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1.
Ann Med ; 56(1): 2401107, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39253859

RESUMEN

INTRODUCTION: RESLES (Reversible splenial lesion syndrome) can be observed secondary to various diseases, and intramyelinic edema may play a crucial role in the pathogenesis of SCC (Splenium of the corpus callosum). Some studies have suggested that hypoxic-ischaemic encephalopathy may constitute a risk factor for SCC lesions. However, the potential impact of high-altitude environments on SCC, especially during chronic exposure, remain obscure. METHODS: Our study included 19 patients who satisfied the diagnostic criteria of RESLES at high altitudes. Ten low-altitude patients with RESLES were included as controls. All participants received MRI (Magnetic resonance imaging) scans twice. Routine blood tests, liver, kidney and thyroid function, coagulation function, electrolytes and vitamins were detected during hospitalization and before discharge. In addition, the patients were followed up in May 2023. RESULTS: Hypoxic environments at high altitudes may increase the risk of RESLES. The two groups showed different clinical symptoms. High-altitude patients had significantly higher CRP levels than low-altitude patients. The lesion size in high-altitude patients showed a positive correlation with SaO2 levels. However, the patients at low altitudes had positive correlation trends between lesion size and several inflammatory markers (WBC, NEU and CRP). All patients had a benign prognosis that may not be affected by the use of prednisone acetate. CONCLUSIONS: Hypoxic environments at high altitudes may play a role in the aetiology of RESLES. Additionally, RESLES is a reversible disease and the administration of glucocorticoids may be dispensable for its treatment.


Asunto(s)
Altitud , Cuerpo Calloso , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Adulto , Pronóstico , Persona de Mediana Edad , Cuerpo Calloso/patología , Cuerpo Calloso/diagnóstico por imagen , Factores de Riesgo , Hipoxia , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Síndrome , Adulto Joven
2.
Endocr Connect ; 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39235844

RESUMEN

OBJECTIVE: Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is rare, and manifestations of autonomic dysregulation are diverse and may be overlooked. We aimed to evaluate the incidence of these manifestations. METHODS: Patients with ROHHAD syndrome reported before and after 2019 were divided into Groups 1 and 2. Patients who were diagnosed at three regional hospitals in China were included in Group 3. We collected the age of each specific term of the ROHHAD (neurogenic tumor, NET) acronym and the detailed manifestations of each term, and compared them among the three groups. RESULTS: A total of 16 patients were diagnosed within the 2-year period. Two had neurogenic tumors and cognitive and behavioral abnormalities before developing rapid obesity. At least 93.8% of the patients had ≥ 4 symptoms of autonomic dysregulation. When comparing autonomic dysregulation among Groups 1-3, the rates of cardiovascular manifestations were NA vs. 12.8% vs. 81.2%; gastrointestinal disturbances were 11.4% vs. 8.5% vs. 62.5%; strabismus was 25.7% vs. 12.8% vs. 62.5%; sleep disturbance was NA vs. 6.4% vs. 50.0%; and abnormal pain threshold was NA vs. 10.6% vs. 25.0% (all p<0.05). The rates of cognitive and behavioral abnormalities were NA vs 29.8% and 87.5% (p<0.01). CONCLUSIONS: Rapid-onset obesity is not always the first sign of ROHHAD syndrome. Higher rates of autonomic dysregulation and cognitive and behavioral abnormalities with multiple manifestations of autonomic dysregulation coexisted in our cohort, indicating that evaluations of autonomic function and the limbic system should be strengthened when assessing this condition.

4.
Microsyst Nanoeng ; 10: 111, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39157211

RESUMEN

Pipe contaminant detection holds considerable importance within various industries, such as the aviation, maritime, medicine, and other pertinent fields. This capability is beneficial for forecasting equipment potential failures, ascertaining operational situations, timely maintenance, and lifespan prediction. However, the majority of existing methods operate offline, and the detectable parameters online are relatively singular. This constraint hampers real-time on-site detection and comprehensive assessments of equipment status. To address these challenges, this paper proposes a sensing method that integrates an ultrasonic unit and an electromagnetic inductive unit for the real-time detection of diverse contaminants and flow rates within a pipeline. The ultrasonic unit comprises a flexible transducer patch fabricated through micromachining technology, which can not only make installation easier but also focus the sound field. Moreover, the sensing unit incorporates three symmetrical solenoid coils. Through a comprehensive analysis of ultrasonic and induction signals, the proposed method can be used to effectively discriminate magnetic metal particles (e.g., iron), nonmagnetic metal particles (e.g., copper), nonmetallic particles (e.g., ceramics), and bubbles. This inclusive categorization encompasses nearly all types of contaminants that may be present in a pipeline. Furthermore, the fluid velocity can be determined through the ultrasonic Doppler frequency shift. The efficacy of the proposed detection principle has been validated by mathematical models and finite element simulations. Various contaminants with diverse velocities were systematically tested within a 14 mm diameter pipe. The experimental results demonstrate that the proposed sensor can effectively detect contaminants within the 0.5-3 mm range, accurately distinguish contaminant types, and measure flow velocity.

