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1.
Eur J Med Chem ; 276: 116688, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39033611

RESUMEN

Autophagy, a crucial intracellular degradation process facilitated by lysosomes, plays a pivotal role in maintaining cellular homeostasis. The elucidation of autophagy key genes and signaling pathways has significantly advanced our understanding of this process and has led to the exploration of autophagy as a promising therapeutic approach. This review comprehensively assesses the latest developments in small molecule modulators targeting autophagy. Moreover, the review delves into the most recent strategies for drug discovery, specifically focusing on selective agents that exploit autophagosomes and lysosomes for targeted protein degradation. Additionally, this article highlights the prevailing challenges and outlines potential future advancements in the field. By amalgamating the cutting-edge knowledge in the field, we aim to offer valuable insights and references for the anti-cancer drug development of autophagy-targeted therapies, thus contributing to the advancement of novel therapeutic interventions.

2.
J Microbiol ; 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967744

RESUMEN

Two bacterial strains (XCT-34T and XCT-53) isolated from sediment samples of an artificial freshwater reservoir were analyzed using a polyphasic approach. The two isolates are aerobic, Gram-stain-negative, oxidase-negative, catalase-positive, motile with polar flagella, rod-shaped, and approximately 1.4-3.4 × 0.4-0.9 µm in size. Phylogenetic analyses based on 16S rRNA gene and whole-genome sequences showed that the two strains formed a distinct branch within the evolutionary radiation of the genus Pannonibacter, closest to Pannonibacter carbonis Q4.6T (KCTC 52466). Furthermore, lower than threshold average nucleotide identity values (ANI, 85.7-86.4%) and digital DNA-DNA hybridization values (dDDH, 22.3-30.5%) of the two strains compared to the nearest type strains also confirmed that they represented a novel species. Genomic analyses, including annotation of the KEGG pathways, prediction of the secondary metabolism biosynthetic gene clusters and PHI phenotypes, supported functional inference and differentiation of the strains from the closely related taxa. Results of chemotaxonomic and physiological studies revealed that their distinct phenotypic characteristics distinguished them from existing Pannonibacter species. Thus, the two strains are considered to represent a novel species of Pannonibacter, for which the name of Pannonibacter tanglangensis sp. nov. is proposed, with XCT-34T (= KCTC 82332T = GDMCC 1.1947T) as the respective type strain.

3.
Appl Dev Sci ; 28(3): 375-390, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39006379

RESUMEN

Studies that distinguish parental monitoring (parent-driven behaviors) from parental knowledge often fail to find protective effects of monitoring on adolescent behavior problems. To answer whether parental monitoring is more strongly associated with adolescent behavior problems among adolescents who may need it most, this study applied group-based trajectory modeling to change in early- to mid-adolescent aggressive behavior problems and examined associations between parental monitoring with different subgroups. Three latent groups of adolescents were found: Low Aggression, Medium-Increasing Aggression, and High-Increasing Aggression. Results show that more maternal and paternal monitoring were associated with fewer adolescent aggressive behavior problems only for adolescents in the High-Increasing Group. This result suggests that parental monitoring is a protective factor against adolescent aggressive behavior problems for subgroups of adolescents who may need it most and less impactful for other adolescents.

4.
Front Microbiol ; 15: 1408701, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39040910

RESUMEN

Introduction: Bacterial resistance presents a major challenge to both the ecological environment and human well-being, with persistence playing a key role. Multiple studies were recently undertaken to examine the factors influencing the formation of persisters and the underlying process, with a primary focus on Gram-negative bacteria and Staphylococcus aureus (Gram-positive bacteria). Enterococcus faecalis (E. faecalis) is capable of causing a variety of infectious diseases, but there have been few studies of E. faecalis persisters. Previous studies have shown that the sex pheromone cCF10 secreted by E. faecalis induces conjugative plasmid transfer. However, whether the pheromone cCF10 regulates the persistence of E. faecalis has not been investigated. Methods: As a result, we investigated the effect and potential molecular mechanism of pheromone cCF10 in regulating the formation of persisters in E. faecalis OG1RF using a persistent bacteria model. Results and discussion: The metabolically active E. faecalis OG1RF reached a persistence state and temporarily tolerated lethal antibiotic concentrations after 8 h of levofloxacin hydrochloride (20 mg/mL) exposure, exhibiting a persistence rate of 0.109 %. During the growth of E. faecalis OG1RF, biofilm formation was a critical factor contributing to antibiotic persistence, whereas 10 ng/mL cCF10 blocked persister cell formation. Notably, cCF10 mediated the antibiotic persistence of E. faecalis OG1RF via regulating metabolic activity rather than suppressing biofilm formation. The addition of cCF10 stimulated the Opp system and entered bacterial cells, inhibiting (p)ppGpp accumulation, thus maintaining the metabolically active state of bacteria and reducing persister cell generation. These findings offer valuable insights into the formation, as well as the control mechanism of E. faecalis persisters.

