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Spike length (SL) is one of the most important agronomic traits affecting yield potential and stability in wheat. In this study, a major stable quantitative trait locus (QTL) for SL, i.e., qSl-2B, was detected in multiple environments in a recombinant inbred line (RIL) mapping population, KJ-RILs, derived from a cross between Kenong 9204 (KN9204) and Jing 411 (J411). The qSl-2B QTL was mapped to the 60.06-73.06 Mb region on chromosome 2B and could be identified in multiple mapping populations. An InDel molecular marker in the target region was developed based on a sequence analysis of the two parents. To further clarify the breeding use potential of qSl-2B, we analyzed its genetic effects and breeding selection effect using both the KJ-RIL population and a natural mapping population, which consisted of 316 breeding varieties/advanced lines. The results showed that the qSl-2B alleles from KN9204 showed inconsistent genetic effects on SL in the two mapping populations. Moreover, in the KJ-RILs population, the additive effects analysis of qSl-2B showed that additive effect was higher when both qSl-2D and qSl-5A harbor negative alleles under LN and HN. In China, a moderate selection utilization rate for qSl-2B was found in the Huanghuai winter wheat area and the selective utilization rate for qSl-2B continues to increase. The above findings provided a foundation for the genetic improvement of wheat SL in the future via molecular breeding strategies.
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Locos de Características Quantitativas , Triticum , Mapeamento Cromossômico , Triticum/genética , Ligação Genética , Melhoramento Vegetal , FenótipoRESUMO
Gallium-based (Ga-based) liquid metals have attracted considerable interest due to their low melting points, enabling them to feature both liquid properties and metallic properties at room temperature. In light of this, Ga-based liquid metals also possess excellent deformability, high electrical and thermal conductivity, superior metal affinity, and unique self-limited surface oxide, making them popular functional materials in energy storage. This provides a possibility to construct high-performance rechargeable batteries that are deformable, free of dendrite growth, and so on. This review primarily starts with the property of Ga-based liquid metal, and then focuses on the potential applications in rechargeable batteries by exploiting these advantages, aiming to construct the correlation between properties and structures. The glorious applications contain interface protection, self-healing electrode construction, thermal management, and flexible batteries. Finally, the opportunities and obstacles for the applications of liquid metal in batteries are presented.
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PURPOSE: T1 mapping is a widely used quantitative MRI technique, but its tissue-specific values remain inconsistent across protocols, sites, and vendors. The ISMRM Reproducible Research and Quantitative MR study groups jointly launched a challenge to assess the reproducibility of a well-established inversion-recovery T1 mapping technique, using acquisition details from a seminal T1 mapping paper on a standardized phantom and in human brains. METHODS: The challenge used the acquisition protocol from Barral et al. (2010). Researchers collected T1 mapping data on the ISMRM/NIST phantom and/or in human brains. Data submission, pipeline development, and analysis were conducted using open-source platforms. Intersubmission and intrasubmission comparisons were performed. RESULTS: Eighteen submissions (39 phantom and 56 human datasets) on scanners by three MRI vendors were collected at 3 T (except one, at 0.35 T). The mean coefficient of variation was 6.1% for intersubmission phantom measurements, and 2.9% for intrasubmission measurements. For humans, the intersubmission/intrasubmission coefficient of variation was 5.9/3.2% in the genu and 16/6.9% in the cortex. An interactive dashboard for data visualization was also developed: https://rrsg2020.dashboards.neurolibre.org. CONCLUSION: The T1 intersubmission variability was twice as high as the intrasubmission variability in both phantoms and human brains, indicating that the acquisition details in the original paper were insufficient to reproduce a quantitative MRI protocol. This study reports the inherent uncertainty in T1 measures across independent research groups, bringing us one step closer to a practical clinical baseline of T1 variations in vivo.
