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1.
J Biol Chem ; 300(3): 105704, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38309506

RESUMEN

Selective gene expression in cells in physiological or pathological conditions is important for the growth and development of organisms. Acetylation of histone H4 at K16 (H4K16ac) catalyzed by histone acetyltransferase 8 (KAT8) is known to promote gene transcription; however, the regulation of KAT8 transcription and the mechanism by which KAT8 acetylates H4K16ac to promote specific gene expression are unclear. Using the lepidopteran insect Helicoverpa armigera as a model, we reveal that the transcription factor FOXO promotes KAT8 expression and recruits KAT8 to the promoter region of autophagy-related gene 8 (Atg8) to increase H4 acetylation at that location, enabling Atg8 transcription under the steroid hormone 20-hydroxyecdysone (20E) regulation. H4K16ac levels are increased in the midgut during metamorphosis, which is consistent with the expression profiles of KAT8 and ATG8. Knockdown of Kat8 using RNA interference results in delayed pupation and repression of midgut autophagy and decreases H4K16ac levels. Overexpression of KAT8-GFP promotes autophagy and increases H4K16ac levels. FOXO, KAT8, and H4K16ac colocalized at the FOXO-binding region to promote Atg8 transcription under 20E regulation. Acetylated FOXO at K180 and K183 catalyzed by KAT8 promotes gene transcription for autophagy. 20E via FOXO promotes Kat8 transcription. Knockdown or overexpression of FOXO appeared to give similar results as knockdown or overexpression of KAT8. Therefore, FOXO upregulates KAT8 expression and recruits KAT8 to the promoter region of Atg8, where the KAT8 induces H4 acetylation to promote Atg8 transcription for autophagy under 20E regulation. This study reveals the mechanism that KAT8 promotes transcription of a specific gene.


Asunto(s)
Autofagia , Ecdisterona , Helicoverpa armigera , Histona Acetiltransferasas , Histonas , Procesamiento Proteico-Postraduccional , Acetilación , Autofagia/genética , Ecdisterona/metabolismo , Regiones Promotoras Genéticas , Helicoverpa armigera/genética , Helicoverpa armigera/metabolismo , Histona Acetiltransferasas/genética , Histona Acetiltransferasas/metabolismo , Histonas/metabolismo
2.
J Magn Reson Imaging ; 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38299767

RESUMEN

BACKGROUND: Serum creatinine (Scr) may be not suited to timely and accurately reflect kidney injury related to chronic liver disease. Currently, the ability of arterial spin labeling (ASL) and blood oxygen level-dependent (BOLD) sequences to evaluate renal blood flow (RBF) and blood oxygen in chronic liver disease remains to be verified. PURPOSE: To investigate the value of ASL and BOLD imaging in evaluating hemodynamics and oxygenation changes during kidney injury in an animal model of chronic liver disease. STUDY TYPE: Prospective. ANIMAL MODEL: Chronic liver disease model was established by subcutaneous injection of carbon tetrachloride. Forty-three male Sprague-Dawley rats (8 weeks) were divided into a pathological group (0, 2, 4, 6, 8, 12 weeks, each group: N = 6) and a continuous-scanning group (N = 7). FIELD STRENGTH/SEQUENCE: 3-T, ASL, BOLD, and T2W. ASSESSMENT: Regions of interest in the cortex (CO), outer stripe of the outer medulla (OSOM), and inner stripe of the outer medulla (ISOM) are manually delineated. The RBF and T2* values at each time point (0, 2, 4, 6, 8, 12 weeks) are measured and compared. Hematoxylin-eosin score (HE Score, damage area scoring method), alpha-smooth muscle actin (α-SMA), hypoxia-inducible factor-1alpha (HIF-1α), peritubular capillar (PTC) density, Scr, and neutrophil gelatinase-associated lipocalin were harvested. STATISTICAL TESTS: Analysis of variance, Spearman correlation analysis, Kruskal-Wallis tests, and receiver operating characteristic analysis with the area under the curve (AUC). A P-value <0.05 was considered statistically significant. RESULTS: Renal RBF and T2* values of CO, OSOM, and ISOM were significantly different from baseline. Both RBF and T2* were significantly correlated with HE Score, α-SMA, HIF-1α, and PTC density (|r| = 0.406-0.853). RBF demonstrated superior diagnostic capability in identifying severe kidney injury in this model of chronic liver disease (AUC = 0.964). DATA CONCLUSION: Imaging by ASL and BOLD may detect renal hemodynamics and oxygenation changes related to chronic liver disease early. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