5.
Jpn J Radiol ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700623

RESUMEN

PURPOSE: To explore the positive predictors of the clinical outcome in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (ACLVO) after endovascular mechanical thrombectomy (EMT) at a 90-day follow-up, and to establish a nomogram model to predict the clinical outcome. MATERIALS AND METHODS: AIS patients with ACLVO detected by multimodal Computed Tomography imaging who underwent EMT were collected. Patients were divided into the favorable and the unfavorable groups according to the 90-day modified Rankin Scale (mRS) score. Univariate and multivariate analyses were performed to investigate predictors of the favorable outcome (mRS of 0-2). A nomogram model for predicting the clinical outcome after EMT was drawn, and the receiver operating characteristic (ROC) curve was used to evaluate its predictive value. RESULTS: Totally 105 patients including 65 patients in the favorable group and 40 in the unfavorable group were enrolled. Multivariate logistic regression analysis showed that admission National Institute of Health Stroke scale (NIHSS) score [0.858 (95% CI 0.778-0.947)], ACLVO at M2 [20.023 (95% CI 2.204-181.907)] and infarct core (IC) volume [0.943 (95% CI 0.917-0.969)] was positively correlated with favorable outcome. The accuracy of the nomogram model in predicting the outcome was 0.923 (95% CI 0.870-0.976), with a cutoff value of 119.6 points. The area under the ROC curve was 0.848 (95% CI 0.780-0.917; sensitivity, 79.7%; specificity, 90.0%). CONCLUSION: A low Admission NIHSS score, ACLVO at M2, and a small IC volume were positive predictors for favorable outcome. The nomogram model may well predict the outcome in AIS patients with ACLVO after EMT.

6.
J Multidiscip Healthc ; 17: 2313-2320, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774624

RESUMEN

Purpose: This study aimed to investigate the maintenance effect of two puncture methods using non-coring needles in children with totally implantable venous access device (TIVAD). Methods: The 110 children who received TIVAD implantation for short bowel syndrome and solid tumors in our department from 2021.12 to 2022.12 were selected as the study subjects. Blinded method was used and divided into experimental group and control group according to random number table The experimental group underwent painless surround puncture method to place the needles and compound lidocaine ointment for topical anesthesia, while the control group underwent traditional puncture method to complete this operation. The effects of the two puncture methods on pain, catheter seal fluid volume, and catheter occlusion rate were evaluated using the Facial Pain Scale Revised, Behavioral Assessment Scale, and in vitro digital subtraction angiography test. Results: In the control group, the degree of puncture pain was mild in 5 patients, moderate in 19 patients, and severe in 28 patients; the amount of catheter sealing solution was 9.32 ± 1.32 mL, and the catheter occlusion rate was 25.00%. In the experimental group, the degree of puncture pain was mild in 16 patients, moderate in 22 patients, and severe in 16 patients; the amount of sealing solution was 7.66 ± 1.08 mL, and the blocking rate was 9.26%. The total pain score in the experimental group was lower than that in the control group (5.23±6.17 VS 7.89±2.38). The difference between the two groups had statistical significance (P < 0.05). Conclusion: The use of the painless surround puncture method can effectively reduce the pain experienced by children during puncture, decrease the volume of catheter sealing fluid, reduce the rate of catheter blockage, provide a valuable basis for enhancing the maintenance effect of TIVAD in clinical practice for children.

