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OVATE family proteins (OFPs) play important roles in plant growth and development, hormone signaling, and stress response pathways. However, the functions of OsOFPs in rice are largely unknown. In this study, a novel gain-of-function rice mutant, Osofp6-D, was identified. This mutant exhibited decreased plant height, erect leaves, reduced panicle size, short and wide seeds, delayed seed germination time, and reduced fertility. These phenotypic changes were attributed to the increased expression of OsOFP6, which was caused by a T-DNA insertion. Complementation of the Osofp6-D phenotype by knockout of OsOFP6 using the CRISPR/Cas9 system confirmed that the Osofp6-D phenotype was caused by OsOFP6 overexpression. In addition, transgenic plants overexpressing OsOFP6 with the 35S promoter mimicked the Osofp6-D phenotype. Cytological observations of the glumes showed that OsOFP6 overexpression altered the grain shape, mainly by altering the cell shape. Hormone response experiments showed that OsOFP6 was involved in the gibberellin (GA) and brassinolide (BR) signaling responses. Further studies revealed that OsOFP6 interacts with E3BB, which is orthologous to the Arabidopsis central organ size-control protein BIG BROTHER (BB). This study further elucidates the regulation mechanism of the rice OFP family on plant architecture and grain shape.
Assuntos
Arabidopsis , Oryza , Proteínas de Plantas/genética , Grão Comestível/genética , Sementes/metabolismo , Transdução de Sinais , Plantas Geneticamente Modificadas/genética , Arabidopsis/genética , Hormônios/metabolismo , Oryza/genética , Regulação da Expressão Gênica de PlantasRESUMO
A single-chip hybrid integrated silicon photonics transmitter based on passive alignment flip-chip bonding technology has been demonstrated. The transmitter is developed by the hybrid integration of a C-band slotted laser with 1â mm cavity length and a Mach-Zehnder modulator with 2â mm long phase shifter. A 3â dB bandwidth of the small signal response is 16.35â GHz at 5.99 VPP superimposed with a reverse bias voltage of 2.43â V. A 25 Gbps data transmission experiment of the hybrid integrated transmitter is performed at 25°C.
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In this Letter, a new, to the best of our knowledge, external cavity structure based on double wavelength division multiplexing external cavities is proposed and demonstrated. The electro-optical conversion efficiency is improved and the brightness of the spectral beam combining diode lasers is enhanced. One wavelength division multiplexing external cavity is placed on the rear-side of the laser emitters to provide the strong optical feedback for wavelength locking and the other wavelength division multiplexing external cavity is placed on the front-side of laser emitters to combine three emitter beams to one beam. A maximum output power of up to 7.5 W is obtained and the brightness of the laser diode is 100 MW cm-2 sr-1 with an electro-optical conversion efficiency of 46.5%. Compared with a standard cavity for spectral beam combining, the use of double wavelength division multiplexing external cavities results in an electro-optical conversion efficiency improvement of 6.5%. The whole structure provides a new technology to achieve high-brightness and high electro-optical conversion efficiency for a laser diode source.
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The rapid emergence of drug-resistant bacteria has raised a great social concern together with the impetus for exploring advanced antibacterial ways. NIR-triggered antimicrobial photodynamic therapy (PDT) by lanthanide-doped upconversion nanoparticles (UCNP) as energy donor exhibits the advantages of high tissue penetration, broad antibacterial spectrum and less acquired resistance, but is still limited by its low efficacy. Now we designed a bio-inorganic nanohybrid and combined lysozyme (LYZ) with UCNP-PDT system to enhance the efficiency against resistant bacteria. Benefiting from the rapid adhesion to bacteria, intelligently bacteria-responsive LYZ release and synergistic LYZ-PDT effect, the nanoplatform achieves an exceptionally strong bactericidal capacity and conspicuous bacteriostasis on methicillin-resistant S. aureus. These findings pave the way for designing efficiently antibacterial nanomaterials and provide a new strategy for combating deep-tissue bacterial infection.