3.
Arch Virol ; 169(3): 60, 2024 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-38430446

RESUMEN

A novel partitivirus, Fusarium commune partitivirus 1 (FcoPV1), was identified in Fusarium commune strain CP-SX-3 isolated from diseased roots of strawberry with symptoms of root rot. The complete genome of FcoPV1 comprises three double-stranded RNAs (dsRNAs): dsRNA1 (1,825 nt), dsRNA2 (1,592 nt), and dsRNA3 (1,421 nt). dsRNA1 contains a single open reading frame (ORF1) encoding an RNA-dependent RNA polymerase (RdRp), and dsRNA2 contains a single ORF (ORF2) encoding a coat protein (CP). dsRNA3 is a possible satellite RNA that does not appear to encode a known protein. BLASTp analysis revealed that RdRp (86.59%) and CP (74.13%) encoded by the two ORFs (ORF1 and ORF2) had the highest sequence similarity to their counterparts in Fusarium equiseti partitivirus 1 (FePV1). Phylogenetic analysis based on the complete amino acid sequence of RdRp suggested that FcoPV1 should be considered a member of a new species in the proposed genus "Zetapartitivirus" within the family Partitiviridae. To the best of our knowledge, this is the first report of a zetapartitivirus infecting phytopathogenic F. commune.


Asunto(s)
Fragaria , Fusarium , Filogenia , Genoma Viral , ARN Polimerasa Dependiente del ARN/genética
4.
Conserv Biol ; : e14253, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38516741

RESUMEN

Because global anthropogenic activities cause vast biodiversity loss, human dimensions research is essential to forming management plans applicable to biodiversity conservation outside wilderness areas. Engaging public participation is crucial in this context to achieve social and environmental benefits. However, knowledge gaps remain in understanding how a balance between conservation and public demands can be reached and how complicated sociocultural contexts in the Anthropocene can be incorporated in conservation planning. We examined China's nationwide conflict between free-ranging cats (owned cats that are allowed to go outdoors or homeless cats living outdoors) and wildlife to examine how a consensus between compassion and biodiversity conservation can help in decision-making. We surveyed a random sample of people in China online. Over 9000 questionnaires were completed (44.2% response). In aggregate, respondents reported approximately 29 million free-ranging owned cats and that over 5 million domestic cats per year become feral in mainland China. Respondents who were cat owners, female, and religious were more likely to deny the negative impacts of cats on wildlife and ongoing management strategies and more supportive of stray cat shelters, adoption, and community-based fund raising than nonowners, male, and nonreligious respondents (p < 0.05). Free-ranging cat ownership and abandonment occurred less with owners with more knowledge of biodiversity and invasive species than with respondents with less knowledge of these subjects (p < 0.05). We recommend that cat enthusiasts and wildlife conservationists participate in community-based initiatives, such as campaigns to keep cats indoors. Our study provides a substantially useful framework for other regions where free-ranging cats are undergoing rapid expansion.


Retos y oportunidades de las dimensiones humanas detrás del conflicto entre gatos y fauna Resumen Debido a que las actividades antropogénicas globales causan una enorme pérdida de la biodiversidad, la investigación sobre las dimensiones humanas es esencial para generar planes de manejo aplicables a la conservación de la biodiversidad fuera de las áreas silvestres. Es muy importante lograr que el público participe en este contexto para obtener los beneficios sociales y ambientales. Sin embargo, todavía existen vacíos en el conocimiento sobre cómo lograr el balance entre la conservación y las demandas públicas y cómo incorporar los contextos socioculturales complejos del Antropoceno a la planeación de la conservación. Analizamos el conflicto nacional entre los gatos libres (gatos callejeros o gatos domésticos que se les permite salir) y la fauna en China para estudiar cómo un consenso entre la compasión y la conservación de la biodiversidad puede ayudar en la toma de decisiones. Encuestamos en línea a una muestra aleatoria de personas en China. Se completaron más de 9000 cuestionarios (44.2% de respuesta). En total, los respondientes reportaron un aproximado de 29 millones de gatos libres y que más de cinco millones de gatos domésticos se vuelven ferales al año en China. Quienes respondieron y son dueños de gatos, mujeres y religiosos tuvieron la mayor probabilidad de negar los impactos negativos de los gatos sobre la fauna y de las estrategias actuales de manejo y de mostrar más apoyo por los refugios de gatos abandonados, la adopción y de la recaudación de fondos comunitaria que quienes no son dueños, no son religiosos y son hombres (p < 0.05). La propiedad de gatos libres y el abandono ocurrieron menos con los dueños con más conocimiento sobre la biodiversidad y las especies invasoras que con los respondientes con menos conocimiento sobre estos temas (p < 0.05). Recomendamos que los aficionados a los gatos y los conservacionistas de la fauna participen en las iniciativas comunitarias; por ejemplo, campañas para mantener a los gatos dentro de casa. Nuestro estudio proporciona un marco sustancialmente útil para otras regiones en donde los gatos libres se encuentran en rápida expansión.

