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Cold stress declines the quality and yield of tea, yet the molecular basis underlying cold tolerance of tea plants (Camellia sinensis) remains largely unknown. Here, we identified a circadian rhythm component LUX ARRHYTHMO (LUX) that potentially regulates cold tolerance of tea plants through a genome-wide association study and transcriptomic analysis. The expression of CsLUX phased with sunrise and sunset and was strongly induced by cold stress. Genetic assays indicated that CsLUX is a positive regulator of freezing tolerance in tea plants. CsLUX was directly activated by CsCBF1 and repressed the expression level of CsLOX2, which regulates the cold tolerance of tea plants through dynamically modulating jasmonic acid content. Furthermore, we showed that the CsLUX-CsJAZ1 complex attenuated the physical interaction of CsJAZ1 with CsICE1, liberating CsICE1 with transcriptional activities to withstand cold stress. Notably, a single-nucleotide variation of C-to-A in the coding region of CsLUX was functionally validated as the potential elite haplotype for cold response, which provided valuable molecular markers for future cold resistance breeding in tea plants.
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BACKGROUND: Observational studies have shown a causal association between dyslipidemia and osteoporosis, but the genetic causation and complete mechanism of which are uncertain. The disadvantage of previous observational studies is that they are susceptible to confounding factors and bias, that makes it difficult to infer a causal link between those two diseases. Abnormal epigenetic modifications, represented by DNA methylation, are important causes of many diseases. However, there are no studies showing a bridging role for methylation modifications in blood lipid metabolism and osteoporosis. METHODS: SNPs for lipid profile (Blood VLDL cholesterol (VLDL-C), blood LDL cholesterol (LDL-C), blood HDL cholesterol (HDL-C), blood triglycerides (TG), diagnosed pure hypercholesterolaemia, blood apolipoprotein B (Apo B), blood apolipoprotein A1(Apo A1)), and bone mineral density (BMD) in different body parts (Heel BMD, lumbar BMD, whole-body BMD, femoral neck BMD) were obtained from large meta-analyses of genome-wide association studies as instrumental variables for two-sample Mendelian randomization. Assessment of the genetic effects of lipid profile-associated methylation sites and bone mineral density was carried out using the summary-data-based Mendelian randomization (SMR) method. RESULTS: Two-sample Mendelian randomization showed that there was a negative causal association between hypercholesterolaemia and heel BMD (p = 0.0103, OR = 0.4590), and total body BMD (p = 0.0002, OR = 0.2826). LDL-C had a negative causal association with heel BMD (p = 8.68E-05, OR = 0.9586). VLDL-C had a negative causal association with heel BMD (p = 0.035, OR = 0.9484), lumbar BMD (p = 0.0316, OR = 0.9356), and total body BMD (p = 0.0035, OR = 0.9484). HDL-C had a negative causal association with heel BMD (p = 1.25E-05, OR = 0.9548), lumbar BMD (p = 0.0129, OR = 0.9358), and total body BMD (p = 0.0399, OR = 0.9644). Apo B had a negative causal association with heel BMD (p = 0.0001, OR = 0.9647). Apo A1 had a negative causal association with heel BMD (p = 0.0132, OR = 0.9746) and lumbar BMD (p = 0.0058, OR = 0.9261). The p-values of all positive results corrected by the FDR method remained significant and sensitivity analysis showed that there was no horizontal pleiotropy in the results despite the heterogeneity in some results. SMR identified 3 methylation sites associated with lipid profiles in the presence of genetic effects on BMD: cg15707428(GREB1), cg16000331(SREBF2), cg14364472(NOTCH1). CONCLUSION: Our study provides insights into the potential causal links and co-pathogenesis between dyslipidemia and osteoporosis. The genetic effects of dyslipidaemia on osteoporosis may be related to certain aberrant methylation genetic modifications.