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Encéfalo , Crowdsourcing , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Imagens de Fantasmas , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Reprodutibilidade dos Testes , Processamento de Imagem Assistida por Computador/métodos , Mapeamento Encefálico/métodos , Masculino , Feminino , Adulto , AlgoritmosRESUMO
Wheat (Triticum aestivum) is particularly susceptible to water deficit at the jointing stage of its development. Sucrose non-fermenting 1-related protein kinase 2 (SnRK2) acts as a signaling hub in the response to drought stress, but whether SnRK2 helps plants cope with water deficit via other mechanisms is largely unknown. Here, we cloned and characterized TaSnRK2.10, which was induced by multiple abiotic stresses and phytohormones. Ectopic expression of TaSnRK2.10 in rice (Oryza sativa) conferred drought tolerance, manifested by multiple improved physiological indices, including increased water content, cell membrane stability, and survival rates, as well as decreased water loss and accumulation of H2O2 and malonaldehyde. TaSnRK2.10 interacted with and phosphorylated early responsive to dehydration 15 (TaERD15) and enolase 1 (TaENO1) in vivo and in vitro. TaERD15 phosphorylated by TaSnRK2.10 was prone to degradation by the 26S proteasome, thereby mitigating its negative effects on drought tolerance. Phosphorylation of TaENO1 by TaSnRK2.10 may account for the substantially increased levels of phosphoenolpyruvate (PEP), a key metabolite of primary and secondary metabolism, in TaSnRK2.10-overexpressing rice, thereby enhancing its viability under drought stress. Our results demonstrate that TaSnRK2.10 not only regulated stomatal aperture and the expression of drought-responsive genes, but also enhanced PEP supply and promoted the degradation of TaERD15, all of which enhanced drought tolerance.
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Oryza , Triticum , Triticum/metabolismo , Oryza/genética , Oryza/metabolismo , Resistência à Seca , Proteínas de Plantas/metabolismo , Peróxido de Hidrogênio/metabolismo , Secas , Água/metabolismo , Estresse Fisiológico/genética , Plantas Geneticamente Modificadas/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
A gas detection method based on CH3NH3PbI3 (MAPbI3) and poly (3,4-ethylenedioxythiophene): poly (4-styrene sulfonate) (PEDOT:PSS) composite photodetectors (PDs) is proposed. The operation of the PD primarily relies on the photoelectric effect within the visible light band. Our study involves constructing a gas detection system based on tunable diode laser spectroscopy (TDLAS) and MAPbI3/PEDOT:PSS PD, and O2 was selected as the target analyte. The system has achieved a minimum detection limit (MDL) of 0.12% and a normalized noise equivalent absorption coefficient (NNEA) of 8.83 × 10-11â cm-1â Wâ Hz-1/2. Furthermore, the Allan deviation analysis results indicate that the system can obtain sensitivity levels as low as 0.058% over an averaging time of 328 seconds. This marks the first use of MAPbI3/PEDOT:PSS PD in gas detection based on TDLAS. Despite the detector's performance leaves much to be desired, this innovation offers a new approach to developing spectral based gas detection system.
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Background: Coronary artery calcification (CAC) is a crucial marker for coronary atherosclerosis, and the extent of CAC is closely linked to the incidence and progression of cardiovascular diseases. The interleukin-2 (IL-2) receptor (IL-2R), which plays a critical role in mediating the proliferation and differentiation of immune cells, may also be involved in the development of CAC. The study aimed to investigate the relationship between IL-2R and CAC, with the goal of providing new insights into cardiovascular diseases. Methods: In this study, we enrolled 606 patients diagnosed with coronary artery disease to assess CAC. Based on coronary artery calcification score (CACS), patients were divided into two groups: the non-severe CAC group (CACS ≤ 400 Agatston units, AU) and the severe CAC group (CACS > 400 AU). Results: The results showed that IL-2R levels were significantly higher in patients with severe CAC compared to those with non-severe CAC (383 vs. 352 pg/mL, p = 0.002). Moreover, the level of IL-2R was positively correlated with the severity of CAC, independent of other clinical risk factors. According to Receiver Operating Characteristic (ROC) curve, the IL-2R prediction model demonstrated a good capability in distinguishing severe CAC with the Area Under the Curve (AUC) value of 0.726. Conclusions: Our study suggests that IL-2R is independently associated with the occurrence of severe CAC in coronary artery disease (CAD) patients. Additionally, IL-2R may play a crucial role in the development of advanced atherosclerosis. Consequently, therapeutic strategies targeting the IL-2/IL-2R pathway may be effective in preventing or treating CAD.
