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1.
J Colloid Interface Sci ; 677(Pt A): 470-480, 2025 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-39098280

RESUMO

Photocatalysis has emerged as a extremely promising green technology for the treatment of uranium-containing wastewater. This study focuses on the fabrication of Ti3C2Tx/Cd0.8Zn0.2S composites with Schottky junctions through the in-situ growth of Cd0.8Zn0.2S on Ti3C2Tx nanosheets, enabling efficient photoreduction of U(VI) without the requirement of sacrificial agents. The results demonstrate that the Ti3C2Tx/Cd0.8Zn0.2S composites achieve remarkable 99.48 % U(VI) reduction efficiency within 60 min in a 100 ppm uranium solution. Furthermore, the removal rate remains above 90 % after five cycles. The formation of Schottky heterojunctions by Ti3C2Tx and Cd0.8Zn0.2S leads to the generation of an internal electric field that significantly promotes the rapid separation and transfer of photogenerated carriers, thereby enhancing the photocatalytic reduction efficiency of Ti3C2Tx/Cd0.8Zn0.2S-3:100 (TC/CZS-3:100). A considerable amount of electrons accumulate on Ti3C2Tx via the Schottky barrier, effectively facilitating the reduction of U(VI) to U(IV). As a co-catalyst, Ti3C2Tx enhances the photocatalytic performance and stability of Cd0.8Zn0.2S. Moreover, the practical application in the waste liquid of rare earth tailings reveals that the removal rate can be as high as 91.24 %. This research is of significant value in the development of effective photocatalysts for the elimination of uranium from wastewater.

2.
J Colloid Interface Sci ; 679(Pt A): 420-429, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39368161

RESUMO

How to achieve controllable preparation of heterostructure and in-situ optimize the interface and internal electron transfer by a fast and economic synthesis method has become a big challenge in the practical application of photocatalysis. Herein, an island-shaped SrTiO3 (STO) perovskite nanodots and TiO2 (T) compounded S-scheme SrTiO3/TiO2 (ST) heterostructure was successfully developed. During the millisecond reaction process, the decomposed Sr2+ penetrated into the TiO2 lattice causing the lattice expansion and inducing local atomic rearrangements, resulting in the generation of STO phase. Owing to the synergy of the efficient electron transport at the perovskite nanodots interface and the stronger reduction capacity, the performance of the optimized ST1 sample is greatly improved to 86.90 µmol g-1 for CO2-to-CO and 21.31 µmol g-1 for CO2-to-CH4. The utilization of electrons reached up to 119.74 µmol g-1 h-1, which was 3.13 times higher than that of T. Detailed characterizations and density functional theory (DFT) calculations proof that the formation of intermediates HCOO- and CO32- is the key to the performance improvement critically. Overall, this work originally reports a feasible strategy for flame synthesis of S-scheme heterostructure photocatalyst.

3.
Biosens Bioelectron ; 267: 116836, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39368295

RESUMO

In recent years, detection technology has made remarkable progress in the field of food safety, in vitro diagnosis, and environment monitoring under the impetus of trace substances detection requirements. However, in sharp contrast to the rapid development of detection technology, its marketization process is relatively lagging behind. One possible approach is to integrate novel sensing strategies with mature commercial devices, such as personal glucose meters (PGMs) and pregnancy test strips (PTS) to speed up their marketization process. In this review, we systematically summarized design principle, evolution, and application progress for the integration of novel sensing strategies with commercial devices PGMs and PTS. Meanwhile, key factors and difficulties for the integration novel sensing strategies with commercial devices were emphasized. More importantly, the future of prospects and remaining challenges were discussed.