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Hipercolesterolemia , Osteoporose , Humanos , Apolipoproteína A-I/genética , Estudo de Associação Genômica Ampla , Metabolismo dos Lipídeos/genética , Análise da Randomização Mendeliana , Hipercolesterolemia/genética , Multiômica , LDL-Colesterol/genética , Osteoporose/genética , Densidade Óssea/genética , Metilação de DNA , Lipídeos , Apolipoproteínas B/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Flavan-3-ols are abundant in the tea plant (Camellia sinensis) and confer tea with flavor and health benefits. We recently found that alternative splicing of genes is likely involved in the regulation of flavan-3-ol biosynthesis; however, the underlying regulatory mechanisms remain unknown. Here, we integrated metabolomics and transcriptomics to construct metabolite-gene networks in tea leaves, collected over five different months and from five spatial positions, and found positive correlations between endogenous jasmonic acid (JA), flavan-3-ols, and numerous transcripts. Transcriptome mining further identified CsJAZ1, which is negatively associated with flavan-3-ols formation and has three CsJAZ1 transcripts, one full-length (CsJAZ1-1), and two splice variants (CsJAZ1-2 and -3) that lacked 3' coding sequences, with CsJAZ1-3 also lacking the coding region for the Jas domain. Confocal microscopy showed that CsJAZ1-1 was localized to the nucleus, while CsJAZ1-2 and CsJAZ1-3 were present in both the nucleus and the cytosol. In the absence of JA, CsJAZ1-1 was bound to CsMYC2, a positive regulator of flavan-3-ol biosynthesis; CsJAZ1-2 functioned as an alternative enhancer of CsJAZ1-1 and an antagonist of CsJAZ1-1 in binding to CsMYC2; and CsJAZ1-3 did not interact with CsMYC2. In the presence of JA, CsJAZ1-3 interacted with CsJAZ1-1 and CsJAZ1-2 to form heterodimers that stabilized the CsJAZ1-1-CsMYC2 and CsJAZ1-2-CsMYC2 complexes, thereby repressing the transcription of four genes that act late in the flavan-3-ol biosynthetic pathway. These data indicate that the alternative splicing variants of CsJAZ1 coordinately regulate flavan-3-ol biosynthesis in the tea plant and improve our understanding of JA-mediated flavan-3-ol biosynthesis.
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Camellia sinensis , Processamento Alternativo/genética , Camellia sinensis/genética , Camellia sinensis/metabolismo , Flavonoides/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Chá/metabolismoRESUMO
Theanine is an important secondary metabolite endowing tea with umami taste and health effects. It is essential to explore the metabolic pathway and regulatory mechanism of theanine to improve tea quality. Here, we demonstrated that the expression patterns of CsGGT2 (γ-glutamyl-transpeptidase), participated in theanine synthesis in vitro in our previous research, are significantly different in the aboveground and underground tissues of tea plants and regulated by light. Light up-regulated the expression of CsHY5, directly binding to the promoter of CsGGT2 and acting as an activator of CsGGT2, with a negative correlation with theanine accumulation. The enzyme activity assays and transient expression in Nicotiana benthamiana showed that CsGGT2, acting as bifunctional protein, synthesize and degrade theanine in vitro and in planta. The results of enzyme kinetics, Surface plasmon resonance (SPR) assays and targeted gene-silencing assays showed that CsGGT2 had a higher substrate affinity of theanine than that of ethylamine, and performed a higher theanine degradation catalytic efficiency. Therefore, light mediates the degradation of theanine in different tissues by regulating the expression of the theanine hydrolase CsGGT2 in tea plants, and these results provide new insights into the degradation of theanine mediated by light in tea plants.
