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Two series of vanillin derivatives containing 1,3,4-oxadiazole and 1,3-thiazolidin-4-one scaffolds were prepared and evaluated for their antifungal activity. The results revealed that compounds 6j (29.73 µg/ml) and 7a (38.15 µg/ml) displayed excellent inhibitory activity against the spore of Fusarium solani. The inhibitory activity of compound 7d (10.53 µg/ml) against the spore of Alternaria solani was more than 42-fold that of vanillin. Compound 7a (37.54 µg/ml) showed better antifungal activity against the spore of B. cinerea than positive controls. The cytotoxicity assay confirmed that compounds 6k, 7a, and 7d showed good selectivity and less toxicity to normal mammalian cells.
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Alternaria , Benzaldeídos , Fusarium , Testes de Sensibilidade Microbiana , Oxidiazóis , Oxidiazóis/farmacologia , Oxidiazóis/química , Benzaldeídos/química , Benzaldeídos/farmacologia , Estrutura Molecular , Fusarium/efeitos dos fármacos , Alternaria/efeitos dos fármacos , Tiazolidinas/farmacologia , Tiazolidinas/química , Botrytis/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/química , Fungicidas Industriais/farmacologia , Fungicidas Industriais/química , Humanos , Relação Estrutura-AtividadeRESUMO
Exposure to (virtual) natural environments may encourage people to care about environmental protection and to engage in pro-environmental behaviour. Previous research on this effect produced inconsistent results, suggesting that it may depend on the type of nature and behaviour under study. In the present study (N = 266), we investigated nature exposure effects on effortful pro-environmental behaviour in an online experiment. After watching pictures of either intact or destroyed natural environments, participants could exert voluntary extra efforts to generate real donations to an environmental organisation. In comparison to the intact nature condition, participants exerted significantly more effort for environmental protection after being exposed to pictures of destroyed nature. No clear differences were observed between the nature exposure conditions and a no-picture control condition. These findings illustrate the complexity of nature exposure effects and suggest that different types of nature exposure may differentially affect people's pro-environmental behaviour.
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Verticillium wilt caused by Verticillium dahliae is a notorious soil-borne fungal disease and seriously threatens the yield of economic crops worldwide. During host infection, V. dahliae secretes many effectors that manipulate host immunity, among which small cysteine-rich proteins (SCPs) play an important role. However, the exact roles of many SCPs from V. dahliae are unknown and varied. In this study, we show that the small cysteine-rich protein VdSCP23 inhibits cell necrosis in Nicotiana benthamiana leaves, as well as the reactive oxygen species (ROS) burst, electrolyte leakage and the expression of defense-related genes. VdSCP23 is mainly localized in the plant cell plasma membrane and nucleus, but its inhibition of immune responses was independent of its nuclear localization. Site-directed mutagenesis and peptide truncation showed that the inhibition function of VdSCP23 was independent of cysteine residues but was dependent on the N-glycosylation sites and the integrity of VdSCP23 protein structure. Deletion of VdSCP23 did not affect the growth and development of mycelia or conidial production in V. dahliae. Unexpectedly, VdSCP23 deletion strains still maintained their virulence for N. benthamiana, Gossypium hirsutum and Arabidopsis thaliana seedlings. This study demonstrates an important role for VdSCP23 in the inhibition of plant immune responses; however, it is not required for normal growth or virulence in V. dahliae.
