Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 391
Filtrar
2.
J Am Stat Assoc ; 119(546): 1274-1285, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948492

RESUMO

Transfer learning provides a powerful tool for incorporating data from related studies into a target study of interest. In epidemiology and medical studies, the classification of a target disease could borrow information across other related diseases and populations. In this work, we consider transfer learning for high-dimensional generalized linear models (GLMs). A novel algorithm, TransHDGLM, that integrates data from the target study and the source studies is proposed. Minimax rate of convergence for estimation is established and the proposed estimator is shown to be rate-optimal. Statistical inference for the target regression coefficients is also studied. Asymptotic normality for a debiased estimator is established, which can be used for constructing coordinate-wise confidence intervals of the regression coefficients. Numerical studies show significant improvement in estimation and inference accuracy over GLMs that only use the target data. The proposed methods are applied to a real data study concerning the classification of colorectal cancer using gut microbiomes, and are shown to enhance the classification accuracy in comparison to methods that only use the target data.

3.
J Hazard Mater ; 476: 135132, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-39002483

RESUMO

The widespread presence of microplastics (MPs) in aquatic environments has become a significant concern, with freshwater sediments acting as terminal sinks, rapidly picking up these emerging anthropogenic particles. However, the accumulation, transport, degradation and biochemical impacts of MPs in freshwater sediments remain unresolved issues compared to other environmental compartments. Therefore, this paper systematically revealed the spatial distribution and characterization information of MPs in freshwater (rivers, lakes, and estuaries) sediments, in which small-size (<1 mm), fibers, transparent, polyethylene (PE), and polypropylene (PP) predominate, and the average abundance of MPs in river sediments displayed significant heterogeneity compared to other matrices. Next, the transport kinetics and drivers of MPs in sediments are summarized, MPs transport is controlled by the particle diversity and surrounding environmental variability, leading to different migration behaviors and transport efficiencies. Also emphasized the spatio-temporal evolution of MPs degradation processes and biodegradation mechanisms in sediments, different microorganisms can depolymerize high molecular weight polymers into low molecular weight biodegradation by-products via secreting hydrolytic enzymes or redox enzymes. Finally, discussed the ecological impacts of MPs on microbial-nutrient coupling in sediments, MPs can interfere with the ecological balance of microbially mediated nutrient cycling by altering community networks and structures, enzyme activities, and nutrient-related functional gene expressions. This work aims to elucidate the plasticity characteristics, fate processes, and potential ecological impact mechanisms of MPs in freshwater sediments, facilitating a better understanding of environmental risks of MPs in freshwater sediments.

4.
Proc Natl Acad Sci U S A ; 121(29): e2400883121, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38980908

RESUMO

Gasdermin D (GSDMD)-mediated pyroptotic cell death drives inflammatory cytokine release and downstream immune responses upon inflammasome activation, which play important roles in host defense and inflammatory disorders. Upon activation by proteases, the GSDMD N-terminal domain (NTD) undergoes oligomerization and membrane translocation in the presence of lipids to assemble pores. Despite intensive studies, the molecular events underlying the transition of GSDMD from an autoinhibited soluble form to an oligomeric pore form inserted into the membrane remain incompletely understood. Previous work characterized S-palmitoylation for gasdermins from bacteria, fungi, invertebrates, as well as mammalian gasdermin E (GSDME). Here, we report that a conserved residue Cys191 in human GSDMD was S-palmitoylated, which promoted GSDMD-mediated pyroptosis and cytokine release. Mutation of Cys191 or treatment with palmitoyltransferase inhibitors cyano-myracrylamide (CMA) or 2-bromopalmitate (2BP) suppressed GSDMD palmitoylation, its localization to the membrane and dampened pyroptosis or IL-1ß secretion. Furthermore, Gsdmd-dependent inflammatory responses were alleviated by inhibition of palmitoylation in vivo. By contrast, coexpression of GSDMD with palmitoyltransferases enhanced pyroptotic cell death, while introduction of exogenous palmitoylation sequences fully restored pyroptotic activities to the C191A mutant, suggesting that palmitoylation-mediated membrane localization may be distinct from other molecular events such as GSDMD conformational change during pore assembly. Collectively, our study suggests that S-palmitoylation may be a shared regulatory mechanism for GSDMD and other gasdermins, which points to potential avenues for therapeutically targeting S-palmitoylation of gasdermins in inflammatory disorders.


