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Grain Rain Period (GRP), one of the 24 solar terms in China, signifies a crucial phase for the transformation of tea quality, especially for Lu'an Guapian (LAGP) tea. During GRP, LAGP teas showed 3 distinct aroma profiles, each spanning 3-4 days. Specifically, the sensory evaluation result revealed that LAGP tea exhibited stronger flowery and fresh aromas in the early phase, with the soybean-like aroma significantly intensifying as the harvest period progressed during GRP. Furthermore, the key contributors to the aroma profile and its variation during GRP were identified as indole, δ-decalactone, geraniol, linalool, decanal, jasmone, (E)-ß-ionone, benzeneacetaldehyde, dihydroactinolide, nonanal, octanal, (E)-isoeugenol, (E,E)-2,4-nonadienal, 4-ketoisophorone, (E,Z)-2,6-nonadienal, and 1-octen-3-one. Additionally, we proposed a binary blending strategy using sensory evaluation with the methods of triangle test and normal distribution fitting to predict the blending threshold accurately. This study elucidated the dynamics of LAGP tea aroma during GRP and offered insights for tea blending optimization.
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Camellia sinensis , Cromatografia Gasosa-Espectrometria de Massas , Odorantes , Paladar , Compostos Orgânicos Voláteis , Odorantes/análise , Humanos , Camellia sinensis/química , Compostos Orgânicos Voláteis/química , Chá/química , ChinaRESUMO
Vitreoretinal diseases pose significant threats to vision, often requiring vitrectomy and substitution of vitreous humor to restore ocular structure and visual function. However, existing substitutes have limitations that compromise patient outcomes. Supramolecular hydrogels, particularly peptide-based formulations, have emerged as promising alternatives due to their superior optical clarity, biocompatibility, and viscoelasticity. In this study, we designed and evaluated two peptide hydrogels, 3K-OX and 3E-OX, bearing positive and negative charges, respectively, as potential vitreous substitutes. Our in vitro findings revealed that the physicochemical properties of the negatively charged peptide hydrogel, 3E-OX, closely resembled those of the native vitreous body, exhibiting optimal light transmittance, refractive index, molecular permeability, and biocompatibility. Animal studies further confirmed the safety and biocompatibility of 3E-OX as a promising vitreous substitute. Notably, we introduced optical coherence tomography for retinal microvascular detection in non-pigmented rabbits, presenting a novel approach to evaluate the performance of intraocular tamponade materials. This work not only expands the utility of peptide hydrogels but also provides valuable insights into the design of vitreous substitutes.
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Diffusion models have demonstrated their ability to generate diverse and high-quality images, sparking considerable interest in their potential for real image editing applications. However, existing diffusion-based approaches for local image editing often suffer from undesired artifacts due to the latent-level blending of the noised target images and diffusion latent variables, which lack the necessary semantics for maintaining image consistency. To address these issues, we propose PFB-Diff, a Progressive Feature Blending method for Diffusion-based image editing. Unlike previous methods, PFB-Diff seamlessly integrates text-guided generated content into the target image through multi-level feature blending. The rich semantics encoded in deep features and the progressive blending scheme from high to low levels ensure semantic coherence and high quality in edited images. Additionally, we introduce an attention masking mechanism in the cross-attention layers to confine the impact of specific words to desired regions, further improving the performance of background editing and multi-object replacement. PFB-Diff can effectively address various editing tasks, including object/background replacement and object attribute editing. Our method demonstrates its superior performance in terms of editing accuracy and image quality without the need for fine-tuning or training. Our implementation is available at https://github.com/CMACH508/PFB-Diff.
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In this study, the stems (ST) and leaves (LT) isolated from Large-leaf yellow tea (LYT) were used for sensory evaluation and quantitative analysis of flavor metabolites by sensomics and flavoromics. The results showed that the flavors of ST and LT in LYT were significantly different, and ST had stronger roasty and nutty aroma and sweet taste, which was mainly due to the accumulation of higher theanine and soluble monosaccharides in ST, and provided more substrates for the production of more pyrazine by the Maillard reaction; whereas LT contributed to the mellow and thick taste quality of LYT, and the abundance of catechins and caffeine were the main reason. The metabolic patterns of flavor metabolites indicated that the flavor differences between ST and LT were mainly due to biological metabolism in tea plants. This study provides the selection of raw materials for LYT in the future and product development of tea stems.