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Ascomicetos , Verticillium , Cisteína/metabolismo , Ascomicetos/metabolismo , Doenças das Plantas/microbiologia , Gossypium/microbiologia , Resistência à Doença/genética , Regulação da Expressão Gênica de PlantasRESUMO
Tirapazamine (TPZ) and its derivatives (TPZD) have shown their great potential for efficiently killing hypoxic cancer cells. However, unsatisfactory clinical outcomes resulting from the low bioavailability of the low-molecular TPZ and TPZD limited their further applications. Precise delivery and release of these prodrugs via functional nanocarriers can significantly improve the therapeutic effects due to the targeted drug delivery and enhanced permeability and retention (EPR) effect. Herein, zwitterionic block copolymer (BCP) micelles with aldehyde functional groups are prepared from the self-assembly of poly(2-methacryloyloxyethyl phosphorylcholine-b-poly(di(ethylene glycol) methyl ether methacrylate-co-4-formylphenyl methacrylate) [PMPC-b-P(DEGMA-co-FPMA)]. TPZD is then grafted onto PMPC-b-P(DEGMA-co-FPMA) to obtain a polymer-drug conjugate, PMPC-b-P(DEGMA-co-FPMA-g-TPZD) (BCP-TPZ), through the formation of a pH-responsive imine bond, exhibiting a pH-dependent drug release profile owing to the cleavage of the imine bond under acidic conditions. Outstandingly, BCP-TPZ shows around 13.7-fold higher cytotoxicity to hypoxic cancer cells in comparison to normoxic cancer cells evaluated through an in vitro cytotoxicity assay. The pH-responsiveness and hypoxia-specific cytotoxicity confer BCP-TPZ micelles a great potential to achieve precise delivery of TPZD and thus enhance the therapeutic effect toward tumor-hypoxia.
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Micelas , Pró-Fármacos , Doxorrubicina/química , Humanos , Concentração de Íons de Hidrogênio , Hipóxia , Iminas , Metacrilatos/química , Polímeros/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , TirapazaminaRESUMO
Injectable and self-healing hydrogels with exemplary biocompatibility and tunable mechanical properties are urgently needed due to their significant advantages for tissue engineering applications. Here, we report a new temperature-responsive aldehyde hydrogel with dual physical-cross-linked networks and injectable and self-healing properties prepared from an ABA-type triblock copolymer, poly{[FPMA(4-formylphenyl methacrylate)-co-DEGMA[di(ethylene glycol) methyl ether methacrylate]-b-MPC(2-methacryloyloxyethyl phosphorylcholine)-b-(FPMA-co-DEGMA)}. The thermoresponsive poly(DEGMA) segments drive the dehydration and hydrophobic interaction, enabling polymer chain winding as the first cross-linking network, when the temperature is raised above the critical gelation temperature. Meanwhile, the benzaldehyde groups offer physical interactions, including hydrogen bonding and hydrophobic and π-π stacking interactions as the second cross-linking network. When increasing the benzaldehyde content in the triblock copolymers from 0 to 8.2 mol %, the critical gelation temperature of the resulted hydrogels dropped from 35.5 to 19.9 °C and the mechanical modulus increased from 21 to 1411 Pa. Owing to the physical-cross-linked networks, the hydrogel demonstrated excellent injectability and self-healing properties. The cell viabilities tested from MTT assays toward both normal lung fibroblast cells (MRC-5) and cancerous cervical (HeLa) cells were found to be 100 and 101%, respectively, for varying polymer concentrations up to 1 mg/mL. The 3D cell encapsulation of the hydrogels was evaluated by a cytotoxicity Live/Dead assay, showing 92% cell viability. With these attractive physiochemical and biological properties, this temperature-responsive aldehyde hydrogel can be a promising candidate as a cell scaffold for tissue engineering.
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Benzaldeídos , Hidrogéis , Aldeídos , Hidrogéis/química , Hidrogéis/farmacologia , Metacrilatos/química , Polímeros/química , TemperaturaRESUMO
Structural optimization using plant secondary metabolites as templates is one of the important approach to discover pesticide molecules with novel skeletons. Xanthatin, a natural sesquiterpene lactone isolated from the Xanthium plants (Family: Compositae), exhibits important biological properties. In this work, a series of Michael-type amino derivatives were prepared from xanthatin and their structures were characterized by 1H NMR, 13C NMR and HR-MS, and their antifungal activities against several phytopathogenic fungi were evaluated according to the spore germination method and mycelium growth rate method in vitro. The results illustrated that compounds 2g (IC50 = 78.91 µg/mL) and 2o (IC50 = 64.51 µg/mL) exhibited more promising inhibition activity against spores of F. solani than precursor xanthatin, compounds 2g, 2l, and 2r exhibited remarkable antifungal effect on C. mandshurica with the average inhibition rates (AIRs) >90%, whereas the AIR of xanthatin was only 59.34%. Meanwhile, the preliminary structure-activity relationships suggested that the amino containing 2-methoxyethyl or 4-chlorophenylmethyl group appended in the C-13 position of xanthatin could yield potential compounds against fungal spores, and the exocyclic double bond of xanthatin is essential to maintain its mycelial growth inhibitory activity. Therefore, the aforementioned findings indicate that partial xanthatin amino-derivatives could be considered for further exploration as the potential lead structures toward development of the new environmentally friendly fungicidal candidates for sustainable crop protection.