5.
PLoS Genet ; 17(4): e1009514, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33901186

RESUMEN

The regulatory subunits (P60 in insects, P85 in mammals) determine the activation of the catalytic subunits P110 in phosphatidylinositol 3-kinases (PI3Ks) in the insulin pathway for cell proliferation and body growth. However, the regulatory subunits also promote apoptosis via an unclear regulatory mechanism. Using Helicoverpa armigera, an agricultural pest, we showed that H. armigera P60 (HaP60) was phosphorylated under insulin-like peptides (ILPs) regulation at larval growth stages and played roles in the insulin/ insulin-like growth factor (IGF) signaling (IIS) to determine HaP110 phosphorylation and cell membrane translocation; whereas, HaP60 was dephosphorylated and its expression increased under steroid hormone 20-hydroxyecdysone (20E) regulation during metamorphosis. Protein tyrosine phosphatase non-receptor type 6 (HaPTPN6, also named tyrosine-protein phosphatase corkscrew-like isoform X1 in the genome) was upregulated by 20E to dephosphorylate HaP60 and HaP110. 20E blocked HaP60 and HaP110 translocation to the cell membrane and reduced their interaction. The phosphorylated HaP60 mediated a cascade of protein phosphorylation and forkhead box protein O (HaFOXO) cytosol localization in the IIS to promote cell proliferation. However, 20E, via G protein-coupled-receptor-, ecdysone receptor-, and HaFOXO signaling axis, upregulated HaP60 expression, and the non-phosphorylated HaP60 interacted with phosphatase and tensin homolog (HaPTEN) to induce apoptosis. RNA interference-mediated knockdown of HaP60 and HaP110 in larvae repressed larval growth and apoptosis. Thus, HaP60 plays dual functions to promote cell proliferation and apoptosis by changing its phosphorylation status under ILPs and 20E regulation, respectively.


Asunto(s)
Proliferación Celular/genética , Insulina/genética , Metamorfosis Biológica/genética , Fosfatidilinositol 3-Quinasas/genética , Animales , Apoptosis/genética , Ecdisterona/genética , Regulación del Desarrollo de la Expresión Génica , Proteínas de Insectos/genética , Larva/genética , Larva/crecimiento & desarrollo , Lepidópteros/genética , Lepidópteros/crecimiento & desarrollo , Péptidos , Fosforilación/genética , Receptores Acoplados a Proteínas G/genética , Somatomedinas
6.
Biochem Genet ; 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38267617

RESUMEN

The aim of this study was to investigate the underlying mechanism of miR-9-5p in airway smooth muscle cells (ASMCs) of asthmatic mice. An asthmatic mouse model was established through the intraperitoneal injection of ovalbumin. Histopathological changes in lung tissues of asthmatic mice were observed using HE staining. ASMCs was identified using immunofluorescence staining and cell morphology. The mRNA expressions of miR-9-5p, KLF5, and IL-1ß were measured using RT-qPCR. Additionally, CCK8 assay and flow cytometry were applied for ASMC proliferation and apoptosis, respectively. The protein levels of OPN, KLF5, and IL-1ß were assessed using western blotting. The results showed that miR-9-5p was abnormally downregulated in lung tissues and ASMCs of asthmatic mice. Dual-Luciferase Reporter Assay and Chromatin immunoprecipitation confirmed that miR-9-5p targeted KLF5 that bounds to IL-1ß promoter. Besides, miR-9-5p negatively regulated IL-1ß mRNA and protein level via KLF5. Moreover, miR-9-5p was found to positively regulate ASMC apoptosis, negatively regulate ASMC proliferation and OPN protein expression, albeit with partial reversal by KLF5. Mechanistically, the regulation of ASMC proliferation and apoptosis by miR-9-5p is achieved by targeting KLF5/IL-1ß axis.

7.
Nano Lett ; 23(6): 2081-2086, 2023 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-36854101

RESUMEN

Precisely organizing functional molecules of the catalytic cores in natural enzymes to promote catalytic performance is a challenging goal in respect to artificial enzyme construction. In this work, we report a DNA-scaffolded mimicry of the catalytic cores of hydrolases, which showed a controllable and hierarchical acceleration of the hydrolysis of fluorescein diacetate (FDA). The results revealed that the efficiency of hydrolysis was greatly increased by the DNA-scaffold-induced proximity of catalytic amino acid residues (histidine and arginine) with up to 4-fold improvement relative to the free amino acids. In addition, DNA-scaffolded one-dimensional and two-dimensional assemblies of multiple catalytic cores could further accelerate the hydrolysis. This work demonstrated that the DNA-guided assembly could be used as a promising platform to build enzyme mimics in a programmable and hierarchical way.