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Camellia sinensis , Regulação da Expressão Gênica de Plantas , Luz , gama-Glutamiltransferase , Camellia sinensis/enzimologia , Camellia sinensis/genética , gama-Glutamiltransferase/genética , gama-Glutamiltransferase/metabolismo , Hidrolases/genética , Hidrolases/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Proteólise/efeitos da radiaçãoRESUMO
Theanine, a tea plant-specific non-proteinogenic amino acid, is the most abundant free amino acid in tea leaves. It is also one of the most important quality components of tea because it endows the "umami" taste, relaxation-promoting, and many other health benefits of tea infusion. Its content in tea leaves is directly correlated with the quality and price of green tea. Theanine biosynthesis primarily occurs in roots and is transported to new shoots in tea plants. Recently, great advances have been made in theanine metabolism and transport in tea plants. Along with the deciphering of the genomic sequences of tea plants, new genes in theanine metabolic pathway were discovered and functionally characterized. Theanine transporters were identified and were characterized on the affinity for: theanine, substrate specificity, spatiotemporal expression, and the role in theanine root-to-shoot transport. The mechanisms underlying the regulation of theanine accumulation by: cultivars, seasons, nutrients, and environmental factors are also being rapidly uncovered. Transcription factors were identified to be critical regulators of theanine biosynthesis. In this review, we summarize the progresses in theanine: biosynthesis, catabolism, and transport processes. We also discuss the future studies on theanine in tea plants, and application of the knowledge to crops to synthesize theanine to improve the health-promoting quality of non-tea crops.
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Camellia sinensis , Camellia sinensis/química , Proteínas de Plantas/metabolismo , Glutamatos , Aminoácidos/metabolismoRESUMO
NOx storage-reduction (NSR), a promising approach for removing NOx pollutants from diesel vehicles, remains elusive to cope with the increasingly lower exhaust temperatures (especially below 250 °C). Here, we develop a conceptual electrified NSR strategy, where electricity with a low input power (0.5-4 W) is applied to conductive Pt and K co-supported antimony-doped tin oxides (Pt-K/ATO), with C3H6 as a reductant. The ignition temperature for 10% NOx conversion is nearly 100 °C lower than that of the traditional thermal counterpart. Furthermore, reducing the power in the fuel-lean period relative to that in the fuel-rich period increases the maximum energy efficiency by 23%. Electrically driven release of lattice oxygen is revealed to play vital roles in multiple steps in NSR, including NO adsorption, desorption, and reduction, for improved NSR activity. This work provides an electrification strategy for developing high-activity NSR catalysis utilizing electricity onboard hybrid vehicles.
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Poluentes Atmosféricos , Óxidos de Nitrogênio , Óxidos de Nitrogênio/análise , Temperatura , Estanho , Antimônio , Óxidos , Emissões de Veículos/análise , Catálise , Poluentes Atmosféricos/análiseRESUMO
BACKGROUND: Low back pain (LBP) has drawn much widespread attention and is a major global health concern. In this field, intervertebral disc degeneration (IVDD) is frequently the focus of classic studies. However, the mechanistic foundation of IVDD is unclear and has led to conflicting outcomes. METHODS: Gene expression profiles (GSE34095, GSE147383) of IVDD patients alongside control groups were analyzed to identify differentially expressed genes (DEGs) in the GEO database. GSE23130 and GSE70362 were applied to validate the yielded key genes from DEGs by means of a best subset selection regression. Four machine-learning models were established to assess their predictive ability. Single-sample gene set enrichment analysis (ssGSEA) was used to profile the correlation between overall immune infiltration levels with Thompson grades and key genes. The upstream targeting miRNAs of key genes (GSE63492) were also analyzed. A single-cell transcriptome sequencing data (GSE160756) was used to define several cell clusters of nucleus pulposus (NP), annulus fibrosus (AF), and cartilaginous endplate (CEP) of human intervertebral discs and the distribution of key genes in different cell clusters was yielded. RESULTS: By developing appropriate p-values and logFC values, a total of 6 DEGs was obtained. 3 key genes (LRPPRC, GREM1, and SLC39A4) were validated by an externally validated predictive modeling method. The ssGSEA results indicated that key genes were correlated with the infiltration abundance of multiple immune cells, such as dendritic cells and macrophages. Accordingly, these 4 key miRNAs (miR-103a-3p, miR-484, miR-665, miR-107) were identified as upstream regulators targeting key genes using the miRNet database and external GEO datasets. Finally, the spatial distribution of key genes in AF, CEP, and NP was plotted. Pseudo-time series and GSEA analysis indicated that the expression level of GREM1 and the differentiation trajectory of NP chondrocytes are generally consistent. GREM1 may mainly exacerbate the degeneration of NP cells in IVDD. CONCLUSIONS: Our study gives a novel perspective for identifying reliable and effective gene therapy targets in IVDD.