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Antifúngicos/farmacologia , Furanos/farmacologia , Xanthium/química , Alternaria/efeitos dos fármacos , Antifúngicos/síntese química , Antifúngicos/química , Botrytis/efeitos dos fármacos , Colletotrichum/efeitos dos fármacos , Relação Dose-Resposta a Droga , Furanos/síntese química , Furanos/química , Fusarium/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Potato is an important crop in Shanxi province, located in north-central China. In 2019 to 2020, 319 potato leaf samples were collected from eight locations distributed in three major potato production areas in Shanxi. BioChip testing revealed the presence of several potato viruses, of which Potato virus Y (PVY) was the most common, reaching an incidence of 87.8% of all symptomatic samples. Immunocaptured multiplex reverse transcription (RT) PCR was used to identify strains for all 280 PVY-positive samples, unveiling 242 samples infected with a single strain of PVY (86.4%) and 38 (13.6%) with a mixed infection. Of samples with a single-strain infection, PVY-SYR-II accounted for 102 (42.1%), followed by PVYN-Wi (33, 13.6%), PVY-SYR-I (28, 11.6%), 261-4 (22, 9.1%), PVYNTNa (20, 8.3%), PVYNTNb (19, 7.9%), and PVY-SYR-III (18, 7.4%). Seven isolates representing different recombinants were selected for whole genome sequencing. Phylogenetic and recombination analyses confirmed the RT-PCR-based strain typing for all seven strains of PVY found in Shanxi. SXKL-12 is the first SYR-III strain from potato reported from China. However, unlike that in other known SYR-III isolates, the region positioned from 1,764 to 1,902 nt in SXKL-12 shared the highest sequence identity of 82.2% with an uncharacterized PVY isolate, JL-23, from China. Interestingly, PVYN-Wi isolate SXZY-40 also possessed a more divergent sequence for the region positioned from 6,156 to 6,276 nt than other N-Wi isolates known to date, sharing the highest identity of 86.6% with an uncharacterized Chinese PVY isolate, JL-11. Pathogenicity analysis of dominant strains PVY-SYR-II and PVYN-Wi in six local popular potato cultivars revealed that 'Kexin 13', 'Helan 15', and 'Jizhangshu 12' were susceptible to these two strains, with mild mottling or mosaic symptom expression, and three cultivars, 'Jinshu 16', 'Qingshu 9', and 'Xisen 6', were fully resistant.
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Potyvirus , Solanum tuberosum , Filogenia , Doenças das Plantas , PrevalênciaRESUMO
Botryosphaeria dothidea is one of the most common fungal pathogens on a large number of hosts worldwide. Botryosphaeria dothidea and B. kuwatsukai are also the main causal agents of apple ring rot. In this study, we sequenced, assembled and annotated the circular mitogenomes of 12 diverse B. dothidea isolates (105.7-114.8 kb) infecting various plants including apple, and five diverse B. kuwatsukai isolates (118.0-124.6 kb) from apple. B. dothidea mitogenomes harboured a set of 29-31 introns and 48-52 ORFs. In contrast, B. kuwatsukai mitogenomes harboured more introns (32-34) and ORFs (51-54). The variation in mitogenome sizes was associated mainly with different numbers of introns and insertions of mobile genetic elements. Interestingly, B. dothidea and B. kuwatsukai displayed distinct intron distribution patterns, with three intron loci showing presence/absence dynamics in each species. Large numbers of introns (57% in B. dothidea and 49% in B. kuwatsukai) were most likely obtained through horizontal transfer from non-Dothideomycetes. The mitochondrial gene phylogeny supported the differentiation of the two species. Overall, this study sheds light into the mitochondrial evolution of the plant pathogens B. dothidea and B. kuwatsukai, and intron distribution patterns could be useful markers for studies on population diversity.