6.
Infect Drug Resist ; 17: 3537-3545, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39161468

RESUMEN

Background: Brucellosis is a zoonotic disease that can affect various organs, including the spine. Cervical spondylitis caused by Brucella is rare but can lead to significant morbidity if not diagnosed and treated promptly. Case Presentation: We report a case of a 46-year-old female who presented with intermittent high fever and intractable neck, shoulder, and back pain for two months. She was diagnosed with Brucella cervical spondylitis based on clinical manifestations, Rose-Bengal Plate Agglutination Test (RBPT, positive), and cervical MRI findings. She was treated with a combination of antibiotics for at least two weeks, followed by surgical intervention including abscess clearance, partial vertebral resection, and titanium mesh bone fusion. Real-time Polymerase Chain Reaction (RT-PCR) confirmed the presence of sheep Brucella DNA. The patient recovered well postoperatively with significant pain reduction and restoration of full mobility in the right upper limb. Conclusion: This case highlights the diagnostic value of RT-PCR and tissue biopsy in cervical brucellosis spondylitis. Our study found that anterior cervical subtotal corpectomy can restore cervical stability, clear abscess, and relieve spinal cord compression on the basis of drug treatment, with good clinical results.

7.
NPJ Precis Oncol ; 8(1): 185, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39215037

RESUMEN

Non-small cell lung cancer (NSCLC) constitutes the majority of lung cancer cases, accounting for over 80%. RNAs in EVs play a pivotal role in various biological and pathological processes mediated by extracellular vesicle (EV). Long non-coding RNAs (lncRNAs) are widely associated with cancer-related functions, including cell proliferation, migration, invasion, and drug resistance. Tumor-associated macrophages are recognized as pivotal contributors to tumorigenesis. Given these insights, this study aims to uncover the impact of lncRNA NORAD in EVs derived from M2 macrophages in NSCLC cell lines and xenograft mouse models of NSCLC. EVs were meticulously isolated and verified based on their morphology and specific biomarkers. The interaction between lncRNA NORAD and SMIM22 was investigated using immunoprecipitation. The influence of SMIM22/GALE or lncRNA NORAD in EVs on glycolysis was assessed in NSCLC cell lines. Additionally, we evaluated the effects of M2 macrophage-derived lncRNA NORAD in EVs on cell proliferation and apoptosis through colony formation and flow cytometry assays. Furthermore, the impact of M2 macrophage-derived lncRNA NORAD in EVs on tumor growth was confirmed using xenograft tumor animal models. The results underscored the potential role of M2 macrophage-derived lncRNA NORAD in EVs in NSCLC. SMIM22/GALE promoted glycolysis and the proliferation of NSCLC cells. Furthermore, lncRNA NORAD in EVs targeted SMIM22 and miR-520g-3p in NSCLC cells. Notably, lncRNA NORAD in EVs promoted the proliferation of NSCLC cells and facilitated NSCLC tumor growth through the miR-520g-3p axis. In conclusion, M2 macrophage-derived lncRNA NORAD in EVs promotes NSCLC progression through the miR-520g-3p/SMIM22/GALE axis.

