 population constructed by a few-ears line Zheng58 and a multi-ears line 647. Our BSA results identified one significant QTL, qBEN1. Importantly, combining the GWAS and BSA, four co-located QTL, involving six genes, were identified. Three of them were expressed in vegetative meristem, shoot tip, internode and tip of ear primordium, with ZmEN1, encodes an unknown auxin-like protein, having the highest expression level in these tissues. It suggested that ZmEN1 plays a crucial role in promoting axillary bud and tillering to encourage the formation of prolificacy. Haplotype analysis of ZmEN1 revealed significant differences between different haplotypes, with inbred lines carrying hap6 having more EN. Overall, this is the first report about using GWAS and BSA to dissect the genetic architecture of EN in maize, which can be valuable for breeding specialty maize varieties and improving maize yield.
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Estudo de Associação Genômica Ampla , Zea mays , Mapeamento Cromossômico , Estudo de Associação Genômica Ampla/métodos , Zea mays/genética , Melhoramento Vegetal , Locos de Características Quantitativas , Polimorfismo de Nucleotídeo Único , FenótipoRESUMO
Starch is a major component of cereals, comprising over 70% of dry weight. It serves as a primary carbon source for humans and animals. In addition, starch is an indispensable industrial raw material. While maize (Zea mays) is a key crop and the primary source of starch, the genetic basis for starch content in maize kernels remains poorly understood. In this study, using an enlarged panel, we conducted a genome-wide association study (GWAS) based on best linear unbiased prediction (BLUP) value for starch content of 261 inbred lines across three environments. Compared with previous study, we identified 14 additional significant quantitative trait loci (QTL), encompassed a total of 42 genes, and indicated that increased marker density contributes to improved statistical power. By integrating gene expression profiling, Gene Ontology (GO) enrichment and haplotype analysis, several potential target genes that may play a role in regulating starch content in maize kernels have been identified. Notably, we found that ZmAPC4, associated with the significant SNP chr4.S_175584318, which encodes a WD40 repeat-like superfamily protein and is highly expressed in maize endosperm, might be a crucial regulator of maize kernel starch synthesis. Out of the 261 inbred lines analyzed, they were categorized into four haplotypes. Remarkably, it was observed that the inbred lines harboring hap4 demonstrated the highest starch content compared to the other haplotypes. Additionally, as a significant achievement, we have developed molecular markers that effectively differentiate maize inbred lines based on their starch content. Overall, our study provides valuable insights into the genetic basis of starch content and the molecular markers can be useful in breeding programs aimed at developing maize varieties with high starch content, thereby improving breeding efficiency. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01437-6.
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Liquid crystal elastomers (LCEs) have garnered attention for their remarkable reversible strains under various stimuli. Early studies on LCEs mainly focused on basic dimensional changes in macrostructures or quasi-three-dimensional (3D) microstructures. However, fabricating complex 3D microstructures and cross-scale LCE-based structures has remained challenging. In this study, we report a compatible method named melt electrowriting (MEW) to fabricate LCE-based microfiber actuators and various 3D actuators on the micrometer to centimeter scales. By controlling printing parameters, these actuators were fabricated with high resolutions (4.5 to 60 µm), actuation strains (10 to 55%), and a maximum work density of 160 J/kg. In addition, through the integration of a deep learning-based model, we demonstrated the application of LCE materials in temperature field sensing. Large-scale, real-time, LCE grid-based spatial temperature field sensors have been designed, exhibiting a low response time of less than 42 ms and a high precision of 94.79%.
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IMPORTANCE: The use of plant extracts is increasing as an alternative to synthetic compounds, especially antibiotics. However, there is no sufficient knowledge on the mechanisms and potential risks of antibiotic resistance induced by these phytochemicals. In the present study, we found that stable drug resistant mutants of E. coli emerged after repetitive exposure to sanguinarine and demonstrated that the AcrB efflux pump contributed to the emerging of induced and intrinsic resistance of E. coli to this phytochemical. Our results offered some insights into comprehending and preventing the onset of drug-resistant strains when utilizing products containing sanguinarine.