7.
Poult Sci ; 103(6): 103745, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38670058

RESUMEN

Fowl adenovirus serotype 11 (FAdV-11) is one of the main causative agents of inclusion body hepatitis (IBH) in broilers. Outbreaks of FAdV-11-related IBH have been increasingly reported in China and many other geographical areas worldwide. However, the critical virulence factors of FAdV-11 remain uncertain due to the lack of technical platforms for efficient manipulation of FAdV-11 genome. Here, we reported the establishment of a FAdV-11 reverse genetic system based on a novel FAdV-11 Chinese isolate FJSW/2021 using the exonuclease combined with RecET (ExoCET), Redαß recombineering and ccdB counter-selection techniques for the first time. A recombinant FAdV-11 was rescued efficiently by using the established reverse genetic platform through swapping the ORF11 gene of the FAdV-11 FJSW/2021 with the ZsGreen fluorescent protein expression cassette. This study provides an effective technical platform for identifying virulence factors of FAdV-11 and developing recombinant FAdV-11-vectored vaccine candidates.


Asunto(s)
Infecciones por Adenoviridae , Aviadenovirus , Pollos , Enfermedades de las Aves de Corral , Genética Inversa , Serogrupo , Animales , Enfermedades de las Aves de Corral/virología , Infecciones por Adenoviridae/veterinaria , Infecciones por Adenoviridae/virología , Aviadenovirus/genética , Genética Inversa/métodos
8.
J Youth Adolesc ; 53(8): 1832-1846, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38600264

RESUMEN

Parent engagement is an important aspect of parenting during childhood. However, little is known about the unique longitudinal associations of mother and father engagement with adolescents' externalizing and internalizing problem behaviors. This study uses Future of Families and Child Wellbeing Study data to examine the potential direct and indirect associations of parent engagement at age 9 on adolescent externalizing and internalizing behaviors at age 15. The analytic sample size is 1349, and at age 9, the mean age of children was 9.40 years (SD = 0.37). Forty-eight percent of children were female and 68% of them were from the married families. The results show that while controlling for mother engagement, higher father engagement at age 9 was directly associated with fewer adolescent internalizing behaviors, only among adolescent boys and in married families. In addition, among adolescent boys, father engagement had an indirect association with externalizing behaviors through father-child closeness. Mother engagement, however, is only found to have an indirect association with adolescents' externalizing and internalizing behaviors through maternal hostility (while controlling for father engagement). The results for mother engagement held for boys and in married families only. The findings indicate that both mother and father engagement during childhood is important and helpful to prevent adolescent problem behaviors directly or indirectly via parent-child relationship.


Asunto(s)
Conducta del Adolescente , Relaciones Padre-Hijo , Responsabilidad Parental , Humanos , Masculino , Femenino , Adolescente , Estudios Longitudinales , Niño , Conducta del Adolescente/psicología , Responsabilidad Parental/psicología , Relaciones Madre-Hijo/psicología , Problema de Conducta/psicología , Hostilidad , Control Interno-Externo
9.
Sensors (Basel) ; 24(7)2024 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-38610404

RESUMEN

Due to the limited semantic information extraction with small objects and difficulty in distinguishing similar targets, it brings great challenges to target detection in remote sensing scenarios, which results in poor detection performance. This paper proposes an improved YOLOv5 remote sensing image target detection algorithm, SEB-YOLO (SPD-Conv + ECSPP + Bi-FPN + YOLOv5). Firstly, the space-to-depth (SPD) layer followed by a non-strided convolution (Conv) layer module (SPD-Conv) was used to reconstruct the backbone network, which retained the global features and reduced the feature loss. Meanwhile, the pooling module with the attention mechanism of the final layer of the backbone network was designed to help the network better identify and locate the target. Furthermore, a bidirectional feature pyramid network (Bi-FPN) with bilinear interpolation upsampling was added to improve bidirectional cross-scale connection and weighted feature fusion. Finally, the decoupled head is introduced to enhance the model convergence and solve the contradiction between the classification task and the regression task. Experimental results on NWPU VHR-10 and RSOD datasets show that the mAP of the proposed algorithm reaches 93.5% and 93.9%respectively, which is 4.0% and 5.3% higher than that of the original YOLOv5l algorithm. The proposed algorithm achieves better detection results for complex remote sensing images.

