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A dual optical switch regulated by visible light has been developed through an integrated strategy, including luminescent Pt(II) and photochromic spiropyran (SP) as a triplet-sensitizer and photo-regulator building block, respectively. An efficient Förster resonance energy transfer (FRET) process is achieved, along with apparent and emissive color changes under visible light irradiation and temperature stimuli, which was utilized to develop advanced anti-counterfeiting materials.
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Fine particulate matter (PM2.5) can cause brain damage and diseases. Of note, ultrafine particles (UFPs) with an aerodynamic diameter less than or equal to 100 nm are a growing concern. Evidence has suggested toxic effects of PM2.5 and UFPs on the brain and links to neurological diseases. However, the underlying mechanism has not yet been fully illustrated due to the variety of the study models, different endpoints, etc. The adverse outcome pathway (AOP) framework is a pathway-based approach that could systematize mechanistic knowledge to assist health risk assessment of pollutants. Here, we constructed AOPs by collecting molecular mechanisms in PM-induced neurotoxicity assessments. We chose particulate matter (PM) as a stressor in the Comparative Toxicogenomics Database (CTD) and identified the critical toxicity pathways based on Ingenuity Pathway Analysis (IPA). We found 65 studies investigating the potential mechanisms linking PM2.5 and UFPs to neurotoxicity, which contained 2, 675 genes in all. IPA analysis showed that neuroinflammation signaling and glucocorticoid receptor signaling were the common toxicity pathways. The upstream regulator analysis (URA) of PM2.5 and UFPs demonstrated that the neuroinflammation signaling was the most initially triggered upstream event. Therefore, neuroinflammation was recognized as the MIE. Strikingly, there is a clear sequence of activation of downstream signaling pathways with UFPs, but not with PM2.5. Moreover, we found that inflammation response and homeostasis imbalance were key cellular events in PM2.5 and emphasized lipid metabolism and mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in UFPs. Previous AOPs, which only focused on phenotypic changes in neurotoxicity upon PM exposure, we for the first time propose AOP framework in which PM2.5 and UFPs may activate pathway cascade reactions, resulting in adverse outcomes associated with neurotoxicity. Our toxicity pathway-based approach not only advances risk assessment for PM-induced neurotoxicity but shines a spotlight on constructing AOP frameworks for new chemicals.
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Rotas de Resultados Adversos , Poluentes Atmosféricos , Material Particulado , Material Particulado/toxicidade , Poluentes Atmosféricos/toxicidade , Humanos , Síndromes Neurotóxicas , Transdução de Sinais/efeitos dos fármacos , Tamanho da Partícula , Medição de RiscoRESUMO
BACKGROUND: Exposure to PM2.5 has been linked to neurodegenerative diseases, with limited understanding of constituent-specific contributions. OBJECTIVES: To explore the associations between long-term exposure to PM2.5 constituents and neurodegenerative diseases. METHODS: We recruited 148,274 individuals aged ≥ 60 from four cities in the Pearl River Delta region, China (2020 to 2021). We calculated twenty-year average air pollutant concentrations (PM2.5 mass, black carbon (BC), organic matter (OM), ammonium (NH4+), nitrate (NO3-) and sulfate (SO42-)) at the individuals' home addresses. Neurodegenerative diseases were determined by self-reported doctor-diagnosed Alzheimer's disease (AD) and Parkinson's disease (PD). Generalized linear mixed models were employed to explore associations between pollutants and neurodegenerative disease prevalence. RESULTS: PM2.5 and all five constituents were significantly associated with a higher prevalence of AD and PD. The observed associations generally exhibited a non-linear pattern. For example, compared with the lowest quartile, higher quartiles of BC were associated with greater odds for AD prevalence (i.e., the adjusted odds ratios were 1.81; 95% CI, 1.45-2.27; 1.78; 95% CI, 1.37-2.32; and 1.99; 95% CI, 1.54-2.57 for the second, third, and fourth quartiles, respectively). CONCLUSIONS: Long-term exposure to PM2.5 and its constituents, particularly combustion-related BC, OM, and SO42-, was significantly associated with higher prevalence of AD and PD in Chinese individuals. ENVIRONMENTAL IMPLICATION: PM2.5 is a routinely regulated mixture of multiple hazardous constituents that can lead to diverse adverse health outcomes. However, current evidence on the specific contributions of PM2.5 constituents to health effects is scarce. This study firstly investigated the association between PM2.5 constituents and neurodegenerative diseases in the moderately to highly polluted Pearl River Delta region in China, and identified hazardous constituents within PM2.5 that have significant impacts. This study provides important implications for the development of targeted PM2.5 prevention and control policies to reduce specific hazardous PM2.5 constituents.