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Anel Fibroso , Proteínas de Transporte de Cátions , Degeneração do Disco Intervertebral , MicroRNAs , Humanos , Degeneração do Disco Intervertebral/genética , MicroRNAs/genética , Biomarcadores , Biologia Computacional , Proteínas de Neoplasias , Peptídeos e Proteínas de Sinalização IntercelularRESUMO
This study discusses the genetic mutations that have a significant association with economically important traits that would benefit tea breeders. The purpose of this study was to analyze the leaf quality and SNPs in quality-related genes in the tea plant collection of 20 mutant genotypes growing without nitrogen fertilizers. Leaf N-content, catechins, L-theanine, and caffeine contents were analyzed in dry leaves via HPLC. Additionally, the photochemical yield, electron transport efficiency, and non-photochemical quenching were analyzed using PAM-fluorimetry. The next generation pooled amplicon-sequencing approach was used for SNPs-calling in 30 key genes related to N metabolism and leaf quality. The leaf N content varied significantly among genotypes (p ≤ 0.05) from 2.3 to 3.7% of dry mass. The caffeine content varied from 0.7 to 11.7 mg g-1, and the L-theanine content varied from 0.2 to 5.8 mg g-1 dry leaf mass. Significant positive correlations were detected between the nitrogen content and biochemical parameters such as theanine, caffeine, and most of the catechins. However, significant negative correlations were observed between the photosynthetic parameters (Y, ETR, Fv/Fm) and several biochemical compounds, including rutin, Quercetin-3-O-glucoside, Kaempferol-3-O-rutinoside, Kaempferol-3-O-glucoside, Theaflavin-3'-gallate, gallic acid. From our SNP-analysis, three SNPs in WRKY57 were detected in all genotypes with a low N content. Moreover, 29 SNPs with a high or moderate effect were specific for #316 (high N-content, high quality) or #507 (low N-content, low quality). The use of a linear regression model revealed 16 significant associations; theaflavin, L-theanine, and ECG were associated with several SNPs of the following genes: ANSa, DFRa, GDH2, 4CL, AlaAT1, MYB4, LHT1, F3'5'Hb, UFGTa. Among them, seven SNPs of moderate effect led to changes in the amino acid contents in the final proteins of the following genes: ANSa, GDH2, 4Cl, F3'5'Hb, UFGTa. These results will be useful for further evaluations of the important SNPs and will help to provide a better understanding of the mechanisms of nitrogen uptake efficiency in tree crops.
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Camellia sinensis , Catequina , Cafeína/metabolismo , Polimorfismo de Nucleotídeo Único , Camellia sinensis/metabolismo , Catequina/metabolismo , Folhas de Planta/metabolismo , Chá/química , Nitrogênio/metabolismoRESUMO
Theanine, a unique non-proteinogenic amino acid, is an important component of tea, as it confers the umami taste and relaxation effect of tea as a beverage. Theanine is primarily synthesized in tea roots and is subsequently transported to young shoots, which are harvested for tea production. Currently, the mechanism for theanine transport in the tea plant remains unknown. Here, by screening a yeast mutant library, followed by functional analyses, we identified the glutamine permease, GNP1 as a specific transporter for theanine in yeast. Although there is no GNP1 homolog in the tea plant, we assessed the theanine transport ability of nine tea plant amino acid permease (AAP) family members, with six exhibiting transport activity. We further determined that CsAAP1, CsAAP2, CsAAP4, CsAAP5, CsAAP6, and CsAAP8 exhibited moderate theanine affinities and transport was H+ -dependent. The tissue-specific expression of these six CsAAPs in leaves, vascular tissues, and the root suggested their broad roles in theanine loading and unloading from the vascular system, and in targeting to sink tissues. Furthermore, expression of these CsAAPs was shown to be seasonally regulated, coincident with theanine transport within the tea plant. Finally, CsAAP1 expression in the root was highly correlated with root-to-bud transport of theanine, in seven tea plant cultivars. Taken together, these findings support the hypothesis that members of the CsAAP family transport theanine and participate in its root-to-shoot delivery in the tea plant.
