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1.
Nucleic Acids Res ; 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38828770

RESUMEN

The Cajal body, a nuclear condensate, is crucial for ribonucleoprotein assembly, including small nuclear RNPs (snRNPs). While Coilin has been identified as an integral component of Cajal bodies, its exact function remains unclear. Moreover, no Coilin ortholog has been found in unicellular organisms to date. This study unveils Mug174 (Meiosis-upregulated gene 174) as the Coilin ortholog in the fission yeast Schizosaccharomyces pombe. Mug174 forms phase-separated condensates in vitro and is often associated with the nucleolus and the cleavage body in vivo. The generation of Mug174 foci relies on the trimethylguanosine (TMG) synthase Tgs1. Moreover, Mug174 interacts with Tgs1 and U snRNAs. Deletion of the mug174+ gene in S. pombe causes diverse pleiotropic phenotypes, encompassing defects in vegetative growth, meiosis, pre-mRNA splicing, TMG capping of U snRNAs, and chromosome segregation. In addition, we identified weak homology between Mug174 and human Coilin. Notably, human Coilin expressed in fission yeast colocalizes with Mug174. Critically, Mug174 is indispensable for the maintenance of and transition from cellular quiescence. These findings highlight the Coilin ortholog in fission yeast and suggest that the Cajal body is implicated in cellular quiescence, thereby preventing human diseases.

2.
Front Immunol ; 15: 1361531, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38698849

RESUMEN

The whole-genome sequence of an African swine fever virus (ASFV) strain (HuB/HH/2019) isolated from Hubei, China, was highly similar to that of the Georgia 2007/1 strain ASFV. After infection with strong strains, domestic pigs show typical symptoms of infection, including fever, depression, reddening of the skin, hemorrhagic swelling of various tissues, and dysfunction. The earliest detoxification occurred in pharyngeal swabs at 4 days post-infection. The viral load in the blood was extremely high, and ASFV was detected in multiple tissues, with the highest viral loads in the spleen and lungs. An imbalance between pro- and anti-inflammatory factors in the serum leads to an excessive inflammatory response in the body. Immune factor expression is suppressed without effectively eliciting an immune defense. Antibodies against p30 were not detected in acutely dead domestic pigs. Sequencing of the peripheral blood mononuclear cell transcriptome revealed elevated transcription of genes associated with immunity, defense, and stress. The massive reduction in lymphocyte counts in the blood collapses the body's immune system. An excessive inflammatory response with a massive reduction in the lymphocyte count may be an important cause of mortality in domestic pigs. These two reasons have inspired researchers to reduce excessive inflammatory responses and stimulate effective immune responses for future vaccine development.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Animales , Porcinos , Fiebre Porcina Africana/virología , Fiebre Porcina Africana/inmunología , Virus de la Fiebre Porcina Africana/inmunología , Virus de la Fiebre Porcina Africana/genética , Citocinas , Linfocitos/inmunología , Linfocitos/metabolismo , Genotipo , Carga Viral , Sus scrofa , Recuento de Linfocitos
3.
Sci Immunol ; 9(95): eabq1558, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38701190

RESUMEN

Steroid resistance poses a major challenge for the management of autoimmune neuroinflammation. T helper 17 (TH17) cells are widely implicated in the pathology of steroid resistance; however, the underlying mechanisms are unknown. In this study, we identified that interleukin-1 receptor (IL-1R) blockade rendered experimental autoimmune encephalomyelitis (EAE) mice sensitive to dexamethasone (Dex) treatment. Interleukin-1ß (IL-1ß) induced a signal transducer and activator of transcription 5 (STAT5)-mediated steroid-resistant transcriptional program in TH17 cells, which promoted inflammatory cytokine production and suppressed Dex-induced anti-inflammatory genes. TH17-specific deletion of STAT5 ablated the IL-1ß-induced steroid-resistant transcriptional program and rendered EAE mice sensitive to Dex treatment. IL-1ß synergized with Dex to promote the STAT5-dependent expression of CD69 and the development of central nervous system (CNS)-resident CD69+ TH17 cells. Combined IL-1R blockade and Dex treatment ablated CNS-resident TH17 cells, reduced EAE severity, and prevented relapse. CD69+ tissue-resident TH17 cells were also detected in brain lesions of patients with multiple sclerosis. These findings (i) demonstrate that IL-1ß-STAT5 signaling in TH17 cells mediates steroid resistance and (ii) identify a therapeutic strategy for reversing steroid resistance in TH17-mediated CNS autoimmunity.