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Poluentes Atmosféricos , Exposição Ambiental , Material Particulado , Material Particulado/análise , China/epidemiologia , Humanos , Idoso , Poluentes Atmosféricos/análise , Exposição Ambiental/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/epidemiologia , Doenças Neurodegenerativas/induzido quimicamente , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/induzido quimicamente , Idoso de 80 Anos ou mais , Doença de Parkinson/epidemiologia , Doença de Parkinson/etiologia , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , PrevalênciaRESUMO
Melon (Cucumis melo L.), being under intensive domestication and selective breeding, displays an abundant phenotypic diversity. Wild germplasm with tolerance to stress represents an untapped genetic resource for discovery of disease-resistance genes. To comprehensively characterize resistance genes in melon, we generate a telomere-to-telomere (T2T) and gap-free genome of wild melon accession PI511890 (C. melo var. chito) with a total length of 375.0 Mb and a contig N50 of 31.24 Mb. The complete genome allows us to dissect genome architecture and identify resistance gene analogs. We construct a pan-NLRome using seven melon genomes, which include 208 variable and 18 core nucleotide-binding leucine-rich repeat receptors (NLRs). Multiple disease-related transcriptome analyses indicate that most up-regulated NLRs induced by pathogens are shell or cloud NLRs. The T2T gap-free assembly and the pan-NLRome not only serve as essential resources for genomic studies and molecular breeding of melon but also provide insights into the genome architecture and NLR diversity.
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Cucumis melo , Resistência à Doença , Genoma de Planta , Genoma de Planta/genética , Cucumis melo/genética , Resistência à Doença/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Doenças das Plantas/genética , Proteínas NLR/genética , Proteínas NLR/metabolismo , Cucurbitaceae/genéticaRESUMO
Melon is an important horticultural crop with extensive diversity in many horticultural groups. To explore its genomic diversity, it is necessary to assemble more high-quality complete genomes from different melon accessions. Meanwhile, a large number of QTLs have been mapped in several studies. Integration of the published QTLs onto a complete genome can provide more accurate information for candidate gene cloning. To address these problems, a telomere-to-telomere (T2T) genome of the elite melon landrace Kuizilikjiz (Cucumis melo L. var. inodorus) was de novo assembled and all the published QTLs were projected onto it in this study. The results showed that a high-quality Kuizilikjiz genome with the size of 379.2 Mb and N50 of 31.7 Mb was de novo assembled using the combination of short reads, PacBio high-fidelity long reads, Hi-C data, and a high-density genetic map. Each chromosome contained the centromere and telomeres at both ends. A large number of structural variations were observed between Kuizilikjiz and the other published genomes. A total of 1294 QTLs published in 67 studies were collected and projected onto the T2T genome. Several clustered, co-localized, and overlapped QTLs were determined. Furthermore, 20 stable meta-QTLs were identified, which significantly reduced the mapping intervals of the initial QTLs and greatly facilitated identification of the candidate genes. Collectively, the T2T genome assembly together with the numerous projected QTLs will not only broaden the high-quality genome resources but also provide valuable and abundant QTL information for cloning the genes controlling important traits in melon.
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Synthesis of chiral molecules for understanding and revealing the expression, transfer, and amplification of chirality is beneficial to explore effective chiral medicines and high-performance chiroptical materials. Herein, we report a series of square-planar phosphorescent platinum(II) complexes adopting a dominantly closed conformation that exhibit efficient chiroptical transfer and enhancement due to the nonclassical intramolecular C-H···O or C-H···F hydrogen bonds between bipyridyl chelating and alkynyl auxiliary ligands as well as the intermolecular π-π stacking and metal-metal interactions. The spectroscopic and theoretical calculation results demonstrate that the chirality and optic properties are regulated from the molecular level to hierarchical assemblies. Notably, a 154 times larger gabs value of the circular dichroism signals is obtained. This study provides a feasible design principle to achieve large chiropticity and control the expression and transfer of the chirality.