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Camellia sinensis/metabolismo , Sistemas de Transporte de Aminoácidos/metabolismo , Glutamatos/metabolismo , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo , Raízes de Plantas/metabolismoRESUMO
PURPOSE: To compare safety and effectiveness among methods to remove sticky silicone oil bubbles adhered to the retinal surface. METHODS: This retrospective nonrandomised case series included 14 eyes of 14 patients who had sticky silicone oil residue during silicone oil removal surgery. For small sticky silicone oil bubbles (< 2-disc diameter), aspiration was performed with a 23-gauge vitreous cutter. Residual tiny oil bubbles were then removed with a silicone-tipped flute needle or internal limiting membrane (ILM) peeling. For large sticky silicone oil bubbles (≥ 2-disc diameter) that could not be removed with a 23-gauge vitreous cutter, we devised a more efficient active removal method involving a modified 22-gauge venous indwelling cannula device. RESULTS: The mean preoperative best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution [logMAR]) significantly improved from 1.28 ± 0.63 logMAR to 0.77 ± 0.58 logMAR (p = 0.014). The postoperative BCVA and improvement in BCVA were significantly better in the ILM peeling group than in the non-ILM peeling group (p = 0.004 and p = 0.045, respectively). Postoperative complications included residual sticky silicone oil bubbles in seven eyes without ILM peeling (50.0%), retinal neuroepithelial layer damage in two eyes (14.3%), and temporary hypotony in five eyes (35.7%). CONCLUSION: Various methods can safely and efficiently remove sticky silicone oil bubbles adhered to the retinal surface. A 22-gauge venous indwelling cannula enabled simple and safe removal of large sticky silicone oil bubbles, while small residual sticky silicone oil bubbles could be completely removed by ILM peeling.
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Descolamento Retiniano , Perfurações Retinianas , Membrana Basal , Tamponamento Interno , Humanos , Descolamento Retiniano/cirurgia , Perfurações Retinianas/cirurgia , Estudos Retrospectivos , Óleos de Silicone , Tomografia de Coerência Óptica , Acuidade Visual , VitrectomiaRESUMO
BACKGROUND: Tea plant is one of the most important non-alcoholic beverage crops worldwide. While potassium (K+) is an essential macronutrient and greatly affects the growth and development of plants, the molecular mechanism underlying K+ uptake and transport in tea plant root, especially under limited-K+ conditions, is still poorly understood. In plants, HAK/KUP/KT family members play a crucial role in K+ acquisition and translocation, growth and development, and response to stresses. Nevertheless, the biological functions of these genes in tea plant are still in mystery, especially their roles in K+ uptake and stress responses. RESULTS: In this study, a total of 21 non-redundant HAK/KUP/KT genes (designated as CsHAKs) were identified in tea plant. Phylogenetic and structural analysis classified the CsHAKs into four clusters (I, II, III, IV), containing 4, 8, 4 and 5 genes, respectively. Three major categories of cis-acting elements were found in the promoter regions of CsHAKs. Tissue-specific expression analysis indicated extremely low expression levels in various tissues of cluster I CsHAKs with the exception of a high root expression of CsHAK4 and CsHAK5, a constitutive expression of clusters II and III CsHAKs, and a moderate cluster IV CsHAKs expression. Remarkably, the transcript levels of CsHAKs in roots were significantly induced or suppressed after exposure to K+ deficiency, salt and drought stresses, and phytohormones treatments. Also notably, CsHAK7 was highly expressed in all tissues and was further induced under various stress conditions. Therefore, functional characterization of CsHAK7 was performed, and the results demostrated that CsHAK7 locates on plasma membrane and plays a key role in K+ transport in yeast. Taken together, the results provide promising candidate CsHAKs for further functional studies and contribute to the molecular breeding for new tea plants varieties with highly efficient utilization of K+. CONCLUSION: This study demonstrated the first genome-wide analysis of CsHAK family genes of tea plant and provides a foundation for understanding the classification and functions of the CsHAKs in tea plants.