10.
J Med Chem ; 67(8): 6425-6455, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38613499

RESUMEN

The RAS-RAF-MEK-ERK signaling cascade is abnormally activated in various tumors, playing a crucial role in mediating tumor progression. As the key component at the terminal stage of this cascade, ERK1/2 emerges as a potential antitumor target and offers a promising therapeutic strategy for tumors harboring BRAF or RAS mutations. Here, we identified 36c with a (thiophen-3-yl)aminopyrimidine scaffold as a potent ERK1/2 inhibitor through structure-guided optimization for hit 18. In preclinical studies, 36c showed powerful ERK1/2 inhibitory activities (ERK1/2 IC50 = 0.11/0.08 nM) and potent antitumor efficacy both in vitro and in vivo against triple-negative breast cancer and colorectal cancer models harboring BRAF and RAS mutations. 36c could directly inhibit ERK1/2, significantly block the phosphorylation expression of their downstream substrates p90RSK and c-Myc, and induce cell apoptosis and incomplete autophagy-related cell death. Taken together, this work provides a promising ERK1/2 lead compound for multiple tumor-treatment drug discovery.


Asunto(s)
Antineoplásicos , Inhibidores de Proteínas Quinasas , Pirimidinas , Humanos , Pirimidinas/farmacología , Pirimidinas/síntesis química , Pirimidinas/química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Animales , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Relación Estructura-Actividad , Ratones , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Tiofenos/farmacología , Tiofenos/síntesis química , Tiofenos/química , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Línea Celular Tumoral , Descubrimiento de Drogas , Apoptosis/efectos de los fármacos , Femenino , Ratones Desnudos , Ensayos de Selección de Medicamentos Antitumorales , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C
11.
BMC Public Health ; 24(1): 698, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443876

RESUMEN

BACKGROUND: Opioid crisis has become a global concern, but whether physical activity (PA) can effectively reduce prescription opioid use remains unclear. The study aimed to examine the relationship of different domains of PA (e.g., occupation-related PA [OPA], transportation-related PA [TPA], leisure-time PA [LTPA]) with prescription opioid use and duration of prescription opioid use. METHODS: This cross-sectional study was conducted on 27,943 participants aged ≥ 18 years from National Health and Nutrition Examination Survey (NHANES, 2007- March 2020). We examined the relationship of different domains of PA with prescription opioid use and duration of prescription opioid use using multivariable logistic regression. Stratified analysis and a series of sensitivity analysis were used to elevate robustness. All analyses were conducted using appropriate sampling weights. RESULTS: Of the 27,943 participants, the mean age was 45.10 years, with 14,018 [weighted, 50.0%] females and 11,045 [weighted, 66.0%] non-Hispanic White. After multivariable adjustment, inverse associations between PA and prescription opioid use were observed for sufficient (≥ 150 min/week) total PA (OR,0.68 95%CI [0.56-0.81]), TPA (OR,0.73 95%CI [0.58-0.92]), and LTPA (OR,0.60 95%CI [0.48-0.75]) compared with insufficient PA(< 150 min/week), but not for sufficient OPA (OR,0.93 95%CI [0.79-1.10]). In addition, the associations were dose-responsive, participants had 22-40%, 27-36%, and 26-47% lower odds of using prescription opioids depending on the duration of total PA, TPA, and LTPA, respectively. Nevertheless, the impact of PA on prescription opioid use varied by duration of opioid use. Sufficient total PA was associated with elevated odds of short-term use of prescription opioids (< 90 days). Comparatively, sufficient total PA, TPA, and LTPA had different beneficial effects on reducing long-term use of prescription opioids (≥ 90 days) depending on the strength of opioids. CONCLUSIONS: This study demonstrated sufficient total PA, TPA, and LTPA were inversely associated with prescription opioid use and varied depending on the duration and strength of prescription opioid use. These findings highlight PA can provide policy guidance to address opioid crisis.


Asunto(s)
Analgésicos Opioides , Trastornos Relacionados con Opioides , Adulto , Femenino , Humanos , Persona de Mediana Edad , Masculino , Analgésicos Opioides/uso terapéutico , Estudios Transversales , Encuestas Nutricionales , Trastornos Relacionados con Opioides/epidemiología , Ejercicio Físico , Prescripciones
12.
Poult Sci ; 103(5): 103642, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38537408