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The astringency of green tea is an integrated result of the synergic and antagonistic effects of individual tea components, whose mechanism is highly complex and not completely understood. Herein, we used an epigallocatechin gallate (EGCG)/caffeine (CAF)/saliva model to simulate the oral conditions during tea drinking. The effect of CAF on the interaction between EGCG and salivary proteins was first investigated using molecular docking and isothermal titration calorimetry (ITC). Then, the rheological properties and the micro-network structure of saliva were studied to relate the molecular interactions and perceived astringency. The results revealed that CAF partially occupied the binding sites of EGCG to salivary proteins, inhibiting their interaction and causing changes in the elastic network structure of the salivary film, thereby reducing astringency.
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Cafeína , Catequina , Simulação de Acoplamento Molecular , Saliva , Proteínas e Peptídeos Salivares , Catequina/análogos & derivados , Catequina/química , Catequina/farmacologia , Humanos , Cafeína/química , Cafeína/farmacologia , Proteínas e Peptídeos Salivares/química , Proteínas e Peptídeos Salivares/metabolismo , Saliva/química , Saliva/metabolismo , Chá/química , Ligação Proteica , Paladar , Adulto , Adstringentes/química , Adstringentes/farmacologia , Masculino , Adulto JovemRESUMO
This study investigated the changes in the aroma of jasmine tea during storage. Solid-phase micro-extraction (SPME)-gas chromatography (GC)-mass spectrometry (MS) and stir bar sorptive extraction (SBSE)-GC-MS were combined to detect all volatile compounds. GC-olfactometry (GC-O), odor activity value (OAV), and p-value were employed to analyze and identify the key aroma compounds in six jasmine tea samples stored for different durations. Nine key aroma compounds were discovered, namely (Z)-3-hexen-1-yl acetate, methyl anthranilate, methyl salicylate, trans-ß-ionone, linalool, geraniol, (Z)-4-heptenal, benzoic acid methyl ester, and benzoic acid ethyl ester. The importance of these compounds was confirmed through the aroma addition experiment. Correlation analysis showed that (Z)-4-heptenal might be the main reason for the increase in the stale aroma of jasmine tea. Through sensory evaluation and specific experimental analysis, it can be concluded that jasmine tea had the best aroma after 3 years of storage, and too long a storage time may cause the overall aroma of the tea to weaken and produce an undesirable odor. The findings can provide a reference for the change in aroma during the storage of jasmine tea and provide the best storage time (3 years) in terms of jasmine tea aroma.
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Large-leaf yellow tea (LYT) is processed from both leaves and stems, resulting in a distinctive rice crust-like aroma. Tea stems may contribute differently to the aroma of LYT than leaves. This study aimed to clarify the specific contribution of stems to LYT. The volatile compounds in different components of LYT were extracted and analyzed using a combination of headspace solid-phase microextraction and stir bar sorptive extraction coupled with gas chromatography-olfactory-mass spectrometry. The results revealed high concentrations of compounds with roasty attributes in stems such as 2-ethyl-3,5-dimethylpyrazine (OAV 153-208) and 2-ethyl-3,6-dimethylpyrazine (OAV 111-140). Aroma recombination and addition experiments confirmed that the roasty aroma provided by stems plays a pivotal role in the formation of the distinctive flavor of LYT. This study offers novel insights into the contribution of stems to the aroma of LYT, which can be used for processing and quality enhancement of roasted tea.