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Camellia sinensis , Proteínas de Transporte de Cátions , Deficiência de Potássio , Camellia sinensis/metabolismo , Proteínas de Transporte de Cátions/genética , Regulação da Expressão Gênica de Plantas , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Potássio/metabolismo , CháRESUMO
BACKGROUND: Until recently, synthetic fiber conjunctival granuloma (SFCG) is rarely reported and has been poorly understood. Our study was to explore the clinical features, histopathologic characteristics, surgical outcomes, and prognosis of SFCG after surgical excision. METHODS: Retrospective review of clinical findings, histopathological and immunohistochemical studies identified 18 cases of SFCG. Specimens were routinely processed and stained with H&E. Immunohistochemical stains for GMS, PAS, CD68 and CK-pan were also performed. RESULTS: Eighteen patients with an average age of 9.3 ± 6.6 years had a tender white to red mass on the conjunctiva. All the lesions were completely removed, and none of the patients relapsed. Histologically, all of the specimens revealed inflammatory granulation tissues with a large number of inflammatory cells infiltration and the presence of synthetic fibers. Immunohistochemical stains were positive for CD68, CK, GMS and PAS. CONCLUSIONS: Synthetic fiber conjunctival granuloma is an uncommon lesion with foreign body sensation caused by inoculation of synthetic exogenous materials. These lesions are mostly unilateral and occur in the inferior conjunctival fornix. SFCGs are characterized by a large number of inflammatory cells infiltration and the presence of synthetic fibers. Surgical excision followed by topical corticosteroids has been clinically proven to be effective.
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Doenças da Túnica Conjuntiva , Conjuntivite , Adolescente , Criança , Pré-Escolar , Doenças da Túnica Conjuntiva/cirurgia , Granuloma/cirurgia , Humanos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In response to phosphate (Pi) deficiency, it has been shown that micro-RNAs (miRNAs) and mRNAs are transported through the phloem for delivery to sink tissues. Growing evidence also indicates that long non-coding RNAs (lncRNAs) are critical regulators of Pi homeostasis in plants. However, whether lncRNAs are present in and move through the phloem, in response to Pi deficiency, remains to be established. Here, using cucumber as a model plant, we show that lncRNAs are enriched in the phloem translocation stream and respond, systemically, to an imposed Pi-stress. A well-known lncRNA, IPS1, the target mimic (TM) of miRNA399, accumulates to a high level in the phloem, but is not responsive to early Pi deficiency. An additional 24 miRNA TMs were also detected in the phloem translocation stream; among them miRNA171 TMs and miR166 TMs were induced in response to an imposed Pi stress. Grafting studies identified 22 lncRNAs which move systemically into developing leaves and root tips. A CU-rich PTB motif was further identified in these mobile lncRNAs. Our findings revealed that lncRNAs respond to Pi deficiency, non-cell-autonomously, and may act as systemic signaling agents to coordinate early Pi deficiency signaling, at the whole-plant level.
