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Initiation is the rate-limiting step in translation, and its dysregulation is vital for carcinogenesis, including hematopoietic malignancy. Thus, discovery of novel translation initiation regulators may provide promising therapeutic targets. Here, combining Ribo-seq, mass spectrometry, and RNA-seq datasets, we discovered an oncomicropeptide, APPLE (a peptide located in ER), encoded by a non-coding RNA transcript in acute myeloid leukemia (AML). APPLE is overexpressed in various subtypes of AML and confers a poor prognosis. The micropeptide is enriched in ribosomes and regulates the initiation step to enhance translation and to maintain high rates of oncoprotein synthesis. Mechanically, APPLE promotes PABPC1-eIF4G interaction and facilitates mRNA circularization and eIF4F initiation complex assembly to support a specific pro-cancer translation program. Targeting APPLE exhibited broad anti-cancer effects in vitro and in vivo. This study not only reports a previously unknown function of micropeptides but also provides new opportunities for targeting the translation machinery in cancer cells.
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Fator de Iniciação 4F em Eucariotos/química , Fator de Iniciação Eucariótico 4G/metabolismo , Neoplasias Hematológicas/metabolismo , Peptídeos/química , Biossíntese de Proteínas , Animais , Progressão da Doença , Genoma Humano , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Fases de Leitura Aberta , Polirribossomos/química , RNA Mensageiro/metabolismo , RNA não Traduzido/metabolismo , Proteínas de Ligação a RNA/genética , Ribossomos/metabolismo , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
The transition of mouse embryonic stem cells (ESCs) between serum/LIF and 2i(MEK and GSK3 kinase inhibitor)/LIF culture conditions serves as a valuable model for exploring the mechanisms underlying ground and confused pluripotent states. Regulatory networks comprising core and ancillary pluripotency factors drive the gene expression programs defining stable naïve pluripotency. In our study, we systematically screened factors essential for ESC pluripotency, identifying TEAD2 as an ancillary factor maintaining ground-state pluripotency in 2i/LIF ESCs and facilitating the transition from serum/LIF to 2i/LIF ESCs. TEAD2 exhibits increased binding to chromatin in 2i/LIF ESCs, targeting active chromatin regions to regulate the expression of 2i-specific genes. In addition, TEAD2 facilitates the expression of 2i-specific genes by mediating enhancer-promoter interactions during the serum/LIF to 2i/LIF transition. Notably, deletion of Tead2 results in reduction of a specific set of enhancer-promoter interactions without significantly affecting binding of chromatin architecture proteins, CCCTC-binding factor (CTCF), and Yin Yang 1 (YY1). In summary, our findings highlight a novel prominent role of TEAD2 in orchestrating higher-order chromatin structures of 2i-specific genes to sustain ground-state pluripotency.
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Cromatina , Proteínas de Ligação a DNA , Células-Tronco Pluripotentes , Fatores de Transcrição de Domínio TEA , Animais , Camundongos , Cromatina/metabolismo , Cromatina/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Elementos Facilitadores Genéticos , Células-Tronco Embrionárias Murinas/metabolismo , Células-Tronco Embrionárias Murinas/citologia , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/citologia , Regiões Promotoras Genéticas , Fatores de Transcrição de Domínio TEA/genética , Fatores de Transcrição de Domínio TEA/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genéticaRESUMO
Transcription factor ELONGATED HYPOCOTYL5 (HY5) is the central hub for seedling photomorphogenesis. E3 ubiquitin (Ub) ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) inhibits HY5 protein accumulation through ubiquitination. However, the process of HY5 deubiquitination, which antagonizes E3 ligase-mediated ubiquitination to maintain HY5 homeostasis has never been studied. Here, we identified that Arabidopsis thaliana deubiquitinating enzyme, Ub-SPECIFIC PROTEASE 14 (UBP14) physically interacts with HY5 and enhances its protein stability by deubiquitination. The da3-1 mutant lacking UBP14 function exhibited a long hypocotyl phenotype, and UBP14 deficiency led to the failure of rapid accumulation of HY5 during dark to light. In addition, UBP14 preferred to stabilize nonphosphorylated form of HY5 which is more readily bound to downstream target genes. HY5 promoted the expression and protein accumulation of UBP14 for positive feedback to facilitate photomorphogenesis. Our findings thus established a mechanism by which UBP14 stabilizes HY5 protein by deubiquitination to promote photomorphogenesis in A. thaliana.