Assuntos
Cisteína , Peptídeos e Proteínas de Sinalização Intracelular , Lipoilação , Proteínas de Ligação a Fosfato , Piroptose , Proteínas de Ligação a Fosfato/metabolismo , Proteínas de Ligação a Fosfato/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Cisteína/metabolismo , Animais , Camundongos , Citocinas/metabolismo , Células HEK293 , Inflamassomos/metabolismo , Gasderminas
5.
Phys Rev Lett ; 132(25): 250204, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38996245

RESUMO

The Hamiltonian, which determines the evolution of a quantum system, is fundamental in quantum physics. Therefore, it is crucial to implement high-precision generation and measurement of the Hamiltonian in a practical quantum system. Here, we experimentally demonstrate ultrahigh-precision Hamiltonian parameter estimation with a significant quantum advantage in a superconducting circuit via sequential control. We first observe the commutation relation for noncommuting operations determined by the system Hamiltonian, both with and without adding quantum control, verifying the commuting property of controlled noncommuting operations. Based on this control-induced commuting property, we further demonstrate Hamiltonian parameter estimation for polar and azimuth angles in superconducting circuits, achieving ultrahigh metrological gains in measurement precision exceeding the standard quantum limit by up to 16.0 and 16.1 dB at N=100, respectively.

6.
AAPS PharmSciTech ; 25(6): 163, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-38997614

RESUMO

Some glycoside drugs can be transported through intestinal glucose transporters (IGTs). The surfactants used in oral drug preparations can affect the function of transporter proteins. This study aimed to investigate the effect of commonly used surfactants, Poloxamer 188 and Tween 80, on the drug transport capacity of IGTs. Previous studies have shown that gastrodin is the optimal drug substrate for IGTs. Gastrodin was used as a probe drug to evaluate the effect of these two surfactants on intestinal absorption in SD rats through pharmacokinetic and in situ single-pass intestinal perfusion. Then, the effects of the two surfactants on the expression of glucose transporters and tight-junction proteins were examined using RT-PCR and western blotting. Additionally, the effect of surfactants on intestinal permeability was evaluated through hematoxylin-eosin staining. The results found that all experimental for Poloxamer 188 (0.5%, 2.0% and 8.0%) and Tween 80 (0.1% and 2.0%) were not significantly different from those of the blank group. However, the AUC(0-∞) of gastrodin increased by approximately 32% when 0.5% Tween 80 was used. The changes in IGT expression correlated with the intestinal absorption of gastrodin. A significant increase in the expression of IGTs was observed at 0.5% Tween 80. In conclusion, Poloxamer 188 had minimal effect on the drug transport capacity of IGTs within the recommended limits of use. However, the expression of IGTs increased in response to 0.5% Tween 80, which significantly enhanced the drug transport capacity of IGTs. However, 0.1% and 2.0% Tween 80 had no significant effect.


Assuntos
Absorção Intestinal , Mucosa Intestinal , Poloxâmero , Polissorbatos , Ratos Sprague-Dawley , Tensoativos , Animais , Poloxâmero/farmacologia , Polissorbatos/farmacologia , Ratos , Absorção Intestinal/efeitos dos fármacos , Masculino , Tensoativos/farmacologia , Transporte Biológico/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Glucosídeos/farmacologia
7.
Life Sci ; 351: 122779, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38851421

RESUMO

Heterotopic ossification (HO) refers to the formation of pathologic bone in nonskeletal tissues (including muscles, tendons or other soft tissues). HO typically occurs after a severe injury and can occur in any part of the body. HO lesions are highly vascularized. Angiogenesis, which is the formation of new blood vessels, plays an important role in the pathophysiology of HO. Surgical resection is considered an effective treatment for HO. However, it is difficult to completely remove new vessels, which can lead to the recurrence of HO and is often accompanied by significant problems such as intraoperative hemorrhage, demonstrating the important role of angiogenesis in HO. Here, we broadly summarize the current understanding of how angiogenesis contributes to HO; in particular, we focus on new insights into the cellular and signaling mechanisms underlying HO angiogenesis. We also review the development and current challenges associated with antiangiogenic therapy for HO.