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Floema/metabolismo , Fosfatos/deficiência , Transporte de RNA , RNA Longo não Codificante/genética , RNA de Plantas/genética , Sequência de Bases , Cucumis sativus/genética , Regulação da Expressão Gênica de Plantas , Motivos de Nucleotídeos/genética , Especificidade de Órgãos/genética , Proteínas de Plantas/metabolismo , RNA Longo não Codificante/metabolismo , RNA de Plantas/metabolismo , Regulação para Cima/genéticaRESUMO
Among different energy storage devices, the lithium-sulfur (Li-S) battery is the subject of recent attention. However, the capacity decay caused by polysulfide shuttle leading to sluggish kinetics of polysulfide redox reactions is the main hindrance for its practical application in Li-S batteries. Herein, molybdenum carbide nanoparticles anchored on carbon nanotubes (Mo2C/CNT) are reported to serve as an efficient cathode material to enhance the electrochemical kinetics of polysulfide conversion in Li-S batteries. Mo2C/CNT shows strong adsorption and activation of polar polysulfides and therefore accelerates the redox kinetics of polysulfides, reduces the energy barrier, effectively mitigates the polarization and polysulfide shuttle, thus improving the electrochemical performance. The S-Mo2C/CNT composite with 70 wt% sulfur loading exhibits high specific discharge capacity (1206 mA h g-1 at 0.5 C), excellent high-rate performance, long cycle life (900 cycles), and outstanding Coulombic efficiency (â¼100%) at a high rate (2 C) corresponding to a capacity decay of only 0.05%. Remarkably, the S-Mo2C/CNT cathode with high areal sulfur loading of 2.5 mg cm-2 exhibits high-rate capacities and stable cycling performance over 100 cycles, offering the potential for use in high energy Li-S batteries.
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In the present study, we designed and synthesized a hydrogelator comprised of ibuprofen (IPF) and GFFY peptide linked through a cleavable ester bond. We found that the synthesized hydrogelator could spontaneously self-assemble into a hydrogel under a heating-cooling process. When the hydrogel was acted upon by an esterase, IPF was released in a sustained manner. Moreover, the hydrogel had significantly elevated anti-inflammatory efficacy, compared with IPF, in RAW264.7 macrophages. The hydrogel showed good cytocompatibility, as well as excellent ocular biocompatibility when instilled topically. In vivo results further demonstrated that the hydrogel had therapeutic efficacy comparable to that of a current treatment, sodium diclofenac (DIC) eyedrops, in suppressing ocular inflammation in lipopolysaccharide (LPS) induced uveitis. Our findings illustrated, for the first time, an effective approach for developing supramolecular assemblies as anti-inflammatory ophthalmic therapeutics for eye disorders.
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Anti-Inflamatórios/farmacologia , Ibuprofeno/farmacologia , Macrófagos/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Uveíte/prevenção & controle , Animais , Anti-Inflamatórios/química , Sistemas de Liberação de Medicamentos , Endotoxinas/toxicidade , Hidrogéis/química , Ibuprofeno/química , Macrófagos/metabolismo , Fragmentos de Peptídeos/química , Coelhos , Uveíte/induzido quimicamente , Uveíte/patologiaRESUMO
Coralline-like N-doped hierarchically porous carbon (CNHPC) was prepared through a hydrothermal carbonization process using a sea pollutant enteromorpha as the starting material. The addition of a small amount of glucose during carbonization improved the yield of carbon, and the inherent N contents, especially for pyrrolic N and pyridinic N atoms. After loading 40â wt. % sulfur, the CNHPC/S composite, as a cathode in a Li-S battery, exhibited an initial discharge capacity of 1617â mAh g-1 (96.5 % of theoretical capacity) at 0.1 C and a capacity loss of 0.05 % per charge-discharge cycle after 500â cycles at 0.5 C with a stable Coulombic efficiency of 100 % in carbonate based electrolyte. Such a great performance can be attributed to the coralline-like hierarchically porous infrastructure and inherently abundant N doping. Given the conversion of waste pollutants into valuable energy-storage materials and the easy process, this work features a promising approach to prepare C/S cathodes for Li-S batteries. The special structural and textural characteristics of CNHPC might be attractive to other practical applications such as supercapacitors and catalysis.