Asunto(s)
ADN , Hidrolasas , Dominio Catalítico , Hidrólisis , ADN/química , Catálisis
8.
Angew Chem Int Ed Engl ; 63(18): e202401950, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38453651

RESUMEN

A mononuclear valence tautomeric (VT) complex, [Co(pycz)2(Sq)(Cat)] (1-trans), where pycz = 9-(pyridin-4-yl)-9H-carbazole, Sq⋅- = 3,5-di-tert-butyl-semiquinonato, and Cat2- = 3,5-di-tert-butyl-catecholato, is synthesized in the trans configuration, which undergoes one-step valence tautomeric transition above room temperature. Remarkably, 1-trans can transform into its isomeric structure, [Co(pycz)2(Sq)(Sq)] (1-cis), at temperature above 350 K in a single-crystal-to-single-crystal way by in situ molecular twist, and the resulting 1-cis exhibits a pronounced two-step VT transition during magnetic measurements that is rare for mononuclear VT complexes. Such drastic solid-state structural transformation is reported in VT compounds for the first time, which is actuated by a crystal surface's melting-recrystallization induced phase transition process. DFT calculations offer an underlying mechanism suggesting a concerted bond rotation during the structural transformation. The results demonstrate an unconventional approach that realizes structural transformation of VT complexes and the control of VT performance.

9.
J Am Chem Soc ; 145(40): 22184-22193, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37768698

RESUMEN

Current lithium-ion batteries degrade under high rates and low temperatures due to the use of carbonate electrolytes with restricted Li+ conduction and sluggish Li+ desolvation. Herein, a strong solvent with dual lithium salts surmounts the thermodynamic limitations by regulating interactions among Li+ ions, anions, and solvents at the molecular level. Highly dissociated lithium bis(fluorosulfonyl)imide (LiFSI) in dimethyl sulfite (DMS) solvent with a favorable dielectric constant and melting point ensures rapid Li+ conduction while the high affinity between difluoro(oxalato)borate anions (DFOB-) and Li+ ions guarantees smooth Li+ desolvation within a wide temperature range. In the meantime, the ultrathin self-limited electrode/electrolyte interface and the electric double layer induced by DFOB- result in enhanced electrode compatibility. The as-formulated electrolyte enables stable cycles at high currents (41.3 mA cm-2) and a wide temperature range from -78 to 60 °C. The 1 Ah graphite||LiCoO2 (2 mAh cm-2) pouch cell achieves 80% reversible capacity at 2 C rate under -20 °C and 86% reversible capacity at 0.1 C rate under -50 °C. This work sheds new light on the electrolyte design with strong solvent and dual lithium salts and further facilitates the development of high-performance lithium-ion batteries operating under extreme conditions.

10.
Drug Metab Dispos ; 51(10): 1324-1331, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37290939

RESUMEN

Antibody-drug conjugates (ADCs) are produced by the chemical linkage of cytotoxic agents and monoclonal antibodies. The complexity and heterogeneity of ADCs and the low concentration of cytotoxic agent released in vivo poses big challenges to their bioanalysis. Understanding the pharmacokinetic behavior, exposure-safety, and exposure-efficacy relationships of ADCs is needed for their successful development. Accurate analytical methods are required to evaluate intact ADCs, total antibody, released small molecule cytotoxins, and related metabolites. The selection of appropriate bioanalysis methods for comprehensive analysis of ADCs is mainly dependent on the properties of cytotoxic agents, the chemical linker, and the attachment sites. The quality of the information about the whole pharmacokinetic profile of ADCs has been improved due to the development and improvement of analytical strategies for detection of ADCs, such as ligand-binding assays and mass spectrometry-related techniques. In this article, we will focus on the bioanalytical assays that have been used in the pharmacokinetic study of ADCs and discuss their advantages, current limitations, and potential challenges. SIGNIFICANCE STATEMENT: This article describes bioanalysis methods which have been used in pharmacokinetic study of ADCs and discusses the advantages, disadvantages and potential challenges of these assays. This review is useful and helpful and will provide insights and reference for bioanalysis and development of ADCs.


