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OBJECTIVE: To explore the performance of ultrasound image-based radiomics in predicting World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading of clear-cell renal cell carcinoma (ccRCC). METHODS: A retrospective study was conducted via histopathological examination on participants with ccRCC from January 2021 to August 2023. Participants were randomly allocated to a training set and a validation set in a 3:1 ratio. The maximum cross-sectional image of the lesion on the preoperative ultrasound image was obtained, with the region of interest (ROI) delineated manually. Radiomic features were computed from the ROIs and subsequently normalized using Z-scores. Wilcoxon test and least absolute shrinkage and selection operator (LASSO) regression were applied for feature reduction and model development. The performance of the model was estimated by indicators including area under the curve (AUC), sensitivity and specificity. RESULTS: A total of 336 participants (median age, 57 y; 106 women) with ccRCC were finally included, of whom 243 had low-grade tumors (grade 1-2) and 93 had high-grade tumors (grade 3-4). A total of 1163 radiomic features were extracted from the ROIs for model construction and 117 informative radiomics features selected by Wilcoxon test were submitted to LASSO. Our ultrasound-based radiomics model included 51 features and achieved AUCs of 0.90 and 0.79 for the training and validation sets, respectively. Within the training set, the sensitivity and specificity measured 0.75 and 0.92, respectively, whereas in the validation set, the sensitivity and specificity measured 0.65 and 0.84, respectively. In the subgroup analysis, for the training and validation sets Philips AUCs were 0.91 and 0.75, Toshiba AUCs were 0.82 and 0.90, and General Electric AUCs were 0.95 and 0.82, respectively. CONCLUSION: Ultrasound-based radiomics can effectively predict the WHO/ISUP grading of ccRCC.
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Carotid-femoral pulse wave velocity (Cf-PWV) can well predict the prognosis of the general population. However, whether Cf-PWV can be used as a prognostic indicator in maintenance hemodialysis (MHD) patients remains mysterious. The present study endeavored to explore the prognostic value of Cf-PWV among the MHD population. Patients who received MHD and underwent Cf-PWV examination at the hemodialysis center of Zhejiang Provincial People's Hospital between March 1, 2017 and October 15, 2019 were enrolled. Relevant clinical data were collected from these patients, who were subsequently followed up for a minimum of 1 year. During the follow-up period, the occurrence of all-cause death was recorded as a prognostic indicator. Based on the predetermined inclusion and exclusion criteria 178 patients were included in the final analysis. These patients were categorized into 2 groups based on Cf-PWV values: group 1 (Cf-PWVâ <â 13.8 m/s), and group 2 (Cf-PWVâ ≥â 13.8 m/s). Thirty-four patients succumbed to their conditions within a median follow-up period of 23.3 months. Kaplan-Meier survival analysis revealed that the median survival time of group 2 was significantly shorter than group 1 (log-rank test, χ2â =â 12.413, Pâ <â .001). After adjusting for various factors, including age, cardiovascular disease, peripheral arterial diastolic pressure, central arterial diastolic pressure, albumin, blood urea nitrogen, serum creatinine, left ventricular ejection fraction, 25 hydroxyvitamin D3, C-reactive protein and serum phosphorus, it was found that Cf-PWVâ ≥â 13.8m/s was an independent risk factor for all-cause mortality in MHD patients (relative riskâ =â 3.04, 95% confidence interval [CI]â =â 1.22-7.57; Pâ =â .017). A high level of Cf-PWV (≥13.8 m/s) is an independent risk factor for all-cause death in MHD patients.