Asunto(s)
Dexametasona , Encefalomielitis Autoinmune Experimental , Interleucina-1beta , Factor de Transcripción STAT5 , Células Th17 , Animales , Células Th17/inmunología , Factor de Transcripción STAT5/metabolismo , Factor de Transcripción STAT5/inmunología , Ratones , Interleucina-1beta/inmunología , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Dexametasona/farmacología , Dexametasona/uso terapéutico , Ratones Endogámicos C57BL , Resistencia a Medicamentos , Transducción de Señal/inmunología , Ratones Noqueados , Enfermedades Neuroinflamatorias/inmunología , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Femenino , Humanos
4.
J Food Sci ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745368

RESUMEN

Lonicera japonica Thunb. (LJT) is known for its valuable medicinal properties that highlight its potential application in the pharmaceutical and health food industry. We predict that LJT polyphenols by network pharmacology may be involved in immunomodulation, and the study of LJT polyphenols regulating immunity is still insufficient; therefore, we experimentally found that LJT enhances immunity by promoting the proliferation and phagocytic activity of RAW246.7 cells. A model of an immunosuppressed mouse was constructed using cyclophosphamide-induced, and LJT was extracted for the intervention. We found that LJT restored immune homeostasis in immune deficiency mice by inhibiting the abnormal apoptosis in lymphocytes, enhancing natural killer cell cytotoxicity, promoting T lymphocyte proliferation, and increasing the CD4+ and CD8+ T lymphocytes in quantity. Moreover, LJT treatment modulates immunity by significantly downregulating lipopolysaccharide-induced inflammation and oxidative stress levels. We verified the immunomodulatory function of LJT through both cell and animal experiments. The combination of potential-protein interactions and molecular docking later revealed that LJT polyphenols were associated with immunomodulatory effects on MAPK1; together, LJT intervention significantly modulates the immune, with the activation of MAPK1 as the underlying mechanism of action, which provided evidence for the utilization of LJT as a nutraceutical in immune function.

5.
Dalton Trans ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38780236

RESUMEN

Herein, a series of N-doped Ti3C2/porous g-C3N4 composites are ultrasonically prepared from N-doped Ti3C2 and porous g-C3N4 under N2 atmosphere. The structure, morphology, and optical characteristics of the as-prepared composites are characterized by X-ray diffraction, transmission electron microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, UV-vis diffuse reflectance spectroscopy, etc. Moreover, photocatalytic measurements show that N-doped Ti3C2 is an excellent modifier for porous g-C3N4 to heighten its photocatalytic activity. Only 44.1% of rhodamine B can be degraded by the photocatalysis of pristine porous g-C3N4, while the photocatalytic degradation ratio of rhodamine B can reach up to 97.5% for the optimal N-doped Ti3C2 loading composites under visible light for 15 min. Moreover, the photocatalytic tests of N2 fixation confirm that the optimal composites show the highest production yield of NH4+ (11.8 µmol gcat-1 h-1), which is 2.11-folds more than that of porous g-C3N4 (5.6 µmol gcat-1 h-1). The reinforced photocatalytic properties are revealed to profit from the more photogenerated electrons and holes' separation, higher ability for light response, and more abundant active sites. This work develops the route for boosting the photocatalytic properties of porous g-C3N4 with N-doped Ti3C2.