9.
J Refract Surg ; 40(7): e490-e498, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39007811

RESUMEN

PURPOSE: To compare the objective visual quality of moderate-to-high myopia corrected by small incision lenticule extraction (SMILE) and transepithelial photorefractive keratectomy (TransPRK) at a 1,050-Hz ablation frequency, assisted by Smart-Pulse technology (SCHWIND eye-tech-solutions). METHODS: This study involved 123 patients (123 eyes) with moderate-to-high myopia between July 2020 and January 2021. They were categorized into the SMILE group (67 patients, 67 eyes) and the TransPRK group (56 patients, 56 eyes). Follow-ups were conducted at 6 months postoperatively to record the logarithm of the minimum angle of resolution visual acuity, and the Strehl ratio and higher order aberrations were measured using the Sirius anterior segment analysis device (SCHWIND eye-tech-solutions) under a 6-mm pupil diameter at various postoperative intervals. RESULTS: At 1 week and 1 month postoperatively, the uncorrected distance visual acuity (UDVA) in the SMILE group was superior to that in the TransPRK group (P < .05 for both). At 1 week and 1 month postoperatively, the Strehl ratio value in the SMILE group was higher than that in the TransPRK group (P < .05 for both). At 1, 3, and 6 months postoperatively, coma was greater in the SMILE group than in the TransPRK group (P < .05 for all). Spherical aberrations were lower in the SMILE group than in the TransPRK group at 3 and 6 months postoperatively (P < .05). At 6 months postoperatively, UDVA was -0.09 ± 0.08 and -0.11 ± 0.05 logMAR in the SMILE and TransPRK groups, respectively, which exceeded their preoperative corrected distance visual acuity of -0.05 ± 0.04 and -0.09 ± 0.08 logMAR (all P < .001). Compared with preoperative values, the Strehl ratio, total higher order, coma, and spherical aberration differences were significantly increased postoperatively in both groups (all P < .001). CONCLUSIONS: Both surgical methods improved UDVA and each had its advantages. The visual quality of SMILE was superior at 1 week and 1 month postoperatively (Strehl ratio values were higher than those of the TransPRK group), and its spherical aberration was lower than that of the TransPRK group at 3 and 6 months; TransPRK with SmartPulse technology with a 1,050-Hz ablation frequency showed that coma was significantly lower than that of the SMILE group at 1, 3, and 6 months postoperatively. [J Refract Surg. 2024;40(7):e490-e498.].


Asunto(s)
Sustancia Propia , Láseres de Excímeros , Queratectomía Fotorrefractiva , Refracción Ocular , Agudeza Visual , Humanos , Agudeza Visual/fisiología , Láseres de Excímeros/uso terapéutico , Femenino , Masculino , Queratectomía Fotorrefractiva/métodos , Adulto , Refracción Ocular/fisiología , Adulto Joven , Sustancia Propia/cirugía , Cirugía Laser de Córnea/métodos , Miopía Degenerativa/cirugía , Miopía Degenerativa/fisiopatología , Aberración de Frente de Onda Corneal/fisiopatología , Topografía de la Córnea , Estudios de Seguimiento , Estudios Prospectivos , Miopía/cirugía , Miopía/fisiopatología , Estudios Retrospectivos
10.
Pest Manag Sci ; 80(9): 4779-4789, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38837578

RESUMEN

BACKGROUND: The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive pests of rice. Owing to the rapid adaptation of BPH to many pesticides and resistant varieties, identifying putative gene targets for developing RNA interference (RNAi)-based pest management strategies has received much attention for this pest. The glucoprotein papilin is the most abundant component in the basement membranes of many organisms, and its function is closely linked to development. RESULTS: In this study, we identified a papilin homologous gene in BPH (NlPpn). Quantitative Real-time PCR analysis showed that the transcript of NlPpn was highly accumulated in the egg stage. RNAi of NlPpn in newly emerged BPH females caused nonhatching phenotypes of their eggs, which may be a consequence of the maldevelopment of their embryos. Moreover, the transcriptomic analysis identified 583 differentially expressed genes between eggs from the dsGFP- and dsNlPpn-treated insects. Among them, the 'structural constituent of cuticle' cluster ranked first among the top 15 enriched GO terms. Consistently, ultrastructural analysis unveiled that dsNlPpn-treated eggs displayed a discrete and distorted serosal endocuticle lamellar structure. Furthermore, the hatchability of BPH eggs was also successfully reduced by the topical application of NlPpn-dsRNA-layered double hydroxide nanosheets onto the adults. CONCLUSION: Our findings demonstrate that NlPpn is essential to maintaining the regular structure of the serosal cuticle and the embryonic development in BPH, indicating NlPpn could be a potential target for pest control during the egg stage. © 2024 Society of Chemical Industry.