Asunto(s)
Antineoplásicos , Inmunoconjugados , Inmunoconjugados/farmacocinética , Distribución Tisular , Anticuerpos Monoclonales/química , Antineoplásicos/farmacocinética , Citotoxinas
11.
Anim Cogn ; 26(4): 1369-1379, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37191910

RESUMEN

In predator-prey interactions, various factors affect the prey's perception of risk and decision to flee. Gaze sensitivity, the ability to react to the presence, direction, or movement of the head and eyes, has been reported in many birds. However, few studies have focussed on variation in sensitivity to human gaze in relation to other risks and potential breeding costs. Here, we studied the influence of human gaze on the escape behaviour of Azure-winged magpies (Cyanopica cyanus) and investigated the effects of breeding state (breeding season and nonbreeding season) and approach direction on gaze sensitivity. In Experiment 1, we tested whether magpies showed different sensitivities to human gaze according to age class and breeding state when approached directly. The results showed that the breeding state could affect the flight initiation distance (FID), with adults in the breeding season having a shorter FID compared to those in the nonbreeding season. Meanwhile, only adults were found to be averse to direct human gaze and juveniles showed no sensitivity. In Experiment 2, we conducted three different gaze treatments on adult magpies in the breeding season under three bypass distances (0 m, 2.5 m, 5 m). The results showed that approach direction had no effect on FID, while the sensitivity to human gaze differed under three bypass distances. Adults could clearly recognise human head and eye direction at a certain bypass distance (2.5 m). Our study reveals the cognitive ability of Azure-winged magpies to human head and eye direction and the effects of age, breeding state and approach direction, which may provide further insights into human-wildlife interactions, especially for birds in urban habitats.


Asunto(s)
Passeriformes , Humanos , Animales , Cognición , Conducta Predatoria , Cruzamiento , Fijación Ocular
12.
Int J Eat Disord ; 56(9): 1807-1813, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37196058

RESUMEN

OBJECTIVE: This study assessed picky eating in pregnant women by exploring whether picky eating is associated with pregnant women's well-being, including life satisfaction, psychological distress, and psychosocial impairment. METHOD: Data collected were from 345 Chinese pregnant women ( M age = 29.95 years, SD = 5.58). Pearson correlation analyses were conducted to examine zero-order correlations between picky eating and well-being variables (i.e., life satisfaction, psychological distress, and psychosocial impairment). Hierarchical multiple regressions were conducted to examine the unique associations of picky eating with well-being variables, adjusting for demographic and pregnancy-related characteristics and thinness-oriented disordered eating. RESULTS: Picky eating was significantly and negatively correlated with life satisfaction (r = -.24, p < .001) and positively correlated with psychological distress (r = .37, p < .001) and psychosocial impairment (r = .50, p < .001). When adjusting for covariates and thinness-oriented disordered eating, picky eating was still significantly associated with lower life satisfaction, higher psychological distress, and higher psychosocial impairment. DISCUSSION: The findings suggest that picky eating may be a significant correlate of pregnant women's poorer well-being. Future research with longitudinal designs is warranted to further examine the temporal associations between picky eating and pregnant women's well-being. PUBLIC SIGNIFICANCE: Picky eating behaviors are poorly understood in pregnant women. Our results revealed that higher picky eating behaviors were associated with lower life satisfaction and higher psychological distress and psychosocial impairment in Chinese pregnant women. Researchers and clinicians may consider picky eating in the assessment and treatment of mental health and disordered eating in pregnant women.


Asunto(s)
Irritabilidad Alimentaria , Distrés Psicológico , Embarazo , Humanos , Femenino , Mujeres Embarazadas , Delgadez , Pueblos del Este de Asia , Encuestas y Cuestionarios , Satisfacción Personal
13.
BMC Med Imaging ; 23(1): 138, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37737166