4.
J Am Chem Soc ; 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382312

RESUMO

Scanning tunneling microscopy (STM) is a powerful technique that provides the ability to manipulate and characterize individual atoms and molecules with atomic-level precision. However, the processes of scanning samples, operating the probe, and analyzing data are typically labor-intensive and subjective. Deep learning (DL) techniques have shown immense potential in automating complex tasks and solving high-dimensional problems. In this study, we developed an autonomous STM framework powered by DL to enable autonomous operations of the STM without human interventions. Our framework employs a convolutional neural network (CNN) for real-time evaluation of STM image quality, a U-net model for identifying bare surfaces, and a deep Q-learning network (DQN) agent for autonomous probe conditioning. Additionally, we integrated an object recognition model for the automated recognition of different adsorbates. This autonomous framework enables the acquisition of space-averaging information using STM techniques without compromising the high-resolution molecular imaging. We achieved measuring an area of approximately 1.9 µm2 within 48 h of continuous measurement and automatedly generated the statistics on the molecular species present within the mesoscopic area. We demonstrate the high robustness of the framework by conducting measurements at the liquid nitrogen temperature (∼78 K). We envision that the integration of DL techniques and high-resolution microscopy will not only extend the functionality and capability of scanning probe microscopes but also accelerate the understanding and discovery of new materials.

5.
Artigo em Chinês | MEDLINE | ID: mdl-39390930

RESUMO

Objective:To analyze the efficacy of endoscopic CO2 laser arytenoidectomy in treating bilateral vocal cord paralysis. Methods:Ninety-five patients who underwent endoscopic CO2 laser arytenoidectomy for bilateral vocal cord paralysis at the First Affiliated Hospital of Naval Medical University(Changhai Hospital) of Shanghai from January 2009 to December 2022 were included in this study. Among them, 59 patients underwent endoscopic CO2 laser arytenoidectomy as their first glottic enlargement surgery(Group A), while 36 patients, who had previously undergone two unsuccessful CO2 laser-assisted posterior cordotomies, underwent endoscopic CO2 laser arytenoidectomy as a subsequent surgery(Group B). Swallowing function, electronic laryngoscopy, perceptual voice evaluation, and objective voice analysis indicators were statistically analyzed before and after surgery to evaluate clinical efficacy. Results:The extubation rate after the first surgery was 84.75% in Group A and 86.11% in Group B, with total extubation rates of 94.92% and 94.44%, respectively. There were no significant differences between the two groups in preoperative and postoperative swallowing function, glottic size, or various voice evaluation indicators(P>0.05). Within-group comparisons showed that postoperative swallowing function, glottic closure during phonation, perceptual evaluations of G(grade of hoarseness), A(asthenia), and B(breathiness) significantly worsened, with increased grades. The maximum transverse diameter of the posterior glottis during inspiration significantly increased, and the VHI-10 score was significantly higher postoperatively. Jitter, shimmer, and the harmonics-to-noise ratio significantly deteriorated, and maximum phonation time significantly shortened(P<0.05). No significant differences were observed in postoperative R(roughness) and S(strain) compared to preoperative values(P>0.05). Conclusion:Endoscopic CO2 laser arytenoidectomy can impair voice quality to some extent but effectively alleviates breathing difficulties in patients with bilateral vocal cord paralysis. For patients who did not achieve successful extubation with CO2 laser-assisted posterior cordotomy, endoscopic CO2laser arytenoidectomy is an effective reoperative method, ensuring a high extubation rate while preserving certain voice functions.


Assuntos
Cartilagem Aritenoide , Lasers de Gás , Paralisia das Pregas Vocais , Humanos , Cartilagem Aritenoide/cirurgia , Lasers de Gás/uso terapêutico , Paralisia das Pregas Vocais/cirurgia , Masculino , Terapia a Laser/métodos , Laringoscopia/métodos , Feminino , Pessoa de Meia-Idade , Cordotomia/métodos , Reoperação , Resultado do Tratamento , Endoscopia/métodos , Adulto
6.
Antib Ther ; 7(4): 283-294, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39381136