Asunto(s)
Hemípteros , Proteínas de Insectos , Óvulo , Interferencia de ARN , Hemípteros/genética , Hemípteros/crecimiento & desarrollo , Hemípteros/fisiología , Animales , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Femenino , Técnicas de Silenciamiento del Gen
11.
J Acupunct Meridian Stud ; 17(3): 100-109, 2024 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-38898647

RESUMEN

Importance: Post-stroke sialorrhea (PSS) refers to excessive saliva flowing out the lip border after a stroke. PSS negatively affects patient self-image and social communication and may lead to depression. Limited evidence supports the link between excessive salivation and PSS. No large-scale, strictly controlled randomized controlled trials have shown the effectiveness of acupuncture in treating PSS patients. Objective: We aim to compare the effects of intraoral and sham acupuncture in PSS patients and explore relationships among salivation and drooling severity and frequency and swallowing function in stroke patients. Design: Clinical study protocol, SPIRIT compliant. Setting: Prospective, single-center, randomized, and sham-controlled trial. Population: We will recruit 106 PSS patients to receive 4-week intraoral or sham acupuncture. Additionally, 53 stroke patients without PSS will undergo a conventional 4-week treatment program to compare salivation between PSS and non-PSS patients. Exposures: Intraoral or sham acupuncture. Main Outcomes and Measures: The main evaluation index will be the 3-minute saliva weight (3MSW), comparing changes in 3MSW from baseline to weeks 4 and 8. Secondary assessment indices will include the "Drooling Severity and Frequency Scale" and "Functional Oral Intake Scale." Results: The results from this study will be published in peer-reviewed journals. Conclusion: Comparing effects of intraoral and sham acupuncture in PSS patients, this study may contribute important evidence for future PSS treatment and provide valuable insights into whether salivation issues in stroke patients are attributed to heightened salivary secretion or dysphagia.


Asunto(s)
Terapia por Acupuntura , Sialorrea , Accidente Cerebrovascular , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia por Acupuntura/métodos , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Salivación , Sialorrea/terapia , Sialorrea/etiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/fisiopatología
12.
Neural Netw ; 178: 106428, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38901091

RESUMEN

In overcoming the challenges faced in adapting to paired real-world data, recent unsupervised single image deraining (SID) methods have proven capable of accomplishing notably acceptable deraining performance. However, the previous methods usually fail to produce a high quality rain-free image due to neglecting sufficient attention to semantic representation and the image content, which results in the inability to completely separate the content from the rain layer. In this paper, we develop a novel cycle contrastive adversarial framework for unsupervised SID, which mainly consists of cycle contrastive learning (CCL) and location contrastive learning (LCL). Specifically, CCL achieves high-quality image reconstruction and rain-layer stripping by pulling similar features together while pushing dissimilar features further in both semantic and discriminant latent spaces. Meanwhile, LCL implicitly constrains the mutual information of the same location of different exemplars to maintain the content information. In addition, recently inspired by the powerful Segment Anything Model (SAM) that can effectively extract widely applicable semantic structural details, we formulate a structural-consistency regularization to fine-tune our network using SAM. Apart from this, we attempt to introduce vision transformer (VIT) into our network architecture to further improve the performance. In our designed transformer-based GAN, to obtain a stronger representation, we propose a multi-layer channel compression attention module (MCCAM) to extract a richer feature. Equipped with the above techniques, our proposed unsupervised SID algorithm, called CCLformer, can show advantageous image deraining performance. Extensive experiments demonstrate both the superiority of our method and the effectiveness of each module in CCLformer. The code is available at https://github.com/zhihefang/CCLGAN.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Redes Neurales de la Computación , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Aprendizaje Automático no Supervisado , Humanos , Semántica
13.
Eur J Endocrinol ; 191(1): 87-96, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38938059

RESUMEN

CONTEXT: Androgen insensitivity syndrome (AIS) manifests itself as variable symptoms of under-virilization in patients with 46,XY disorders caused by androgen receptor (AR) gene variants. This large-sample study aimed to correlate the genotypes and phenotypes to the fertility of individuals. METHODS: This was a cohort study that analyzed the genetic and clinical characteristics of patients with AIS from a single center in China. RESULTS: The 117 patients were divided into 53 with complete AIS (CAIS) and 64 with partial AIS (PAIS). At their first visit, the median age was 1.83 years (0.92-4.17), and the external masculinization score was 3.0 (2.0-6.0). At the last follow-up, 92% (49/53) of patients with CAIS maintained their female gender, and 94% (60/64) of patients with PAIS were raised as males. No gender anxiety was observed in this study. Eighty-eight AR variants were identified, with 31 (35%) being unreported. Moreover, 24% (21/88) occurred more than once. The variants that appeared most frequently were located at amino acid 841, including p.R841H (n = 5) and p.R841C (n = 2). Variants p.N706S, p.R856H, and p.A871V were each observed 4 times. In terms of inheritance, 83% of patients with parental verification inherited variants from their mothers. We also observed that the variants from 1 case were inherited from his maternal grandfather who had hypospadias. CONCLUSION: Most children with PAIS were raised as males. The abundance of maternally inheritable variants and the presence of case of preserved fertility indicate the fertility potential in patients with AIS. Hence, we recommend a careful evaluation of gonadectomy when fertility preservation is being considered.