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Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Muramidase/química , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antibacterianos/química , Humanos , Testes de Sensibilidade Microbiana , Muramidase/metabolismo , Nanopartículas/metabolismo , Tamanho da Partícula , Fármacos Fotossensibilizantes/químicaRESUMO
KEY MESSAGE: Moderate overexpression of CYP734A4 improves grain number per main panicle and seed setting rate. Brassinosteroid (BR) homeostasis and signaling are crucial for plant growth and development. CYP734A genes encode cytochrome P450 monooxygenases that control the level of bioactive BRs by degrading BRs. However, fertile plants overexpressing CYP734As have not been reported in rice. Here, we isolated a novel semi-dominant mutant brd3-D, in which T-DNA was inserted approximately 4 kb upstream of the CYP734A4 gene (GenBank Accession AB488667), causing its overexpression. The mutant is characterized by dwarfism, small grains, and erect leaves and is less sensitive to brassinolide-induced lamina joint inclination and primary root elongation. However, increased grain number per main panicle and improved seed setting rate were also found in heterozygous brd3-D. To our knowledge, these traits have not been reported in other BR deficient mutants. Quantitative real-time PCR analysis indicated that phenotypic severity of the brd3-D mutant is positively correlated with the CYP734A4 transcription level. In accordance with the increased expression of CYP734A4, a lower castasterone (a rice BR) content was detected in the brd3-D mutants. Knockout of brd3-D by using the CRISPR/Cas9 system rescued the mutation. In addition, transgenic plants overexpressing CYP734A4 with the 35S enhancer mimicked the brd3-D phenotypes, confirming that moderate overexpression of the CYP734A4 gene can improve grain number per main panicle and the seed setting rate in rice. Further studies showed that overexpression of CYP734A4 influences the expressions of multiple genes involved in the BR pathway, and the expression of CYP734A4 is induced by exogenous brassinolide, confirming the negative regulatory role of CYP734A4 in the BR pathway. CYP734A4 might provide a useful gene resource for developing new high-yielding rice varieties.
Assuntos
Sistema Enzimático do Citocromo P-450/genética , Regulação da Expressão Gênica de Plantas , Oryza/genética , Proteínas de Plantas/genética , Sistema Enzimático do Citocromo P-450/metabolismo , DNA Bacteriano/química , Mutagênese Sítio-Dirigida , Mutação , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de SinaisRESUMO
A noninvasive strategy for in situ diagnosis and precise treatment of bacterial biofilm infections is highly anticipated but still a great challenge. Currently, no in vivo biofilm-targeted theranostic agent is available. Herein, we fabricated intelligent theranostic alginate lyase (Aly)-NaNdF4 nanohybrids with a 220 nm sunflower-like structure (NaNdF4@DMS-Aly) through an enrichment-encapsulating strategy, which exhibited excellent photothermal conversion efficiency and the second near-infrared (NIR-II) luminescence. Benefiting from the site-specific targeting and biofilm-responsive Aly release from NaNdF4@DMS-Aly, we not only enabled noninvasive diagnosis but also realized Aly-photothermal synergistic therapy and real-time evaluation of therapeutic effect in mice models with Pseudomonas aeruginosa biofilm-induced pulmonary infection. Furthermore, such nanobiohybrids with a sheddable siliceous shell are capable of delaying the NaNdF4 dissolution and biodegradation upon accomplishing the therapy, which is highly beneficial for the biosafety of theranostic agents.