RESUMEN

BACKGROUND: This study aimed to develop a computed tomography (CT) model to predict Ki-67 expression in hepatocellular carcinoma (HCC) and to examine the added value of radiomics to clinico-radiological features. METHODS: A total of 208 patients (training set, n = 120; internal test set, n = 51; external validation set, n = 37) with pathologically confirmed HCC who underwent contrast-enhanced CT (CE-CT) within 1 month before surgery were retrospectively included from January 2014 to September 2021. Radiomics features were extracted and selected from three phases of CE-CT images, least absolute shrinkage and selection operator regression (LASSO) was used to select features, and the rad-score was calculated. CE-CT imaging and clinical features were selected using univariate and multivariate analyses, respectively. Three prediction models, including clinic-radiologic (CR) model, rad-score (R) model, and clinic-radiologic-radiomic (CRR) model, were developed and validated using logistic regression analysis. The performance of different models for predicting Ki-67 expression was evaluated using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis (DCA). RESULTS: HCCs with high Ki-67 expression were more likely to have high serum α-fetoprotein levels (P = 0.041, odds ratio [OR] 2.54, 95% confidence interval [CI]: 1.04-6.21), non-rim arterial phase hyperenhancement (P = 0.001, OR 15.13, 95% CI 2.87-79.76), portal vein tumor thrombus (P = 0.035, OR 3.19, 95% CI: 1.08-9.37), and two-trait predictor of venous invasion (P = 0.026, OR 14.04, 95% CI: 1.39-144.32). The CR model achieved relatively good and stable performance compared with the R model (AUC, 0.805 [95% CI: 0.683-0.926] vs. 0.678 [95% CI: 0.536-0.839], P = 0.211; and 0.805 [95% CI: 0.657-0.953] vs. 0.667 [95% CI: 0.495-0.839], P = 0.135) in the internal and external validation sets. After combining the CR model with the R model, the AUC of the CRR model increased to 0.903 (95% CI: 0.849-0.956) in the training set, which was significantly higher than that of the CR model (P = 0.0148). However, no significant differences were found between the CRR and CR models in the internal and external validation sets (P = 0.264 and P = 0.084, respectively). CONCLUSIONS: Preoperative models based on clinical and CE-CT imaging features can be used to predict HCC with high Ki-67 expression accurately. However, radiomics cannot provide added value.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Antígeno Ki-67 , Estudios Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X
14.
Proc Natl Acad Sci U S A ; 117(48): 30191-30200, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33184175

RESUMEN

Escalating global water scarcity necessitates high-performance desalination membranes, for which fundamental understanding of structure-property-performance relationships is required. In this study, we comprehensively assess the ionization behavior of nanoporous polyamide selective layers in state-of-the-art nanofiltration (NF) membranes. In these films, residual carboxylic acids and amines influence permeability and selectivity by imparting hydrophilicity and ionizable moieties that can exclude coions. We utilize layered interfacial polymerization to prepare physically and chemically similar selective layers of controlled thickness. We then demonstrate location-dependent ionization of carboxyl groups in NF polyamide films. Specifically, only surface carboxyl groups ionize under neutral pH, whereas interior carboxyl ionization requires pH >9. Conversely, amine ionization behaves invariably across the film. First-principles simulations reveal that the low permittivity of nanoconfined water drives the anomalous carboxyl ionization behavior. Furthermore, we report that interior carboxyl ionization could improve the water-salt permselectivity of NF membranes over fourfold, suggesting that interior charge density could be an important tool to enhance the selectivity of polyamide membranes. Our findings highlight the influence of nanoconfinement on membrane transport properties and provide enhanced fundamental understanding of ionization that could enable novel membrane design.

15.
Int J Mol Sci ; 24(2)2023 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-36674718

RESUMEN

Our previous studies have confirmed that cadmium (Cd) exposure causes hepatotoxicity; it also induces autophagy and blocks the autophagy flux. Therefore, we hypothesized that Cd hepatotoxicity could be alleviated through nutritional intervention. Taurine (Tau) has various biological functions such as acting as an antioxidant, acting as an anti-inflammatory, and stabilizing cell membranes. In order to explore the protective effect and internal mechanism of Tau on Cd-induced hepatotoxicity, normal rat liver cell line BRL3A cells were treated with Cd alone or in combination with Tau to detect cell injury and autophagy-related indexes in this study. We found that Tau can alleviate Cd-induced cell-proliferation decline and morphological changes in the cell. In addition, Tau activates autophagy and alleviates the blockage of Cd-induced autophagy flux. In this process, lysosome acidification and degradation were enhanced, and autophagosomes were further fused with lysosomes. Then, we found that Tau alleviated autophagic flux block by promoting the transfer of membrane fusion proteins STX17 and SNAP29 to autophagosomes and the translocation of VAMP8 to lysosomes, which in turn attenuated the hepatocyte injury induced by Cd exposure. This will further reveal the hepatotoxicity mechanism of Cd and provide the theoretical basis for the prevention and treatment of Cd poisoning.