Asunto(s)
Síndrome de Resistencia Androgénica , Receptores Androgénicos , Humanos , Síndrome de Resistencia Androgénica/genética , Masculino , Femenino , Receptores Androgénicos/genética , Estudios de Cohortes , Preescolar , Lactante , China/epidemiología , Fenotipo , Niño , Genotipo , Mutación , Fertilidad/genética
14.
Inorg Chem ; 63(27): 12624-12634, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38910548

RESUMEN

Four Ag(I) complexes with mefenamato and nitrogen heterocyclic ligands, [Ag(2-apy)(mef)]2 (1), [Ag(3-apy)(mef)] (2), [Ag2(tmpyz)(mef)2] (3), and {[Ag(4,4'-bipy)(mef)]2(CH3CN)1.5(H2O)2}n (4), (mef = mefenamato, 2-apy = 2-aminopyridine, 3-apy = 3-aminopyridine, tmpyz = 2,3,5,6-tetramethylpyrazine, 4,4'-bipy = 4,4'-bipyridine), were synthesized and characterized. The interactions of these complexes with BSA were investigated by fluorescence spectroscopy, which indicated that these complexes quench the fluorescence of BSA by a static mechanism. The fluorescence data also indicated that the complexes showed good affinity for BSA, and one binding site on BSA was suitable for the complexes. The in vitro cytotoxicity of the four complexes against human cancer cell lines (MCF-7, HepG-2, A549, and MDA-MB-468) and one normal cell line (HTR-8) was evaluated by the MTT assay. Complex 1 displayed high cytotoxic activity against A549 cells. Further studies revealed that complex 1 could enhance the intracellular levels of ROS (reactive oxygen species) in A549 cells, cause cell cycle arrest in the G0/G1 phase, and induce apoptosis in A549 cells in a dose-dependent manner.


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Ensayos de Selección de Medicamentos Antitumorales , Ácido Mefenámico , Plata , Humanos , Plata/química , Plata/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ligandos , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Ácido Mefenámico/farmacología , Ácido Mefenámico/química , Apoptosis/efectos de los fármacos , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Compuestos Heterocíclicos/síntesis química , Proliferación Celular/efectos de los fármacos , Nitrógeno/química , Estructura Molecular , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/metabolismo , Línea Celular Tumoral
15.
BioData Min ; 17(1): 19, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926718

RESUMEN

The loss of electronic medical records has seriously affected the practical application of biomedical data. Therefore, it is a meaningful research effort to effectively fill these lost data. Currently, state-of-the-art methods focus on using Generative Adversarial Networks (GANs) to fill the missing values of electronic medical records, achieving breakthrough progress. However, when facing datasets with high missing rates, the imputation accuracy of these methods sharply deceases. This motivates us to explore the uncertainty of GANs and improve the GAN-based imputation methods. In this paper, the GRUD (Gate Recurrent Unit Decay) network and the UGAN (Uncertainty Generative Adversarial Network) are proposed and organically combined, called UGAN-GRUD. In UGAN-GRUD, it highlights using GAN to generate imputation values and then leveraging GRUD to compensate them. We have designed the UGAN and the GRUD network. The former is employed to learn the distribution pattern and uncertainty of data through the Generator and Discriminator, iteratively. The latter is exploited to compensate the former by leveraging the GRUD based on time decay factor, which can learn the specific temporal relations in electronic medical records. Through experimental research on publicly available biomedical datasets, the results show that UGAN-GRUD outperforms the current state-of-the-art methods, with average 13% RMSE (Root Mean Squared Error) and 24.5% MAPE (Mean Absolute Percentage Error) improvements.