Assuntos
Biofilmes , Elementos da Série dos Lantanídeos , Pseudomonas aeruginosa , Nanomedicina Teranóstica , Biofilmes/efeitos dos fármacos , Animais , Camundongos , Pseudomonas aeruginosa/efeitos dos fármacos , Elementos da Série dos Lantanídeos/química , Elementos da Série dos Lantanídeos/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Humanos , Terapia Fototérmica , Camundongos Endogâmicos BALB CRESUMO
Emitting light toward on-demand directions is important for various optoelectronic applications, such as optical communication, displaying, and ranging. However, almost all existing directional emitters are assemblies of passive optical antennae and external light sources, which are usually bulky and fragile and show unendurable loss of light power. Here we theoretically propose and experimentally demonstrate a conceptual design of a directional emitter, by using a single surface-emitting laser source itself to achieve dynamically controlled beam steering. The laser is built on photonic crystals that operate near the band edges in the continuum. By shrinking laser sizes to tens-of-wavelength, the optical modes quantize in three-dimensional momentum space, and each of them directionally radiates toward the far-field. Further utilizing the luminescence spectrum shifting effect under current injection, we consecutively select a sequence of modes into lasing action and show the laser maintaining single-mode operation with line widths at a minimum of 1.8 MHz and an emitting power of â¼10 milliwatts, and we demonstrate fast beam steering across a range of 3.2° × 4° on a time scale of 500 ns. Our work proposes a method for on-chip active beam steering for the development of automotive, industrial, and robotic applications.
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Aims: This study aims to delve into the anti-fatigue and sleep-aiding effects of various formulations containing Ganoderma lucidum extracts. Materials and methods: PGB [incorporating Ganoderma lucidum extract (GE), broken Ganoderma lucidum spore powder (GB) and Paecilomyces hepiali mycelium (PH)] and GBS [composed of GE, GB, and Ganoderma sinense powder (GS)] were chosen as representative recipes for this study. Mice were treated with these recipes or key components of Ganoderma lucidum for 14 consecutive days. Subsequently, a weight-bearing swimming experiment was conducted to assess the mice's exhaustion time and evaluate the anti-fatigue properties of the recipes. Sleep-aiding effects were analyzed by measuring the sleep latency and duration. Furthermore, levels of blood lactic acid, serum urea nitrogen, hepatic glycogen, muscle glycogen, and malondialdehyde (MDA) were measured in the livers and muscles. Key findings: The anti-fatigue abilities of the tested mice were significantly improved after treatment with PGB and their sleep quality improved as well with GBS treatment. PGB treatment for 14 days could significantly prolong the exhaustion time in weight-bearing swimming (from 10.1 ± 0.5 min to 15.2 ± 1.3 min). Meanwhile, glycogen levels in the livers and muscles were significantly increased, while the levels of serum lactic acid, serum urea nitrogen, and MDA in the livers and muscles were significantly decreased. In contrast, mice treated with GBS for 14 days experienced significant improvements in sleep quality, with shortened sleep latency (from 6.8 ± 0.7 min to 4.2 ± 0.4 min), extended sleep duration (from 88.3 ± 1.4 min to 152.5 ± 9.3 min), and decreased muscle MDA levels. These results indicated that Ganoderma lucidum extracts can be used for anti-fatigue and or aid in sleeping, depending on how they are prepared and administered. Significance: This study provides experimental evidence and theoretical basis for the development of Ganoderma lucidum recipes that are specifically designed to help with anti-fatigue and sleep.
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A narrow leaf mutant was isolated from transgenic rice (Oryza sativa L.) lines carrying a T-DNA insertion. The mutant is characterized by narrow leaves during its whole growth period, and was named nal9 (narrow leaf 9). The mutant also has other phenotypes, such as light green leaves at the seedling stage, reduced plant height, a small panicle and increased tillering. Genetic analysis revealed that the mutation is controlled by a single recessive gene. A hygromycin resistance assay showed that the mutation was not caused by T-DNA insertion, so a map-based cloning strategy was employed to isolate the nal9 gene. The mutant individuals from the F2 generations of a cross between the nal9 mutant and Longtepu were used for mapping. With 24 F2 mutants, the nal9 gene was preliminarily mapped near the marker RM156 on the chromosome 3. New INDEL markers were then designed based on the sequence differences between japonica and indica at the region near RM156. The nal9 gene was finally located in a 69.3 kb region between the markers V239B and V239G within BAC OJ1212_C05 by chromosome walking. Sequence and expression analysis showed that an ATP-dependent Clp protease proteolytic subunit gene (ClpP) was most likely to be the nal9 gene. Furthermore, the nal9 mutation was rescued by transformation of the ClpP cDNA driven by the 35S promoter. Accordingly, the ClpP gene was identified as the NAL9 gene. Our results provide a basis for functional studies of NAL9 in future work.