6.
Artículo en Inglés | MEDLINE | ID: mdl-38806983

RESUMEN

Carbon emissions are important factors causing global warming, which requires global efforts to deal with. In this paper, we investigate the mechanism of financial innovation on reducing carbon emissions in China by constructing a financial innovation development index with factors of green finance as well as fintech development. Empirical results show that financial innovation contributes to reduce carbon intensity by promoting energy structure transition as well as public fiscal expenditure on energy conservation and environmental protection. Moreover, heterogeneity exists in the effect of financial innovation on carbon emission reduction. Financial innovation has a significant role in reducing carbon intensity in eastern regions, but has a relatively small influence on central and western regions. Furthermore, financial innovation has a lag effect on reducing carbon intensity.

7.
Arch Dermatol Res ; 316(6): 262, 2024 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-38795156

RESUMEN

Skin cutaneous melanoma (SKCM), a form of skin cancer, ranks among the most formidable and lethal malignancies. Exploring tumor microenvironment (TME)-based prognostic indicators would help improve the efficacy of immunotherapy for SKCM patients. This study analyzed SKCM scRNA-seq data to cluster non-malignant cells that could be used to explore the TME into nine immune/stromal cell types, including B cells, CD4 T cells, CD8 T cells, dendritic cells, endothelial cells, Fibroblasts, macrophages, neurons, and natural killer (NK) cells. Using data from The Cancer Genome Atlas (TCGA), we employed SKCM expression profiling to identify differentially expressed immune-associated genes (DEIAGs), which were then incorporated into weighted gene co-expression network analysis (WGCNA) to investigate TME-associated hub genes. Discover candidate small molecule drugs based on pivotal genes. Tumor immune microenvironment-associated genes (TIMAGs) for constructing TIMAS were identified and validated. Finally, the characteristics of TIAMS subgroups and the ability of TIMAS to predict immunotherapy outcomes were analyzed. We identified five TIMAGs (CD86, CD80, SEMA4D, C1QA, and IRF1) and used them to construct TIMAS. In addition, five potential SKCM drugs were identified. The results showed that TIMAS-low patients were associated with immune-related signaling pathways, high MUC16 mutation frequency, high T cell infiltration, and M1 macrophages, and were more favorable for immunotherapy. Collectively, TIMAS constructed by comprehensive analysis of scRNA-seq and bulk RNA-seq data is a promising marker for predicting ICI treatment outcomes and improving individualized therapy for SKCM patients.


Asunto(s)
Inmunoterapia , Melanoma , RNA-Seq , Neoplasias Cutáneas , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Melanoma/genética , Melanoma/inmunología , Melanoma/terapia , Melanoma/tratamiento farmacológico , Inmunoterapia/métodos , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Perfilación de la Expresión Génica , Pronóstico , Melanoma Cutáneo Maligno , Masculino , Transcriptoma , Femenino , Resultado del Tratamiento , Análisis de Expresión Génica de una Sola Célula
8.
Molecules ; 29(10)2024 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-38792246

RESUMEN

Natural deep eutectic solvents (NADESs), as emerging green solvents, can efficiently extract natural products from natural resources. However, studies on the extraction of phenolic compounds from celtuce (Lactuca sativa var. augustana) leaves (CLs) by NADESs are still lacking. This study screened the NADES L-proline-lactic acid (Pr-LA), combined it with ultrasound-assisted extraction (UAE) to extract phenolic compounds from CLs, and conducted a comparative study on the extraction effect with traditional extraction solvents. Both SEM and FT-IR confirmed that Pr-LA can enhance the degree of fragmentation of cell structures and improve the extraction rate of phenolic compounds. Molecular dynamics simulation results show that Pr-LA can improve the solubility of phenolic compounds and has stronger hydrogen bonds and van der Waals interactions with phenolic compounds. Single-factor and Box-Behnken experiments optimized the process parameters for the extraction of phenolic compounds from CLs. The second-order kinetic model describes the extraction process of phenolic compounds from CLs under optimal process parameters and provides theoretical guidance for actual industrial production. This study not only provides an efficient and green method for extracting phenolic compounds from CLs but also clarifies the mechanism of improved extraction efficiency, which provides a basis for research on the NADES extraction mechanism.