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The purpose of this research was to investigate the possibility of dexamethasone (DEX)-loaded PLGA-TPGS nanoparticles (NPs) in rabbits after intravitreal administration for the treatment of posterior segment diseases. The DEX-loaded PLGA-TPGS NPs were fabricated and characterized in terms of surface morphology, particle size and size distribution, entrapment efficiency, and in vitro drug release. The animals were classified randomly into two groups: experimental group with thirty rabbits, and control group with eighteen rabbits. Rabbits in the experimental group received intravitreal injections of 0.1 mL of DEX-loaded PLGA-TPGS NPs suspension and the control rabbits received intravitreal injection of 0.1 mL DEX (20 g/L in saline). The DEX concentrations in plasma and the ocular tissues such as the cornea, aqueous humor, lens, iris, vitreous humor, and chorioretina were determined by HPLC. The DEX-loaded PLGA-TPGS nanoparticle suspension were transparent and maintained a sustained release of DEX for about 45 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.93 mg/L. Based on the area-under-the-curve (AUC), the bioavailability of DEX in the experimental group was significantly higher than that in the control group administrated with regular DEX. These results suggest that intravitreal administration of DEX-loaded PL.3A-TPGS NPs leads to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to treat posterior segment diseases.
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Dexametasona/administração & dosagem , Dexametasona/farmacocinética , Ácido Láctico/química , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Ácido Poliglicólico/química , Segmento Posterior do Olho/metabolismo , Vitamina E/análogos & derivados , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Dexametasona/química , Difusão , Oftalmopatias/tratamento farmacológico , Oftalmopatias/metabolismo , Injeções Intravítreas/métodos , Teste de Materiais , Taxa de Depuração Metabólica , Polietilenoglicóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Coelhos , Distribuição Tecidual , Vitamina E/químicaRESUMO
The brine shrimp, Artemia, reproduces either oviparously, producing encysted embryos (diapause cysts), or ovoviviparously, producing free-swimming nauplii. Environmental factors, such as photoperiod, have been applied to control the reproduction mode of Artemia, but when the determination of a reproductive mode occurs remains unknown. We analysed the differential gene expression between oocytes from oviparous and ovoviviparous Artemia reared under different photoperiods. A total of 692 qualified cDNA clones were obtained by subtractive hybridization, 327 of which matched GenBank® Nucleotide Sequence Database entries. Gene expressions of 44 cDNAs (representing 56 clones) were analysed in oocytes using real-time PCR. Among these genes, 11 (21 clones) were significantly (P<0.05) up-regulated and 7 (9 clones) down-regulated in Artemia oocytes that subsequently enter diapause. Remarkably, known diapause-related proteins such as ArHsp22 (Artemia heat-shock protein 22) and chitin-binding proteins are found to be already differentially expressed. Furthermore, RNAi (RNA interference) knockdown of a differentially expressed gene, polo-like kinase 1, in oocyte of ovoviviparous Artemia led to the production of white embryos rather than free-swimming nauplii. In summary, our results provide evidence at the molecular level that the reproductive mode of Artemia is already determined at the oocyte stage of their life cycle.
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Artemia/embriologia , Artemia/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Oócitos/metabolismo , Fotoperíodo , Reprodução/genética , Animais , Artemia/citologia , Proteínas de Ciclo Celular/genética , DNA Complementar/genética , Embrião não Mamífero/embriologia , Embrião não Mamífero/fisiologia , Proteínas de Choque Térmico/genética , Oócitos/citologia , Oviparidade/genética , Ovoviviparidade/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Interferência de RNA/fisiologia , Quinase 1 Polo-LikeRESUMO
Diffusion tensor magnetic resonance imaging (DT-MRI, shortened as DTI) produces, from a set of diffusion-weighted magnetic resonance images, tensor-valued images where each voxel is assigned a 3x3 symmetric, positive-definite matrix. This tensor is simply the covariance matrix of a local Gaussian process with zero mean, modelling the average motion of water molecules. We propose a three-dimensional geometric flow-based model to segment the main core of cerebral white matter fibre tracts from DTI. The segmentation is carried out with a front propagation algorithm. The front is a three-dimensional surface that evolves along its normal direction with speed that is proportional to a linear combination of two measures: a similarity measure and a consistency measure. The similarity measure computes the similarity of the diffusion tensors at a voxel and its neighbouring voxels along the normal to the front; the consistency measure is able to speed up the propagation at locations where the evolving front is more consistent with the diffusion tensor field, to remove noise effect to some extent, and thus to improve results. We validate the proposed model and compare it with some other methods using synthetic and human brain DTI data; experimental results indicate that the proposed model improves the accuracy and efficiency in segmentation.