Asunto(s)
Cadmio , Enfermedad Hepática Inducida por Sustancias y Drogas , Ratas , Animales , Cadmio/metabolismo , Autofagia , Autofagosomas/metabolismo , Línea Celular , Lisosomas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Proteínas Qb-SNARE/metabolismo , Proteínas Qc-SNARE/metabolismo
16.
J Environ Sci (China) ; 128: 107-116, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36801026

RESUMEN

The degradation of metoprolol (MTP) by the UV/sulfite with oxygen as an advanced reduction process (ARP) and that without oxygen as an advanced oxidation process (AOP) was comparatively studied herein. The degradation of MTP by both processes followed the first-order rate law with comparable reaction rate constants of 1.50×10-3sec-1 and 1.20×10-3sec-1, respectively. Scavenging experiments demonstrated that both eaq- and H• played a crucial role in MTP degradation by the UV/sulfite as an ARP, while SO4•- was the dominant oxidant in the UV/sulfite AOP. The degradation kinetics of MTP by the UV/sulfite as an ARP and AOP shared a similar pH dependence with a minimum rate obtained around pH 8. The results could be well explained by the pH impacts on the MTP speciation and sulfite species. Totally six transformation products (TPs) were identified from MTP degradation by the UV/sulfite ARP, and two additional ones were detected in the UV/sulfite AOP. The benzene ring and ether groups of MTP were proposed as the major reactive sites for both processes based on molecular orbital calculations by density functional theory (DFT). The similar degradation products of MTP by the UV/sulfite process as an ARP and AOP indicated that eaq-/H• and SO4•- might share similar reaction mechanisms, primarily including hydroxylation, dealkylation, and H abstraction. The toxicity of MTP solution treated by the UV/sulfite AOP was calculated to be higher than that in the ARP by the Ecological Structure Activity Relationships (ECOSAR) software, due to the accumulation of TPs with higher toxicity.


Asunto(s)
Contaminantes Químicos del Agua , Purificación del Agua , Metoprolol/química , Oxígeno , Rayos Ultravioleta , Contaminantes Químicos del Agua/química , Oxidación-Reducción , Sulfitos/química , Cinética , Purificación del Agua/métodos
17.
J Biol Chem ; 296: 100318, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33484713

RESUMEN

The insulin receptor (INSR) binds insulin to promote body growth and maintain normal blood glucose levels. While it is known that steroid hormones such as estrogen and 20-hydroxyecdysone counteract insulin function, the molecular mechanisms responsible for this attenuation remain unclear. In the present study, using the agricultural pest lepidopteran Helicoverpa armigera as a model, we proposed that the steroid hormone 20-hydroxyecdysone (20E) induces dephosphorylation of INSR to counteract insulin function. We observed high expression and phosphorylation of INSR during larval feeding stages that decreased during metamorphosis. Insulin upregulated INSR expression and phosphorylation, whereas 20E repressed INSR expression and induced INSR dephosphorylation in vivo. Protein tyrosine phosphatase 1B (PTP1B, encoded by Ptpn1) dephosphorylated INSR in vivo. PTEN (phosphatase and tensin homolog deleted on chromosome 10) was critical for 20E-induced INSR dephosphorylation by maintaining the transcription factor Forkhead box O (FoxO) in the nucleus, where FoxO promoted Ptpn1 expression and repressed Insr expression. Knockdown of Ptpn1 using RNA interference maintained INSR phosphorylation, increased 20E production, and accelerated pupation. RNA interference of Insr in larvae repressed larval growth, decreased 20E production, delayed pupation, and accumulated hemolymph glucose levels. Taken together, these results suggest that a high 20E titer counteracts the insulin pathway by dephosphorylating INSR to stop larval growth and accumulate glucose in the hemolymph.


Asunto(s)
Ecdisterona/genética , Proteína Forkhead Box O1/genética , Fosfohidrolasa PTEN/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 1/genética , Receptor de Insulina/genética , Animales , Ecdisterona/metabolismo , Estrógenos/metabolismo , Regulación de la Expresión Génica/genética , Humanos , Insulina/genética , Insulina/metabolismo , Metamorfosis Biológica/genética , Mariposas Nocturnas/genética , Mariposas Nocturnas/crecimiento & desarrollo , Fosforilación/genética , Interferencia de ARN , Transducción de Señal
18.
Environ Sci Technol ; 56(16): 11707-11717, 2022 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-35930744

RESUMEN

Peracetic acid (PAA) serves as a potent and low-toxic oxidant for contaminant removal. Radical-mediated catalytic PAA oxidation processes are typically non-selective, rendering weakened oxidation efficacy under complex water matrices. Herein, we explored the usage of reduced graphene oxide (rGO) for PAA activation via a non-radical pathway. Outperforming the most catalytic PAA oxidation systems, the rGO-PAA system exhibits near-complete removal of typical micropollutants (MPs) within a short time (<2 min). Non-radical direct electron transfer (DET) from MPs to PAA plays a decisive role in the MP degradation, where accelerated DET is achieved by a higher potential of the rGO-PAA reactive surface complexes. Benefitting from DET, the rGO-PAA system shows robust removal of multiple MPs under complex water matrices and with low toxicity. Notably, in the DET regime, the electrostatic attraction of rGO to both PAA and target MP is a critical prerequisite for achieving efficient oxidation, depending on the conditions of solution pH and MP pKa. A heatmap model building on such an electrostatic interaction is further established as guidance for regulating the performance of the DET-mediated PAA oxidation systems. Overall, our work unveils the imperative role of DET for rGO-activated PAA oxidation, expanding the knowledge of PAA-based water treatment strategies.