16.
J Am Chem Soc ; 146(25): 16982-16989, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38870424

RESUMEN

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

18.
Chem Biodivers ; 21(8): e202401146, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38772912

RESUMEN

Hepatitis B Virus (HBV) infection is a global public health challenge that seriously endangers human health. Soft coral, as a major source of terpenoids, contains many structurally novel and highly bioactive compounds. Sixteen cembranoids (1-16), including a new one named sinupedunol B (16), were isolated from the South China Sea Soft coral Sinularia pedunculata. The structure of the sinupedunol B (16) was determined through a combination of spectroscopic analysis and X-ray single-crystal diffraction. In this study, cembranoids isolated from Sinularia pedunculata were found of anti-HBV activity for the first time. Among them, flexilarin D (6) showed significant anti-HBV activity with an IC50 value of 5.57 µM without cytotoxicity. We then analyzed the structure-activity relationship (SAR). Furthermore, it is demonstrated that flexilarin D (6) can accelerate the formation of capsid, inhibit HBeAg, HBV core particle DNA, HBV total RNA and pregenomic RNA in a dose dependent manner. We also confirmed the anti-HBV activity of 6 in HepG2-NTCP infection system. Finally, we demonstrated the anti-HBV mechanism of these compounds by inhibiting the ENI/Xp enhancer/promoter.


Asunto(s)
Antozoos , Antivirales , Diterpenos , Virus de la Hepatitis B , Antozoos/química , Virus de la Hepatitis B/efectos de los fármacos , Antivirales/farmacología , Antivirales/química , Antivirales/aislamiento & purificación , Animales , Relación Estructura-Actividad , Diterpenos/farmacología , Diterpenos/química , Diterpenos/aislamiento & purificación , Humanos , China , Células Hep G2 , Relación Dosis-Respuesta a Droga , Conformación Molecular , Estructura Molecular , Pruebas de Sensibilidad Microbiana , Cristalografía por Rayos X
19.
Sci Rep ; 14(1): 10507, 2024 05 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714727

RESUMEN

Glioma, particularly glioblastomas (GBM), is incurable brain tumor. The most targeted receptor tyrosine kinase (RTKs) drugs did not bring benefit to GBM patients. The mechanism of glioma growth continues to be explored to find more effective treatment. Here, we reported that Ser/Thr protein kinase YANK2 (yet another kinase 2) is upregulated in glioma tissues and promotes the growth and proliferation of glioma in vitro and in vivo. Further, we confirmed that oncogene Fyn directly activated YANK2 through phosphorylation its Y110, and Fyn-mediated YANK2 phosphorylation at Y110 site promotes glioma growth by increasing its stability. Finally, YANK2 was proved to be a novel upstream kinase of p70S6K and promotes glioma growth by directly phosphorylating p70S6K at T389. Taken together, we found a new mTOR-independent p70S6K activation pathway, Fyn-YANK2-p70S6K, which promotes glioma growth, and YANK2 is a potential oncogene and serves as a novel therapeutic target for glioma.


Asunto(s)
Proliferación Celular , Glioma , Proteínas Proto-Oncogénicas c-fyn , Proteínas Quinasas S6 Ribosómicas 70-kDa , Transducción de Señal , Serina-Treonina Quinasas TOR , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/genética , Humanos , Proteínas Proto-Oncogénicas c-fyn/metabolismo , Proteínas Proto-Oncogénicas c-fyn/genética , Serina-Treonina Quinasas TOR/metabolismo , Glioma/metabolismo , Glioma/patología , Glioma/genética , Animales , Línea Celular Tumoral , Fosforilación , Carcinogénesis/genética , Carcinogénesis/metabolismo , Ratones , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/genética , Ratones Desnudos , Regulación Neoplásica de la Expresión Génica
20.
Opt Lett ; 49(10): 2557-2560, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748104

RESUMEN

The inherent nonseparability of vector beams presents a unique opportunity to explore novel optical functionalities, expanding new degrees of freedom for optical information processing. In this Letter, we introduce a novel, to the best of our knowledge, method for tailoring the local nonseparability along the propagation axis of vector beams. Employing higher-order Bessel vector beams, the longitudinal control over the local nonseparability is achieved through targeted amplitude modulation of constituent orthogonal polarization components within the main ring region. Experimental demonstrations of diverse longitudinal nonseparability profiles corroborate the efficacy and versatility of our approach, opening avenues for further exploration of the nonseparability manipulation in vector beams.

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