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Time crystal is a class of nonequilibrium phases with broken time-translational symmetry. Here, we demonstrate the time crystal in a single-mode nonlinear cavity. The time crystal originates from the self-oscillation induced by a linear gain and is stabilized by a nonlinear damping. We show in the time crystal phase there are sharp dissipative gap closing and pure imaginary eigenvalues of the Liouvillian spectrum in the thermodynamic limit. Dynamically, we observe a metastable regime with the emergence of quantum oscillation, followed by a dissipative evolution with a timescale much longer than the oscillating period. Moreover, we show there is a dissipative phase transition at the Hopf bifurcation, which can be characterized by the photon number fluctuation in the steady state. These results pave a new promising way for further experiments and deepen our understanding of time crystals.
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KEY MESSAGE: A total of 38 putative additive QTLs and 55 pairwise putative epistatic QTLs for tiller-related traits were reported, and the candidate genes underlying qMtn-KJ-5D, a novel major and stable QTL for maximum tiller number, were characterized. Tiller-related traits play an important role in determining the yield potential of wheat. Therefore, it is important to elucidate the genetic basis for tiller number when attempting to use genetic improvement as a tool for enhancing wheat yields. In this study, a quantitative trait locus (QTL) analysis of three tiller-related traits was performed on the recombinant inbred lines (RILs) of a mapping population, referred to as KJ-RILs, that was derived from a cross between the Kenong 9204 (KN9204) and Jing 411 (J411) lines. A total of 38 putative additive QTLs and 55 pairwise putative epistatic QTLs for spike number per plant (SNPP), maximum tiller number (MTN), and ear-bearing tiller rate (EBTR) were detected in eight different environments. Among these QTLs with additive effects, three major and stable QTLs were first documented herein. Almost all but two pairwise epistatic QTLs showed minor interaction effects accounting for no more than 3.0% of the phenotypic variance. The genetic effects of two colocated major and stable QTLs, i.e., qSnpp-KJ-5D.1 and qMtn-KJ-5D, for yield-related traits were characterized. The breeding selection effect of the beneficial allele for the two QTLs was characterized, and its genetic effects on yield-related traits were evaluated. The candidate genes underlying qMtn-KJ-5D were predicted based on multi-omics data, and TraesKN5D01HG00080 was identified as a likely candidate gene. Overall, our results will help elucidate the genetic architecture of tiller-related traits and can be used to develop novel wheat varieties with high yields.
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Locos de Características Quantitativas , Triticum , Triticum/genética , Mapeamento Cromossômico/métodos , Ligação Genética , Melhoramento Vegetal , FenótipoRESUMO
It is well known that bubbles will form on a hydrophobic rough surface immersed in water, which can create a surface covered with bubbles and leads to drag reduction. However, it is still not clear how bubbles grow on the surface under flow conditions. In this work, a rotating flow field is created using a parallel-plate setup of a rotational rheometer, and sample surfaces with different roughnesses and wettabilities are examined with different shear rates. The growth of bubbles is exclusively observed on the hydrophobic rough surface, and subsequent drag reduction is also detected simultaneously. The growth of bubbles is attributed to heterogeneous nucleation in the crevices under a local pressure reduction generated by the shear flow. A geometric model is established to describe the profile evolution of the trapped bubble in the crevice based on the contact angle and the pressure balance across the gas-liquid interface, which involves the variations of the Laplace pressure resulting from changes in the local liquid pressure. The growth of bubbles on the hydrophobic rough surface does not need a large decrease of the surrounding pressure or a high moving speed, which will have potential applications in drag reduction under the condition of a moderate shear rate.