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Velocidade da Onda de Pulso Carótido-Femoral , Diálise Renal , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Prognóstico , Idoso , Estimativa de Kaplan-Meier , Falência Renal Crônica/terapia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/mortalidade , Fatores de Risco , Análise de Onda de Pulso , AdultoRESUMO
Lamiales, comprising over 23,755 species across 24 families, stands as a highly diverse and prolific plant group, playing a significant role in the cultivation of horticultural, ornamental, and medicinal plant varieties. Whole-genome duplication (WGD) and its subsequent post-polyploid diploidization (PPD) process represent the most drastic type of karyotype evolution, injecting significant potential for promoting the diversity of this lineage. However, polyploidization histories, as well as genome and subgenome fractionation following WGD events in Lamiales species, are still not well investigated. In this study, we constructed a chromosome-level genome assembly of Lindenbergia philippensis (Orobanchaceae) and conducted comparative genomic analyses with 14 other Lamiales species. L. philippensis is positioned closest to the parasitic lineage within Orobanchaceae and has a conserved karyotype. Through a combination of Ks analysis and syntenic depth analysis, we reconstructed and validated polyploidization histories of Lamiales species. Our results indicated that Primulina huaijiensis underwent three rounds of diploidization events following the γ-WGT event, rather than two rounds as reported. Besides, we reconfirmed that most Lamiales species shared a common diploidization event (L-WGD). Subsequently, we constructed the Lamiales Ancestral Karyotype (LAK), comprising 11 proto-chromosomes, and elucidated its evolutionary trajectory, highlighting the highly flexible reshuffling of the Lamiales paleogenome. We identified biased fractionation of subgenomes following the L-WGD event across eight species, and highlighted the positive impacts of non-WGD genes on gene family expansion. This study provides novel genomic resources and insights into polyploidy and karyotype remodeling of Lamiales species, essential for advancing our understanding of species diversification and genome evolution.
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The IscB proteins, as the ancestors of Cas9 endonuclease, hold great promise due to their small size and potential for diverse genome editing. However, their activity in mammalian cells is unsatisfactory. By introducing three residual substitutions in IscB, we observed an average 7.5-fold increase in activity. Through fusing a sequence-non-specific DNA-binding protein domain, the eIscB-D variant achieved higher editing efficiency, with a maximum of 91.3%. Moreover, engineered ωRNA was generated with a 20% reduction in length and slightly increased efficiency. The engineered eIscB-D/eωRNA system showed an average 20.2-fold increase in activity compared with the original IscB. Furthermore, we successfully adapted eIscB-D for highly efficient cytosine and adenine base editing. Notably, eIscB-D is highly active in mouse cell lines and embryos, enabling the efficient generation of disease models through mRNA/ωRNA injection. Our study suggests that these miniature genome-editing tools have great potential for diverse applications.
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Sistemas CRISPR-Cas , Edição de Genes , Animais , Edição de Genes/métodos , Camundongos , Humanos , Embrião de Mamíferos/metabolismo , Células HEK293 , Engenharia de Proteínas/métodosRESUMO
How dysregulated liquid-liquid phase separation (LLPS) contributes to the oncogenesis of female triple-negative breast cancer (TNBC) remains unknown. Here we demonstrate that phosphorylated histone deacetylase 6 (phospho-HDAC6) forms LLPS condensates in the nuclei of TNBC cells that are essential for establishing aberrant chromatin architecture. The disordered N-terminal domain and phosphorylated residue of HDAC6 facilitate effective LLPS, whereas nuclear export regions exert a negative dominant effect. Through phase-separation-based screening, we identified Nexturastat A as a specific disruptor of phospho-HDAC6 condensates, which effectively suppresses tumor growth. Mechanistically, importin-ß interacts with phospho-HDAC6, promoting its translocation to the nucleus, where 14-3-3θ mediates the condensate formation. Disruption of phospho-HDAC6 LLPS re-established chromatin compartments and topologically associating domain boundaries, leading to disturbed chromatin loops. The phospho-HDAC6-induced aberrant chromatin architecture affects chromatin accessibility, histone acetylation, RNA polymerase II elongation and transcriptional profiles in TNBC. This study demonstrates phospho-HDAC6 LLPS as an emerging mechanism underlying the dysregulation of chromatin architecture in TNBC.