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Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição de Zíper de Leucina Básica , Regulação da Expressão Gênica de Plantas , Ubiquitinação , Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Proteases Específicas de Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/genética , Estabilidade Proteica/efeitos da radiação , Luz , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/metabolismo , Hipocótilo/genéticaRESUMO
N6 -Methyladenosine (m6 A) is an important RNA modification catalyzed by methyltransferase-like 3 (METTL3) and METTL14. m6 A homeostasis mediated by the methyltransferase (MTase) complex plays key roles in various biological processes. However, the mechanism underlying METTL14 protein stability and its role in m6 A homeostasis remain elusive. Here, we show that METTL14 stability is regulated by the competitive interaction of METTL3 with the E3 ligase STUB1. STUB1 directly interacts with METTL14 to mediate its ubiquitination at lysine residues K148, K156, and K162 for subsequent degradation, resulting in a significant decrease in total m6 A levels. The amino acid regions 450-454 and 464-480 of METTL3 are essential to promote METTL14 stabilization. Changes in STUB1 expression affect METTL14 protein levels, m6 A modification and tumorigenesis. Collectively, our findings uncover an ubiquitination mechanism controlling METTL14 protein levels to fine-tune m6 A homeostasis. Finally, we present evidence that modulating STUB1 expression to degrade METTL14 could represent a promising therapeutic strategy against cancer.
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Adenosina , Metiltransferases , Adenosina/metabolismo , Metiltransferases/genética , HomeostaseRESUMO
A widely used psychotherapeutic treatment for post-traumatic stress disorder (PTSD) involves performing bilateral eye movement (EM) during trauma memory retrieval. However, how this treatment-described as eye movement desensitization and reprocessing (EMDR)-alleviates trauma-related symptoms is unclear. While conventional theories suggest that bilateral EM interferes with concurrently retrieved trauma memories by taxing the limited working memory resources, here, we propose that bilateral EM actually facilitates information processing. In two EEG experiments, we replicated the bilateral EM procedure of EMDR, having participants engaging in continuous bilateral EM or receiving bilateral sensory stimulation (BS) as a control while retrieving short- or long-term memory. During EM or BS, we presented bystander images or memory cues to probe neural representations of perceptual and memory information. Multivariate pattern analysis of the EEG signals revealed that bilateral EM enhanced neural representations of simultaneously processed perceptual and memory information. This enhancement was accompanied by heightened visual responses and increased neural excitability in the occipital region. Furthermore, bilateral EM increased information transmission from the occipital to the frontoparietal region, indicating facilitated information transition from low-level perceptual representation to high-level memory representation. These findings argue for theories that emphasize information facilitation rather than disruption in the EMDR treatment.
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Eletroencefalografia , Dessensibilização e Reprocessamento através dos Movimentos Oculares , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Dessensibilização e Reprocessamento através dos Movimentos Oculares/métodos , Movimentos Oculares/fisiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/psicologia , Percepção Visual/fisiologia , Memória/fisiologia , Encéfalo/fisiologia , Estimulação Luminosa/métodos , Memória de Curto Prazo/fisiologiaRESUMO
BACKGROUND: The introduction of non-native species is a primary driver of biodiversity loss in freshwater ecosystems. The redclaw crayfish (Cherax quadricarinatus) is a freshwater species that exhibits tolerance to hypoxic stresses, fluctuating temperatures, high ammonia concentration. These hardy physiological characteristics make C. quadricarinatus a popular aquaculture species and a potential invasive species that can negatively impact tropical and subtropical ecosystems. Investigating the genomic basis of environmental tolerances and immune adaptation in C. quadricarinatus will facilitate the development of management strategies of this potential invasive species. RESULTS: We constructed a chromosome-level genome of C. quadricarinatus by integrating Nanopore and PacBio techniques. Comparative genomic analysis suggested that transposable elements and tandem repeats drove genome size evolution in decapod crustaceans. The expansion of nine immune-related gene families contributed to the disease resistance of C. quadricarinatus. Three hypoxia-related genes (KDM3A, KDM5A, HMOX2) were identified as being subjected to positive selection in C. quadricarinatus. Additionally, in vivo analysis revealed that upregulating KDM5A was crucial for hypoxic response in C. quadricarinatus. Knockdown of KDM5A impaired hypoxia tolerance in this species. CONCLUSIONS: Our results provide the genomic basis for hypoxic tolerance and immune adaptation in C. quadricarinatus, facilitating the management of this potential invasive species. Additionally, in vivo analysis in C. quadricarinatus suggests that the role of KDM5A in the hypoxic response of animals is complex.