RESUMEN

Fowl adenovirus serotype 11 (FAdV-11) is one of the primary causative agents of inclusion body hepatitis (IBH), which causes substantial economic losses in the world poultry industry. In this study, we characterized the genome of the fowl adenovirus serotype 11 (FAdV-11) isolate FJSW/2021. The full genome of FJSW/2021 was 44, 154 base pairs (bp) in length and had a similar organization to that of previously reported FAdV-11 isolates. Notably, compared with those of other reported FAdV-11 strains, the preterminal protein (pTP) of FAdV-11 FJSW/2021 has six amino acid (aa) insertions (S-L-R-I-I-C) between 470 and 475 and one aa mutation of L476F; moreover, the tandem repeat (TR) regions of TR1 and TR2 were 33 bp (1 repeat) and 1,080 bp (8 repeats) shorter than those of the Canadian nonpathogenic isolate ON NP2, respectively. The pathogenicity of FJSW/2021 was studied in 10-day-old specific pathogen-free chicken embryos following allantoic cavity inoculation and in 1-day-old, 1-wk-old and 2-wk-old SPF chickens following intramuscular inoculation with 107 TCID50 of the virus. The results showed that FJSW/2021 can induce typical severe IBH in chicks less than 2 wk old. These findings highlighted the genetic differences between the pathogenic and non-pathogenic FAdV-11 isolates. The data will provide guidance for identifying the virulence factors of FAdV-11 strains. The animal challenge model developed in our study will allow precise evaluation of the efficacy of potential FAdV-11 vaccine candidates.


Asunto(s)
Aviadenovirus , Pollos , Genoma Viral , Enfermedades de las Aves de Corral , Serogrupo , Animales , Enfermedades de las Aves de Corral/virología , China , Aviadenovirus/genética , Aviadenovirus/patogenicidad , Virulencia , Organismos Libres de Patógenos Específicos , Hepatitis Viral Animal/virología , Embrión de Pollo , Infecciones por Adenoviridae/veterinaria , Infecciones por Adenoviridae/virología
13.
Anticancer Drugs ; 35(6): 525-534, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38502854

RESUMEN

Salidroside is a natural product of phenols with a wide range of pharmacological functions, but whether it plays a role in regulating autophagy is unclear. We systematically investigated the regulatory effect and molecular mechanism of salidroside on autophagy through network pharmacology, which provided a theoretical basis for subsequent experimental research. First, the target genes of salidroside were obtained using the Chinese Medicine System Pharmacology Database and Analysis Platform, and the target genes were converted into standardized gene names using the Uniprot website. At the same time, autophagy-related genes were collected from GeneCards, and preliminary handling of data to obtain intersecting genes. Then, the String website was used to construct a protein-protein interaction network, and to perform the Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis. To observe the specific molecular mechanism by which salidroside regulates autophagy, we constructed a drug component-target genes-autophagy network. Finally, we performed molecular docking to verify the possible binding conformation between salidroside and the candidate target. By searching the database and analyzing the data, we found that 113 target genes in salidroside interact with autophagy. Salidroside regulate autophagy in relation to a number of important oncogenes and signaling pathways. Molecular docking confirmed that salidroside has high affinity with mTOR, SIRT1, and AKT1. Through network pharmacology combined with molecular docking-validated research methods, we revealed the underlying mechanism of salidroside regulation of autophagy. This study not only provides new systematic insights into the underlying mechanism of salidroside in autophagy, but also provides new ideas for network approaches for autophagy-related research.


Asunto(s)
Autofagia , Glucósidos , Simulación del Acoplamiento Molecular , Farmacología en Red , Fenoles , Autofagia/efectos de los fármacos , Fenoles/farmacología , Fenoles/química , Glucósidos/farmacología , Humanos , Mapas de Interacción de Proteínas , Transducción de Señal/efectos de los fármacos , Sirtuina 1/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo
14.
J Environ Manage ; 353: 120147, 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38325278