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Objectives: To investigate the role of the intestinal flora and metabolites in the development of hyperuricemic renal injury in chronic kidney disease (CKD).Methods: Unilaterally nephrectomized mice were fed with adenine and potassium oxonate for 9 weeks. HE staining combined with plasma biochemical indicators was used to evaluate renal pathological and functional changes. We conducted 16S rRNA sequencing and untargeted metabolomics on feces and plasma samples to reveale changes in intestinal microbiota and metabolites.Result: Our analysis revealed significant differences in 15 bacterial genera, with 7 being upregulated and 8 being downregulated. Furthermore, metabolomic analysis revealed changes in the distribution of amino acid and biotin metabolites in basic metabolic pathways in both feces and serum. Specifically, differentially abundant metabolites in feces were associated primarily with histidine metabolism; the biosynthesis of phenylalanine, tyrosine, and tryptophan; and tyrosine metabolism. In plasma, the differentially abundant metabolites were involved in multiple metabolic pathways, including aminoacyl-tRNA biosynthesis; glycine, serine, and threonine amino acid metabolism; valine, leucine, and isoleucine biosynthesis; tyrosine biosynthesis and metabolism; biotin metabolism; and taurine and hypotaurine metabolism. Furthermore, correlation analysis revealed that Akkermansia, UCG-005, Lachnospiraceae_NK4A136_group, Lactococcus, and Butymonas were associated with various differentially abundant metabolites as well as renal function, oxidative stress, and mitophagy. The changes in the intestinal flora observed in hyperuricemia may lead to imbalances in amino acid and biotin metabolism in both the intestine and host, ultimately affecting oxidative stress and mitophagy in mice and accelerating the progression of CKD.Conclusion: Our findings provide insights into a potential pathogenic mechanism by which hyperuricemia exacerbates renal injury in mice with renal insufficiency. Understanding these pathways may offer new therapeutic strategies for managing hyperuricemic renal injury in CKD patients.
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Modelos Animais de Doenças , Microbioma Gastrointestinal , Hiperuricemia , Animais , Hiperuricemia/metabolismo , Camundongos , Masculino , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/microbiologia , Metabolômica/métodos , Fezes/microbiologia , RNA Ribossômico 16S , Camundongos Endogâmicos C57BL , Rim/metabolismo , Rim/patologiaRESUMO
A novel 3D nitrogen-doped porous carbon supported Fe-Cu bimetallic nanoparticles composite (Fe-Cu-N-PC) was prepared via direct pyrolysis by employing black liquor lignin as a main precursor, and it was utilized as a novel catalyst for PMS activation in degrading naphthalene. Under the optimum experimental conditions, the naphthalene degradation rate was up to 93.2% within 60 min in the Fe-Cu-N-PC/PMS system. The porous carbon framework of Fe-Cu-N-PC could facilitate the quick molecule diffusion of reactants towards the inner bimetallic nanoparticles and enriched naphthalene molecules from the solution by a specific adsorption, which increased the odds of contact between naphthalene and reactive oxygen species and improved the reaction efficiency. The quenching reaction proved that the non-free radical pathway dominated by 1O2 was the main way in naphthalene degradation, while the free radical pathway involving SO4·- and ·OH only played a secondary role. Moreover, owing to its high magnetization performance, Fe-Cu-N-PC could be magnetically recovered and maintained excellent naphthalene degradation rate after four degradation cycles. This research will offer a theoretical basis for the construction of facile, efficient, and green technologies to remediate persistent organic pollutants in the environment.
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Carbono , Cobre , Ferro , Lignina , Nanopartículas Metálicas , Naftalenos , Nitrogênio , Naftalenos/química , Carbono/química , Cobre/química , Ferro/química , Porosidade , Lignina/química , Nitrogênio/química , Nanopartículas Metálicas/química , AdsorçãoRESUMO
Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aß and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aß, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aß: ß-amyloid, GABA: gamma-aminobutyric acid.
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Neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD), pose significant global health risks and represent a substantial public health concern in the contemporary era. A primary factor in the pathophysiology of these disorders is aberrant accumulation and aggregation of pathogenic proteins within the brain and spinal cord. Recent investigations have identified extracellular vesicles (EVs) in the central nervous system (CNS) as potential carriers for intercellular transport of misfolded proteins associated with neurodegenerative diseases. EVs are involved in pathological processes that contribute to various brain disorders including neurodegenerative disorders. Proteins linked to neurodegenerative disorders are secreted and distributed from cell to cell via EVs, serving as a mechanism for direct intercellular communication through the transfer of biomolecules. Astrocytes, as active participants in CNS intercellular communication, release astrocyte-derived extracellular vesicles (ADEVs) that are capable of interacting with diverse target cells. This review primarily focuses on the involvement of ADEVs in the development of neurological disorders and explores their potential dual roles - both advantageous and disadvantageous in the context of neurological disorders. Furthermore, this review examines the current studies investigating ADEVs as potential biomarkers for the diagnosis and treatment of neurodegenerative diseases. The prospects and challenges associated with the application of ADEVs in clinical settings were also comprehensively reviewed.