Assuntos
Mutação/genética , Oryza/anatomia & histologia , Oryza/genética , Mapeamento Físico do Cromossomo , Folhas de Planta/anatomia & histologia , Folhas de Planta/genética , Segregação de Cromossomos/genética , DNA Bacteriano/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Estudos de Associação Genética , Teste de Complementação Genética , Pleiotropia Genética , Mutagênese Insercional/genética , Oryza/citologia , Oryza/ultraestrutura , Fenótipo , Pigmentos Biológicos/metabolismo , Folhas de Planta/citologia , Folhas de Planta/ultraestrutura , Plantas Geneticamente ModificadasRESUMO
Photodynamic therapy (PDT) with aggregation-induced emission photosensitizers (AIE-PSs) has attracted increasing attention for their enhanced fluorescence and reactive oxygen species (ROS) generation abilities upon aggregation. However, it is difficult for AIE-PSs to simultaneously achieve long-wavelength excitation (>600 nm) and high singlet oxygen quantum yield, which restricts their application in deep-tissue PDT. In this study, four novel AIE-PSs were developed by appropriate molecular engineering, and their absorption peaks shifted from 478 to 540 nm with a tail extending to 700 nm. Meanwhile, their emission peaks were also moved from 697 nm to 779 nm with a tail extending over 950 nm. Importantly, their singlet oxygen quantum yields successfully increased from 0.61 to 0.89. Moreover, TBQ, the best photosensitizer developed by us, has been successfully applied to image-guided PDT in BALB/C mice bearing 4T1 breast cancer under red light (605 ± 5 nm) irradiation, with IC50 less than 2.5 µM at a low light dose (10.8 J cm-2). The success of this molecular engineering indicates that increasing the number of acceptors is more effective at red-shifting the absorption band of AIE-PSs than increasing the number of donors, and extending the π-conjugation of acceptors will red-shift the absorption-emission band, increase the maximum molar extinction coefficient, and improve the ROS generation ability of AIE-PSs, thus providing a new strategy for the design of advanced AIE-PSs for deep-tissue PDT.
Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Animais , Camundongos , Fármacos Fotossensibilizantes/farmacologia , Espécies Reativas de Oxigênio , Oxigênio Singlete , Camundongos Endogâmicos BALB CRESUMO
P-glycoprotein (P-gp/ABCB1)-mediated multidrug resistance (MDR) in cancers severely limit chemotherapeutic efficacy. We recently reported that phosphatidylinositol-3-kinase (PI3K) 110α and 110ß subunits can be novel targets for reversal of P-gp mediated MDR in cancers, and BAY-1082439 as an inhibitor specific for PI3K 110α and 110ß subunits could reverse P-gp-mediated MDR by downregulating P-gp expression in cancer cells. However, BAY-1082439 has very low solubility, short half-life and high in-vivo clearance rate. Till now, nano-system with the functions to target PI3K P110α and P110ß and reverse P-gp mediated MDR in cancers has not been reported. In our study, a tumor targeting drug delivery nano-system PBDF was established, which comprised doxorubicin (DOX) and BAY-1082439 respectively encapsulated by biodegradable PLGA-SH nanoparticles (NPs) that were grafted to gold nanorods (Au NRs) modified with FA-PEG-SH, to enhance the efficacy to reverse P-gp mediated MDR and to target tumor cells, further, to enhance the efficiency to inhibit MDR tumors overexpressing P-gp. In-vitro experiments indicated that PBDF NPs greatly enhanced uptake of DOX, improved the activity to reverse MDR, inhibited the cell proliferation, and induced S-phase arrest and apoptosis in KB-C2 cells, as compared with free DOX combining free BAY-1082439. In-vivo experiments further demonstrated that PBDF NPs improved the anti-tumor ability of DOX and inhibited development of KB-C2 tumors. Notably, the metastasis of KB-C2 cells in livers and lungs of nude mice were inhibited by treatment with PBDF NPs, which showed no obvious in-vitro or in-vivo toxicity.