RESUMO

Background: Single domain antibodies (sdAbs) possess unique characteristics that make them highly effective for developing complex therapeutics. Methods: Our process uses a fully synthetic phage display library to generate single domain antibodies that can bind to disease relevant antigen conformations. A human IGHV3 family scaffold makes up the phage display libraries, and these VHO libraries are applied to diverse phage biopannings against target antigens. After NGS processing, unique VHOs undergo automated cloning into expression constructs followed by transfections and purifications. Binding assays were used to determine VHO binding behaviors to the target proteins. Additional VHO interactions are measured against endogenous targets on cells by way of flow cytometry, cell internalization, and activation assays. Results: We show that a fully synthetic phage display library can generate VHOs that bind to disease relevant antigen conformations. The diverse biopanning methods and processing of next-generation sequencing generated many VHO paratopes. These different VHO sequences can be expressed as Fc fusion proteins. Various screening assays resulted in VHOs representing different epitopes or activities. During the hit evaluation, we demonstrate how screening can identify distinct VHO activities that have been used to generate differentiated drug molecules in various bispecific and multispecific antibody formats. Conclusion: We demonstrate how screening can identify distinct VHO activities that have been used to generate differentiated drug molecules in various bispecific and multispecific antibody formats.

7.
J Control Release ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39384152

RESUMO

Mild autophagy accompanied with immunogenic cell death (ICD) effect destructs immune-associated antigens, weakening the immune response against tumor growth. To address this dilemma, we develop a peptide-based bicomponent nanocarrier with encapsulation of a cellular hyperautophagy activator (STF-62247) for near-infrared (NIR) photo/immunotherapy to eliminate primary and metastatic breast tumors. The electrostatic-driven nanodrug (PPNPs@STF) with active-targeting and efficient endosomal escape can induce specific ICD effect upon NIR laser irradiation, and trigger autophagy to a mild activation state. Notably, the simultaneously released STF-62247 precisely promotes autophagy to an overactivated state, resulting in autophagic death of tumor cells and further boosting ICD-related antigen presentation. More importantly, the combined photo/immunotherapy of PPNPs@STF not only inhibits tumor cell proliferation, but also promotes dendritic cells (DCs)-associated immune response. In 4 T1 tumor-bearing mice, PPNPs@STF effectively inhibits growth of primary and distant tumors, and suppresses lung metastasis with a minimized side effect. This study provides a hyperautophagy activator-assisted strategy that can enhance ICD-based antitumor immune response for the treatment of metastatic breast cancer.

8.
Front Med (Lausanne) ; 11: 1413964, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39376649

RESUMO

Infection remains the leading cause of mortality in severe aplastic anemia (SAA) patients, with invasive fungal infections being the great threat. Aspergillus fumigatus accounts for most of the reported fungal infection cases. Here, we present a case of A. flavus infection in a patient with acute very severe aplastic anemia (VSAA) despite persistently negative clinical fungal tests. The patient was admitted to the hospital due to pancytopenia presisting for over a month and intermittent fever for 10 days. Elevated inflammatory indicators and abnormal lung imaging suggested infection, prompting consideration of fungal involvement. Despite negative results from multiple blood, sputum fungal cultures and the serum (1,3)-ß-D-glucan/galactomannan tests. Metagenomic next-generation sequencing (mNGS) on multiple blood samples, alongside clinical symptoms, confirmed A. flavus infection. Targeted antifungal treatment with liposomal amphotericin B and voriconazole significantly ameliorated pulmonary symptoms. Additionally, this study reviewed and compared the symptoms, diagnostic approaches, and treatments from prior Aspergillus infections in AA patients. It emphasizes critical role of early mNGS utilization in diagnosing and managing infectious diseases, offering insights for diagnosing and treating fungal infections in VSAA.