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Ascomicetos , Evolução Molecular , Genoma Mitocondrial , Malus , Ascomicetos/genética , Genoma Fúngico , Genoma Mitocondrial/genética , Íntrons/genéticaRESUMO
The genetic regulation of Colletotrichum (Glomerella) sexual reproduction does not strictly adhere to the Ascomycota paradigm and remains poorly understood. Morphologically different but sexually compatible strain types, termed plus and minus, have been recognized, but the biological and molecular distinctions between these strain types remain elusive. In this study, we characterized the sexual behaviors of a pair of plus and minus strains of C. fructicola with the aid of live-cell nucleus-localized fluorescent protein labeling, gene expression, and gene mutation analyses. We confirmed a genetically stable plus-to-minus switching phenomenon and demonstrated the presence of both cross-fertilized and self-fertilized perithecia within the mating line (perithecia cluster at the line of colony contact) between plus and minus strains. We demonstrated that pheromone signaling genes (a-factor-like and α-factor-like pheromones and their corresponding GPCR receptors) were differently expressed between vegetative hyphae of the two strains. Moreover, deletion of pmk1 (a FUS/KSS1 mitogen-activate protein kinase) in the minus strain severely limited mating line formation, whereas deletion of a GPCR (FGSG_05239 homolog) and two histone modification factors (hos2, snt2) in the minus strain did not affect mating line development but altered the ratio between cross-fertilization and self-fertilization within the mating line. We propose a model in which mating line formation in C. fructicola involves enhanced protoperithecium differentiation and enhanced perithecium maturation of the minus strain mediated by both cross-fertilization and diffusive effectors. This study provides insights into mechanisms underlying the mysterious phenomenon of plus-minus-mediated sexual enhancement being unique to Colletotrichum fungi. IMPORTANCE Plus-minus regulation of Colletotrichum sexual differentiation was reported in the early 1900s. Both plus and minus strains produce fertile perithecia in a homothallic but inefficient manner. However, when the two strain types encounter each other, efficient differentiation of fertile perithecia is triggered. The plus strain, by itself, can also generate minus ascospore progeny at high frequency. This nontypical mating system facilitates sexual reproduction and is Colletotrichum specific; the underlying molecular mechanisms, however, remain elusive. The current study revisits this longstanding mystery using C. fructicola as an experimental system. The presence of both cross-fertilized and self-fertilized perithecia within the mating line was directly evidenced by live-cell imaging with fluorescent markers. Based on further gene expression and gene mutation analysis, a model explaining mating line development (plus-minus-mediated sexual enhancement) is proposed. Data reported here have the potential to allow us to better understand Colletotrichum mating and filamentous ascomycete sexual regulation.
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Colletotrichum/genética , Colletotrichum/fisiologia , Reprodução/genética , Proteínas Fúngicas/genética , FenótipoRESUMO
Dual-cross-linked network (DCN) hydrogels with multiresponsive and self-healing properties are attracting intensive interests due to their enhanced mechanical strength for a wide range of applications. Herein, we developed a DCN hydrogel that combines a dynamic imine and a benzoxaboronic ester with a neutral pKa value (â¼7.2) as dual linkages and contains biocompatible zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) [poly(MPC)] as the backbone. Oscillatory rheology result indicated shear strengthening mechanical properties compared to the single-cross-linked network (SCN) hydrogels, which use either imine bond or benzoxaboronic ester as the linkage alone. Due to the coexistence of stimuli-responsive imine and benzoxaboronic ester, the DCN hydrogels show sensitive multiple responsiveness to pH, sugar, and hydrogen peroxide. The dynamic nature of the dual linkages endows the DCN hydrogels with excellent self-healing ability after fracture. More importantly, the excellent biocompatibility and performance in three-dimensional (3D) cell encapsulation were established by a cytotoxicity Live/Dead assay, indicating DCN hydrogel's great potential as a cell culture scaffold. The biocompatible poly(MPC)-based backbone and the rapid formation of the cross-linking network make the DCN hydrogels promising candidates for future biomedical applications.