Assuntos
Antineoplásicos , Neoplasias , Animais , Camundongos , Antineoplásicos/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Camundongos Nus , Neoplasias/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , HumanosRESUMO
In recent years, aggregation-induced emission photosensitizers (AIE-PSs) for antibacterial photodynamic therapy (aPDT) have received increasing attention because of their ability to increase reactive oxygen species (ROS) generation in the aggregation state. However, their antibacterial effect still has great room for improvement. Herein, we propose that if the rotation of some bonds in AIE-PSs is restricted, the nonradiative decay could be further suppressed to boost the generation of fluorescence and ROS, so as to improve their antibacterial efficacy. Following this molecular design strategy, we developed a new class of carbazole group-based AIE-PSs (CPVBA, CPVBP, CPVBP2, and CPVBP3), in which the rotation of phenyl-N bonds is restricted in the carbazole ring. Compared with diphenylamine group-based AIE-PSs with free rotation of phenyl-N bonds, carbazole group-based AIE-PSs showed stronger fluorescence, ROS generation, and antibacterial abilities, demonstrating the feasibility of this new design strategy. Notably, CPVBP3 can enter the entire cell of E. coli to exert its antibacterial effect, and there are few reports of photosensitizers with similar functions. Furthermore, to the best of our knowledge, the light dose (1.2 J/cm2) we used for CPVBP2 to kill Staphylococcus aureus is much lower than that of many reported photosensitizers, indicating great prospects for AIE antimicrobial photosensitizers.
Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Escherichia coli , Fármacos Fotossensibilizantes/química , Espécies Reativas de OxigênioRESUMO
BACKGROUND: High Salinity is a major environmental stress influencing growth and development of rice. Comparative proteomic analysis of hybrid rice shoot proteins from Shanyou 10 seedlings, a salt-tolerant hybrid variety, and Liangyoupeijiu seedlings, a salt-sensitive hybrid variety, was performed to identify new components involved in salt-stress signaling. RESULTS: Phenotypic analysis of one protein that was upregulated during salt-induced stress, cyclophilin 2 (OsCYP2), indicated that OsCYP2 transgenic rice seedlings had better tolerance to salt stress than did wild-type seedlings. Interestingly, wild-type seedlings exhibited a marked reduction in maximal photochemical efficiency under salt stress, whereas no such change was observed for OsCYP2-transgenic seedlings. OsCYP2-transgenic seedlings had lower levels of lipid peroxidation products and higher activities of antioxidant enzymes than wild-type seedlings. Spatiotemporal expression analysis of OsCYP2 showed that it could be induced by salt stress in both Shanyou 10 and Liangyoupeijiu seedlings, but Shanyou 10 seedlings showed higher OsCYP2 expression levels. Moreover, circadian rhythm expression of OsCYP2 in Shanyou 10 seedlings occurred earlier than in Liangyoupeijiu seedlings. Treatment with PEG, heat, or ABA induced OsCYP2 expression in Shanyou 10 seedlings but inhibited its expression in Liangyoupeijiu seedlings. Cold stress inhibited OsCYP2 expression in Shanyou 10 and Liangyoupeijiu seedlings. In addition, OsCYP2 was strongly expressed in shoots but rarely in roots in two rice hybrid varieties. CONCLUSIONS: Together, these data suggest that OsCYP2 may act as a key regulator that controls ROS level by modulating activities of antioxidant enzymes at translation level. OsCYP2 expression is not only induced by salt stress, but also regulated by circadian rhythm. Moreover, OsCYP2 is also likely to act as a key component that is involved in signal pathways of other types of stresses-PEG, heat, cold, or ABA.