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Adaptação Fisiológica , Astacoidea , Genoma , Animais , Astacoidea/genética , Astacoidea/imunologia , Adaptação Fisiológica/genética , Hipóxia/genética , GenômicaRESUMO
The development of a catalytic method for stereogenic carbon center formation holds immense significance in organic synthesis. Transition-metal-catalyzed cross-coupling reaction has been regarded as a straightforward and efficient tool for stereoselectively forging C-C bond. Nevertheless, the creation of acyclic all-carbon quaternary-containing vicinal stereocenters remains notoriously challenging within the domain of cross-coupling chemistry despite their prominence in various bioactive small molecules. Herein, we describe a palladium-catalyzed asymmetric multicomponent cross-coupling of trisubstituted alkene with aryl diazonium salts and arylboronic acids to realize the formation of tertiary-quaternary carbon centers with high regio-, distereo-, and enantioselectivity. Specifically, the precise manipulation of the stereoconfiguration of trisubstituted alkenes enables the divergent stereoselective cross-coupling reaction, thus allowing for the facile construction of all four enantiomers. Harnessing the ligand-swap strategy involving a chiral bisoxazoline and an achiral fumarate individually accelerates the enantioselective migratory insertion and reductive elimination step in the cross-coupling process, as supported by density functional theory (DFT) calculations, thus obviating the requirement for a neighboring directing group within the internal olefin skeleton.
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BACKGROUND: There are limited clinical data regarding the additional yields of random biopsies (RBs) during colorectal cancer surveillance in patients with inflammatory bowel disease. To assess the additional yield of RB, a systematic review and meta-analysis was conducted. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies investigating the preferred colonoscopy surveillance approach for inflammatory bowel disease patients. The additional yield, detection rate, procedure time, and withdrawal time were pooled. RESULTS: Thirty-seven studies (48 arms) were included in the meta-analysis with 9051 patients. The additional yields of RB were 10.34% in per-patient analysis and 16.20% in per-lesion analysis. The detection rates were 1.31% and 2.82% in per-patient and per-lesion analysis, respectively. Subgroup analysis showed a decline in additional yields from 14.43% to 0.42% in the per-patient analysis and from 19.20% to 5.32% in the per-lesion analysis for studies initiated before and after 2011. In per-patient analysis, the additional yields were 4.83%, 10.29%, and 56.05% for primary sclerosing cholangitis (PSC) proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 0.56%, 1.40%, and 19.45%. In the per-lesion analysis, additional yields were 11.23%, 21.06%, and 45.22% for PSC proportions of 0% to 10%, 10% to 30%, and 100%, respectively. The corresponding detection rates were 2.09%, 3.58%, and 16.24%. CONCLUSIONS: The additional yields of RB were 10.34% and 16.20% for per-patient and per-lesion analyses, respectively. Considering the decreased additional yields in studies initiated after 2011, and the influence of PSC, endoscopy centers lacking full high-definition equipment should consider incorporating RB in the standard colonoscopy surveillance for inflammatory bowel disease patients, especially in those with PSC.