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Ésteres , Hidrogéis , ReologiaRESUMO
We report here the synthesis of a series of ethylene glycol-based triblock copolymers containing a hydrophilic middle segment of poly(ethylene glycol) methyl ether methacrylate (PEGMA) and two temperature-responsive segments of diethylene glycol methyl ether methacrylate (DEGMA) at both ends via the reversible addition-fragmentation chain-transfer (RAFT) polymerization. While the corresponding temperature-responsive homopolymer (PDEGMA) and the diblock copolymer (PDEGMA-b-PPEGMA) could not form a gel, the triblock copolymers (PDEGMA-b-PPEGMA-b-PDEGMA) could form a physical gel at certain concentrations and at temperatures above the lower critical solution temperature (LCST). This sol-gel transition is fully reversible and can be repeated several times. Depending on the chain length of the middle block and two end blocks, a physical gel could be formed at a minimum polymer concentration of 5 wt %. In addition, a mechanically strong gel could be easily formed within 5 s at the maximum concentration of 20 wt % and at a temperature of 37 °C. Considering the good cell compatibility and soft rubbery nature of the triblock copolymers, they can potentially be used as injectable scaffold for cell culture and tissue engineering applications.
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Materiais Biocompatíveis , Polietilenoglicóis , Técnicas de Cultura de Células , Hidrogéis , Polímeros , TemperaturaRESUMO
Poly(amidoamine)(PAMAM)/epoxy/acetic acid-doped polyaniline (PAni) coatings were successfully prepared and coated on magnesium alloy substrates. X-ray diffraction pattern, Fourier transform infrared spectroscopy, scanning electron microscopy technique were used to characterize the composition and morphology of acetic acid-doped PAni and composite coatings. The effect of the usage amount of doped PAni on the corrosion protection performance was evaluated with electrochemical measurement in 3.5 wt.% NaCl solutions. Tafel and electrochemical impedance spectroscopy analysis revealed that the addition of 1.0 wt.% doped PAni provided the superior corrosion protection properties. The corrosion protection mechanism was investigated by using electron probe microanalysis test and theoretical physical model. The doped PAni could obviously shrink the pits and made epoxy resin matrix denser by cross-linking and hydrogen bonding. The composite coatings exhibited better corrosion protection properties compared to pure epoxy coating. The in situ generated corrosion products provided anodic corrosion inhibition due to the easier penetration of acetate ions, and better physical barrier mechanism was promoted by the addition of doped PAni.
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The use of biomacromolecular therapeutics has revolutionized disease treatment, but frequent injections are required owing to their short half-life in vivo. Thus there is a need for a drug delivery system that acts as a reservoir and releases the drug remotely "on demand". Here we demonstrate a simple light-triggered local drug delivery system through photo-thermal interactions of polymer-coated gold nanoparticles (AuNPs) inside an agarose hydrogel as therapeutic depot. Localized temperature increase induced by the visible light exposure caused reversible softening of the hydrogel matrix to release the pre-loaded therapeutics. The release profile can be adjusted by AuNPs and agarose concentrations, light intensity and exposure time. Importantly, the biological activity of the released bevacizumab was highly retained. In this study we demonstrate the potential application of this facile AuNPs/hydrogel system for ocular therapeutics delivery through its versatility to release multiple biologics, compatibility to ocular cells and spatiotemporal control using visible light.
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Sistemas de Liberação de Medicamentos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Luz , Fotoquimioterapia , Proteínas/química , Ouro/química , Humanos , Nanopartículas Metálicas/química , Tamanho da Partícula , Polímeros/química , Propriedades de SuperfícieRESUMO
Self-assembled lipid lyotropic liquid crystalline nanoparticles such as hexosomes and cubosomes contain internal anisotropic and isotropic nanostructures, respectively. Despite the remarkable potential of such nanoparticles in various biomedical applications, the stabilisers used in formulating the nanoparticles are often limited to commercially available polymers such as the Pluronic block copolymers. This study explored the potential of using Reversible Addition-Fragmentation chain Transfer (RAFT) technology to design amphiphilic brush-type polymers for the purpose of stabilising phytantriol and monoolein-based lipid dispersions. The synthesised brush-type polymers consisted of a hydrophobic C12 short chain and a hydrophilic poly(ethylene glycol)methyl ether acrylate (PEGA) long chain with multiple 9-unit poly(ethylene oxide) (PEO) brushes with various molecular weights. It was observed that increasing the PEO brush density and thus the length of the hydrophilic component improved the stabilisation effectiveness for phytantriol and monoolein-based cubosomes. Synchrotron small-angle X-ray scattering (SAXS) experiments confirmed that the RAFT polymer-stabilised cubosomes had an internal double-diamond cubic phase with tunable water channel sizes. These properties were dependent on the molecular weight of the polymers, which were considered in some cases to be anisotropically distributed within the cubosomes. The in vitro toxicity of the cubosomes was assessed by cell viability of two human adenocarcinoma cell lines and haemolytic activities to mouse erythrocytes. The results showed that phytantriol cubosomes stabilised by the RAFT polymers were less toxic compared to their Pluronic F127-stabilised analogues. This study provides valuable insight into designing non-linear amphiphilic polymers for the effective stabilisation and cellular toxicity improvement of self-assembled lipid lyotropic liquid crystalline nanoparticles.