Assuntos
Ciclofilinas/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Plantas Tolerantes a Sal/metabolismo , Cloreto de Sódio/farmacologia , Sequência de Aminoácidos , Regulação da Expressão Gênica de Plantas , Peroxidação de Lipídeos , Dados de Sequência Molecular , Oryza/efeitos dos fármacos , Estresse Oxidativo , Fenótipo , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/metabolismo , Proteoma , Espécies Reativas de Oxigênio/metabolismo , Salinidade , Plantas Tolerantes a Sal/efeitos dos fármacos , Plântula/efeitos dos fármacos , Plântula/metabolismo , Estresse FisiológicoRESUMO
Appropriate leaf shape has proved to be useful in improving photosynthesis and increasing grain yield. To understand the molecular mechanism of leaf morphogenesis, we identified a rice mutant nrl1, which was characterized by a phenotype of narrow and rolled leaves. Microscopic observation showed that the mutation significantly decreased the number of vascular bundles of leaf and stem. Genetic analysis revealed that the mutation was controlled by a single nuclear-encoded recessive gene. To isolate the nrl1 gene, 756 F(2) and F(3) mutant individuals from a cross of the nrl1 mutant with Longtepu were used and a high-resolution physical map of the chromosomal region around the nrl1 gene was made. Finally, the gene was mapped in 16.5 kb region between marker RL21 and marker RL36 within the BAC clone OSJNBa0027H05. Cloning and sequencing of the target region from the mutant showed that there was a 58 bp deletion within the second exon of the cellulose synthase-like D4 gene (TIGR locus Os12g36890). The nrl1 mutation was rescued by transformation with the wild-type cellulose synthase-like D4 gene. Accordingly, the cellulose synthase-like D4 gene was identified as the NRL1 gene. NRL1 was transcribed in various tissues and was mainly expressed in panicles and internodes. NAL7 and SLL1 were found to be upregulated, whereas OsAGO7 were downregulated in the nrl1 mutant. These findings suggested that there might be a functional association between these genes in regulating leaf development.
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Oryza/anatomia & histologia , Oryza/crescimento & desenvolvimento , Folhas de Planta/anatomia & histologia , Folhas de Planta/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Dados de Sequência Molecular , Mutação , Oryza/genética , Folhas de Planta/genética , Proteínas de Plantas/classificação , Proteínas de Plantas/genética , Proteínas de Plantas/fisiologia , Reação em Cadeia da PolimeraseRESUMO
Extensively drug-resistant Acinetobacter baumannii (XDR-AB) has raised considerable concerns due to its mortal damage to humans and its high transmission rate of infections in hospitals. However, current antibiotics not only show poor anti-infection effects in vivo but also frequently cause high nephrotoxicity and neurotoxicity. Herein, we report a near-infrared (NIR) light-initiated antimicrobial photodynamic therapy (aPDT) to effectively treat in vivo XDR-AB infections based on photosensitizer (PS) loaded upconversion nanoparticles (UCNPs, LiYF4:Yb/Er). Such nanoagents feature robust NIR triggered UC luminescence and high-efficiency energy transfer from UCNPs to the loaded PS, thereby allowing NIR-triggered generation of reactive oxygen species (ROS) for destroying the bacterial cell membrane. This strategy permits a high antibacterial activity against XDR-AB, resulting in a decline of 4.72 log10 in viability at a dose of 50 µg mL-1 UCNPs-PVP-RB with 980 nm laser irradiation (1 W cm-2). More significantly, we can achieve excellent therapeutic efficacy against deep-tissue (about 5 mm) XDR-AB infections without causing any side effects in the murine model. In brief, such NIR-activated aPDT may open up new avenues for treating various deep-tissue intractable infections.
Assuntos
Acinetobacter baumannii , Elementos da Série dos Lantanídeos , Nanopartículas Metálicas , Nanopartículas , Preparações Farmacêuticas , Fotoquimioterapia , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Fármacos Fotossensibilizantes/uso terapêuticoRESUMO
Xiaolong Mountain, located in warm temperate subtropical transition zone, is one of the important biodiversity conservation areas in China. We analyzed species composition, community structure, and habitat preferences of all woody plant species with DBH (diameter at breast height)≥1 cm in a 6 hm2 plot in Xiaolong Mountain, Gansu Province, Northwest China. A total of 29251 individuals (41735 stems) belonging to 33 families, 65 genera, and 124 species were recorded. The 28 species with importance value ≥1 contributed 82.9% to the total abundance. The top four species with the highest importance value were Quercus aliena var. acuteserrata, Betula platyphylla, Lindera aggregata var. playfairii and Corylus heterophylla. The structure of DBH size class of all stems showed an inverse 'J' type, indicating a successful regeneration tendency in the understory. Results from the indicator species analysis showed that 11 species had significant habitat prefe-rences, an two species (Ostrya japonica and Acer stachyophyllum subsp. betulifolium) had the most obvious preferences. Results from the redundancy analysis and partial methods showed that topographic factors played a dominant role in determining species distribution.