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Day length modulates hypocotyl elongation in seedlings to optimize their overall fitness. Variations in cell growth-associated genes are regulated by several transcription factors. However, the specific transcription factors through which the plant clock increases plant fitness are still being elucidated. In this study, we identified the no apical meristem, Arabidopsis thaliana-activating factor (ATAF-1/2), and cup-shaped cotyledon (NAC) family transcription factor ATAF1 as a novel repressor of hypocotyl elongation under a short-day (SD) photoperiod. Variations in day length profoundly affected the transcriptional and protein levels of ATAF1. ATAF1-deficient mutant exhibited increased hypocotyl length and cell growth-promoting gene expression under SD conditions. Moreover, ATAF1 directly targeted and repressed the expression of the cycling Dof factor 1/5 (CDF1/5), two key transcription factors involved in hypocotyl elongation under SD conditions. Additionally, ATAF1 interacted with and negatively modulated the effects of phytochrome-interacting factor (PIF), thus inhibiting PIF-promoted gene expression and hypocotyl elongation. Taken together, our results revealed ATAF1-PIF as a crucial pair modulating the expression of key transcription factors to facilitate plant growth during day/night cycles under fluctuating light conditions.
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Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Hipocótilo , Fotoperíodo , Fatores de Transcrição , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/genética , Hipocótilo/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genéticaRESUMO
Single-molecule localization microscopy (SMLM) enables three-dimensional (3D) super-resolution imaging of nanoscale structures within biological samples. However, prolonged acquisition introduces a drift between the sample and the imaging system, resulting in artifacts in the reconstructed super-resolution image. Here, we present a novel, to our knowledge, 3D drift correction method that utilizes both the reflected and scattered light from the sample. Our method employs the reflected light of a near-infrared (NIR) laser for focus stabilization while synchronously capturing speckle images to estimate the lateral drift. This approach combines high-precision active compensation in the axial direction with lateral post-processing compensation, achieving the abilities of 3D drift correction with a single laser light. Compared to the popular localization events-based cross correlation method, our approach is much more robust, especially for datasets with sparse localization points.
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RATIONALE: Sinomenine, a major bioactive compound isolated from Sinomenium acutum, has been used for the treatment of rheumatoid arthritis and other cardio-cerebrovacular diseases. However, the metabolism of this drug has not been fully investigated. The current work was carried out to investigate the in vitro metabolism of sinomenine in liver microsomes. METHODS: The metabolites were generated by incubating sinomenine (3 µM) with the liver microsomes in the presence of NADPH at 37°C. The structure of the metabolites was characterized using liquid chromatography coupled to high-resolution mass spectrometry (HRMS). Two major metabolites synthesized and their structures were further confirmed using nuclear magnetic resonance spectroscopy. RESULTS: Under the current conditions, 12 metabolites were found and structurally identified using high resolution MS and MS2 spectra. Among these metabolites, M1, M2, M3, M4, M5, M6, M7, M9, M11, and M12 were first reported. The metabolites M8 and M10 were synthesized and unambiguously identified as N-desmethyl-sinomenine and sinomenine N-oxide, respectively. The phenotyping study revealed that the formation of M8 was catalyzed by CYP2C8, 2C19, 2D6, and 3A4, whereas the formation of M3, M6, and M10 were exclusively catalyzed by CYP3A4. The metabolic pathways of sinomenine include N-demethylation, O-demethylation, dehydrogenation, oxygenation, and N-oxygenation. CONCLUSIONS: N-Demethylation and N-oxygenation were the primary metabolic pathways of sinomenine. This study provides new insight into the in vitro metabolism of sinomenine, which would help prospects of sinomenine disposition and safety assessments.