Assuntos
Neovascularização Patológica , Ossificação Heterotópica , Ossificação Heterotópica/patologia , Ossificação Heterotópica/fisiopatologia , Humanos , Neovascularização Patológica/patologia , Animais , Transdução de Sinais , Inibidores da Angiogênese/uso terapêutico , Relevância Clínica , Angiogênese
8.
J Transl Med ; 22(1): 593, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918793

RESUMO

BACKGROUND: Sorafenib resistance is becoming increasingly common and disadvantageous for hepatocellular carcinoma (HCC) treatment. Ferroptosis is an iron dependent programmed cell death underlying the mechanism of sorafenib. Iron is crucial for synthesis of cofactors essential to mitochondrial enzymes and necessary for HCC proliferation, while mitochondrial iron overload and oxidative stress are associated with sorafenib induced ferroptosis. However, the crosstalk among iron homeostasis and sorafenib resistance is unclear. METHODS: We conducted bioinformatics analysis of sorafenib treated HCC datasets to analyze GCN5L1 and iron related gene expression with sorafenib resistance. GCN5L1 deleted HCC cell lines were generated by CRISPR technology. Sorafenib resistant HCC cell line was established to validate dataset analysis and evaluate the effect of potential target. RESULTS: We identified GCN5L1, a regulator of mitochondrial acetylation, as a modulator in sorafenib-induced ferroptosis via affecting mitochondrial iron homeostasis. GCN5L1 deficiency significantly increased sorafenib sensitivity in HCC cells by down-regulating mitochondrial iron transporters CISD1 expression to induce iron accumulation. Mitochondrial iron accumulation leads to an acceleration in cellular and lipid ROS. Sorafenib resistance is related to CISD1 overexpression to release mitochondrial iron and maintaining mitochondrial homeostasis. We combined CISD1 inhibitor NL-1 with sorafenib, which significantly enhanced sorafenib-induced ferroptosis by promoting mitochondrial iron accumulation and lipid peroxidation. The combination of NL-1 with sorafenib enhanced sorafenib efficacy in vitro and in vivo. CONCLUSIONS: Our findings demonstrate that GCN5L1/CISD1 axis is crucial for sorafenib resistance and would be a potential therapeutic strategy for sorafenib resistant HCC.


Assuntos
Carcinoma Hepatocelular , Resistencia a Medicamentos Antineoplásicos , Ferroptose , Homeostase , Ferro , Neoplasias Hepáticas , Mitocôndrias , Sorafenibe , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamento farmacológico , Ferro/metabolismo , Humanos , Homeostase/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , Ferroptose/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Camundongos Nus , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
9.
Pharm Res ; 41(6): 1201-1216, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38834905

RESUMO

BACKGROUND: Some glucoside drugs can be transported via intestinal glucose transporters (IGTs), and the presence of carbohydrate excipients in pharmaceutical formulations may influence the absorption of them. This study, using gastrodin as probe drug, aimed to explore the effects of fructose, lactose, and arabic gum on intestinal drug absorption mediated by the glucose transport pathway. METHODS: The influence of fructose, lactose, and arabic gum on gastrodin absorption was assessed via pharmacokinetic experiments and single-pass intestinal perfusion. The expression of sodium-dependent glucose transporter 1 (SGLT1) and sodium-independent glucose transporter 2 (GLUT2) was quantified via RT‒qPCR and western blotting. Alterations in rat intestinal permeability were evaluated through H&E staining, RT‒qPCR, and immunohistochemistry. RESULTS: Fructose reduced the area under the curve (AUC) and peak concentration (Cmax) of gastrodin by 42.7% and 63.71%, respectively (P < 0.05), and decreased the effective permeability coefficient (Peff) in the duodenum and jejunum by 58.1% and 49.2%, respectively (P < 0.05). SGLT1 and GLUT2 expression and intestinal permeability remained unchanged. Lactose enhanced the AUC and Cmax of gastrodin by 31.5% and 65.8%, respectively (P < 0.05), and increased the Peff in the duodenum and jejunum by 33.7% and 26.1%, respectively (P < 0.05). SGLT1 and GLUT2 levels did not significantly differ, intestinal permeability increased. Arabic gum had no notable effect on pharmacokinetic parameters, SGLT1 or GLUT2 expression, or intestinal permeability. CONCLUSION: Fructose, lactose, and arabic gum differentially affect intestinal drug absorption through the glucose transport pathway. Fructose competitively inhibited drug absorption, while lactose may enhance absorption by increasing intestinal permeability. Arabic gum had no significant influence.