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Traqueófitas , Árvores , China , Ecossistema , Florestas , HumanosRESUMO
AIMS: The study aims to investigate the effect of plasminogen activator inhibitor 1 (PAI-1), a primary inhibitor of fibrinolytic process, on blood glucose in type 2 diabetes mellitus (T2DM) and its mechanism. MATERIALS AND METHODS: We developed a highly potent and highly specific PAI-1 inhibitor, named PAItrap3, based on the inactivated urokinase. Meanwhile, a single point mutation of PAItrap3 (i.e., PAItrapNC) was parallelly prepared as negative control. PAItrap3 was intravenously injected into type 2 diabetic (T2D) mice and its effect on metabolic system was evaluated by measuring the levels of blood glucose, PAI-1, and tumor necrosis factor alpha (TNF-α) in T2D mice. KEY FINDINGS: PAItrap3 significantly reduced the high blood glucose level and PAI-1 level in streptozotocin-induced T2D mice. PAItrapNC did not have any hypoglycemic effect at all on T2D mice. Mechanistically, both PAI-1 and TNF-α levels were attenuated by the administration of PAItrap3. In addition, we observed that PAItrap3 reduced the amount of fat droplets in adipocytes. SIGNIFICANCE: These findings provide clear evidence for PAI-1 to participate in inflammation and obesity mediated hyperglycemia, and open up a new prospect for the treatment of T2DM by PAI-1 inhibition.
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Glicemia/análise , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Inibidor 1 de Ativador de Plasminogênio/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Adipócitos/efeitos dos fármacos , Animais , Masculino , Inibidor 1 de Ativador de Plasminogênio/sangueRESUMO
Cancer therapeutics are varied and target diverse processes in cancer progression. Photodynamic therapy (PDT), photothermal therapy (PTT), and the inhibition of pro-cancer proteases are non-invasive anticancer therapeutics that attract increasing attentions for their enhanced specificities and milder systemic toxicities compared to traditional therapeutics. These modalities offer advantages to compensate for the shortcomings of their counterparts. For instance, PDT or PTT efficiently eliminates locally confined tumor cells while exhibiting no effect on metastatic tumor cells. In contrast, the inhibition of pro-cancer proteases systemically suppresses the proliferation and metastasis of cancer cells but does not eradicate existing cancer cells. To synergize these therapeutics, we hereby report a versatile nanoparticle that integrates the effects of PDT, PTT, and enzyme-inhibition. This nanoparticle (CIKP-NP) was synthesized by covalently or non-covalently modifying a photothermal nanoparticle with a photosensitizer, a pro-cancer protease inhibitor, and an albumin-binding molecule. After confirming the PDT, PTT, albumin-binding, and enzyme-inhibition properties at the molecular level, we demonstrated that CIKP-NP killed tumor cells through PDT or PTT and suppressed tumor cell invasion through enzyme-inhibition. In addition, through a breast cancer xenograft mouse model, we demonstrated that CIKP-NP suppressed tumor growth by PDT or PTT effect. Notably, the synergism of PDT and PTT significantly enhanced its anticancer efficiency. Furthermore, CIKP-NP significantly suppressed cancer metastasis in a lung metastatic mouse model. Last, biodistribution and the in vivo retention of CIKP-NP confirmed the tumor-targeting property. Beyond demonstrating the anti-tumor and anti-metastatic efficacy of CIKP-NP, our study also suggests a new strategy to synergize multiple anticancer therapeutics.