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Microssomos Hepáticos , Morfinanos , Espectrometria de Massas/métodos , Cromatografia Líquida , Espectroscopia de Ressonância Magnética , Microssomos Hepáticos/metabolismo , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Epidemiological evidence on the impact of airborne organic pollutants on lung function among the elderly is limited, and their underlying biological mechanisms remain largely unexplored. Herein, a longitudinal panel study was conducted in Jinan, Shandong Province, China, involving 76 healthy older adults monitored over a span of five months repetitively. We systematically evaluated personal exposure to a diverse range of airborne organic pollutants using a wearable passive sampler and their effects on lung function. Participants' pulmonary function indicators were assessed, complemented by comprehensive multi-omics analyses of blood and urine samples. Leveraging the power of interaction analysis, causal inference test (CIT), and integrative pathway analysis (IPA), we explored intricate relationships between specific organic pollutants, biomolecules, and lung function deterioration, elucidating the biological mechanisms underpinning the adverse impacts of these pollutants. We observed that bis (2-chloro-1-methylethyl) ether (BCIE) was significantly associated with negative changes in the forced vital capacity (FVC), with glycerolipids mitigating this adverse effect. Additionally, 31 canonical pathways [e.g., high mobility group box 1 (HMGB1) signaling, phosphatidylinositol 3-kinase (PI3K)/AKT pathway, epithelial mesenchymal transition, and heme and nicotinamide adenine dinucleotide (NAD) biosynthesis] were identified as potential mechanisms. These findings may hold significant implications for developing effective strategies to prevent and mitigate respiratory health risks arising from exposure to such airborne pollutants. However, due to certain limitations of the study, our results should be interpreted with caution.
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Poluentes Atmosféricos , Humanos , Idoso , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Masculino , Feminino , China , Estudos Longitudinais , Pessoa de Meia-Idade , Pulmão/efeitos dos fármacos , Exposição Ambiental/efeitos adversos , Testes de Função Respiratória , Capacidade Vital/efeitos dos fármacosRESUMO
Although extended pluripotent stem cells (EPSCs) have the potential to form both embryonic and extraembryonic lineages, how their transcriptional regulatory mechanism differs from that of embryonic stem cells (ESCs) remains unclear. Here, we discovered that YY1 binds to specific open chromatin regions in EPSCs. Yy1 depletion in EPSCs leads to a gene expression pattern more similar to that of ESCs than control EPSCs. Moreover, Yy1 depletion triggers a series of epigenetic crosstalk activities, including changes in DNA methylation, histone modifications and high-order chromatin structures. Yy1 depletion in EPSCs disrupts the enhancer-promoter (EP) interactions of EPSC-specific genes, including Dnmt3l. Yy1 loss results in DNA hypomethylation and dramatically reduces the enrichment of H3K4me3 and H3K27ac on the promoters of EPSC-specific genes by upregulating the expression of Kdm5c and Hdac6 through facilitating the formation of CCCTC-binding factor (CTCF)-mediated EP interactions surrounding their loci. Furthermore, single-cell RNA sequencing (scRNA-seq) experiments revealed that YY1 is required for the derivation of extraembryonic endoderm (XEN)-like cells from EPSCs in vitro. Together, this study reveals that YY1 functions as a key regulator of multidimensional epigenetic crosstalk associated with extended pluripotency.
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Blastocisto , Epigênese Genética , Fator de Transcrição YY1 , Cromatina/genética , Cromatina/metabolismo , Células-Tronco Embrionárias/metabolismo , Regiões Promotoras Genéticas , Fator de Transcrição YY1/metabolismo , Camundongos , Animais , Blastocisto/citologia , Blastocisto/metabolismoRESUMO
In this paper, the kinematic models of the Strapdown Inertial Navigation System (SINS) and its errors on the SE(3) group in the Earth-Centered Inertial frame (ECI) are established. On the one hand, with the ECI frame being regarded as the reference, based on the joint representation of attitude and velocity on the SE(3) group, the dynamic of the local geographic coordinate system (n-frame) and the body coordinate system (b-frame) evolve on the differentiable manifold, respectively, and the high-order expansion of the Baker-Campbell-Haussdorff equation compensates for the non-commutative motion errors stimulated by strong maneuverability. On the other hand, the kinematics of the left- and right-invariant errors of the n-frame and the b-frame on the SE(3) group are separately derived, where the errors of the b-frame completely depend on inertial sensor errors, while the errors of the n-frame rely on position errors and velocity errors. In this way, the errors brought by the inconsistency of the reference coordinate system are tackled, and a novel attitude error definition is introduced to separate and decouple the factors affecting the dynamic of the n-frame errors and the b-frame errors for better attitude estimation. Through a turntable experiment and a car-mounted field experiment, the effectiveness of the proposed kinematic models in estimating attitude has been verified, with a remarkable improvement in yaw angle accuracy in the case of large initial misalignment angles, and the models developed have better robustness compared to the traditional SE(3) group-based model.