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Camellia sinensis , Cromatografia Gasosa-Espectrometria de Massas , Odorantes , Folhas de Planta , Caules de Planta , Chá , Compostos Orgânicos Voláteis , Odorantes/análise , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/análise , Camellia sinensis/química , Caules de Planta/química , Folhas de Planta/química , Chá/química , Paladar , Microextração em Fase Sólida , Aromatizantes/químicaRESUMO
The electroreduction of nitrate to ammonia via a selective eight-electron transfer nitrate reduction reaction offers a promising, low energy consumption, pollution-free, green NH3 synthesis strategy alternative to the Haber-Bosch method. However, it remains a great challenge to achieve high NH4+ selectivity and complete conversion from NO3--N to NH4+-N. Herein, we report ingredients adjustable Cu2O@CoO yolk-shell nanocubes featured with tunable inner void spaces and diverse activity centers, favoring the rapid cascade conversion of NO3- into NO2- on Cu2O and NO2- into NH4+ on CoO. Cu2O@CoO yolk-shell nanocubes exhibit super NH4+ Faradaic efficiencies (>99%) over a wide potential window (-0.2 V to -0.9 V versus RHE) with a considerable NH4+ yield rate of 15.27 mg h-1 cm-2 and fantastic cycling stability and long-term chronoamperometric durability. Cu2O@CoO yolk-shell nanocubes exhibited glorious NO3--N to NH4+-N conversion efficiency in both dilute (500 ppm) and highly concentrated (0.1 and 1 M) NO3- electrolytes, respectively. The nitrate electrolysis membrane electrode assembly system equipped with Cu2O@CoO yolk-shell nanocubes delivers over 99.8% NH4+ Faradaic efficiency at cell voltages of 1.9-2.3 V.
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The neurological effects and underlying pathophysiological mechanisms of sports-related concussion (SRC) in active young boxers remain poorly understood. This study aims to investigate the impairment of white matter microstructure and assess changes in glymphatic function following SRC by utilizing neurite orientation dispersion and density imaging (NODDI) on young boxers who have sustained SRC. A total of 60 young participants were recruited, including 30 boxers diagnosed with SRC and 30 healthy individuals engaging in regular exercise. The assessment of whole-brain white matter damage was conducted using diffusion metrics, while the evaluation of glymphatic function was performed through diffusion tensor imaging (DTI) analysis along the perivascular space (DTI-ALPS) index. A two-sample t-test was utilized to examine group differences in DTI and NODDI metrics. Spearman correlation and generalized linear mixed models were employed to investigate the relationship between clinical assessments of SRC and NODDI measurements. Significant alterations were observed in DTI and NODDI metrics among young boxers with SRC. Additionally, the DTI-ALPS index in the SRC group exhibited a significantly higher value than that of the control group (left side: 1.58 vs. 1.48, PFDR = 0.009; right side: 1.61 vs. 1.51, PFDR = 0.02). Moreover, it was observed that the DTI-ALPS index correlated with poorer cognitive test results among boxers in this study population. Repetitive SRC in active young boxers is associated with diffuse white matter injury and glymphatic dysfunction, highlighting the detrimental impact on brain health. These findings highlight the importance of long-term monitoring of the neurological health of boxers.
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Boxe , Concussão Encefálica , Imagem de Tensor de Difusão , Sistema Glinfático , Neuritos , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Sistema Glinfático/diagnóstico por imagem , Masculino , Concussão Encefálica/diagnóstico por imagem , Concussão Encefálica/fisiopatologia , Adolescente , Neuritos/fisiologia , Boxe/lesões , Boxe/fisiologia , Feminino , Estudos de Casos e Controles , Adulto Jovem , Traumatismos em Atletas/diagnóstico por imagem , Traumatismos em Atletas/fisiopatologiaRESUMO
The harvest date is a crucial factor in determining tea quality. For Lu'an Guapian (LAGP) tea, Grain Rain period (GRP) represents a pivotal phase in the transformation of tea quality. The sensory evaluation, computer vision and E-tongue revealed that the liquor color score, B and G values of tea infusion were increased during GRP, while the astringency, bitterness intensities and the R value of the tea infusion were decreased. Consequently, the tea infusion exhibited a greener hue and the taste became appropriate during GRP. Non-targeted metabolomics revealed that the majority of amino acids and derivatives was reduced during GRP. Furthermore, flavonoids, in particular flavonol glycosides, exhibited considerable variation during GRP. Finally, nine metabolites were identified as markers for quality transformation during GRP by PLS and Random Forest. This study investigated the quality of LAGP teas during GRP and filled the gap in the variation of LAGP tea quality during GRP.