Assuntos
Neoplasias , Fotoquimioterapia , Animais , Proliferação de Células , Ouro , Camundongos , Camundongos Endogâmicos BALB C , Nanomedicina , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Terapia Fototérmica , Distribuição TecidualRESUMO
Tiller number is highly regulated by controlling the formation of tiller bud and its subsequent outgrowth in response to endogenous and environmental signals. Here, we identified a rice mutant htd2 from one of the 15,000 transgenic rice lines, which is characterized by a high tillering and dwarf phenotype. Phenotypic analysis of the mutant showed that the mutation did not affect formation of tiller bud, but promoted the subsequent outgrowth of tiller bud. To isolate the htd2 gene, a map-based cloning strategy was employed and 17 new insertions-deletions (InDels) markers were developed. A high-resolution physical map of the chromosomal region around the htd2 gene was made using the F(2) and F(3) population. Finally, the gene was mapped in 12.8 kb region between marker HT41 and marker HT52 within the BAC clone OSJNBa0009J13. Cloning and sequencing of the target region from the mutant showed that the T-DNA insertion caused a 463 bp deletion between the promoter and first exon of an esterase/lipase/thioesterase family gene in the 12.8 kb region. Furthermore, transgenic rice with reduced expression level of the gene exhibited an enhanced tillering and dwarf phenotype. Accordingly, the esterase/lipase/thioesterase family gene (TIGR locus Os03g10620) was identified as the HTD2 gene. HTD2 transcripts were expressed mainly in leaf. Loss of function of HTD2 resulted in a significantly increased expression of HTD1, D10 and D3, which were involved in the strigolactone biosynthetic pathway. The results suggest that the HTD2 gene could negatively regulate tiller bud outgrowth by the strigolactone pathway.
Assuntos
Flores/crescimento & desenvolvimento , Flores/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Oryza/crescimento & desenvolvimento , Oryza/genética , Proteínas de Plantas/genética , Segregação de Cromossomos , Clonagem Molecular , DNA Bacteriano/genética , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Inativação Gênica , Mutagênese Insercional , Mutação/genética , Oryza/anatomia & histologia , Fenótipo , Filogenia , Mapeamento Físico do Cromossomo , Proteínas de Plantas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de AminoácidosRESUMO
An alarming worldwide increase in microbial resistance to traditional drugs and classical pharmacophores has spurred the search for new antimicrobial compounds. Antimicrobial photodynamic therapy (aPDT) has recently emerged as an effective modality for the selective destruction of bacteria and other pathogenic microorganisms. However, some of the factors, including the aggregation of the hydrophobic photosensitizer (PS) in aqueous media and the inefficient biodistribution of PS limit its expansion to clinical conditions. In addition, the photoactivation under visible-light irradiation limits the therapeutic effect of aPDT for deep-tissue infection. To overcome these limitations, a PS (ß-carboxyphthalocyanine zinc, CPZ) delivery system with lanthanide-doped upconversion nanoparticles (UCNPs, LiYF4:Yb/Er) and polyvinylpyrrolidone (PVP) was prepared and its antimicrobial (antibacterial and antifungal) activities were investigated. Such a near-infrared (NIR) triggered UCNPs-CPZ-PVP system significantly reduced the aggregation of CPZ and presented a high anti-infectious activity against multi-drug resistant (MDR) bacteria (methicillin-resistant Staphylococcus aureus by 4.7 log10 and MDR Escherichia coli by 2.1 log10) post aPDT (at 50 µg mL-1 UCNPs-CPZ-PVP with 0.5 W cm-2 980 nm light). In particular, UCNPs-CPZ-PVP showed high antifungal efficacy against Candida albicans. In vivo aPDT experiments were further carried out using an MDR bacterial infection murine model in the presence of 5 mm thick tissue specimens, demonstrating the great potential of UCNPs-CPZ-PVP against infections in deep tissue. Altogether, we reveal an efficient NIR-triggered nano-photosensitizer with promising antifungal and antibacterial efficacy for clinical antimicrobial therapy.