Assuntos
Álcoois Benzílicos , Excipientes , Frutose , Transportador de Glucose Tipo 2 , Glucose , Glucosídeos , Goma Arábica , Absorção Intestinal , Lactose , Ratos Sprague-Dawley , Transportador 1 de Glucose-Sódio , Animais , Absorção Intestinal/efeitos dos fármacos , Glucosídeos/farmacologia , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Transportador 1 de Glucose-Sódio/metabolismo , Transportador 1 de Glucose-Sódio/genética , Masculino , Transportador de Glucose Tipo 2/metabolismo , Transportador de Glucose Tipo 2/genética , Ratos , Excipientes/química , Excipientes/farmacologia , Glucose/metabolismo , Lactose/química , Álcoois Benzílicos/farmacologia , Álcoois Benzílicos/farmacocinética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Permeabilidade/efeitos dos fármacos
10.
Phys Rev Lett ; 132(20): 203602, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38829095

RESUMO

Fock states with a well-defined number of photons in an oscillator have shown a wide range of applications in quantum information science. Nonetheless, their usefulness has been marred by single and multiphoton losses due to unavoidable environment-induced dissipation. Though several dissipation engineering methods have been developed to counteract the leading single-photon-loss error, averting multiple-photon losses remains elusive. Here, we experimentally demonstrate a dissipation engineering method that autonomously stabilizes multiphoton Fock states against losses of multiple photons using a cascaded selective photon-addition operation in a superconducting quantum circuit. Through measuring the photon-number populations and Wigner tomography of the oscillator states, we observe a prolonged preservation of nonclassical Wigner negativities for the stabilized Fock states |N⟩ with N=1, 2, 3 for a duration of about 10 ms. Furthermore, the dissipation engineering method demonstrated here also facilitates the implementation of a nonunitary operation for resetting a binomially encoded logical qubit. These results highlight potential applications in error-correctable quantum information processing against multiple-photon-loss errors.

11.
Nanoscale ; 16(23): 11187-11202, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38771650

RESUMO

This research introduces a method to enhance the mechanical properties of elastomers by grafting polymer chains onto single-chain flexible nanoparticles (SCNPs) and incorporating dynamic functional groups. Drawing on developments in grafting polymers onto hard nanoparticle fillers, this method employs the distinct flexibility of SCNPs to diminish heterogeneity and enhance core size control. We use molecular dynamics (MD) simulations for a mesoscale analysis of structural properties, particularly the effects of dynamic functional group quantities and their distribution. The findings demonstrate that increased quantities of functional groups are correlated with enhanced mechanical strength and toughness, showing improved stress-strain responses and energy dissipation capabilities. Moreover, the uniformity in the distribution of these functional groups is crucial, promoting a more cohesive and stable dynamic bonding network. The insights gained from MD simulations not only advance our understanding of the microstructural control necessary for optimizing macroscopic properties, but also provide valuable guidance for the design and engineering of advanced polymer nanocomposites, thereby enhancing the material performance through strategic molecular design.