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Lipídeos/química , Cristais Líquidos , Nanopartículas/toxicidade , Polímeros , Animais , Linhagem Celular Tumoral , Eritrócitos/efeitos dos fármacos , Humanos , Espalhamento a Baixo Ângulo , Difração de Raios XRESUMO
Although heat stress reduces seed size in rice (Oryza sativa), little is known about the molecular mechanisms underlying the observed reduction in seed size and yield. To elucidate the mechanistic basis of heat sensitivity and reduced seed size, we imposed a moderate (34°C) and a high (42°C) heat stress treatment on developing rice seeds during the postfertilization stage. Both stress treatments reduced the final seed size. At a cellular level, the moderate heat stress resulted in precocious endosperm cellularization, whereas severe heat-stressed seeds failed to cellularize. Initiation of endosperm cellularization is a critical developmental transition required for normal seed development, and it is controlled by Polycomb Repressive Complex2 (PRC2) in Arabidopsis (Arabidopsis thaliana). We observed that a member of PRC2 called Fertilization-Independent Endosperm1 (OsFIE1) was sensitive to temperature changes, and its expression was negatively correlated with the duration of the syncytial stage during heat stress. Seeds from plants overexpressing OsFIE1 had reduced seed size and exhibited precocious cellularization. The DNA methylation status and a repressive histone modification of OsFIE1 were observed to be temperature sensitive. Our data suggested that the thermal sensitivity of seed enlargement could partly be caused by altered epigenetic regulation of endosperm development during the transition from the syncytial to the cellularized state.
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Endosperma/anatomia & histologia , Endosperma/embriologia , Fertilização , Temperatura Alta , Oryza/anatomia & histologia , Oryza/embriologia , Proteínas de Plantas/metabolismo , Metilação de DNA/genética , Endosperma/genética , Fertilização/genética , Regulação da Expressão Gênica de Plantas , Inativação Gênica , Genes de Plantas , Resposta ao Choque Térmico/genética , Histonas/metabolismo , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Tamanho do Órgão , Especificidade de Órgãos/genética , Oryza/genética , Proteínas de Plantas/genéticaRESUMO
The use of medical imaging contrast agents may lead to improved patient prognosis by potentially enabling an earlier detection of diseases and therefore an earlier initiation of treatments. In this study, we fabricated superparamagnetic iron oxide (SPIO) nanoparticles within the inner cavity of multiwalled carbon nanotubes (MWCNTs) for the first time; thereby ensuring high mechanical stability of the nanoparticles. A simple, but effective, self-assembled coating with RAFT diblock copolymers ensured the SPIO-MWCNTs have a high dispersion stability under physiological conditions. In vivo acute tolerance testing in mice showed a high tolerance dose up to 100 mg kg(-1). Most importantly, after administration of the material a 55% increase in tumor to liver contrast ratio was observed with in vivo MRI measurements compared to the preinjection image enhancing the detection of the tumor.