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Surface enhanced Raman spectroscopy (SERS) utilizes the fingerprint features of molecular vibrations to identify and detect substances. However, in traditional single focus excitation scenarios, its signal collection efficiency of the objective is restricted. Furthermore, the uneven distribution of samples on the SERS substrate would result in poor signal stability, while the excitation power is limited to avoid sample damage. SERS detection system always requires precise adjustment of focal length and spot size, making it difficult for point-of-care testing applications. Here, we proposed a SERS microfluidic chip with barium titanate microspheres array (BTMA) embedded using vacuum self-assembled hot-pressing method for SERS detection with simultaneous enhancement of sensitivity and stability. Due to photonic nano-jets and directional antenna effects, high index microspheres are perfect micro-lens for effective light focusing and signal collecting. The BTMA can not only disperse excitation beam into an array of focal points covering the target uniformly with very low signal fluctuation, but enlarge the power threshold for higher signal intensity. We conducted a proof-of-principle experiment on chip for the detection of bacteria with immuno-magnetic tags and immuno-SERS tags. Together with magnetic and ultrasonic operations, the target bacteria in the flow were evenly congregated on the focal plane of BTMA. It demonstrated a limit of detection of 5 cells/mL, excellent signal reproducibility (errorâ¼4.84%), and excellent position tolerance of 500 µm in X-Y plane (errorâ¼5.375%). It can be seen that BTMA-SERS microfluidic chip can effectively solve the contradiction between sensitivity and stability in SERS detection.
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Técnicas Biossensoriais , Dispositivos Lab-On-A-Chip , Microesferas , Análise Espectral Raman , Análise Espectral Raman/instrumentação , Análise Espectral Raman/métodos , Técnicas Biossensoriais/instrumentação , Limite de Detecção , Desenho de Equipamento , Titânio/química , Lentes , Escherichia coli/isolamento & purificaçãoRESUMO
Cancer, a prevalent and complex disease, presents a significant challenge to the medical community. It is characterized by irregular cell differentiation, excessive proliferation, uncontrolled growth, invasion of nearby tissues, and spread to distant organs. Its progression involves a complex interplay of several elements and processes. Extracellular vesicles (EVs) serve as critical intermediaries in intercellular communication, transporting critical molecules such as lipids, RNA, membrane, and cytoplasmic proteins between cells. They significantly contribute to the progression, development, and dissemination of primary tumors by facilitating the exchange of information and transmitting signals that regulate tumor growth and metastasis. However, EVs do not have a singular impact on cancer; instead, they play a multifaceted dual role. Under specific circumstances, they can impede tumor growth and influence cancer by delivering oncogenic factors or triggering an immune response. Furthermore, EVs from different sources demonstrate distinct advantages in inhibiting cancer. This research examines the biological characteristics of EVs and their involvement in cancer development to establish a theoretical foundation for better understanding the connection between EVs and cancer. Here, we discuss the potential of EVs from various sources in cancer therapy, as well as the current status and future prospects of engineered EVs in developing more effective cancer treatments.
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Vesículas Extracelulares , Neoplasias , Vesículas Extracelulares/metabolismo , Humanos , Neoplasias/terapia , Neoplasias/patologia , Neoplasias/metabolismo , Comunicação Celular , AnimaisRESUMO
Polycyclic aromatic hydrocarbons (PAHs) are the primary organic carbons in soot. In addition to PAHs with even carbon numbers (PAHeven), substantial odd-carbon PAHs (PAHodd) have been widely observed in soot and ambient particles. Analyzing and understanding the photoaging of these compounds are essential for assessing their environmental effects. Here, using laser desorption ionization mass spectrometry (LDI-MS), we reveal the substantially different photoreactivity of PAHodd from PAHeven in the aging process and their MS detection through their distinct behaviors in the presence and absence of elemental carbon (EC) in soot. During direct photooxidation of organic carbon (OC) alone, the PAHeven are oxidized more rapidly than the PAHodd. However, the degradation of PAHodd becomes preponderant over PAHeven in the presence of EC during photoaging of the whole soot. All of these observations are proposed to originate from the more rapid hydrogen abstraction reaction from PAHodd in the EC-photosensitized reaction, owing to its unique structure of a single sp3-hybridized carbon site. Our findings reveal the photoreactivity and reaction mechanism of PAHodd for the first time, providing a comprehensive understanding of the oxidation of PAHs at a molecular level during soot aging and highlight the enhanced effect of EC on PAHodd ionization in LDI-MS analysis.