12.
Cancer Res ; 84(14): 2352-2363, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38718316

RESUMO

Pulmonary delivery of immunostimulatory agents such as poly(I:C) to activate double-stranded RNA sensors MDA5 and RIG-I within lung-resident antigen-presenting cells is a potential strategy to enhance antitumor immunity by promoting type I interferon secretion. Nevertheless, following pulmonary delivery, poly(I:C) suffers from rapid degradation and poor endosomal escape, thus limiting its potency. Inspired by the structure of a virus that utilizes internal viral proteins to tune the loading and cytosolic delivery of viral nucleic acids, we developed a liponanogel (LNG)-based platform to overcome the delivery challenges of poly(I:C). The LNG comprised an anionic polymer hyaluronic acid-based nanogel core coated by a lipid shell, which served as a protective layer to stabilize the nanogel core in the lungs. The nanogel core was protonated within acidic endosomes to enhance the endosomal membrane permeability and cytosolic delivery of poly(I:C). After pulmonary delivery, LNG-poly(I:C) induced 13.7-fold more IFNß than poly(I:C) alone and two-fold more than poly(I:C) loaded in the state-of-art lipid nanoparticles [LNP-poly(I:C)]. Additionally, LNG-poly(I:C) induced more potent CD8+ T-cell immunity and stronger therapeutic effects than LNP-poly(I:C). The combination of LNG-poly(I:C) and PD-L1 targeting led to regression of established lung metastases. Due to the ease of manufacturing and the high biocompatibility of LNG, pulmonary delivery of LNG may be broadly applicable to the treatment of different lung tumors and may spur the development of innovative strategies for cancer immunotherapy. Significance: Pulmonary delivery of poly(I:C) with a virus-inspired inhalable liponanogel strongly activates cytosolic MDA5 and RIG-I and stimulates antitumor immunity, representing a promising strategy for safe and effective treatment of metastatic lung tumors.


Assuntos
Neoplasias Pulmonares , Poli I-C , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/tratamento farmacológico , Animais , Camundongos , Poli I-C/administração & dosagem , Humanos , Camundongos Endogâmicos C57BL , Nanogéis/química , Linhagem Celular Tumoral , Feminino , Administração por Inalação , Lipídeos/química , Lipídeos/administração & dosagem
13.
Luminescence ; 39(5): e4765, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38769927

RESUMO

Isovitexin is a main natural flavonoid component in various plants. Currently, the inhibitory effect of isovitexin on pancreatic lipase (PL) and its mechanism have not been elucidated yet. In the present study, we investigated the inhibitory effect of isovitexin on PL, as well as its interaction mechanism, using enzyme inhibition methods, spectroscopic analysis, and molecular simulations. Results showed that isovitexin possessed significant PL inhibitory activity, with IC50 values of 0.26 ± 0.02 mM. The interaction between isovitexin and PL was dominated by static quenching, and mainly through hydrogen bonding and hydrophobic interaction forces. Analysis of fluorescence spectroscopy confirmed that isovitexin binding altered the conformation of the PL. Circular dichroism (CD) spectrum indicated that isovitexin altered the secondary structure of PL by decreasing the α-helix content and increasing the ß-fold content. Molecular simulations further characterize the conformational changes produced by the interaction between isovitexin with PL. The performed study may provide a new insight into the inhibitory mechanism of isovitexin as a novel PL inhibitor.


Assuntos
Apigenina , Dicroísmo Circular , Inibidores Enzimáticos , Lipase , Pâncreas , Espectrometria de Fluorescência , Lipase/antagonistas & inibidores , Lipase/metabolismo , Lipase/química , Pâncreas/enzimologia , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Apigenina/química , Apigenina/farmacologia , Animais
14.
Small ; : e2401970, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770987

RESUMO

Transition metal compounds (TMCs) have long been potential candidate catalysts in persulfate-based advanced oxidation process (PS-AOPs) due to their Fenton-like catalyze ability for radical generation. However, the mechanism involved in TMCs-catalyzed nonradical PS-AOPs remains obscure. Herein, the growth of FeO on the Fe3O4/carbon precursor is regulated by restricted pyrolysis of MIL-88A template to activate peroxymonosulfate (PMS) for tetracycline (TC) removal. The higher FeO incorporation conferred a 2.6 times higher degradation performance than that catalyzed by Fe3O4 and also a higher interference resistance to anions or natural organic matter. Unexpectedly, the quenching experiment, probe method, and electron paramagnetic resonance quantitatively revealed that the FeO reassigned high nonradical species (1O2 and FeIV═O) generation to replace original radical system created by Fe3O4. Density functional theory calculation interpreted that PMS molecular on strongly-adsorbed (200) and (220) facets of FeO enjoyed unique polarized electronic reception for surface confinement effect, thus the retained peroxide bond energetically supported the production of 1O2 and FeIV═O. This work promotes the mechanism understanding of TMCs-induced surface-catalyzed persulfate activation and enables them better perform catalytic properties in wastewater treatment.