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Meios de Contraste , Neoplasias Hepáticas Experimentais/diagnóstico , Nanopartículas de Magnetita , Nanotubos de Carbono , Animais , Linhagem Celular Tumoral , Coloides , Feminino , Humanos , Imageamento por Ressonância Magnética , Camundongos Endogâmicos BALB C , NanocompostosRESUMO
The use of alginate based microcapsules to deliver drugs and cells with a minimal host interaction is increasingly being proposed. A proficient method to track the position of the microcapsules during such therapies, particularly if they are amenable to commonly used instrumentation, would greatly help the development of such treatments. Here we propose to label the microcapsules with gold nanoparticles to provide a bright contrast on small animal x-ray micro-CT systems enabling single microcapsule detection. The microcapsules preparation is based on a simple protocol using inexpensive compounds. This, combined with the widespread availability of micro-CT apparatus, renders our method more accessible compared with other methods. Our labeled microcapsules showed good mechanical stability and low cytotoxicity in-vitro. Our post-mortem rodent model data strongly suggest that the high signal intensity generated by the labeled microcapsules permits the use of a reduced radiation dose yielding a method fully compatible with longitudinal in-vivo studies. FROM THE CLINICAL EDITOR: The authors of this study report the development of a micro-CT based tracking method of alginate-based microcapsules by incorporating gold nanoparticles in the microcapsules. They demonstrate the feasibility of this system in rodent models, where due to the high signal intensity, even reduced radiation dose is sufficient to track these particles, providing a simple and effective method to track these commonly used microcapsules and allowing longitudinal studies.
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Alginatos/química , Cápsulas/química , Ouro/química , Nanopartículas Metálicas/química , Animais , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Tomografia Computadorizada por Raios XRESUMO
The controlled conformational changes of planar graphene nanosheets are of great importance to the realization of their practical applications. Despite substantial effort in the area, the controlled folding of two-dimensional (2D) graphene sheets into one-dimensional (1D) structures still remains a significant challenge. Here, for the first time, we report an ice crystal guided folding strategy to fabricate 1D folded graphene nanobelts (FGBs), where the formation and growth of ice crystals in a confined space function to guide the folding of 2D graphene oxide (GO) nanosheets into 1D nanobelts (i.e. folded graphene oxide belts, FGOBs), which were subsequently converted to FGBs after annealing. Thin aqueous GO containing films were obtained by blowing air through a GO dispersion in the presence of a surfactant, polyoxypropylenediamine (D400), resulting in a foam containing uniform air bubbles. Subsequent shock cooling of the foam using liquid nitrogen resulted in the facile fabrication of FGOBs. This technique provides a general approach to encapsulate catalytic nanomaterials such as Fe3O4 nanorods, TiO2 and Co3O4 nanoparticles into the folded graphene structure for practical applications such as Li-ion batteries.
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In recent decades, natural products have been considered important resources for developing of new agrochemicals because of their novel architectures and multibioactivities. Consequently, herein, 1-O-acetylbritannilactone (ABL), a natural sesquiterpene lactone from Inula britannica L., was used as a lead for further modification to discover fungicidal candidates. Six series of ABL-based derivatives containing an oxadiazole, triazole, or imidazole moiety were designed and synthesized, and their antifungal activities were also evaluated in vitro and in vivo. Bioassay results revealed that compounds 8d, 8h, and 8j (EC50 = 61.4, 30.9, and 12.4 µg/mL, respectively) exhibited more pronounced inhibitory activity against Fusarium oxysporum than their precursor ABL (EC50 > 500 µg/mL) and positive control hymexazol (EC50 = 77.2 µg/mL). Derivatives 8d and 11j (EC50 = 19.6 and 41.5 µg/mL, respectively) exhibited more potent antifungal activity toward Cytospora mandshurica than ABL (EC50 = 68.3 µg/mL). Compound 10 exhibited excellent and broad-spectrum antifungal activity against seven phytopathogenic fungal mycelia. Particularly, the inhibitory activity of compound 10 against the mycelium of Botrytis cinerea was more than 10.8- and 2.3-fold those of ABL and hymexazol, respectively. Meanwhile, derivative 10 (IC50 = 47.7 µg/mL) displayed more pronounced inhibitory activity against the spore of B. cinerea than ABL (IC50 > 500 µg/mL) and difenoconazole (IC50 = 80.8 µg/mL). Additionally, the in vivo control efficacy of compound 10 against B. cinerea was further studied using infected tomatoes (protective effect = 58.4%; therapeutic effect = 48.7%). The preliminary structure-activity relationship analysis suggested that the introduction of the 1,3,4-oxadiazole moiety (especially the 1,3,4-oxadiazole heterocycle containing the 4-chlorophenyl, 2-furyl, or 2-pyridinyl group) on the skeleton of ABL was more likely to produce potential antifungal compounds. These findings pave the way for further design and development of ABL-based derivatives as potential antifungal agents.