9.
Front Oncol ; 14: 1450020, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39376979

RESUMO

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of a number of patients with advanced cancer, and while this has resulted in increased survival times, it has also led to the emergence of novel immune-related adverse events (irAEs). In individuals with advanced cancer, sarcopenia is a significant symptom of cachexia and is linked to poor nutritional status and increased mortality. The present study aimed to evaluate sarcopenia and other risk variables that can affect the emergence of irAEs in patients with lung cancer. Methods: A single-center retrospective analysis of 129 patients with advanced lung cancer treated with programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) checkpoint inhibitors was conducted from August 2020 to August 2022. Data on baseline characteristics and adverse events of participants were collected. Computed tomography was used to determine the skeletal muscle index at the third lumbar vertebra (L3-SMI) and whether sarcopenia is present. Results: The median age of all participants was 60 years old (range, 52-66 years), with men accounting for 68.9% of the total patient cohort. The present study showed that 44 (34%) participants presented with any degree of irAEs, and 79 (61.2%) patients presented with sarcopenia. There were no statistically significant differences in baseline characteristics, such as age and sex, between patients who presented with irAEs and those without irAEs. Using logistic regression analysis, individuals with sarcopenia were 2.635-times more likely to experience any grade of irAEs than those without sarcopenia. Discussion: irAEs are prevalent side effects of PD-1/PD-L1 inhibitor therapy for patients with cancer. By diagnosing and treating sarcopenia early, it is possible to lower the potential risk of irAEs in patients with advanced cancer. Furthermore, sarcopenia can be utilized as a predictor of irAEs.

10.
Int J Chron Obstruct Pulmon Dis ; 19: 2181-2192, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39371920

RESUMO

Background: Opioids and benzodiazepines are frequently prescribed for managing pain and anxiety in chronic obstructive pulmonary disease (COPD) patients. This study aimed to determine whether opioid use, with or without benzodiazepine use, is associated with increased all-cause mortality in COPD patients. Methods: This prospective cohort study included adults aged ≥20 years with COPD from the US National Health and Nutrition Examination Survey 2007-2012. The primary outcome was all-cause mortality, which were obtained through linkage to registries. Weighted Cox proportional hazards regression models were used to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. Additionally, subgroup and sensitivity analyses were used to evaluate the robustness of our findings. Results: This study enrolled 811 participants, representing 10.84 million COPD individuals in the United States (mean [standard error] age, 58.7 [0.6] years). During a median follow-up of 9.6 years, mortality rates were 57.8 per 1000 person-years in patients using only opioids, 41.3 per 1000 person-years in patients using only benzodiazepines, 45.7 per 1000 person-years in patients using both opioids and benzodiazepines, and 27.0 per 1000 person-years in patients using neither. In the fully adjusted model, COPD patients prescribed both opioids and benzodiazepines (HR: 1.76; 95% CI: 1.11-2.78) and those prescribed opioids only (HR: 1.68; 95% CI: 1.13-2.49) had significantly higher all-cause mortality compared to non-users. After adjusting for propensity scores, the mortality risk for opioid-only users slightly increased (HR: 1.87; 95% CI: 1.25-2.81). Further, subgroup analysis revealed an elevated mortality risk in patients over 60 years receiving coprescriptions or opioids only, but not in younger participants. In contrast, benzodiazepine-only users aged 60 or younger showed increased mortality risk. Conclusion: Opioid use, with or without benzodiazepine use, was associated with higher mortality in COPD patients over 60, while benzodiazepine-only use was associated with higher mortality aged 60 or younger.


Assuntos
Analgésicos Opioides , Benzodiazepinas , Causas de Morte , Inquéritos Nutricionais , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Analgésicos Opioides/uso terapêutico , Analgésicos Opioides/efeitos adversos , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Prospectivos , Estados Unidos/epidemiologia , Idoso , Fatores de Risco , Fatores de Tempo , Medição de Risco , Adulto , Resultado do Tratamento
11.
J Appl Clin Med Phys ; : e14540, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39374312

RESUMO

This review examines the recent developments in deep learning (DL) techniques applied to multimodal fusion image segmentation for liver cancer. Hepatocellular carcinoma is a highly dangerous malignant tumor that requires accurate image segmentation for effective treatment and disease monitoring. Multimodal image fusion has the potential to offer more comprehensive information and more precise segmentation, and DL techniques have achieved remarkable progress in this domain. This paper starts with an introduction to liver cancer, then explains the preprocessing and fusion methods for multimodal images, then explores the application of DL methods in this area. Various DL architectures such as convolutional neural networks (CNN) and U-Net are discussed and their benefits in multimodal image fusion segmentation. Furthermore, various evaluation metrics and datasets currently used to measure the performance of segmentation models are reviewed. While reviewing the progress, the challenges of current research, such as data imbalance, model generalization, and model interpretability, are emphasized and future research directions are suggested. The application of DL in multimodal image segmentation for liver cancer is transforming the field of medical imaging and is expected to further enhance the accuracy and efficiency of clinical decision making. This review provides useful insights and guidance for medical practitioners.

13.
Artigo em Inglês | MEDLINE | ID: mdl-39361523

RESUMO

Osteosarcoma (OS) is a lethal malignant orthotopic bone tumor that primarily affects children and adolescents. Biomimetic nanocarriers have attracted wide attention as a new strategy for delivering chemotherapy agents to the OS. However, challenges such as rapid clearance and limited targeting hinder the effectiveness of OS chemotherapy. In this study, we designed reactive oxygen species (ROS)-responsive nanoparticles (NPs) coated with an interleukin (IL)11-engineered macrophage membrane (MM). The camouflage by MMs prevents clearance of IL-11-engineered MM-coated NPs loaded with doxorubicin (IL-11/MM@NPs/Dox) by the immune system. Moreover, the macrophage membrane combined with surface-expressed IL-11 not only directed IL-11/MM@NPs/Dox to OS tissues but also selectively identified IL-11 receptor alpha (IL-11Rα)-enriched OS cells. Within these cells, elevated levels of ROS triggered the controlled release of Dox from the ROS-responsive NPs. The synergistic modification of targeted ligand conjugation and cell membrane coating on the ROS-responsive NPs enhanced drug availability and reduced toxic side effects, thereby boosting the efficacy of OS chemotherapy. In summary, our findings suggest that IL-11/MM@NPs/Dox represents a promising approach to improving OS chemotherapy efficacy while ensuring excellent biocompatibility.

14.
ACS Sens ; 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39364916

RESUMO

Cardiovascular disease (CVD) is a chronic disease characterized by the accumulation of lipids and fibrous tissue within the arterial walls, potentially leading to vascular obstruction and an increased risk of heart disease and stroke. Hydroxyl radicals play a significant role in the formation and progression of CVD as they can instigate lipid peroxidation, resulting in cellular damage and inflammatory responses. However, precisely detecting hydroxyl radicals in CVD lesions presents significant challenges due to their high reactivity and short lifespan. Herein, we present the development and application of a novel activatable optical probe, Cy-OH-LP, designed to detect hydroxyl radicals in lipid-rich environments specifically. Built on the Cy7 molecular skeleton, Cy-OH-LP exhibits near-infrared absorption and fluorescence characteristics, and its specific response to hydroxyl radicals enables a turn-on signal in both photoacoustic and fluorescence spectra. The probe demonstrated excellent selectivity and stability in various tests. Furthermore, Cy-OH-LP was successfully applied in an in vivo model to detect hydroxyl radicals in mouse models, providing a potential tool for diagnosing and monitoring AS. The biosafety of Cy-OH-LP was also verified, showing low cytotoxicity and no significant organ damage in mice. The findings suggest that Cy-OH-LP is a promising tool for the specific detection of hydroxyl radicals in lipid-rich environments, providing new possibilities for research and clinical applications in the field of oxidative stress-related diseases.

15.
Heliyon ; 10(18): e37233, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39309949

RESUMO

Background: Microvascular invasion (MVI) is associated with an unfavorable prognosis and early recurrence of hepatocellular carcinoma (HCC), which is the crucial pathological hallmark of immunotherapy. While microvascular invasion (MVI) in hepatocellular carcinoma (HCC) currently lacks a detailed single-cell analysis of the tumor microenvironment (TME), it holds significant promise for immunotherapy using immune checkpoint inhibitors (ICI). Methods: We performed single-cell RNA sequencing (scRNA-seq) on 3 MVI positive (MVIP) and 14 MVI-negative (MVIN) tumor tissues, as well as their paired adjacent non-tumoral tissues. Results: We identified SPP1+ macrophages and CD4+ proliferative T cells as intertumoral populations critical for the formation of cold tumors and immunosuppressive environments in MVI-positive patients and verified their prognostic value in correlation with MVIP HCC patients. Additionally, we identified SPP1+ dominated interactions between SPP1+ macrophages and the immunosuppressive T population as contributors to MVI destruction and tumorigenesis. Conclusions: We provide a comprehensive single-cell atlas of HCC patients with MVI, shedding light on the immunosuppressive ecosystem and upregulated signaling associated with MVI. These findings demonstrate that intercellular mechanisms drive MVI and provide a potential immunotherapeutic target for HCC patients with HCC and underlying MVI.

16.
Anal Chem ; 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39263911

RESUMO

Eu isotopes are promising tracers across various scientific domains such as planetary, earth, and marine science, yet their high-precision analysis has been challenging due to the similar geochemical properties of rare earth elements (REEs). In this study, a novel two-column chromatographic approach was developed utilizing AG50W-X12 and TODGA resins to separate Eu effectively from matrix and interfering elements like Ba, Nd, Sm, and Gd, while ensuring high Eu yields (99.4 ± 0.4%, n = 19) and low blanks (<20 pg). The robustness of this method is evidenced by various rock types and different Eu loading masses. The efficient purification of Eu facilitated the establishment of a high-precision calibration technique with standard-sample bracketing (SSB) and internal normalization (Nd). When a Nu Plasma 1700 multicollector-inductively coupled plasma-mass spectrometry (MC-ICP-MS) instrument was employed, repeated purification and analysis of various Geological Reference Materials (GRMs) confirmed that the long-term external precision of δ153/151Eu is better than 0.04‰ (2 standard deviation (2SD)), which represents a 2-5-fold increase in precision compared to previously reported methods. Additionally, the high-precision Eu isotopic compositions of five GRMs, including basalts, andesite, syenite, and marine sediment, were measured. The high-precision Eu isotope techniques presented herein open up new avenues for Eu isotope geochemistry.

17.
J Hazard Mater ; 479: 135627, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39217948

RESUMO

Unraveling the geochemical and microbial controls on methylmercury (MeHg) dynamics in mangrove sediments is important, as MeHg can potentially pose risks to marine biota and people that rely on these ecosystems. While the important role of sulfate-reducing bacteria in MeHg formation has been examined in this ecologically important habitat, the contribution of non-Hg methylating communities on MeHg production remains particularly unclear. Here, we collected sediment samples from 13 mangrove forests in south China and examined the geochemical parameters and microbial communities related to the Hg methylation. MeHg concentrations were significantly correlated to the OM-related parameters such as organic carbon content, total nitrogen, and dissolved organic carbon concentrations, suggesting the importance of OM in the MeHg production. Sulfate-reducing bacteria were the major Hg-methylators in mangrove sediments. Desulfobacteraceae and Desulfobulbaceae dominated the Hg-methylating microbes. Classification random forest analysis detected strong co-occurrence between Hg methylators and putative non-Hg methylators, thus suggesting that both types of microorganisms contribute to the MeHg dynamics in the sediments. Our study provides an overview of MeHg contamination in south China and advances our understanding of Hg methylation in mangrove ecosystems.


Assuntos
Sedimentos Geológicos , Compostos de Metilmercúrio , Poluentes Químicos da Água , Áreas Alagadas , Compostos de Metilmercúrio/análise , Compostos de Metilmercúrio/metabolismo , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/análise , China , Metilação , Bactérias/metabolismo , Deltaproteobacteria/metabolismo , Monitoramento Ambiental
18.
Cell Rep ; 43(9): 114739, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39276350