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Benzofenantridinas , Proteínas de Escherichia coli , Escherichia coli , Isoquinolinas , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Farmacorresistência Bacteriana Múltipla , Antibacterianos/farmacologia , Antibacterianos/química , Testes de Sensibilidade Microbiana , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genéticaRESUMO
Mercury (Hg) pollution not only poses a threat to the environment but also adversely affects the growth and development of plants, with potential repercussions for animals and humans through bioaccumulation in the food chain. Maize, a crucial source of food, industrial materials, and livestock feed, requires special attention in understanding the genetic factors influencing mercury accumulation. Developing maize varieties with low mercury accumulation is vital for both maize production and human health. In this study, a comprehensive genome-wide association study (GWAS) was conducted using an enlarged SNP panel comprising 1.25 million single nucleotide polymorphisms (SNPs) in 230 maize inbred lines across three environments. The analysis identified 111 significant SNPs within 78 quantitative trait loci (QTL), involving 169 candidate genes under the Q model. Compared to the previous study, the increased marker density and optimized statistical model led to the discovery of 74 additional QTL, demonstrating improved statistical power. Gene ontology (GO) enrichment analysis revealed that most genes participate in arsenate reduction and stress responses. Notably, GRMZM2G440968, which has been reported in previous studies, is associated with the significant SNP chr6.S_155668107 in axis tissue. It encodes a cysteine proteinase inhibitor, implying its potential role in mitigating mercury toxicity by inhibiting cysteine. Haplotype analyses provided further insights, indicating that lines carrying hap3 exhibited the lowest mercury content compared to other haplotypes. In summary, our study significantly enhances the statistical power of GWAS, identifying additional genes related to mercury accumulation and metabolism. These findings offer valuable insights into unraveling the genetic basis of mercury content in maize and contribute to the development of maize varieties with low mercury accumulation.
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Mercúrio , Locos de Características Quantitativas , Humanos , Mapeamento Cromossômico , Zea mays/genética , Zea mays/metabolismo , Polimorfismo de Nucleotídeo Único , Estudo de Associação Genômica Ampla , Mercúrio/toxicidade , Mercúrio/metabolismo , FenótipoRESUMO
Magnetic resonance imaging (MRI) contrast agents, such as Magnevist (Gd-DTPA), are routinely used for detecting tumors at an early stage. However, the rapid clearance by the kidney of Gd-DTPA leads to short blood circulation time, which limits further improvement of the contrast between tumorous and normal tissue. Inspired by the deformability of red blood cells, which improves their blood circulation, this work fabricates a novel MRI contrast agent by incorporating Gd-DTPA into deformable mesoporous organosilica nanoparticles (D-MON). In vivo distribution shows that the novel contrast agent is able to depress rapid clearance by the liver and spleen, and the mean residence time is 20 h longer than Gd-DTPA. Tumor MRI studies demonstrated that the D-MON-based contrast agent is highly enriched in the tumor tissue and achieves prolonged high-contrast imaging. D-MON significantly improves the performance of clinical contrast agent Gd-DTPA, exhibiting good potential in clinical applications.
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Meios de Contraste , Nanopartículas , Gadolínio DTPA , Gadolínio , Imageamento por Ressonância Magnética/métodosRESUMO
Purpose: For early diagnosis of osteoporosis (OP), plasma metabolomics of OP was studied by untargeted LC/GC-MS in a Chinese elderly population to find possible diagnostic biomarkers. Methods: A total of 379 Chinese community-dwelling older adults aged ≥65 years were recruited for this study. The BMD of the calcaneus was measured using quantitative ultrasound (QUS), and a T value ≤-2.5 was defined as OP. Twenty-nine men and 47 women with OP were screened, and 29 men and 36 women were matched according to age and BMI as normal controls using propensity matching. Plasma from these participants was first analyzed by untargeted LC/GC-MS, followed by FC and P values to screen for differential metabolites and heatmaps and box plots to differentiate metabolites between groups. Finally, metabolic pathway enrichment analysis of differential metabolites was performed based on KEGG, and pathways with P ≤ 0.05 were selected as enrichment pathways. Results: We screened metabolites with FC>1.2 or FC<1/1.2 and P<0.05 and found 33 differential metabolites in elderly men and 30 differential metabolites in elderly women that could be potential biomarkers for OP. 2-Aminomuconic acid semialdehyde (AUC=0.72, 95% CI 0.582-0.857, P=0.004) is highly likely to be a biomarker for screening OP in older men. Tetradecanedioic acid (AUC=0.70, 95% CI 0.575-0.818, P=0.004) is highly likely to be a biomarker for screening OP in older women. Conclusion: These findings can be applied to clinical work through further validation studies. This study also shows that metabolomic analysis has great potential for application in the early diagnosis and recurrence monitoring of OP in elderly individuals.