RESUMEN

Aqueous thallium has posed an increasing threat to environment as human's intensified activities in mining, refining, process and discharge. Remediation on thallium pollution has been of up-most importance to water treatment. In present work, MnO2 and magnetic Fe3O4 have been implanted to sodium alginate (SA) in presence of carboxyl methyl cellulose (CMC), and the resultant beads consisted of SA/CMC/MnO2/Fe3O4 were characterized. The materials were applied to treatment of Tl-contaminated water as adsorbent in lab. The removal results revealed that the adsorption capacity reached 38.8 mg (Tl)·g (beads)-1 and almost 100 % removal efficiency was achieved. The residual Tl was below 0.1 µg·L-1, meeting the discharge standard regulated in China. The kinetic adsorption was better described as a pseudo-second-order and three-step intra-particle diffusion model. Freundlich isotherm was well fitted the experimental data. The absorbent shown an excellent competitive specificity (KTl/M: ∼104!) over common hazardous ions Cu2+, Cd2+, Co2+, Pb2+ and Cr3+, as well as naturally abundant K+ and Na+ (KTl/M: 10-102) in mimic environmental conditions. Regeneration and reusability of the absorbent was also verified by five absorption-desorpotion cycles. XPS results revealed that a redox reaction between Mn4+ with Tl+, and an ion exchange of H+ (-O-Fe) and Tl+ were assumed to be main process for the specific capturing. This study provided an efficient SA/CMC/MnO2/Fe3O4 composite beads that could be a promising adsorbent for Tl-polluted water treatment.


Asunto(s)
Talio , Contaminantes Químicos del Agua , Humanos , Compuestos de Manganeso , Óxidos , Oxidación-Reducción , Adsorción , Fenómenos Magnéticos , Contaminantes Químicos del Agua/análisis , Cinética , Concentración de Iones de Hidrógeno
15.
Plant Sci ; 342: 112026, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38342186

RESUMEN

Anthocyanins are among the main pigments involved in the colouration of Asiatic hybrid lily (Lilium spp.). Ethylene, a plant ripening hormone, plays an important role in promoting plant maturation and anthocyanin biosynthesis. However, whether and how ethylene regulates anthocyanin biosynthesis in lily tepals have not been characterized. Using yeast one-hybrid screening, we previously identified an APETALA2 (AP2)/ETHYLENE RESPONSE FACTOR (ERF) named LhERF4 as a potential inhibitor of LhMYBSPLATTER-mediated negative regulation of anthocyanin biosynthesis in lily. Here, transcript and protein analysis of LhERF4, a transcriptional repressor, revealed that LhERF4 directly binds to the promoter of LhMYBSPLATTER. In addition, overexpression of LhERF4 in lily tepals negatively regulates the expression of key structural genes and the total anthocyanin content by suppressing the LhMYBSPLATTER gene. Moreover, the LhERF4 gene inhibits anthocyanin biosynthesis in response to ethylene, affecting anthocyanin accumulation and pigmentation in lily tepals. Collectively, our findings will advance and elucidate a novel regulatory network of anthocyanin biosynthesis in lily, and this research provides new insight into colouration regulation.


Asunto(s)
Antocianinas , Lilium , Antocianinas/metabolismo , Lilium/metabolismo , Flores/genética , Factores de Transcripción/metabolismo , Etilenos/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo
16.
J Med Chem ; 67(4): 2777-2801, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38323982

RESUMEN

Activation of the alternative pathways and abnormal signaling transduction are frequently observed in third-generation EGFR-TKIs (epidermal growth factor receptor tyrosine kinase inhibitors)-resistant patients. Wherein, hyperphosphorylation of ACK1 contributes to EGFR-TKIs acquired resistance. Dual inhibition of EGFRL858R/T790M and ACK1 might improve therapeutic efficacy and overcome resistance in lung cancers treatment. Here, we identified a EGFRL858R/T790M/ACK1 dual-targeting compound 21a with aminoquinazoline scaffold, which showed excellent inhibitory activities against EGFRL858R/T790M (IC50 = 23 nM) and ACK1 (IC50 = 263 nM). The cocrystal and docking analysis showed that 21a occupied the ATP binding pockets of EGFRL858R/T790M and ACK1. Moreover, 21a showed potent antiproliferative activities against the H1975 cells, MCF-7 cells and osimertinib-resistant cells AZDR. Further, 21a showed significant antitumor effects and good safety in ADZR xenograft-bearing mice. Taken together, 21a was a potent dual inhibitor of EGFRL858R/T790M/ACK1, which is deserved as a potential lead for overcoming acquired resistance to osimertinib during the EGFR-targeted therapy.


Asunto(s)
Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas , Indoles , Neoplasias Pulmonares , Pirimidinas , Humanos , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Receptores ErbB/metabolismo , Resistencia a Antineoplásicos , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/química , Línea Celular Tumoral
17.
Plant Dis ; 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38240710

RESUMEN

Lilium davidii var. willmottiae, known as Lanzhou lily, is widely cultivated in China for its edible bulbs. In July 2023, symptoms of bulb rot were observed on Lanzhou lilies harvested from Lanzhou, Gansu Province, during storage at the Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences (Beijing, China), at an incidence of nearly 70%. The surface of the lily scales had dark water-stained spots, after the development of which the color gradually darkened, the bulbs became soft, accompanied by a pungent smell. Finally, the whole bulb became ruined and rotten, and there were thick mycelium layers on the bulbs. The infected bulbs were washed with clean water, sterilized with 75% ethanol for 30 s and 2% sodium hypochlorite for 5 min, and then rinsed three times with sterile distilled water. The 5 mm×5 mm tissue pieces from the junction of the diseased part and the healthy part were clipped, placed on potato dextrose agar (PDA) medium and subsequently incubated at 25 °C. Pure cultures were obtained by transferring hyphal tips to new PDA plates. A total of 10 fungal isolates were obtained, all of which exhibited typical Fusarium characteristics. The colonies were white to pink with white to cream-colored aerial mycelia. After 10 to 15 days of incubation, the macroconidia (n = 50) were hyaline, relatively slender with a curve, three to five septate, and 8.73 to 33.24 × 2.16 to 4.19 µm in length. The microconidia (n = 50) were hyaline and pyriform, without septa, and measured 4.04 to 8.48 × 1.24 to 2.65 µm. These morphological characteristics were similar to those described for Fusarium proliferatum (Leslie and Summerell 2006). For molecular identification, a cetyltrimethylammonium bromide (CTAB) protocol was used to extract total genomic DNA (O'Donnell et al., 1998), after which the internal transcribed spacer (ITS), translation elongation factor subunit 1-alpha (TEF1-α) and RNA polymerase Ⅱ subunit 2 (RPB2) genes were amplified using the universal primers ITS1/ITS4, EF1/EF2 and RPB2-5f2/fRPB2-7cr, respectively, and subsequently sequenced (White et al., 1990; O'Donnell et al., 1998; Liu et al., 1999; Reeb et al., 2004; O'Donnell et al., 2007; Jiang et al., 2018). The sequences of a representative isolate (CAAS01) were analyzed and submitted to GenBank under accession numbers OR554007 (ITS), OR594233 (TEF1-α) and OR603932 (RPB2). A BLAST analysis revealed that the sequences of the ITS, TEF1-α, and RPB2 genes shared 100%, 100%, and 100% identity, respectively, with those of Fusarium proliferatum (MT466521.1, MK952792.1, and LT841266.1) in GenBank. In addition, the ITS, TEF1-α and RPB2 sequences shared 100%, 100%, and 100% identity with those of Fusarium annulatum (LC13675, the Fusarium fujikuroi species complex; previously known as the Gibberella fujikuroi species complex) in the Fusarium-ID database. Fusarium proliferatum, whose common synonyms are Gibberella fujikuroi mating population D and Gibberella fujikuroi var. intermedia, is the anamorphic form of the Gibberella fujikuroi complex that belongs to the Nectriaceae family. A phylogenetic tree was constructed based on the combined TEF1-α and RPB2 sequences of CAAS01 and other Fusarium isolates, revealing that CAAS01 was grouped with Fusarium proliferatum. Based on sequence alignment and phylogenetic analysis, the isolate was identified as Fusarium proliferatum. To determine the pathogenicity of the isolated fungi, healthy bulbs were punctured with disposable sterilized needles and soaked in equal amounts of sterile water and conidial suspension (1×107 conidia/mL) for 30 min respectively. The pathogenicity experiment was repeated three times. After 7 days of inoculation at 25 °C and 80% relative humidity, the surface of the inoculated bulbs produced water-stained spots and mycelium layers consistent with the symptoms exhibited by Lilium davidii var. willmottiae bulbs during storage, while the uninoculated lily bulbs remained symptomless. Fusarium proliferatum was reisolated from the infected bulbs and identified based on morphological and molecular characteristics, fulfilling Koch's postulates. To our knowledge, this is the first report of bulb rot on Lilium davidii var. willmottiae caused by Fusarium proliferatum in China. This study will contribute to the development of management strategies for this postharvest disease in Lilium davidii var. willmottiae.