RESUMO

FOXA1 serves as a crucial pioneer transcription factor during developmental processes and plays a pivotal role as a mitotic bookmarking factor to perpetuate gene expression profiles and maintain cellular identity. During mitosis, the majority of FOXA1 dissociates from specific DNA binding sites and redistributes to non-specific binding sites; however, the regulatory mechanisms governing molecular dynamics and activity of FOXA1 remain elusive. Here, we show that mitotic kinase Aurora B specifies the different DNA binding modes of FOXA1 and guides FOXA1 biomolecular condensation in mitosis. Mechanistically, Aurora B kinase phosphorylates FOXA1 at Serine 221 (S221) to liberate the specific, but not the non-specific, DNA binding. Interestingly, the phosphorylation of S221 attenuates the FOXA1 condensation that requires specific DNA binding. Importantly, perturbation of the dynamic phosphorylation impairs accurate gene reactivation and cell proliferation, suggesting that reversible mitotic protein phosphorylation emerges as a fundamental mechanism for the spatiotemporal control of mitotic bookmarking.


Assuntos
Aurora Quinase B , Fator 3-alfa Nuclear de Hepatócito , Mitose , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Fator 3-alfa Nuclear de Hepatócito/genética , Fosforilação , Aurora Quinase B/metabolismo , Humanos , Células HeLa , Proliferação de Células , DNA/metabolismo
19.
World J Oncol ; 15(5): 825-836, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39328338

RESUMO

Background: In this study, we aimed to develop a method for the simultaneous quantification of methotrexate (MTX) samples extracted from human plasma and cerebrospinal fluid (CSF), using two-dimensional liquid chromatography (2D-LC). Furthermore, we intended to verify whether intravenous mannitol could increase MTX concentration in the CSF of patients. Methods: The mobile phase of PUMP1 consisted of 10.0 mmol/L ammonium acetate and acetonitrile. PUMP2 solution consisted of an aqueous solution of 10.0 mmol/L ammonium acetate. The mobile phase of PUMP3 comprised 50.0 mmol/L ammonium acetate and acetonitrile, with a flow rate of 1.0 mL/min. Results: The developed method was successfully employed to simultaneously determine drug levels in plasma and CSF from the patients treated with MTX. CSF samples were obtained by lumbar puncture 0.5 - 2 h after starting the high-dose methotrexate (HD-MTX) infusion (over 4 h) and immediately before the intrathecal (IT) administration of MTX. Venous blood samples were drawn 4 h after the start of infusion. The calibration curve was linear, with a range of 0.07 - 2.38 µmol/L for CSF samples and a range of 0.11 - 5.51 µmol/L for plasma samples. Precision (> 95%) and accuracy (> 97%) were within the acceptance criteria for each quality control (QC) level. Inter- and intra-day accuracy and precision values met the acceptance criteria for each QC level. The correlation between MTX concentrations in the plasma and CSF was moderate (r = 0.502). No significant difference was observed in MTX concentration in CSF between patients using intravenous mannitol and those not using intravenous mannitol (P = 0.682). Conclusion: The developed method was useful for therapeutic drug monitoring of MTX and suitable for assessing the risks and benefits of chemotherapy in patients with primary central nervous system lymphoma. Intravenous mannitol did not increase MTX concentration in the CSF of patients.

20.
Nat Commun ; 15(1): 8347, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333579

RESUMO

Light encodes multidimensional information, such as intensity, polarization, and spectrum. Traditional extraction of this light information requires discrete optical components by subdividing the detection area into many "one-to-one" functional pixels. The broadband photodetection of high-dimensional optical information with a single integrated on-chip detector is highly sought after, yet it poses significant challenges. In this study, we employ a metasurface-assisted graphene photodetector, enabling to simultaneously detect and differentiate various polarization states and wavelengths of broadband light (1-8 µm) at the wavelength prediction accuracy of 0.5 µm. The bipolar polarizability empowered by this design allows to decouple multidimensional information (encompassing polarization and wavelength), which can be achieved by encoding vectorial photocurrents with varying polarities and amplitudes. Furthermore, cooperative multiport metasurfaces are adopted and boosted by machine learning techniques. It enables precise spin-wavelength differentiation over an extremely broad wavelength range (1-8 µm). Our innovation offers a recipe for highly compact and high-dimensional spectral-polarization co-detection.

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