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Stachybatranones A-F (1a/1b and 2-6) and three known analogues, namely methylatranones A and B (7 and 8) and atranone B (9), were isolated and identified from a toxigenic fungus Stachybotrys chartarum. Their structures and absolute configurations were elucidated via the extensive spectroscopic data, comparison of the experimental electronic circular dichroism (ECD) data, and single-crystal X-ray diffraction analyses. Structurally, compounds 2-6 belonged to a rare class of C-alkylated dolabellanes, featuring a unique five-membered hemiketal ring and a γ-butyrolactone moiety both fused to an 11-membered carbocyclic system, while compound 1 (1a/1b) represented the first example of a 5-11-6-fused atranone possessing a 2,3-butanediol moiety. The cardiomyocyte protective activity assay revealed that compounds 1-9 ameliorated cold ischemic injury at 24 h post cold ischemia (CI), with compounds 1 and 4 acting in a dose-dependent manner. Moreover, compound 1 prevented cold ischemia induced dephosphorylation of PI3K and AKT acting in a dose-dependent manner. In this study, a new class of natural products were found to protect cardiomyocytes against cold ischemic injury, providing a potential option for the development of novel cardioprotectants in heart transplant medicine.
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Miócitos Cardíacos , Stachybotrys , Stachybotrys/química , Animais , Miócitos Cardíacos/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Ratos , Descoberta de Drogas , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificaçãoRESUMO
The bleomycin-induced scleroderma model is a well-established and dependable method for creating a mouse model of SSc (systemic sclerosis). In the field of skin connective tissue diseases, increasing evidence from clinical and animal experiments suggests that TLRs (Toll-like receptors) play an important role in several diseases. This study aimed to determine the role of TLR7 (Toll-like receptor 7) and TLR9 (Toll-like receptor 9) in the mechanisms of immune abnormalities and fibrosis in SSc. This study used TLR7-KO mice (TLR7-knockout mice with a balb/c background) and TLR9-KO mice (TLR9-knockout mice with a balb/c background) as well as WT mice (wild-type balb/c mice). All three kinds of mice were induced by BLM (bleomycin) in a scleroderma model as the experimental group; meanwhile, WT mice treated with PBS (phosphate-buffered saline) were used as the control group. We analyzed the fibrotic phenotype and the immunological abnormality phenotype of TLR7-deficient and TLR9-deficient mice in the SSc disease model using flow cytometry, RT-PCR (reverse transcription-polymerase chain reaction), a histological examination, and IHC (immunohistochemical staining). In a mouse model of SSc disease, the deletion of TLR7 attenuated skin and lung fibrosis, while the deletion of TLR9 exacerbated skin and lung fibrosis. The deletion of TLR7 resulted in a relative decrease in the infiltration and expression of various pro-inflammatory and fibrotic cells and cytokines in the skin. On the other hand, the deletion of TLR9 resulted in a relative increase in the infiltration and expression of various pro-inflammatory and cytokine-inhibiting cells and cytokines in the skin. Under the influence of pDCs (plasmacytoid dendritic cells), the balances of Beff/Breg (IL-6 + CD19 + B cell/IL-10 + CD19 + B cell), Th17/Treg (IL-17A + CD4 + T cell/Foxp3 + CD25 + CD4 + T cell), M1/M2 (CD86 + macrophage/CD206 + macrophage), and Th1/Th2 (TNFα + CD3 + CD4 + T cell/IL-4 + CD3 + CD4 + T cell) were biased towards the suppression of inflammation and fibrosis as a result of the TLR7 deletion. Comparatively, the balance was biased towards promoting inflammation and fibrosis due to the TLR9 deletion. In the SSc model, TLR7 promoted inflammation and fibrosis progression, while TLR9 played a protective role. These results suggest that TLR7 and TLR9 play opposite roles in triggering SSc to produce immune system abnormalities and skin fibrosis.