Asunto(s)
Ácido Peracético , Contaminantes Químicos del Agua , Electrones , Grafito , Peróxido de Hidrógeno , Oxidación-Reducción
19.
Environ Sci Technol ; 56(12): 8733-8745, 2022 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-35537210

RESUMEN

The superior catalytic property of single-atom catalysts (SACs) renders them highly desirable in the energy and environmental fields. However, using SACs for water decontamination is hindered by their limited spatial distribution and density on engineered surfaces and low stability in complex aqueous environments. Herein, we present copper SACs (Cu1) anchored on a thiol-doped reactive membrane for water purification. We demonstrate that the fabricated Cu1 features a Cu-S2 coordination─one copper atom is bridged by two thiolate sulfur atoms, resulting in high-density Cu-SACs on the membrane (2.1 ± 0.3 Cu atoms per nm2). The Cu-SACs activate peroxide to generate hydroxyl radicals, exhibiting fast kinetics, which are 40-fold higher than those of nanoparticulate Cu catalysts. The Cu1-functionalized membrane oxidatively removes organic pollutants from feedwater in the presence of peroxide, achieving efficient water purification. We provide evidence that a dual-site cascade mechanism is responsible for in situ regeneration of Cu1. Specifically, one of the two linked sulfur atoms detaches the oxidized Cu1 while donating one electron, and an adjacent free thiol rebinds the reduced Cu(I)-S pair, retrieving the Cu-S2 coordination on the reactive membrane. This work presents a universal, facile approach for engineering robust SACs on water-treatment membranes and broadens the application of SACs to real-world environmental problems.


Asunto(s)
Contaminantes Ambientales , Peróxido de Hidrógeno , Cobre , Peróxidos , Compuestos de Sulfhidrilo , Azufre , Agua
20.
PLoS Genet ; 15(8): e1008331, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31412019

RESUMEN

Holometabolous insects stop feeding at the final larval instar stage and then undergo metamorphosis; however, the mechanism is unclear. In the present study, using the serious lepidopteran agricultural pest Helicoverpa armigera as a model, we revealed that 20-hydroxyecdysone (20E) binds to the dopamine receptor (DopEcR), a G protein-coupled receptor, to stop larval feeding and promote pupation. DopEcR was expressed in various tissues and its level increased during metamorphic molting under 20E regulation. The 20E titer was low during larval feeding stages and high during wandering stages. By contrast, the dopamine (DA) titer was high during larval feeding stages and low during the wandering stages. Injection of 20E or blocking dopamine receptors using the inhibitor flupentixol decreased larval food consumption and body weight. Knockdown of DopEcR repressed larval feeding, growth, and pupation. 20E, via DopEcR, promoted apoptosis; and DA, via DopEcR, induced cell proliferation. 20E opposed DA function by repressing DA-induced cell proliferation and AKT phosphorylation. 20E, via DopEcR, induced gene expression and a rapid increase in intracellular calcium ions and cAMP. 20E induced the interaction of DopEcR with G proteins αs and αq. 20E, via DopEcR, induced protein phosphorylation and binding of the EcRB1-USP1 transcription complex to the ecdysone response element. DopEcR could bind 20E inside the cell membrane or after being isolated from the cell membrane. Mutation of DopEcR decreased 20E binding levels and related cellular responses. 20E competed with DA to bind to DopEcR. The results of the present study suggested that 20E, via binding to DopEcR, arrests larval feeding and promotes pupation.


Asunto(s)
Ecdisterona/metabolismo , Proteínas de Insectos/metabolismo , Mariposas Nocturnas/fisiología , Receptores Dopaminérgicos/metabolismo , Animales , Dopamina/metabolismo , Antagonistas de Dopamina/farmacología , Conducta Alimentaria/efectos de los fármacos , Conducta Alimentaria/fisiología , Flupentixol/farmacología , Técnicas de Silenciamiento del Gen , Proteínas de Insectos/genética , Larva/efectos de los fármacos , Larva/fisiología , Muda/efectos de los fármacos , Muda/fisiología , Mariposas Nocturnas/efectos de los fármacos , Interferencia de ARN , Receptores Dopaminérgicos/genética , Células Sf9
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