15.
Clinics (Sao Paulo) ; 79: 100374, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38718696

RESUMO

OBJECTIVE: The aim of the study was to create two consensus nomograms for predicting Overall Survival (OS) and Cancer-Specific Survival (CSS) in adults with papillary Renal Cell Carcinoma (pRCC). METHODS: Using the Surveillance, Epidemiology, and End Results databases, a retrospective analysis of 1,074 adults with pRCC from 2004 to 2015 was performed. These patients were then randomly divided into two independent cohorts with a ratio of 7:3 (training cohort: 752; validation cohort: 322). In a retrospective analysis of 752 patients from the training cohort, independent prognostic variables affecting OS and CSS were found. R software was used to create prognostic nomograms based on the findings of Cox regression analysis. The performance of the nomograms was assessed using the Concordance Index (C-index), the Area Under Curve (AUC), a calibration curve, and Decision Curve Analysis (DCA). Data from the 107 postoperative pRCC patients at the Affiliated Hospital of Xuzhou Medical University were used for external validation of the nomogram. RESULTS: For OS and CSS, the C-indices and AUCs of the training cohort and the validation cohort indicated that the model had excellent discrimination. The DCA demonstrated that the model was clinically applicable, and the calibration curves in the internal and external validations showed that the model's accuracy was high. CONCLUSION: The authors developed and validated a prognostic nomogram that accurately predicted the 3-, 5-, and 8-year OS and CSS of adults with pRCC. Clinicians can use this knowledge to direct the clinical management and counseling of patients with pRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Nomogramas , Humanos , Masculino , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Prognóstico , Adulto , Idoso , Reprodutibilidade dos Testes , Estadiamento de Neoplasias , Programa de SEER
16.
Liver Int ; 44(8): 1924-1936, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38597373

RESUMO

BACKGROUND AND AIMS: Iron overload, oxidative stress and ferroptosis are associated with liver injury in alcohol-associated liver disease (ALD), however, the crosstalk among these regulatory pathways in ALD development is unclear. METHODS: ALD mouse model and general control of amino acid synthesis 5 like 1 (GCN5L1) liver knockout mice were generated to investigate the role of GCN5L1 in ALD development. Proteomic screening tests were performed to identify the key factors mediating GCN5L1 loss-induced ALD. RESULTS: Gene Expression Omnibus data set analysis indicates that GCN5L1 expression is negatively associated with ALD progression. GCN5L1 hepatic knockout mice develop severe liver injury and lipid accumulation when fed an alcohol diet. Screening tests identified that GCN5L1 targeted the mitochondrial iron transporter CISD1 to regulate mitochondrial iron homeostasis in ethanol-induced ferroptosis. GCN5L1-modulated CISD1 acetylation and activity were crucial for iron accumulation and ferroptosis in response to alcohol exposure. CONCLUSION: Pharmaceutical modulation of CISD1 activity is critical for cellular iron homeostasis and ethanol-induced ferroptosis. The GCN5L1/CISD1 axis is crucial for oxidative stress and ethanol-induced ferroptosis in ALD and is a promising avenue for novel therapeutic strategies.


Assuntos
Modelos Animais de Doenças , Ferroptose , Hepatopatias Alcoólicas , Camundongos Knockout , Estresse Oxidativo , Animais , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/patologia , Camundongos , Ferro/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Etanol , Camundongos Endogâmicos C57BL , Humanos , Proteínas do Tecido Nervoso , Proteínas Mitocondriais
17.
Open Med (Wars) ; 19(1): 20240939, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38623458