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Modelos Animais de Doenças , Camundongos Knockout , Escleroderma Sistêmico , Receptor 7 Toll-Like , Receptor Toll-Like 9 , Animais , Receptor 7 Toll-Like/metabolismo , Receptor 7 Toll-Like/genética , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/genética , Receptor Toll-Like 9/metabolismo , Receptor Toll-Like 9/genética , Camundongos , Bleomicina/efeitos adversos , Camundongos Endogâmicos BALB C , Citocinas/metabolismo , Pele/patologia , Pele/metabolismo , Pele/imunologia , Fibrose , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Fibrose Pulmonar/etiologia , Glicoproteínas de MembranaRESUMO
Education expenditure is essential in mitigating air pollution, but the relationship between education expenditure and air pollution lacks in-depth discussion. Utilizing data at the county level in China during 2007-2021, this study estimates the effect of education expenditure from local governments on air pollution. Our findings demonstrate that education expenditure significantly and negatively affects air pollution, which remains robust after addressing endogeneity. The mechanism analysis presents that education expenditure reduces air pollution through the composition, technique, and income effects. The heterogeneity analysis indicates that the impact of education expenditure exhibits marked regional heterogeneity. Specifically, the role of education expenditure is significant in strong regulation, key, eastern, and central regions. By considering interaction terms, we identify the moderating effects of human capital, economic development, infrastructure construction, and public service for education expenditure. The cost-benefit analysis emphasizes that education expenditure improves social welfare. Our findings can inspire local governments to place more emphasis on air quality and public education expenditure.
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Poluição do Ar , China , Humanos , Educação , Análise Custo-BenefícioRESUMO
BACKGROUND: Casein hydrolysates have attracted much interest as anti-diabetic food, but their hypoglycemic mechanism and biopeptides are not well understood. This study aimed to explore the anti-diabetic mechanism and potential biopeptides of casein hydrolysates in streptozotocin/high-fat-diet-induced diabetic rats and HepG2 cells. RESULTS: Oral administration of casein hydrolysate prepared with papain-Flavourzyme combination (P-FCH) decreased fasting blood glucose, improved oral glucose tolerance, and reduced HbA1c values in diabetic rats. P-FCH was ineffective in alleviating insulin resistance (homeostasis model assessment and insulin sensitivity index) and enhancing hepatic insulin signaling transduction (phosphorylated Akt, hexokinase activity, and pyruvate kinase activity) in diabetic rats. However, P-FCH significantly upregulated adenosine monophosphate-activated protein kinase phosphorylation and glucose transporter-2 expression, inhibited phosphoenolpyruvate carboxylase kinase activity, and elevated glycogen content in liver tissue of diabetic rats. Furthermore, P-FCH increased glucose consumption independently in normal and insulin-resistant HepG2 cells without the presence of insulin. The peptide composition of P-FCH was characterized. The potential biopeptides in P-FCH showed the sequence characteristic of a Val at the N-terminal or a Pro at the P2 position, and the hypoglycemic activity of Val-Pro-Leu-Gly (the most potential biopeptide in P-FCH) was verified by oral glucose tolerance test in mice. CONCLUSION: These results suggested that activation of the non-insulin-mediated AMPK pathway might be the determinant mechanism of P-FCH on the hypoglycemic effect. The novel peptide Val-Pro-Leu-Gly in P-FCH was effective in reducing blood glucose levels when orally administered to mice. © 2023 Society of Chemical Industry.
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Diabetes Mellitus Experimental , Resistência à Insulina , Ratos , Camundongos , Animais , Caseínas/química , Glicemia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Estreptozocina , Hipoglicemiantes , Peptídeos/química , Insulina , Fígado/metabolismoRESUMO
Two guanine base editors created using an engineered N-methylpurine DNA glycosylase with CRISPR systems achieved targeted G-to-T editing with 4.94-12.50% efficiency in rice (Oryza sativa). The combined use of the DNA glycosylase and deaminases enabled co-editing of target guanines with adenines or cytosines.