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Carbono , Hidrocarbonetos Policíclicos Aromáticos , Fuligem , Hidrocarbonetos Policíclicos Aromáticos/química , Carbono/química , Fuligem/química , Processos Fotoquímicos , Oxirredução , FotoquímicaRESUMO
Increasing planting density is a key strategy for enhancing maize yields1-3. An ideotype for dense planting requires a 'smart canopy' with leaf angles at different canopy layers differentially optimized to maximize light interception and photosynthesis4-6, among other features. Here we identified leaf angle architecture of smart canopy 1 (lac1), a natural mutant with upright upper leaves, less erect middle leaves and relatively flat lower leaves. lac1 has improved photosynthetic capacity and attenuated responses to shade under dense planting. lac1 encodes a brassinosteroid C-22 hydroxylase that predominantly regulates upper leaf angle. Phytochrome A photoreceptors accumulate in shade and interact with the transcription factor RAVL1 to promote its degradation via the 26S proteasome, thereby inhibiting activation of lac1 by RAVL1 and decreasing brassinosteroid levels. This ultimately decreases upper leaf angle in dense fields. Large-scale field trials demonstrate that lac1 boosts maize yields under high planting densities. To quickly introduce lac1 into breeding germplasm, we transformed a haploid inducer and recovered homozygous lac1 edits from 20 diverse inbred lines. The tested doubled haploids uniformly acquired smart-canopy-like plant architecture. We provide an important target and an accelerated strategy for developing high-density-tolerant cultivars, with lac1 serving as a genetic chassis for further engineering of a smart canopy in maize.
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Produção Agrícola , Fotossíntese , Folhas de Planta , Zea mays , Brassinosteroides/metabolismo , Produção Agrícola/métodos , Escuridão , Haploidia , Homozigoto , Luz , Mutação , Fotossíntese/efeitos da radiação , Fitocromo A/metabolismo , Melhoramento Vegetal , Folhas de Planta/anatomia & histologia , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Folhas de Planta/efeitos da radiação , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Fatores de Transcrição/metabolismo , Zea mays/anatomia & histologia , Zea mays/enzimologia , Zea mays/genética , Zea mays/crescimento & desenvolvimento , Zea mays/efeitos da radiaçãoRESUMO
The anaerobic membrane bioreactor (AnMBR) is a promising technology for not only water reclamation but also virus removal; however, the virus removal efficiency of AnMBR has not been fully investigated. Additionally, the removal efficiency estimation requires datasets of virus concentration in influent and effluent, but its monitoring is not easy to perform for practical operation because the virus quantification process is generally time-consuming and requires specialized equipment and trained personnel. Therefore, in this study, we aimed to identify the key, monitorable variables in AnMBR and establish the data-driven models using the selected variables to predict virus removal efficiency. We monitored operational and environmental conditions of AnMBR in Sendai, Japan and measured virus concentration once a week for six months. Spearman's rank correlation analysis revealed that the pH values of influent and mixed liquor suspended solids (MLSS) were strongly correlated with the log reduction value of pepper mild mottle virus, indicating that electrostatic interactions played a dominant role in AnMBR virus removal. Among the candidate models, the random forest model using selected variables including influent and MLSS pH outperformed the others. This study has demonstrated the potential of AnMBR as a viable option for municipal wastewater reclamation with high microbial safety.