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N4-acetylcytidine (ac4C), a conserved but recently rediscovered RNA modification on tRNAs, rRNAs and mRNAs, is catalyzed by N-acetyltransferase 10 (NAT10). Lysine acylation is a ubiquitous protein modification that controls protein functions. Our latest study demonstrates a NAT10-dependent ac4C modification, which occurs on the polyadenylated nuclear RNA (PAN) encoded by oncogenic DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV), can induce KSHV reactivation from latency and activate inflammasome. However, it remains unclear whether a novel lysine acylation occurs in NAT10 during KSHV reactivation and how this acylation of NAT10 regulates tRNAs ac4C modification. Here, we showed that NAT10 was lactylated by α-tubulin acetyltransferase 1 (ATAT1), as a writer at the critical domain, to exert RNA acetyltransferase function and thus increase the ac4C level of tRNASer-CGA-1-1. Mutagenesis at the ac4C site in tRNASer-CGA-1-1 inhibited its ac4C modifications, translation efficiency of viral lytic genes, and virion production. Mechanistically, KSHV PAN orchestrated NAT10 and ATAT1 to enhance NAT10 lactylation, resulting in tRNASer-CGA-1-1 ac4C modification, eventually boosting KSHV reactivation. Our findings reveal a novel post-translational modification in NAT10, as well as expand the understanding about tRNA-related ac4C modification during KSHV replication, which may be exploited to design therapeutic strategies for KSHV-related diseases.
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Acetiltransferases , Citidina , Herpesvirus Humano 8 , Ativação Viral , Herpesvirus Humano 8/metabolismo , Herpesvirus Humano 8/genética , Herpesvirus Humano 8/fisiologia , Humanos , Acetiltransferases/metabolismo , Acetiltransferases/genética , Citidina/análogos & derivados , Citidina/metabolismo , Células HEK293 , Acetiltransferases N-Terminal/metabolismo , RNA de Transferência/metabolismo , RNA de Transferência/genética , AcilaçãoRESUMO
The second near-infrared window (NIR-II) in the range of 1000-1400 nm is ideal for in vivo imaging and sensing through reduced scattering, absorption, and autofluorescence. However, there are only a few nanophosphor systems with emission in the NIR-II region. Here, we report on Mn5+-doped Ba5(PO4)3Cl nanoparticles (BPCl:Mn5+ NPs, d < 50 nm) toward NIR-II temperature sensing. BPCl:Mn5+ NPs are made by a two-step (hydrothermal and anion exchange) method. XRD, SEM, and TEM results showed that the as-prepared BPCl:Mn5+ NPs show high crystallinity, uniform size, and sphere-like morphology. The nanoparticles exhibit a broad excitation band of 500-850 nm and a temperature-sensitive peak emission at 1175 nm in the NIR-II range. NIR-II temperature sensing by 1E emission intensity is demonstrated with good linear fitting (R2 = 0.9895), high sensitivity (2.30% at 373 K), and good repeatability (99.0%). Thus, our study provides a path to develop a new NIR-II thermometer based on tetrahedral Mn(V) coordination.
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Low glucose is a common microenvironment for rapidly growing solid tumors, which has developed multiple approaches to survive under glucose deprivation. However, the specific regulatory mechanism remains largely elusive. In this study, we demonstrate that glucose deprivation, while not amino acid or serum starvation, transactivates the expression of DCAF1. This enhances the K48-linked polyubiquitination and proteasome-dependent degradation of Rheb, inhibits mTORC1 activity, induces autophagy, and facilitates cancer cell survival under glucose deprivation conditions. This study identified DCAF1 as a new cellular glucose sensor and uncovered new insights into mechanism of DCAF1-mediated inactivation of Rheb-mTORC1 pathway for promoting cancer cell survival in response to glucose deprivation.
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Sobrevivência Celular , Glucose , Alvo Mecanístico do Complexo 1 de Rapamicina , Proteína Enriquecida em Homólogo de Ras do Encéfalo , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteína Enriquecida em Homólogo de Ras do Encéfalo/metabolismo , Proteína Enriquecida em Homólogo de Ras do Encéfalo/genética , Glucose/metabolismo , Linhagem Celular Tumoral , Autofagia , Ubiquitinação , Transdução de Sinais , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Células HEK293 , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Proteínas Monoméricas de Ligação ao GTP/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: There is an urgent need to find a reliable and effective imaging method to evaluate the therapeutic efficacy of immunochemotherapy in advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the capability of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) histogram analysis based on different region of interest (ROI) selection methods for predicting treatment response to chemoimmunotherapy in advanced NSCLC. METHODS: Seventy-two stage III or IV NSCLC patients who received chemoimmunotherapy were enrolled in this study. IVIM and DKI were performed before treatment. The patients were classified as responders group and non-responders group according to the Response Evaluation Criteria in Solid Tumors 1.1. The histogram parameters of ADC, Dslow, Dfast, f, Dk and K were measured using whole tumor volume ROI and single slice ROI analysis methods. Variables with statistical differences would be included in stepwise logistic regression analysis to determine independent parameters, by which the combined model was also established. And the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of histogram parameters and the combined model. RESULTS: ADC, Dslow, Dk histogram metrics were significantly lower in the responders group than in the non-responders group, while the histogram parameters of f were significantly higher in the responders group than in the non-responders group (all P < 0.05). The mean value of each parameter was better than or equivalent to other histogram metrics, where the mean value of f obtained from whole tumor and single slice both had the highest AUC (AUC = 0.886 and 0.812, respectively) compared to other single parameters. The combined model improved the diagnostic efficiency with an AUC of 0.968 (whole tumor) and 0.893 (single slice), respectively. CONCLUSIONS: Whole tumor volume ROI demonstrated better diagnostic ability than single slice ROI analysis, which indicated whole tumor histogram analysis of IVIM and DKI hold greater potential than single slice ROI analysis to be a promising tool of predicting therapeutic response to chemoimmunotherapy in advanced NSCLC at initial state.
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Carcinoma Pulmonar de Células não Pequenas , Imagem de Difusão por Ressonância Magnética , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Imunoterapia/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Resultado do Tratamento , Adulto , Curva ROCRESUMO
Small molecule drugs sourced from natural products are pivotal for novel therapeutic discoveries. However, their clinical deployment is often impeded by non-specific activity and severe adverse effects. This study focused on 3-fluoro-10-hydroxy-Evodiamine (F-OH-Evo), a potent derivative of Evodiamine, whose development is curtailed due to suboptimal tumor selectivity and heightened cytotoxicity. By harnessing the remarkable stability, specificity, and αvß3 integrin affinity of c(RGDFK), a novel prodrug by conjugating F-OH-Evo with cRGD was synthesized. This innovative prodrug substantially enhanced the tumor-specific targeting of F-OH-Evo and improved the anti-tumor activities. Among them, compound 3c demonstrated the best selective inhibitory activity toward U87 cancer cells in vitro. It selectively enterd U87 cells by binding to αvß3 integrin, releasing the parent molecule under the dual response of ROS and GSH to exert inhibitory activity on topo I. The results highlight the potential of cRGD-conjugated prodrugs in targeted cancer therapy. This approach signifies a significant advancement in developing safer and more effective chemotherapy drugs, emphasizing the role of prodrug strategies in overcoming the limitations of traditional cancer treatments.
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Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Peptídeos Cíclicos , Pró-Fármacos , Quinazolinas , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Integrina alfaVbeta3/metabolismo , Integrina alfaVbeta3/antagonistas & inibidores , Estrutura Molecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/síntese química , Relação Estrutura-Atividade , Quinazolinas/química , Quinazolinas/farmacologiaRESUMO
Arsenic (As) poisoning has become a global public problem threatening human health. Chelation therapy (CT) is the preferred treatment for arsenic poisoning. Nevertheless, efficient and safe arsenic removal in vivo remains a daunting challenge due to the limitations of chelators, including weak affinity, poor cell membrane penetration, and short half-life. Herein, a mercapto-functionalized and size-tunable hierarchical porous Zr-MOF (UiO-66-TC-SH) is developed, which possesses abundant arsenic chemisorption sites, effective cell uptake ability, and long half-life, thereby efficiently removing toxic arsenic in vivo. Moreover, the strong binding affinity of UiO-66-TC-SH for arsenic reduces systemic toxicity caused by off-target effects. In animal trials, UiO-66-TC-SH decreases the blood arsenic levels of acute arsenic poisoning mice to a normal value within 48â¯h, and the efficacy is superior to clinical drugs 2,3-dimercaptopropanesulfonic acid sodium salt (DMPS). Meanwhile, UiO-66-TC-SH also significantly mitigates the arsenic accumulation in the metabolic organs of chronic arsenic poisoning mice. Surprisingly, UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates the side effects of arsenic drugs antitumor therapy. STATEMENT OF SIGNIFICANCE: Arsenic (As) contamination has become a global problem threatening public health. The present clinical chelation therapy (CT) still has some limitations, including the weak affinity, poor cell membrane permeability and short half-life of hydrophilic chelators. Herein, a metal-organic framework (MOF)-based multieffective arsenic removal strategy in vivo is proposed for the first time. Mercapto-functionalized and size-tunable hierarchical porous Zr-MOF nanoantidote (denoted as UiO-66-TC-SH) is accordingly designed and synthesized. After injection, UiO-66-TC-SH can form Zr-O-As bonds and As-S bonds with arsenic, thus enhancing arsenic adsorption capacity, cycling stability and systemic safety simultaneously. The acute arsenic poisoning model results indicate that UiO-66-TC-SH shows superior efficacy to the clinical drug sodium dimercaptopropanesulfonate (DMPS). More meaningfully, we find that UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates side effects of arsenic drugs anti-tumor therapy.
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Intoxicação por Arsênico , Arsênio , Estruturas Metalorgânicas , Zircônio , Animais , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Zircônio/química , Zircônio/farmacologia , Arsênio/farmacocinética , Camundongos , Intoxicação por Arsênico/tratamento farmacológico , Intoxicação por Arsênico/metabolismo , Humanos , Quelantes/química , Quelantes/farmacologia , Porosidade , Ácidos FtálicosRESUMO
Alternaria alternata is a ubiquitous soil-borne fungus capable of causing diseases in a variety of plants and occasionally in humans. While populations of A. alternata from infected plants have received significant attention, relatively little is known about its soil populations, including its population genetic structure and antifungal susceptibilities. In addition, over the last two decades, greenhouses have become increasingly important for food and ornamental plant production throughout the world, but how greenhouses might impact microbial pathogens such as A. alternata populations remains largely unknown. Different from open crop fields, greenhouses are often more intensively cultivated, with each greenhouse being a relatively small and isolated space where temperature and humidity are higher than surrounding environments. Previous studies have shown that greenhouse populations of two common molds, Aspergillus fumigatus and A. alternata, within a small community in southwestern China were variably differentiated. However, the relative contribution of physical separation among local greenhouses to the large-scale population structure remains unknown. Here, we isolated strains of A. alternata from seven greenhouses in Shijiazhuang, northeast China. Their genetic diversity and triazole susceptibilities were analyzed and compared with each other and with 242 isolates from nine greenhouses in Kunming, southwest China. Results showed that the isolation of greenhouses located <1 km from each other locally contributed similarly to the overall genetic variation as that between the two distant geographic regions. In addition, our results indicate that greenhouses could be significant sources of triazole resistance, with greenhouses often differing in their frequencies of resistant strains to different triazoles. IMPORTANCE: Greenhouses have become increasingly important for food production and food security. However, our understanding of how greenhouses may contribute to genetic variations in soil microbial populations is very limited. In this study, we obtained and analyzed soil populations of the cosmopolitan fungal pathogen Alternaria alternata in seven greenhouses in Shijiazhuang, northeast China. Our analyses revealed high proportions of isolates being resistant to agricultural triazole fungicides and medical triazole drugs, including cross-resistance to both groups of triazoles. In addition, we found that greenhouse populations of A. alternata located within a few kilometers showed similar levels of genetic differentiation as those separated by over 2,000 km between northeast and southwest China. Our study suggests that greenhouse populations of this and potentially other fungal pathogens represent an important ecological niche and an emerging threat to food security and human health.
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Alternaria , Antifúngicos , Variação Genética , Doenças das Plantas , Microbiologia do Solo , Alternaria/genética , China , Doenças das Plantas/microbiologia , Antifúngicos/farmacologia , Filogenia , Farmacorresistência Fúngica/genética , Triazóis/farmacologiaRESUMO
A novel and efficient method for functionalizing organosulfones has been established, utilizing a visible-light-driven intermolecular radical cascade cyclization of α-allyl-ß-ketosulfones. This process employs fac-Ir(ppy)3 as the photoredox catalyst and α-carbonyl alkyl bromide as the oxidizing agent. Via this approach, the substrates experience intermolecular addition of α-carbonyl alkyl radicals to the alkene bonds, initiating a sequence of C-C bond formations that culminate in the production of organosulfone derivatives. Notably, this technique features gentle reaction conditions and an exceptional compatibility with a wide array of functional groups, making it a versatile and valuable addition to the field of organic synthesis.
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Liver injury and progressive liver failure are severe life-threatening complications in sepsis, further worsening the disease and leading to death. Macrophages and their mediated inflammatory cytokine storm are critical regulators in the occurrence and progression of liver injury in sepsis, for which effective treatments are still lacking. l-Ascorbic acid 6-palmitate (L-AP), a food additive, can inhibit neuroinflammation by modulating the phenotype of the microglia, but its pharmacological action in septic liver damage has not been fully explored. We aimed to investigate L-AP's antisepticemia action and the possible pharmacological mechanisms in attenuating septic liver damage by modulating macrophage function. We observed that L-AP treatment significantly increased survival in cecal ligation and puncture-induced WT mice and attenuated hepatic inflammatory injury, including the histopathology of the liver tissues, hepatocyte apoptosis, and the liver enzyme levels in plasma, which were comparable to NLRP3-deficiency in septic mice. L-AP supplementation significantly attenuated the excessive inflammatory response in hepatic tissues of septic mice in vivo and in cultured macrophages challenged by both LPS and ATP in vitro, by reducing the levels of NLRP3, pro-IL-1ß, and pro-IL-18 mRNA expression, as well as the levels of proteins for p-I-κB-α, p-NF-κB-p65, NLRP3, cleaved-caspase-1, IL-1ß, and IL-18. Additionally, it impaired the inflammasome ASC spot activation and reduced the inflammatory factor contents, including IL-1ß and IL-18 in plasma/cultured superannuants. It also prevented the infiltration/migration of macrophages and their M1-like inflammatory polarization while improving their M2-like polarization. Overall, our findings revealed that L-AP protected against sepsis by reducing macrophage activation and inflammatory cytokine production by suppressing their activation in NF-κB and NLRP3 inflammasome signal pathways in septic liver.
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Inflamassomos , Sepse , Camundongos , Animais , Inflamassomos/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Caspase 1/genética , Caspase 1/metabolismo , Interleucina-18 , Ativação de Macrófagos , Transdução de Sinais , Fígado/metabolismo , Ácido Ascórbico , Sepse/complicações , Sepse/tratamento farmacológico , Lipopolissacarídeos/farmacologiaRESUMO
Transcriptome sequencing was employed to mine the simple sequence repeat(SSR) locus information of Saposhnikovia divaricata and design specific primers, which aimed to provide a basis for the research on the genetic diversity of S. divaricata germplasm resources. The seed purity, 1 000-seed weight, germination rate, and seed vigor were determined. MISA was used to obtain the SSR locus information from 12 606 unigene longer than 1 kb in the transcriptome database. Forty-three pairs of SSR primers designed in Primer 3 were used to analyze the polymorphism of 28 S. divaricata samples of different sources. The results showed that there were differences in the seed purity, 1 000-seed weight, germination rate, vigor, and seed length and width among S. divaricata samples of different sources. Particularly, the germination rate and seed vigor had significant differences, and HB-ZJK1, NMG-CF4, NMG-BT, NMG-HLE1, and NMG-CF2 had significantly higher 1 000-seed weight, germination rate, and seed vigor than the samples of other sources. Among the 86 233 unigene, 12 606(14.62%) unigene contained 15 958 SSR loci, with one SSR locus every 5 009 bp on average. The SSR loci were mainly single nucleotide and dinucleotide repeats, which were dominated by G/C and TC/AG, respectively. All the primers were screened by using 28 S. divaricata sample from different habitats, and the primers corresponding to the amplification products with clear bands and stable polymorphism were obtained. The clustering results of the biological characteristics and genetic diversity of the 28 S. divaricata samples were basically consistent, and the samples of the same origin(HB-AG1, HB-AG2, HB-ZJK1, and HB-ZJK2) generally gathered together and had close genetic relationship. The SSRs in S. divaricata transcriptome has high frequency, rich types, and high polymorphism, which provides candidate molecular markers for the germplasm identification, genetic map construction, and molecular-assisted breeding.