RESUMO

Objective: The aim of this research was to compile a self-management assessment scale for patients with aortic dissection (AD). The questionnaire is useful in making the patient aware of the need for post-operative care in order to contribute to improving the outcome and quality of life. Methods: The initial version of the "postoperative self-management assessment scale for patients with aortic dissection" was developed using the Delphi expert consultation method based on qualitative research results, consultation of self-management-related literature, reference to the existing self-management scale, and self-efficacy theory, combined with the disease characteristics of AD. By using the convenience sampling method, a total of 201 patients with AD who had undergone surgery were selected as the research participants. The initial version of the scale was used for follow-up investigation, and the scale entries were evaluated and exploratory factor analysis carried out to form the formal version of the "postoperative self-management assessment scale for patients with aortic dissection." A total of 214 patients with AD after surgery were selected as the research participants. The formal version of the scale was used for follow-up investigation, and its reliability and validity were evaluated. Results: The formal version of the scale had 6 dimensions and 35 entries. The Cronbach's α coefficient for the total scale was 0.908, the split-half reliability was 0.790, and the test-retest reliability after 2 weeks was 0.471. The content validity index of the total scale was 0.963. Exploratory factor analysis yielded six common factors, and the cumulative contribution rate of variance was 66.303%. Confirmatory factor analysis showed that except for the incremental fit index, Tucker-Lewis index, and comparative fit index >0.85, slightly lower than 0.90, χ 2/df <3, root mean square of approximation <0.08, parsimonious goodness-of-fit index, and parsimonious normed fit index >0.50; all other model fitting requirements were satisfied, indicating that the model fitting was acceptable. Conclusion: We compiled the postoperative self-management assessment scale for patients with AD, which has demonstrated excellent reliability and validity and can be used as a tool to evaluate the postoperative self-management level in patients with aortic dissection.

18.
World J Gastrointest Oncol ; 16(4): 1564-1577, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660648

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related mortality globally. Resistance to chemotherapy, especially during CRC treatment, leads to reduced effectiveness of drugs and poor patient outcomes. Long noncoding RNAs (lncRNAs) have been implicated in various pathophysiological processes of tumor cells, including chemotherapy resistance, yet the roles of many lncRNAs in CRC remain unclear. AIM: To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance. METHODS: Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance. Various bioinformatics tools were employed to elucidate molecular mechanisms. The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction. Functional assays, including MTT, wound healing, and Transwell, were conducted to investigate the functional implications of lncRNA alterations. Interactions between lncRNAs and transcription factors were examined using RIP and luciferase reporter assays, while Western blotting was used to confirm downstream pathways. Additionally, a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance. RESULTS: LncRNA prion protein testis specific (PRNT) was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2 (HIPK2) expression. PRNT was demonstrated to sponge transcription factor zinc finger protein 184 (ZNF184), which in turn could regulate HIPK2 expression. Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin, with overexpression leading to decreased sensitivity and decreased expression reducing resistance. Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT. The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo. CONCLUSION: The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.

19.
Structure ; 32(3): 253-257, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38458156

RESUMO

We have asked young scientists who spoke at our recent Cell Symposium "Structural biology from the nanoscale to cellular mesoscale" in Huangshan, China to tell us more about themselves and their exciting research in this collection of Voices.


Assuntos
Biologia Molecular , China
20.
Small ; : e2311862, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501876

RESUMO

In recent years, the research of FeSe2 and its composites in environmental remediation has been gradually carried out. And the FeSe2 materials show great catalytic performance in photocatalysis, electrocatalysis, and Fenton-like reactions for pollutants removal. Therefore, the studies and applications of FeSe2 materials are reviewed in this work, including the common synthesis methods, the role of Fe and Se species as well as the catalyst structure, and the potential for practical environmental applications. Hereinto, it is worth noting in particular that the lower-valent Se (Se2- ), unsaturated Se (Se- ), and Se vacancies (VSe ) can play different roles in promoting pollutants removal. In addition, the FeSe2 material also demonstrates high stability, reusability, and adaptability over a wider pH range as well as universality to different pollutants. In view of the overall great properties and performance of FeSe2 materials compared with other typical Fe-based materials, it deserves and needs further research. And finally, this paper presents some challenges and perspectives in future development, looking forward to providing helpful guidance for the subsequent research of FeSe2 and its composites for environmental application.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA