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1.
Exp Cell Res ; 437(2): 114012, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38565343

RESUMEN

Ovarian cancer is one of the most common gynecological tumors worldwide. Despite the availability of multiple treatments for ovarian cancer, its resistance to chemotherapy remains a significant challenge. miRNAs play crucial roles in the initiation and progression of cancer by affecting processes such as differentiation, proliferation, and chemoresistance. According to microarray and qPCR analyses, miR-7704 is significantly downregulated in cisplatin-resistant cells compared to parental cells. In this study, we found that miR-7704 inhibited the proliferation and promoted cisplatin sensitivity of ovarian cancer cells in vitro and in vivo. Moreover, ectopic expression of miR-7704 had the same effect as IL2RB knockdown. Further mechanistic studies revealed that miR-7704 played an inhibitory role by regulating IL2RB expression to inactivate the AKT signaling pathway. Furthermore, IL2RB reversed the miR-7704 mediated resistance to cisplatin in ovarian cancer. Based on these findings, miR-7704 and IL2RB show the potential as novel therapeutic targets for ovarian cancer.


Asunto(s)
MicroARNs , Neoplasias Ováricas , Femenino , Humanos , Carcinogénesis , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica , Cisplatino/farmacología , Resistencia a Antineoplásicos , Retroalimentación , Regulación Neoplásica de la Expresión Génica , Subunidad beta del Receptor de Interleucina-2/metabolismo , Subunidad beta del Receptor de Interleucina-2/farmacología , Subunidad beta del Receptor de Interleucina-2/uso terapéutico , MicroARNs/metabolismo , Neoplasias Ováricas/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo
2.
J Biol Chem ; 299(12): 105436, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37944616

RESUMEN

Structural variations (SV) are critical genome changes affecting human diseases. Although many hybridization-based methods exist, evaluating SVs through next-generation sequencing (NGS) data is still necessary for broader research exploration. Here, we comprehensively compared the performance of 16 SV callers and multiple NGS platforms using NA12878 whole genome sequencing (WGS) datasets. The results indicated that several SV callers performed well relatively, such as Manta, GRIDSS, LUMPY, TARDIS, FermiKit, and Wham. Meanwhile, all NGS platforms have a similar performance using a single software. Additionally, we found that the source of undetected SVs was mostly from long reads datasets, therefore, the more appropriate strategy for accurate SV detection will be an integration of long and shorter reads in the future. At present, in the period of NGS as a mainstream method in bioinformatics, our study would provide helpful and comprehensive guidelines for specific categories of SV research.


Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Programas Informáticos , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Biología Computacional , Secuenciación Completa del Genoma , Genoma Humano
3.
New Phytol ; 243(4): 1455-1471, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38874377

RESUMEN

Wood is resulted from the radial growth paced by the division and differentiation of vascular cambium cells in woody plants, and phytohormones play important roles in cambium activity. Here, we identified that PagJAZ5, a key negative regulator of jasmonate (JA) signaling, plays important roles in enhancing cambium cell division and differentiation by mediating cytokinin signaling in poplar 84K (Populus alba × Populus glandulosa). PagJAZ5 is preferentially expressed in developing phloem and cambium, weakly in developing xylem cells. Overexpression (OE) of PagJAZ5m (insensitive to JA) increased cambium activity and xylem differentiation, while jaz mutants showed opposite results. Transcriptome analyses revealed that cytokinin oxidase/dehydrogenase (CKXs) and type-A response regulators (RRs) were downregulated in PagJAZ5m OE plants. The bioactive cytokinins were significantly increased in PagJAZ5m overexpressing plants and decreased in jaz5 mutants, compared with that in 84K plants. The PagJAZ5 directly interact with PagMYC2a/b and PagWOX4b. Further, we found that the PagRR5 is regulated by PagMYC2a and PagWOX4b and involved in the regulation of xylem development. Our results showed that PagJAZ5 can increase cambium activity and promote xylem differentiation through modulating cytokinin level and type-A RR during wood formation in poplar.


Asunto(s)
Cámbium , Ciclopentanos , Citocininas , Regulación de la Expresión Génica de las Plantas , Oxilipinas , Proteínas de Plantas , Populus , Transducción de Señal , Xilema , Populus/genética , Populus/crecimiento & desarrollo , Populus/metabolismo , Cámbium/genética , Cámbium/crecimiento & desarrollo , Cámbium/metabolismo , Citocininas/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Xilema/metabolismo , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Oxilipinas/farmacología , Mutación/genética , Unión Proteica/efectos de los fármacos , Diferenciación Celular
4.
Phys Chem Chem Phys ; 26(26): 18196-18204, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38904087

RESUMEN

The Zr-2.5Nb alloy is a typical pressure tube material in heavy water nuclear reactors, and an increase of hydrogen isotope content in the alloy during service can pose major safety risks; hot vacuum extraction-mass spectrometry is an efficient method for evaluating hydrogen isotope concentrations in the Zr-2.5Nb alloy. This work investigates the kinetics and thermodynamic properties of deuterium (D) absorption and desorption of the Zr-2.5Nb alloy using the constant volume adsorption method and the hot vacuum extraction method. In addition to the previously reported volume contraction model, it was observed that at 600 °C and above, the reaction between D2 and Zr-2.5Nb is dominated by diffusion, while the reaction is predominantly influenced by surface adsorption and dissociation below 600 °C. Phase transition sequence of Zr-2.5Nb deuterides during non-isothermal desorption was established using quantitatively calibrated thermal desorption spectra combined with the phase transition process of deuteride decomposition. These results can provide important references for optimizing the process parameters of the hot vacuum extraction-mass spectrometry method.

5.
J Nanobiotechnology ; 22(1): 587, 2024 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-39342211

RESUMEN

Spatiotemporally controlled cargo release is a key advantage of nanocarriers in anti-tumor therapy. Various external or internal stimuli-responsive nanomedicines have been reported for their ability to increase drug levels at the diseased site and enhance therapeutic efficacy through a triggered release mechanism. Redox-manipulating nanocarriers, by exploiting the redox imbalances in tumor tissues, can achieve precise drug release, enhancing therapeutic efficacy while minimizing damage to healthy cells. As a typical redox-sensitive bond, the disulfide bond is considered a promising tool for designing tumor-specific, stimulus-responsive drug delivery systems (DDS). The intracellular redox imbalance caused by tumor microenvironment (TME) regulation has emerged as an appealing therapeutic target for cancer treatment. Sustained glutathione (GSH) depletion in the TME by redox-manipulating nanocarriers can exacerbate oxidative stress through the exchange of disulfide-thiol bonds, thereby enhancing the efficacy of ROS-based cancer therapy. Intriguingly, GSH depletion is simultaneously associated with glutathione peroxidase 4 (GPX4) inhibition and dihydrolipoamide S-acetyltransferase (DLAT) oligomerization, triggering mechanisms such as ferroptosis and cuproptosis, which increase the sensitivity of tumor cells. Hence, in this review, we present a comprehensive summary of the advances in disulfide based redox-manipulating nanocarriers for anticancer drug delivery and provide an overview of some representative achievements for combinational therapy and theragnostic. The high concentration of GSH in the TME enables the engineering of redox-responsive nanocarriers for GSH-triggered on-demand drug delivery, which relies on the thiol-disulfide exchange reaction between GSH and disulfide-containing vehicles. Conversely, redox-manipulating nanocarriers can deplete GSH, thereby enhancing the efficacy of ROS-based treatment nanoplatforms. In brief, we summarize the up-to-date developments of the redox-manipulating nanocarriers for cancer therapy based on DDS and provide viewpoints for the establishment of more stringent anti-tumor nanoplatform.


Asunto(s)
Antineoplásicos , Sistema de Administración de Fármacos con Nanopartículas , Neoplasias , Oxidación-Reducción , Animales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Disulfuros/química , Liberación de Fármacos , Glutatión/metabolismo , Glutatión/química , Neoplasias/tratamiento farmacológico , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Microambiente Tumoral/efectos de los fármacos , Sistema de Administración de Fármacos con Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/farmacología
6.
BMC Ophthalmol ; 24(1): 244, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858630

RESUMEN

BACKGROUND: This study aimed to report a case of neurotrophic keratitis caused by lightning. CASE PRESENTATION: A 38-year-old man was hit by lightning and suffered eye injury. He eventually developed neurotrophic keratitis. RESULTS: The patient's injury history and burn site were analyzed, and it was judged that lightning directly damaged his cornea, eventually resulting in neurotrophic keratitis. Fortunately, the patient's vision improved after treatment. CONCLUSION: Lightning can cause eye damage, and the clinical manifestations are diverse. Lightning currents cause corneal nerve loss, resulting in neurotrophic keratitis. To maintain corneal integrity and prevent disease progression, early assessment and appropriate treatment are necessary.


Asunto(s)
Queratitis , Traumatismos por Acción del Rayo , Humanos , Masculino , Adulto , Traumatismos por Acción del Rayo/complicaciones , Queratitis/etiología , Queratitis/diagnóstico , Agudeza Visual , Córnea/patología
7.
Nano Lett ; 23(10): 4502-4509, 2023 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-37171532

RESUMEN

Extending the fabrication methodology of solid-state nanopores in a wide range of materials is significant in the fields of single molecule detection, nanofluidic devices, and nanofiltration membranes. Here, we demonstrate a new method to directly fabricate size- and density-controllable sub-10 nm nanopores in WO3 nanosheets using single swift heavy ions (SHIs) without any chemical etching process. By selecting ions of different electronic energy losses (Se), nanopores with sizes from 1.8 to 7.4 nm can be created in WO3 nanosheets. The creation efficiency of nanopores achieves ∼100% for Se > 20 keV/nm, and there exists a critical thickness below which nanopores can be created. Combined with molecular dynamics simulations, we propose that the viscosity and surface tension of the transient molten phase caused by SHIs are the key factors for the formation of nanopores. This method paves a way to fabricate solid-state nanopores in materials with a low viscosity and surface tension.

8.
Int J Mol Sci ; 25(18)2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39337596

RESUMEN

Perylenequinones (PQs) are important natural compounds that have been extensively utilized in recent years as agents for antimicrobial, anticancer, and antiviral photodynamic therapies. In this study, we investigated the molecular mechanisms regulating PQ biosynthesis by comparing Shiraia sp. Slf14 with its low PQ titer mutant, Slf14(w). The results indicated that the strain Slf14 exhibited a higher PQ yield, a more vigorous energy metabolism, and a more pronounced oxidation state compared to Slf14(w). Transcriptome analysis consistently revealed that the differences in gene expression between Slf14 and Slf14(w) are primarily associated with genes involved in redox processes and energy metabolism. Additionally, reactive oxygen species (ROS) were shown to play a crucial role in promoting PQ synthesis, as evidenced by the application of ROS-related inhibitors and promoters. Further results demonstrated that mitochondria are significant sources of ROS, which effectively regulate PQ biosynthesis in Shiraia sp. Slf14. In summary, this research revealed a noteworthy finding: the higher energy metabolism of the strain Slf14 is associated with increased intracellular ROS accumulation, which in turn triggers the activation and expression of gene clusters responsible for PQ synthesis.


Asunto(s)
Metabolismo Energético , Mitocondrias , Perileno , Especies Reactivas de Oxígeno , Especies Reactivas de Oxígeno/metabolismo , Perileno/análogos & derivados , Perileno/metabolismo , Mitocondrias/metabolismo , Quinonas/metabolismo , Ascomicetos/metabolismo , Ascomicetos/genética , Regulación Fúngica de la Expresión Génica , Perfilación de la Expresión Génica
9.
J Perianesth Nurs ; 39(5): 853-858, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38944791

RESUMEN

PURPOSE: The purpose of this study was to analyze the reliability and validity of the Perioperative Anxiety Scale-7 (PAS-7), which was created by Chinese medical professionals, by using the State-Trait Anxiety Scale (STAI-S) as the standard for the diagnosis of preoperative anxiety, and to compare whether there is a difference between the PAS-7 and the Amsterdam Preoperative Anxiety and Information Scale (APAIS) in the diagnosis of preoperative anxiety in the Chinese population. DESIGN: This study was an observational study. METHODS: The PAS-7, APAIS, and STAI-S were all completed the day before surgery. The internal consistency test was used to evaluate the scale's reliability, and exploratory factor analysis and confirmatory factor analysis were used to assess the scale's construct validity. Pearson correlation was used to analyze the correlation between PAS-7 and STAI-S, and APAIS. The area under the receiver operating characteristic (ROC) curve was used to compare the diagnostic value of PAS-7 and APAIS. FINDINGS: The PAS-7 Cronbach's α coefficient was 0.804. The indicators of the overall fitting coefficient were within the acceptable range. PAS-7 scores correlated well with STAI-S and APAIS scores (P < .01). The area under the ROC curve of PAS-7 was 0.808 (0.752-0.856), and the area under the ROC curve of APAIS was 0.674 (0.611-0.733). The difference between areas was 0.133 (0.0612-0.206), P < .001, and the diagnostic value of PAS-7 was higher than that of APAIS. CONCLUSIONS: The PAS-7 scale has high reliability and validity and can be used to assess preoperative anxiety in patients undergoing elective surgery. PAS-7 is superior to APAIS for assessing preoperative anxiety in the Chinese population.


Asunto(s)
Ansiedad , Humanos , Femenino , Masculino , Ansiedad/diagnóstico , Ansiedad/psicología , Ansiedad/epidemiología , Adulto , Persona de Mediana Edad , China , Reproducibilidad de los Resultados , Periodo Preoperatorio , Psicometría/métodos , Encuestas y Cuestionarios/normas , Curva ROC , Anciano , Cuidados Preoperatorios/métodos , Pueblos del Este de Asia
10.
Angew Chem Int Ed Engl ; 63(43): e202411047, 2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39008226

RESUMEN

Ternary cuprous (Cu+)-based metal halides, represented by cesium copper iodide (e.g., CsCu2I3 and Cs3Cu2I5), are garnering increasing interest for light-emitting applications owing to their intrinsically high photoluminescence quantum yield and direct band gap. Toward electrically driven light-emitting diodes (LEDs), it is highly desirable for the light emitters to have a high structural dimensionality as it may favor efficient electrical injection. However, unlike lead-based halide perovskites whose light-emitting units can be facilely arranged in three-dimensional (3D) ways, to date, nearly all ternary Cu+-based metal halides crystallize into 0D or 1D networks of Cu-X (X=Cl, Br, I) polyhedra, whereas 3D and even 2D structures remain mostly uncharted. Here, by employing a fluorinated organic cation, we report a new kind of ternary Cu+-based metal halides, (DFPD)CuX2 (DFPD+=4,4-difluoropiperidinium), which exhibits unique 2D layered crystal structure. Theoretical calculations reveal a highly dispersive conduction band of (DFPD)CuBr2, which is beneficial for charge carrier injection. It is also of particular significance to find that the 2D (DFPD)CuBr2 crystals show appealing properties, including improved ambient stability and an efficient warm white-light emission, making it a promising candidate for single-component lighting and display applications.

11.
J Vasc Surg ; 78(2): 430-437.e4, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37076105

RESUMEN

OBJECTIVE: Carotid artery stenting (CAS) has become an alternative strategy to carotid endarterectomy for carotid artery stenosis. Residual stenosis was an independent risk factor for restenosis, with the latter affecting the long-term outcomes of CAS. This multicenter study aimed to evaluate the echogenicity of plaques and hemodynamic alteration by color duplex ultrasound (CDU) examination and investigate their effects on the residual stenosis after CAS. METHODS: From June 2018 to June 2020, 454 patients (386 males and 68 females) with a mean age of 67.2 ± 7.9 years, who underwent CAS from 11 advanced stroke centers in China were enrolled. One week before recanalization, CDU was used to evaluate the responsible plaques, including the morphology (regular or irregular), echogenicity of the plaques (iso-, hypo-, or hyperechoic) and calcification characteristics (without calcification, superficial calcification, inner calcification, and basal calcification). One week after CAS, the alteration of diameter and hemodynamic parameters were evaluated by CDU, and the occurrence and degree of residual stenosis were determined. In addition, magnetic resonance imaging was performed before and during the 30-day postprocedural period to identify new ischemic cerebral lesions. RESULTS: The rate of composite complications, including cerebral hemorrhage, symptomatic new ischemic cerebral lesions, and death after CAS, was 1.54% (7/454 cases). The rate of residual stenosis after CAS was 16.3% (74/454 cases). After CAS, both the diameter and peak systolic velocity (PSV) improved in the preprocedural 50% to 69% and 70% to 99% stenosis groups (P < .05). Compared with the groups without residual stenosis and with <50% residual stenosis, the PSV of all three segments of stent in the 50% to 69% residual stenosis group were the highest, and the difference in the midsegment of stent PSV was the largest (P < .05). Logistic regression analysis showed that preprocedural severe (70% to 99%) stenosis (odds ratio [OR], 9.421; P = .032), hyperechoic plaques (OR, 3.060; P = .006) and plaques with basal calcification (OR, 1.885; P = .049) were independent risk factors for residual stenosis after CAS. CONCLUSIONS: Patients with hyperechoic and calcified plaques of the carotid stenosis are at a high risk of residual stenosis after CAS. CDU is an optimal, simple and noninvasive imaging method to evaluate plaque echogenicity and hemodynamic alterations during the perioperative period of CAS, which can help surgeons to select the optimal strategies and prevent the occurrence of residual stenosis.


Asunto(s)
Estenosis Carotídea , Endarterectomía Carotidea , Placa Aterosclerótica , Accidente Cerebrovascular , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/terapia , Constricción Patológica/etiología , Stents/efectos adversos , Endarterectomía Carotidea/efectos adversos , Accidente Cerebrovascular/epidemiología , Placa Aterosclerótica/complicaciones , Arterias Carótidas/cirugía , Hemodinámica , Resultado del Tratamiento
12.
Cell Commun Signal ; 21(1): 231, 2023 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-37710249

RESUMEN

Cholesterol plays a significant role in stabilizing lipid or membrane rafts, which are specific cellular membrane structures. Cholesterol is involved in numerous cellular processes, including regulating virus entry into the host cell. Multiple viruses have been shown to rely on cholesterol for virus entry and/or morphogenesis. Research indicates that reprogramming of the host's lipid metabolism is associated with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in the progression to severe liver disease for viruses that cause chronic hepatitis. Moreover, knowing the precise mode of viral interaction with target cells sheds light on viral pathogenesis and aids in the development of vaccines and therapeutic targets. As a result, the area of cholesterol-lowering therapy is quickly evolving and has many novel antiviral targets and medications. It has been shown that microRNAs (miRNAs) either directly or indirectly target the viral genome, preventing viral replication. Moreover, miRNAs have recently been shown to be strong post-transcriptional regulators of the genes involved in lipid metabolism, particularly those involved in cholesterol homeostasis. As important regulators of lipid homeostasis in several viral infections, miRNAs have recently come to light. In addition, multiple studies demonstrated that during viral infection, miRNAs modulate several enzymes in the mevalonate/cholesterol pathway. As cholesterol metabolism is essential to the life cycle of viral hepatitis and other viruses, a sophisticated understanding of miRNA regulation may contribute to the development of a novel anti-HCV treatment. The mechanisms underlying the effectiveness of miRNAs as cholesterol regulators against viral hepatitis are explored in this review. Video Abstract.


Asunto(s)
Anticuerpos , Hepatitis Viral Humana , Humanos , Membrana Celular , Colesterol , Virus de la Hepatitis B
13.
Artículo en Inglés | MEDLINE | ID: mdl-36735588

RESUMEN

The human gastrointestinal tract is inhabited by various microorganisms, including thousands of bacterial taxa that have yet to be cultured and characterized. In this report, we describe the isolation, cultivation, genotypic and phenotypic characterization and taxonomy of five novel anaerobic bacterial strains that were recovered during the massive cultivation and isolation of gut microbes from human faecal samples. On the basis of the polyphasic taxonomic results, we propose two novel genera and five novel species. They are Acidaminococcus hominis sp. nov. (type strain NSJ-142T=CGMCC 1.17903T=KCTC 25346T), Amedibacillus hominis sp. nov. (type strain NSJ-176T=CGMCC 1.17933T=KCTC 25355T), Lientehia hominis gen. nov. sp. nov. (type strain NSJ-141T=CGMCC 1.17902T=KCTC 25345T), Merdimmobilis hominis gen. nov. sp. nov. (type strain NSJ-153T=CGMCC 1.17915T=KCTC 25350T) and Paraeggerthella hominis sp. nov. (type strain NSJ-152T=CGMCC 1.17914T=KCTC 25349T).


Asunto(s)
Actinobacteria , Tenericutes , Humanos , Ácidos Grasos/química , Acidaminococcus , Filogenia , ADN Bacteriano/genética , ARN Ribosómico 16S/genética , Composición de Base , Técnicas de Tipificación Bacteriana , Análisis de Secuencia de ADN , Firmicutes , Heces/microbiología , Fosfolípidos
14.
Appetite ; 182: 106448, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36608768

RESUMEN

Food addiction is associated with both physical and mental health conditions, such as obesity and depression, and is considered a public health problem. Based on life history (LH) theory, this study aimed to test the association between unpredictable childhood environment and food addiction in adulthood and to examine LH strategies and attitudes toward self as psychological mediators of this association. A random sample of 1010 adults, aged from 18 to 88 years (44.8% male; Mage = 38.52, SDage = 14.53), voluntarily participated in an anonymous telephone survey conducted in Macao, China. The results of a path analysis showed the significant and positive direct effect of childhood unpredictability on food addiction and its negative association with slow LH strategy, which in turn was negatively correlated with food addiction. In addition, slow LH strategy and self-judgment, rather than self-kindness, acted as serial mediators in the association between childhood unpredictability and food addiction. These findings support the applicability of LH theory to understanding food addiction, as well as pointing to the potential risk effect of self-judgment for food addiction in adulthood. Self-judgment reduction may be a potential supplementary approach for future food addiction intervention.


Asunto(s)
Adicción a la Comida , Rasgos de la Historia de Vida , Adulto , Humanos , Masculino , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Femenino , Adicción a la Comida/psicología , Obesidad , Actitud , China
15.
J Mol Struct ; 1284: 135409, 2023 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-36993878

RESUMEN

The outbreak of novel coronavirus disease 2019 (COVID-19), caused by the novel coronavirus (SARS-CoV-2), has had a significant impact on human health and the economic development. SARS-CoV-2 3CL protease (3CLpro) is highly conserved and plays a key role in mediating the transcription of virus replication. It is an ideal target for the design and screening of anti-coronavirus drugs. In this work, seven ß-nitrostyrene derivatives were synthesized by Henry reaction and ß-dehydration reaction, and their inhibitory effects on SARS-CoV-2 3CL protease were identified by enzyme activity inhibition assay in vitro. Among them, 4-nitro-ß-nitrostyrene (compound a) showed the lowest IC50 values of 0.7297 µM. To investigate the key groups that determine the activity of ß-nitrostyrene derivatives and their interaction mode with the receptor, the molecular docking using the CDOCKER protocol in Discovery Studio 2016 was performed. The results showed that the hydrogen bonds between ß-NO2 and receptor GLY-143 and the π-π stacking between the aryl ring of the ligand and the imidazole ring of receptor HIS-41 significantly contributed to the ligand activity. Furthermore, the ligand-receptor absolute binding Gibbs free energies were calculated using the Binding Affinity Tool (BAT.py) to verify its correlation with the activity of ß-nitrostyrene 3CLpro inhibitors as a scoring function. The higher correlation(r2=0.6) indicates that the absolute binding Gibbs free energy based on molecular dynamics can be used to predict the activity of new ß-nitrostyrene 3CLpro inhibitors. These results provide valuable insights for the functional group-based design, structure optimization and the discovery of high accuracy activity prediction means of anti-COVID-19 lead compounds.

16.
Int J Mol Sci ; 24(13)2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37446103

RESUMEN

To examine the effects of membrane charge, the electrolyte species and glycosyl on the distribution of negatively charged radical of superoxide anion (·O2-) around the cell membrane, different phospholipid bilayer systems containing ·O2- radicals, different electrolytes and phospholipid bilayers were constructed through Charmm-GUI and Amber16. These systems were equilibrated with molecular dynamics by using Gromacs 5.0.2 to analyze the statistical behaviors of ·O2- near the lipid membrane under different conditions. It was found that in the presence of potassium rather than sodium, the negative charge of the phospholipid membrane is more likely to rarefy the superoxide anion distribution near the membrane surface. Further, the presence of glycosyl significantly reduced the density of ·O2- near the phospholipid bilayer by 78.3% compared with that of the neutral lipid membrane, which may have a significant contribution to reducing the lipid peroxidation from decreasing the ·O2- density near the membrane.


Asunto(s)
Simulación de Dinámica Molecular , Superóxidos , Superóxidos/metabolismo , Fosfolípidos/metabolismo , Membrana Celular/metabolismo , Membranas/metabolismo , Membrana Dobles de Lípidos/metabolismo
17.
Int J Mol Sci ; 24(21)2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37958985

RESUMEN

Aortic wall inflammation, abnormal oxidative stress and progressive degradation of extracellular matrix proteins are the main characteristics of abdominal aortic aneurysms (AAAs). The nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome dysregulation plays a crucial role in aortic damage and disease progression. The first aim of this study was to examine the effect of baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one) on AAA formation in apolipoprotein E-deficient (ApoE-/-) mice. The second aim was to define whether baicalein attenuates aberrant vascular smooth muscle cell (VSMC) proliferation and inflammation in VSMC culture. For male ApoE-/- mice, a clinically relevant AAA model was randomly divided into four groups: saline infusion, baicalein intraperitoneal injection, Angiotensin II (Ang II) infusion and Ang II + baicalein. Twenty-seven days of treatment with baicalein markedly decreased Ang II-infused AAA incidence and aortic diameter, reduced collagen-fiber formation, preserved elastic structure and density and prevented smooth muscle cell contractile protein degradation. Baicalein inhibited rat VSMC proliferation and migration following the stimulation of VSMC cultures with Ang II while blocking the Ang II-inducible cell cycle progression from G0/G1 to the S phase in the synchronized cells. Cal-520 AM staining showed that baicalein decreased cellular calcium in Ang II-induced VSMCs; furthermore, a Western blot assay indicated that baicalein inhibited the expression of PCNA and significantly lowered levels of phospho-Akt and phospho-ERK, along with an increase in baicalein concentration in Ang II-induced VSMCs. Immunofluorescence staining showed that baicalein pretreatment reduced NF-κB nuclear translocation in Ang II-induced VSMCs and furthered the protein expressions of NLRP3 while ASC and caspase-1 were suppressed in a dose-dependent manner. Baicalein pretreatment upregulated Nrf2/HO-1 signaling in Ang II-induced VSMCs. Thus, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining showed that its reactive oxygen species (ROS) production decreased, along with the baicalein pretreatment. Our overall results indicate that baicalein could have therapeutic potential in preventing aneurysm development.


Asunto(s)
Angiotensina II , Aneurisma de la Aorta Abdominal , Masculino , Ratones , Ratas , Animales , Angiotensina II/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Aneurisma de la Aorta Abdominal/inducido químicamente , Aneurisma de la Aorta Abdominal/tratamiento farmacológico , Estrés Oxidativo , Inflamación/tratamiento farmacológico , Inflamación/complicaciones , Apolipoproteínas E/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL
18.
J Integr Plant Biol ; 65(5): 1134-1146, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36647609

RESUMEN

Lignin is a major component of plant cell walls and is essential for plant growth and development. Lignin biosynthesis is controlled by a hierarchical regulatory network involving multiple transcription factors. In this study, we showed that the gene encoding an APETALA 2/ethylene-responsive element binding factor (AP2/ERF) transcription factor, PagERF81, from poplar 84 K (Populus alba × P. glandulosa) is highly expressed in expanding secondary xylem cells. Two independent homozygous Pagerf81 mutant lines created by gene editing, produced significantly more but smaller vessel cells and longer fiber cells with more lignin in cell walls, while PagERF81 overexpression lines had less lignin, compared to non-transgenic controls. Transcriptome and reverse transcription quantitative PCR data revealed that multiple lignin biosynthesis genes including Cinnamoyl CoA reductase 1 (PagCCR1), Cinnamyl alcohol dehydrogenase 6 (PagCAD6), and 4-Coumarate-CoA ligase-like 9 (Pag4CLL9) were up-regulated in Pagerf81 mutants, but down-regulated in PagERF81 overexpression lines. In addition, a transient transactivation assay revealed that PagERF81 repressed the transcription of these three genes. Furthermore, yeast one hybrid and electrophoretic mobility shift assays showed that PagERF81 directly bound to a GCC sequence in the PagCCR1 promoter. No known vessel or fiber cell differentiation related genes were differentially expressed, so the smaller vessel cells and longer fiber cells observed in the Pagerf81 lines might be caused by abnormal lignin deposition in the secondary cell walls. This study provides insight into the regulation of lignin biosynthesis, and a molecular tool to engineer wood with high lignin content, which would contribute to the lignin-related chemical industry and carbon sequestration.


Asunto(s)
Lignina , Populus , Lignina/metabolismo , Populus/metabolismo , Xilema/metabolismo , Madera/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Diferenciación Celular , Pared Celular/metabolismo , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/metabolismo
19.
Environ Monit Assess ; 195(6): 675, 2023 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-37188927

RESUMEN

Biological effect-based monitoring is essential for predicting or alerting to a possible deterioration in drinking water quality. In the present study, a reporter gene assay based on oxidative stress-mediated Pgst-4::GFP induction in the Caenorhabditis elegans strain VP596 (VP596 assay) was assessed for its applicability in evaluating drinking water safety and quality. This assay was used to measure the oxidative stress response in VP596 worms exposed to six ubiquitous components (As3+, Al3+, F-, NO3--N, CHCl3, and residual chlorine) in drinking water, eight mixtures of these six components designed through orthogonal design, ninety-six unconcentrated water samples from source to tap water in two supply systems, and organic extracts (OEs) of twenty-five selected water samples. Pgst-4::GFP fluorescence was not induced by Al3+, F-, NO3--N, and CHCl3, and was significantly enhanced by As3+ and residual chlorine only at concentrations higher than their respective drinking water guideline levels. Pgst-4::GFP induction was not detected in any of the six-component mixtures. Induction of Pgst-4::GFP was observed in 9.4% (3/32) of the source water samples but not in the drinking water samples. However, a notable induction effect was revealed in the three OEs of drinking water, with a relative enrichment factor of 200. These results suggest that the VP596 assay has limited utility for screening drinking water safety by testing unconcentrated water samples; however, it offers a supplemental in vivo tool for prioritizing water samples for an enhanced quality assessment, monitoring pollutant removal performance by drinking water treatment plants, and evaluating water quality in water supplies.


Asunto(s)
Agua Potable , Purificación del Agua , Animales , Calidad del Agua , Caenorhabditis elegans , Cloro , Monitoreo del Ambiente/métodos , Abastecimiento de Agua
20.
Angew Chem Int Ed Engl ; 62(52): e202316336, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-37966337

RESUMEN

The achievement of significant photoluminescence (PL) in lanthanide ions (Ln3+ ) has primarily relied on host sensitization, where energy is transferred from the excited host material to the Ln3+ ions. However, this luminous mechanism involves only one optical antenna, namely the host material, which limits the accessibility of excitation wavelength-dependent (Ex-De) PL. Consequently, the wider application of Ln3+ ions in light-emitting devices is hindered. In this study, we present an organic-inorganic compound, (DMA)4 LnCl7 (DMA+ =[CH3 NH2 CH3 ]+ , Ln3+ =Ce3+ , Tb3+ ), which serves as an independent host lattice material for efficient Ex-De emission by doping it with trivalent antimony (Sb3+ ). The pristine (DMA)4 LnCl7 compounds exhibit high luminescence, maintaining the characteristic sharp emission bands of Ln3+ and demonstrating a high PL quantum yield of 90-100 %. Upon Sb3+ doping, the compound exhibits noticeable Ex-De emission with switchable colors. Through a detailed spectral study, we observe that the prominent energy transfer process observed in traditional host-sensitized systems is absent in these materials. Instead, they exhibit two independent emission centers from Ln3+ and Sb3+ , each displaying distinct features in luminous color and radiative lifetime. These findings open up new possibilities for designing Ex-De emitters based on Ln3+ ions.

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