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Reatores Biológicos , Membranas Artificiais , Reatores Biológicos/virologia , Anaerobiose , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/virologia , Projetos Piloto , Purificação da Água/métodos , Purificação da Água/instrumentação , Tobamovirus/isolamento & purificação , JapãoRESUMO
Photothermal microscopy is a highly sensitive pump-probe method for mapping nanostructures and molecules through the detection of local thermal gradients. While visible photothermal microscopy and mid-infrared photothermal microscopy techniques have been developed, they possess inherent limitations. These techniques either lack chemical specificity or encounter significant light attenuation caused by water absorption. Here, we present an overtone photothermal (OPT) microscopy technique that offers high chemical specificity, detection sensitivity, and spatial resolution by employing a visible probe for local heat detection in the C-H overtone region. We demonstrate its capability for high-fidelity chemical imaging of polymer nanostructures, depth-resolved intracellular chemical mapping of cancer cells, and imaging of multicellular C. elegans organisms and highly scattering brain tissues. By bridging the gap between visible and mid-infrared photothermal microscopy, OPT establishes a new modality for high-resolution and high-sensitivity chemical imaging. This advancement complements large-scale shortwave infrared imaging approaches, facilitating multiscale structural and chemical investigations of materials and biological metabolism.
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Caenorhabditis elegans , Microscopia , Animais , Microscopia/métodos , Humanos , Vibração , Nanoestruturas/química , Encéfalo/diagnóstico por imagem , Polímeros/química , Linhagem Celular TumoralRESUMO
Mycobacterium tuberculosis causes 6.4 million cases of tuberculosis and claims 1.6 million lives annually. Mycobacterial adhesion, invasion of host cells, and subsequent intracellular survival are crucial for the infection and dissemination process, yet the cellular mechanisms underlying these phenomena remain poorly understood. This study created a Bacillus Calmette-Guérin (BCG) transposon library using a MycomarT7 phage carrying a Himar1 Mariner transposon to identify genes related to mycobacteria adhesion and invasion. Using adhesion and invasion model screening, we found that the mutant strain B2909 lacked adhesion and invasion abilities because of an inactive fadD18 gene, which encodes a fatty-acyl CoA ligase, although the specific function of this gene remains unclear. To investigate the role of FadD18, we constructed a complementary strain and observed that fadD18 expression enhanced the colony size and promoted the formation of a stronger cord-like structure; FadD18 expression also inhibited BCG growth and reduced BCG intracellular survival in macrophages. Furthermore, FadD18 expression elevated levels of the proinflammatory cytokines IL-6, IL-1ß, and TNF-α in infected macrophages by stimulating the NF-κB and MAPK signaling pathways. Overall, the FadD18 plays a key role in the adhesion and invasion abilities of mycobacteria while modulating the intracellular survival of BCG by influencing the production of proinflammatory cytokines.
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Citocinas , Mycobacterium tuberculosis , Citocinas/metabolismo , Macrófagos/microbiologia , Macrófagos/metabolismo , Mycobacterium bovis , Camundongos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Animais , Humanos , NF-kappa B/metabolismo , Viabilidade Microbiana , Aderência BacterianaRESUMO
Spin in semiconductors facilitates magnetically controlled optoelectronic and spintronic devices. In metal halide perovskites (MHPs), doping magnetic ions is proven to be a simple and efficient approach to introducing a spin magnetic momentum. In this work, we present a facile metal ion doping protocol through the vapor-phase metal halide insertion reaction to the chemical vapor deposition (CVD)-grown ultrathin Cs3BiBr6 perovskites. The Fe-doped bismuth halide (Fe:CBBr) perovskites demonstrate that the iron spins are successfully incorporated into the lattice, as revealed by the spin-phonon coupling below the critical temperature Tc around 50 K observed through temperature-dependent Raman spectroscopy. Furthermore, the phonons exhibit significant softening under an applied magnetic field, possibly originating from magnetostriction and spin exchange interaction. The spin-phonon coupling in Fe:CBBr potentially provides an efficient way to tune the spin and lattice parameters for halide perovskite-based spintronics.
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OBJECTIVE: To summary radiating blood flow signals and evaluate their diagnostic value in differentiating benign and malignant thyroid nodules. MATERIALS AND METHODS: We retrospectively recruited consecutive patients undergoing US at 4 hospitals from 2018 to 2022. In a training dataset, the correlations of US features with malignant thyroid nodules were assessed by multivariate logistic analysis. Multivariate logistic regression models involving the ACR TI-RADS score, radiating blood flow signals and their combination were built and validated internally and externally. The AUC with 95% asymptotic normal confidence interval as well as sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with 95% exact binomial confidence intervals were calculated. RESULTS: Among 2475 patients (1818 women, age: 42.47 ± 11.57; 657 men, age: 42.16 ± 11.69), there were 3187 nodules (2342 malignant nodules and 845 benign nodules). Radiating blood flow signals were an independent risk factor for diagnosing thyroid carcinoma. In the training set, the AUC of the model using the combination of radiating blood flow signals and the ACR TI-RADS score (0.95 95 % CI: [0.94, 0.97]; P < 0.001) was significantly higher than that of the ACR TI-RADS model (0.91 [0.89, 0.93]). In the two internal validation sets and the external validation set, the AUCs of the combination model were 0.97 [0.96, 0.98], 0.92 [0.88, 0.96], and 0.91 [0.86, 0.95], respectively, and were all significantly higher than that of the ACR TI-RADS score (0.92 [0.90, 0.95], 0.86 [0.81, 0.91], 0.84 [0.79, 0.89]; P < 0.001). CONCLUSION: Radiating blood flow is a new US feature of thyroid carcinomas that can significantly improve the diagnostic performance vs. the ACR TI-RADS score.
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Sensibilidade e Especificidade , Neoplasias da Glândula Tireoide , Ultrassonografia , Humanos , Masculino , Feminino , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adulto , Estudos Retrospectivos , Ultrassonografia/métodos , Diagnóstico Diferencial , Pessoa de Meia-Idade , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/irrigação sanguíneaRESUMO
The exposure to cooking organic aerosols (COA) is closely related to people's daily lives. Despite extensive investigations into COA's model compounds like oleic acid, the intricacies of heterogeneous ozonolysis of real COA and the effects of ambient conditions like humidity remain elusive. In this work, the ozonolysis of COA proxies from heated peanut oil emissions was investigated using diffuse reflectance infrared Fourier transform (DRIFTS) spectroscopy, and proton transfer reaction time-of-flight mass spectrometer (PTR-ToF-MS). We found that humidity hinders the reaction between ozone and CC double bonds due to the competitive adsorption of water and ozone on COA. Although visible light has little influence on the ozonolysis of COA in the absence of humidity, the ozonolytic CO production is significantly promoted by visible light in the presence of humidity. It may be attributed to the formation of water-derived reactive oxygen species (ROS, mainly HOâ¢) from the photosensitization of polycyclic aromatic hydrocarbons (PAHs) in COA. We also found that humidity can enhance the depolymerization of carboxylic acid dimers and hydrolysis of intrinsic acetals in the COA. Moreover, humidity promotes the release of VOCs during both the dark and light ozonolysis of COA. This work reveals the important roles of humidity-responsive and photo-responsive components in COA during its ozonolysis, and the change in VOC release may guide the control of human VOC exposure in indoor air.
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Understanding nitrogen (N) uptake rates respect to nutrient availability and the biogeography of phytoplankton communities is crucial for untangling the complexities of marine ecosystems and the physical, biological, and chemical forces shaping them. In the summer of 2016, we conducted measurements of bulk microbial uptake rates for six 15N-labeled substrates: nitrate, nitrite, ammonium, urea, cyanate, and dissolve free amino acids across distinct marine provinces, including the continental shelf of the Mid-and South Atlantic Bights (MAB and SAB), the Slope Sea, and the Gulf Stream, marking the first instance of simultaneously measuring six different N uptake rates in this dynamic region. Total measured N uptake rates were lowest in the Gulf Stream followed by the SAB. Notably, the MAB exhibited significantly higher N uptake rates compared to the SAB, likely due to the excess levels of pre-existing phosphorus present in the MAB. Together, urea and nitrate uptake contributed approximately 50% of the total N uptake across the study region. Although cyanate uptake rates were consistently low, they accounted for up to 11% of the total measured N uptake at some Gulf Stream stations. Phytoplankton groups were identified based on specific pigment markers, revealing a dominance of diatoms in the shelf community, while Synechococcus, Prochlorococcus, and pico-eukaryotes dominated in oligotrophic Gulf Stream waters. The reported uptake rates in this study were mostly in agreement with previous studies conducted in coastal waters of the North Atlantic Ocean. This study suggests there are distinct regional patterns of N uptake in this physically dynamic region, correlating with nutrient availability and phytoplankton community composition. These findings contribute valuable insights into the intricate interplay of biological and chemical factors shaping N dynamics in disparate marine ecosystems.