18.
Diagn Pathol ; 19(1): 23, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38291475

RESUMEN

OBJECTIVE: This study aimed to investigate the clinicopathological features and prognostic indicators of alveolar soft part sarcoma (ASPS). METHODS: The characteristics of 26 ASPS patients diagnosed at our hospital between January 2011 and January 2019 were retrospectively analysed. RESULTS: The data for 12 male and 14 female patients, with a median age of 27.5 years, were assessed. The clinical symptoms mainly included painless enlarged masses in deep soft tissues. ASPS had a characteristic pathological morphology. Twenty-four patients were positive for TFE3, and TFE3 gene rearrangement was detected in 12 patients. Among the 26 patients who completed follow-up, 14 had metastasis, 1 had local recurrence, and 7 died. Kaplan-Meier survival analysis revealed that prognosis was significantly correlated with sex, tumour size and metastasis (P < 0.05). Multivariate Cox regression analysis revealed that sex and metastasis were independent prognostic risk factors for patients with ASPS (P < 0.05). CONCLUSION: ASPS is a rare soft tissue sarcoma of unknown origin that occurs in young people, has a slow but metastatic course, and is associated with a poor 5-year survival rate among patients with metastasis. ASPS has character TFE3 protein and gene expression, and the diagnosis is relatively specific. The diagnosis requires comprehensive analysis of clinical history, histological morphology, and immunohistochemistry.


Asunto(s)
Sarcoma de Parte Blanda Alveolar , Humanos , Masculino , Femenino , Adolescente , Adulto , Estudios Retrospectivos , Sarcoma de Parte Blanda Alveolar/diagnóstico , Sarcoma de Parte Blanda Alveolar/genética , Sarcoma de Parte Blanda Alveolar/patología , Pronóstico , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Factores de Riesgo
19.
Comput Biol Med ; 170: 107989, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38286105

RESUMEN

Accurate segmentation of the pancreas from abdominal computed tomography (CT) images is challenging but essential for the diagnosis and treatment of pancreatic disorders such as tumours and diabetes. In this study, a dataset with 229 sets of high-resolution CT images was generated and annotated. We proposed a novel 3D segmentation model named nnTransfer (nonisomorphic transfer learning) net, which employs generative model structure for self-supervision to facilitate the network's learning of image attributes from unlabelled data. The effectiveness for pancreas segmentation of nnTransfer was assessed using the Hausdorff distance (HD) and Dice similarity coefficient (DSC) on the dataset. Additionally, a histogram analysis with local thresholding was used to achieve automated whole-volume measurement of pancreatic fat (fat volume fraction, FVF). The proposed technique performed admirably on the dataset, with DSC: 0.937 ± 0.019 and HD: 2.655 ± 1.479. The mean pancreas volume and FVF of the pancreas were 91.95 ± 23.90 cm3 and 12.67 % ± 9.84 %, respectively. The nnTransfer functioned flawlessly and autonomously, facilitating the use of the FVF to evaluate pancreatic disease, particularly in patients with diabetes.


Asunto(s)
Aprendizaje Profundo , Diabetes Mellitus , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Páncreas/diagnóstico por imagen , Tomografía Computarizada por Rayos X
20.
Food Chem ; 432: 137214, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-37651782

RESUMEN

Soybean protein isolate (SPI) is an important plant protein in food processing; however, its spherical structure prevents the exposure of its hydrophobic residues and affects its functional properties. In this study, we elucidate the effects of deamidation, phosphorylation, and glycosylation on the structure (Fourier-transform infrared spectroscopy, circular dichroism, fluorescence, and scanning electron microscopy) and functional properties (solubility, emulsifying activity index (EAI), and emulsifying stability index (ESI)) of SPI. The zeta potentials of the deamidated, phosphorylated, and glycosylated (DSPI, PSPI, and MSPI, respectively) samples decreased significantly (p < 0.05) relative to those of SPI. The functional properties of the modified SPI samples were improved, with MSPI-2 showing the best solubility (86.73 ± 0.34%), EAI (118.89 ± 0.73 m2/g), and ESI (273.33 ± 0.59 min). Moreover, the effects of the three modifications on the SPI functional properties increase in the order MSPI > PSPI > DSPI. These results provide a theoretical understanding the relationship between the modifications and SPI structure.


Asunto(s)
Glycine max , Proteínas de Soja , Proteínas de Plantas , Dicroismo Circular , Manipulación de Alimentos
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