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This paper aims to study the spectrum-effect relationship between the fingerprints before and after salt processing of Dipsacus asper and the efficacy of warming and tonifying kidney Yang and find the main active components against kidney Yang deficiency before and after salt processing of D. asper, so as to provide the basis for clarifying the effect of salt processing on kidney Yang deficiency. The HPLC fingerprint before and after salt processing of D. asper was established by the HPLC-DAD. 15 common peaks were obtained, and 11 components were identified. The content changes of various components in rat serum were detected, and the difference in efficacy before and after salt processing was compared. The results of pharmacological experiments showed that salt processing of D. asper could enhance the kidney index. At the same dose, there was a significant difference between the raw D. asper and D. asper after salt processing groups. Compared with the model group, the contents of ACTH, cAMP, CORT, E_2, GH, Na~+-K~+-ATPase, T, and T4 in the serum of rats in the administration group increased to a certain extent, and the contents of cGMP and TNF-α decreased to a certain extent. Among them, there were significant differences in the above indexes in the serum of rats in the high-dose group of raw D. asper, middle-dose group of D. asper after salt processing, high-dose group of D. asper after salt processing, and the positive drug group. The overall results showed that D. asper after salt processing was more effective than raw D. asper in preventing kidney yang deficiency. The efficacy of D. asper was evaluated by grey correlation analysis, entropy method, and Pearson correlation analysis, and the components of D. asper after salt processing against kidney yang deficiency were screened out. According to the results of correlation degree ranking, the components with increased ranking before and after salt processing of D. asper were loganin, chlorogenic acid, dipsacoside A, asperosaponin â ¥, caffeic acid, and isochlorogenic acid B. It was preliminarily speculated that these compounds may be the potential pharmacodynamic components for the treatment of kidney yang deficiency before and after salt processing of D. asper. The changing components before and after the salt processing of D. asper were determined, which proved that D. asper after salt processing was superior to D. asper in the treatment of kidney yang deficiency. The spectrum-effect relationship between the efficacy of D. asper before and after salt processing and the treatment of kidney yang deficiency was established, which laid a foundation for the subsequent study on the pharmacodynamic components and molecular mechanism of salt processing of D. asper.
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Dipsacaceae , Medicamentos de Ervas Chinesas , Rim , Deficiência da Energia Yang , Animais , Ratos , Dipsacaceae/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino , Deficiência da Energia Yang/tratamento farmacológico , Deficiência da Energia Yang/fisiopatologia , Rim/efeitos dos fármacos , Ratos Sprague-Dawley , Cromatografia Líquida de Alta Pressão , Nefropatias/tratamento farmacológico , Nefropatias/fisiopatologiaRESUMO
The inhalation exposure of pesticide applicators and residents who live close to pesticide-treated fields is a worldwide concern in public health. Quantitative assessment of exposure to pesticide inhalation health risk highlights the need to accurately assess the bioaccessibility rather than the total content in ambient air. Herein, we developed an in vitro method to estimate the inhalation bioaccessibility of emamectin benzoate and validated its applicability using a rat plasma pharmacokinetic bioassay. Emamectin benzoate was extracted using the Gamble solution, with an optimized solid-to-liquid ratio (1/250), extraction time (24 h), and agitation (200 rpm), which obtained in vitro inhalation bioaccessibility consistent with its inhalation bioavailability in vivo (32.33%). The margin of exposure (MOE) was used to assess inhalation exposure risk. The inhalation unit exposures to emamectin benzoate of applicators and residents were 11.05-28.04 and 0.02-0.04 ng/m3, respectively, varying markedly according to the methods of application, e.g., formulations and nozzles. The inhalation risk assessment using present application methods appeared to be acceptable; however, the MOE of emamectin benzoate might be overestimated by 32% without considering inhalation bioaccessibility. Collectively, our findings contribute insights into the assessment of pesticide inhalation exposure based on bioaccessibility and provide guidance for the safe application of pesticides.