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Edição de Genes , Guanina , Oryza , Oryza/genética , Edição de Genes/métodos , Guanina/metabolismo , Sistemas CRISPR-Cas/genética , DNA Glicosilases/metabolismo , DNA Glicosilases/genética , Timina/metabolismoRESUMO
BACKGROUND: The feasibility of DNA methylation-based assays in detecting minimal residual disease (MRD) and postoperative monitoring remains unestablished. We aim to investigate the dynamic characteristics of cancer-related methylation signals and the feasibility of methylation-based MRD detection in surgical lung cancer patients. METHODS: Matched tumor, tumor-adjacent tissues, and longitudinal blood samples from a cohort (MEDAL) were analyzed by ultra-deep targeted sequencing and bisulfite sequencing. A tumor-informed methylation-based MRD (timMRD) was employed to evaluate the methylation status of each blood sample. Survival analysis was performed in the MEDAL cohort (n = 195) and validated in an independent cohort (DYNAMIC, n = 36). RESULTS: Tumor-informed methylation status enabled an accurate recurrence risk assessment better than the tumor-naïve methylation approach. Baseline timMRD-scores were positively correlated with tumor burden, invasiveness, and the existence and abundance of somatic mutations. Patients with higher timMRD-scores at postoperative time-points demonstrated significantly shorter disease-free survival in the MEDAL cohort (HR: 3.08, 95% CI: 1.48-6.42; P = 0.002) and the independent DYNAMIC cohort (HR: 2.80, 95% CI: 0.96-8.20; P = 0.041). Multivariable regression analysis identified postoperative timMRD-score as an independent prognostic factor for lung cancer. Compared to tumor-informed somatic mutation status, timMRD-scores yielded better performance in identifying the relapsed patients during postoperative follow-up, including subgroups with lower tumor burden like stage I, and was more accurate among relapsed patients with baseline ctDNA-negative status. Comparing to the average lead time of ctDNA mutation, timMRD-score yielded a negative predictive value of 97.2% at 120 days prior to relapse. CONCLUSIONS: The dynamic methylation-based analysis of peripheral blood provides a promising strategy for postoperative cancer surveillance. TRIAL REGISTRATION: This study (MEDAL, MEthylation based Dynamic Analysis for Lung cancer) was registered on ClinicalTrials.gov on 08/05/2018 (NCT03634826). https://clinicaltrials.gov/ct2/show/NCT03634826 .
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Ácidos Nucleicos Livres , DNA Tumoral Circulante , Neoplasias Pulmonares , Humanos , Ácidos Nucleicos Livres/genética , DNA Tumoral Circulante/genética , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Metilação de DNA/genética , Biomarcadores Tumorais/genéticaRESUMO
Janus particles are a kind of materials with asymmetric morphology or surface chemical environment. But so far, the preparation of particles with dual asymmetry is still a challenging problem. Hence the cation surfactant hexadecyl trimethyl ammonium bromide and co-surfactant octadecylamine are applied to improve the Pickering emulsion stability, and the micron-sized silica particles are arranged in a single layer at the toluene-water interface through electrostatic interaction. Furthermore, organosilane reagents are added in the preparation process, resulting in the construction of asymmetric hydrophilic or hydrophobic mesoporous precisely onto the micron-sized silica particles surface. The cation surfactant-assisted Pickering emulsion method is simple, effective, and convenience, which can be applied in the synthesis of various dual Janus silica particles for specific applications.
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Glioblastoma (GBM) is the most common lethal brain tumor with dismal treatment outcomes and poor response to chemotherapy. As the regulatory center of cytogenetics and metabolism, most tumor chemotherapeutic molecules exert therapeutic effects in the nucleus. Nanodrugs showing the nuclear aggregation effect are expected to eliminate and fundamentally suppress tumor cells. In this study, a nanodrug delivery system based on polyhedral oligomeric silsesquioxane (POSS) is introduced to deliver drugs into the nuclei of GBM cells, effectively enhancing the therapeutic efficacy of chemotherapy. The nanoparticles are modified with folic acid and iRGD peptides molecules to improve their tumor cell targeting and uptake via receptor-mediated endocytosis. Nuclear aggregation allows for the direct delivery of chemotherapeutic drug temozolomide (TMZ) to the tumor cell nuclei, resulting in more significant DNA damage and inhibition of tumor cell proliferation. Herein, TMZ-loaded POSS nanoparticles can significantly improve the survival of GBM-bearing mice. Therefore, the modified POSS nanoparticles may serve as a promising drug-loaded delivery platform to improve chemotherapy outcomes in GBM patients.