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The plant vascular system serves as a conduit for delivery of both nutrients and signaling molecules to various distantly located organs. The anucleate sieve tube system of the angiosperm phloem delivers sugars and amino acids to developing organs, and has recently been shown to contain a unique population of RNA and proteins. Grafting studies have established that a number of these macromolecules are capable of moving long distances between tissues, thus providing support for operation of a phloem-mediated inter-organ communication network. Currently, our knowledge of the roles played by such phloem-borne macromolecules is in its infancy. Here, we show that, in tomato, translocation of a phloem-mobile cyclophilin, SlCyp1, from a wild-type scion into a mutant rootstock results in restoration of vascular development and lateral root initiation. This process occurs through reactivation of auxin response pathways and reprogramming of the root transcriptome. Moreover, we show that long-distance trafficking of SlCyp1 is associated with regulation of the shoot-to-root ratio in response to changing light intensities, by modulating root growth. We conclude that long-distance trafficking of SlCyp1 acts as a rheostat to control the shoot-to-root ratio, by mediating root development to integrate photosynthesis and light intensity with requirements for access to water and mineral nutrients.
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Ciclofilinas/metabolismo , Ácidos Indolacéticos/metabolismo , Floema/metabolismo , Proteínas de Plantas/metabolismo , Solanum lycopersicum/metabolismo , Transporte Biológico , Ciclofilinas/genética , Regulação da Expressão Gênica de Plantas , Solanum lycopersicum/genética , Mutação , Floema/genética , Fotossíntese/fisiologia , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Plantas Geneticamente Modificadas , Transdução de SinaisRESUMO
In this paper, we describe a simple method for constructing a micellar supramolecular hydrogel, composed of a low-molecular-weight methoxy poly(ethylene glycol) (Mn = 2000 Da) block polymer and α-cyclodextrin (α-CD), for topical ocular drug delivery. Adding aqueous block polymer micelles into an α-CD aqueous solution resulted in the formation of a micellar supramolecular hydrogel through host-guest inclusion. The effects of the drug payload, block polymer, and α-CD concentrations as well as the block polymer structure on gelation time were investigated. The resultant micellar supramolecular hydrogels were thoroughly characterized by X-ray diffraction, rheological studies, and scanning electron microscopy. The hydrogels exhibited thixotropic properties, which are beneficial to ocular drug delivery. In vitro release studies indicated that the α-CD concentration strongly influenced the release rate of diclofenac (DIC) from supramolecular hydrogel. The hydrogels showed relatively low cytotoxicity toward L-929 and HCEC cells and did not significantly affect the migration of the latter after 24 h incubation. The hydrogel was nonirritant toward the rabbit eye, as indicated by the Draize test, fluorescein staining, and histological observation. Nile Red-labeled micellar supramolecular hydrogel showed that it could significantly extend the retention time on the corneal surface in rabbits, compared with a plain micellar formulation. In vivo pharmacokinetics indicated that the hydrogel could greatly improve ocular drug bioavailability, compared with that of micellar formulation. Our results suggest that the micellar supramolecular hydrogel is a promising system for ocular drug delivery.
Assuntos
Administração Oftálmica , Liberação Controlada de Fármacos , Hidrogéis/efeitos adversos , Micelas , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacocinética , Linhagem Celular , Diclofenaco/administração & dosagem , Diclofenaco/farmacocinética , Humanos , Hidrogéis/química , Masculino , Camundongos , Polietilenoglicóis/química , Coelhos , Distribuição TecidualRESUMO
Emissions of particulate matters (PMs) and volatile organic compounds (VOCs) from open burning of biomass often cause severe air pollution; a viable approach is to allow biomass to burn in a furnace to collectively control these emissions, but practical control technologies for this purpose are lacking. Here, we report a hollandite manganese oxide (HMO) catalyst that can efficiently control both typical PMs and VOCs emissions from biomass burning. The results reveal that typical alkali-rich PMs such as KCl particles are disintegrated and the K(+) ions are trapped in the HMO "single-walled" tunnels with a great trapping capacity. The K(+)-trapping HMO increases the electron density of the lattice oxygen and the redox ability, thus promoting the combustion of soot PMs and the oxidation of typical VOCs such as aldehydes and acetylates. This could pave a way to control emissions from biomass burning concomitant with its utilization for energy or heat generation.