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Resíduos de Praguicidas , Praguicidas , Animais , Ratos , Exposição por Inalação , Ivermectina/análise , Resíduos de Praguicidas/análiseRESUMO
Real-time monitoring and quantitative measurement of molecular exchange between different microdomains are useful to characterize the local dynamics in porous media and biomedical applications of magnetic resonance. Diffusion exchange spectroscopy (DEXSY) is a noninvasive technique for such measurements. However, its application is largely limited by the involved long acquisition time and complex parameter estimation. In this study, we introduce a physics-guided deep neural network that accelerates DEXSY acquisition in a data-driven manner. The proposed method combines sampling pattern optimization and physical parameter estimation into a unified framework. Comprehensive simulations and experiments based on a two-site exchange system are conducted to demonstrate this new sampling optimization method in terms of accuracy, repeatability, and efficiency. This general framework can be adapted for other molecular exchange magnetic resonance measurements.
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Highly photoactive 3D nanoflower-like FeIn2S4/CdS heterostructures were synthesized by hydrothermal treatment and low-temperature cation exchange. The FeIn2S4/CdS displayed 14.5 times signal amplification in contrast to FeIn2S4 alone. It was applied as a photoactive substrate to construct a label-free photoelectrochemical (PEC) aptasensor for ultrasensitive determination of kanamycin (KAN). Under the optimal conditions, the constructed PEC aptasensor displayed a wide linear range (5.0 × 10-4 ~ 5.0 × 101 ng mL-1) and a low detection limit (S/N = 3) of 40.01 fg mL-1. This study provides some constructive insights for preparation of advanced photoactive materials and exhibits great potential for quantitative determination of antibiotics in foods and environmental samples.
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Aptâmeros de Nucleotídeos , Técnicas Eletroquímicas , Canamicina , Aptâmeros de Nucleotídeos/química , AntibacterianosRESUMO
The development of inertial confinement fusion (ICF) experiments necessitates the diagnostic instrument to have multiple frames with a high spatial and temporal resolution for the two-dimensional detection of the hot spot at the implosion end of the ICF. The existing sampling two-dimensional imaging technology in the world has superior performance; however, its subsequent development requires a streak tube with large lateral magnification. In this work, an electron beam separation device was designed and developed for the first time. The device can be used without changing the structure of the streak tube. It can be combined directly with the corresponding device and matched with a special control circuit. Based on the original transverse magnification, 1.77 times the secondary amplification can be achieved, which is conducive to expanding the recording range of the technology. The experimental results showed that the static spatial resolution of the streak tube after the inclusion of the device can still reach 10 lp/mm.
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PURPOSE: The study aimed to examine the pattern of motorization and the mortality rate related to road traffic crashes in Zunyi (a city in northern Guizhou province of China) from 2013 to 2022, and to identify the epidemiological characteristics of these crashes with to provide insights that could help improve road safety. METHODS: Data were obtained from the Zunyi traffic management data platform, and the mortality rates were calculated. We deployed various analytical methods, including descriptive analysis, Chi-square test or Fisher's exact test of categorical variable, circular distribution map analysis, and Rayleigh test to characterize the traits of road traffic crashes in the region. RESULTS: During the 10-year study period, 7488 people died due to road traffic accidents, with males accounting for 70.4% and females 29.6% (χ2 = 101.97, p < 0.001). The mortality rate increased from 7.80 deaths per 100,000 people in 2013 to 10.70 deaths per 100,000 people in 2016, but then decreased to 9.54 deaths per 100,000 people in 2019. A notable finding was that the death rate per 10,000 vehicles declined from 16.09 deaths per 10,000 vehicles in 2013 to 5.48 deaths per 10,000 vehicles in 2022. The study also found that vulnerable road users represented nearly half (48.76%) of all accident fatalities, and unlicensed or inexperienced driving contributed significantly to the occurrence of road traffic accidents. CONCLUSION: Although the number of road traffic accidents in Zunyi has decreased, there are still some critical issues that need to be addressed, particularly for vulnerable road users and unlicensed drivers. Our results highlight the need of targeted interventions to address the specific risk factors of road traffic crashes, particularly those affecting vulnerable road users and drivers without sufficient experience or license.