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Glioblastoma , Nanopartículas , Camundongos , Animais , Glioblastoma/patologia , Linhagem Celular Tumoral , Temozolomida/química , Temozolomida/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/químicaRESUMO
Antimicrobial resistance (AMR) poses a threat to global public health. To mitigate the impacts of AMR, it is important to identify the molecular mechanisms of AMR and thereby determine optimal therapy as early as possible. Conventional machine learning-based drug-resistance analyses assume genetic variations to be homogeneous, thus not distinguishing between coding and intergenic sequences. In this study, we represent genetic data from Mycobacterium tuberculosis as a graph, and then adopt a deep graph learning method-heterogeneous graph attention network ('HGAT-AMR')-to predict anti-tuberculosis (TB) drug resistance. The HGAT-AMR model is able to accommodate incomplete phenotypic profiles, as well as provide 'attention scores' of genes and single nucleotide polymorphisms (SNPs) both at a population level and for individual samples. These scores encode the inputs, which the model is 'paying attention to' in making its drug resistance predictions. The results show that the proposed model generated the best area under the receiver operating characteristic (AUROC) for isoniazid and rifampicin (98.53 and 99.10%), the best sensitivity for three first-line drugs (94.91% for isoniazid, 96.60% for ethambutol and 90.63% for pyrazinamide), and maintained performance when the data were associated with incomplete phenotypes (i.e. for those isolates for which phenotypic data for some drugs were missing). We also demonstrate that the model successfully identifies genes and SNPs associated with drug resistance, mitigating the impact of resistance profile while considering particular drug resistance, which is consistent with domain knowledge.
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Antituberculosos/farmacologia , Farmacorresistência Bacteriana/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Scientists have developed many approaches based on PCR or next-generation sequencing to localize and characterize integrated T-DNAs in transgenic plants generated by Agrobacterium tumefaciens-mediated T-DNA transfer. However, none of these methods has the robust ability to handle all transgenic plants with diversified T-DNA patterns. Utilizing the valuable information in the whole-genome sequencing data of transgenic plants, we have developed a comprehensive approach (T-LOC) to localize and characterize T-DNA integration sites (TISs). We evaluated the performance of T-LOC on genome sequencing data from 48 transgenic rice (Oryza sativa) plants that provide real and unbiased resources of T-DNA integration patterns. T-LOC discovered 75 full TISs and reported a diversified pattern of T-DNA integration: the ideal single-copy T-DNA between two borders, multiple-copy of T-DNAs in tandem or inverted repeats, truncated partial T-DNAs with or without the selection hygromycin gene, the inclusion of T-DNA backbone, the integration at the genome repeat region, and the concatenation of multiple ideal or partial T-DNAs. In addition, we reported that DNA fragments from the two A. tumefaciens plasmids can be fused with T-DNA and integrated into the plant genome. Besides, T-LOC characterizes the genomic changes at TISs, including deletion, duplication, accurate repair, and chromosomal rearrangement. Moreover, we validated the robustness of T-LOC using PCR, Sanger sequencing, and Nanopore sequencing. In summary, T-LOC is a robust approach to studying the TISs independent of the integration pattern and can recover all types of TISs in transgenic plants.
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Agrobacterium tumefaciens , Oryza , Transformação Genética , DNA Bacteriano/genética , Plantas Geneticamente Modificadas/genética , Agrobacterium tumefaciens/genética , Oryza/genéticaRESUMO
We explore the influence of the artificial atomic chain on the input-output relation of the cavity. Specifically, we extend the atom chain to the one-dimensional Su-Schrieffer-Heeger (SSH) chain to check the role of atomic topological non-trivial edge state on the transmission characteristics of the cavity. The superconducting circuits can realize the artificial atomic chain. Our results show that the atom chain is not equivalent to atom gas, and the transmission properties of the cavity containing the atom chain are entirely different from that of the cavity containing atom gas. When the atom chain is arranged in the form of topological non-trivial SSH model, the atom chain can be equivalent to the three-level atom, in which the edge state contributes to the second level and is resonant with the cavity, while the high-energy bulk state contributes to form the third level and is greatly detuned with the cavity. Therefore, the transmission spectrum shows no more than three peaks. This allows us to infer the topological phase of the atomic chain and the coupling strength between the atom and the cavity only from the profile of the transmission spectrum. Our work is helping to understand the role of topology in quantum optics.