Asunto(s)
Disolventes Eutécticos Profundos , Lactuca , Fenoles , Hojas de la Planta , Fenoles/química , Fenoles/aislamiento & purificación , Hojas de la Planta/química , Lactuca/química , Disolventes Eutécticos Profundos/química , Extractos Vegetales/química , Ondas Ultrasónicas , Espectroscopía Infrarroja por Transformada de Fourier , Simulación de Dinámica Molecular , Solventes/química
9.
Materials (Basel) ; 17(9)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38730915

RESUMEN

The amount of heat input during welding impacts the weld's thermal and mechanical behavior and the joint's properties. The current study involved conducting AA 6061 and AZ31B Mg dissimilar welding, using friction stir lap welding (FSLW) and ultrasonic vibration-enhanced FSLW (UVeFSLW). The comparison and analysis of the welding load, the weld's macro-microstructure, intermetallic compounds (IMCs), and joint properties were conducted by adjusting the process parameters. The study also examined the effect of ultrasonic vibration (UV) variations on welding heat input. The study demonstrated that it is possible to reduce the welding load by employing UV. Moreover, this impact becomes more pronounced as the welding heat input decreases. Additionally, the material flow in the weld, the width of the weld nugget zone, and the continuous IMC layer are significantly influenced by ultrasonic vibration, irrespective of the heat input during welding. However, the impact on large areas of irregular IMCs or eutectic structures is relatively small. Furthermore, achieving better joint properties becomes more feasible when a higher welding speed is employed for the Al alloy placed on top. Specifically, the impact of UV becomes more evident at higher welding speeds (≥220 mm/min).

10.
Spectrochim Acta A Mol Biomol Spectrosc ; 316: 124331, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38669983

RESUMEN

Herein, a collection of novel N-Ti3C2/BiOClxBr1-x composites are fabricated via a simple in-situ sonochemical process. Not only the preparation method for N-Ti3C2 but also the photocatalytic system of N-Ti3C2/BiOClxBr1-x are firstly developed. Multiple characterizations jointly demonstrate the successful fabrication of the composites. Compared to that of BiOClxBr1-x, the maximum improvements of 1.16, 1.25 and 1.26 folds are severally confirmed for the photocatalytic degradation of levofloxacin, Rhodamine B, and methylene blue over N-Ti3C2/BiOClxBr1-x composites. In addition, through radicals trapping tests, the primary active species in photocatalytic degradation process are verified to be O2-. Moreover, N-Ti3C2/BiOClxBr1-x composites also exhibit 1.18 and 1.14 times enhancements for NH3 production compared with that of BiOClxBr1-x with or without the presence of methanol, respectively. In addition, the maximum improvements of photo-current and photo-potential for BiOClxBr1-x are 1.29 and 1.86 folds with the introduction of N-Ti3C2, respectively. The enhanced photocatalytic activity of N-Ti3C2/BiOClxBr1-x composites is owing to the heightened light absorption, increased specific surface area, and accelerated separation of photoinduced carriers. Additionally, the stable photocatalytic properties of N-Ti3C2/BiOClxBr1-x are confirmed by three photocatalytic recycle tests on pollutant degradation and nitrogen reduction combined with X-ray diffraction patterns before and after three recycles. This study suggests that N-Ti3C2 is an efficient ornamentation for boosting photocatalytic activity ofBiOClxBr1-x, which can also be expanded as a promising modifier for other semiconductors.

11.
Prostate ; 84(10): 932-944, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38629249

RESUMEN

BACKGROUND: KI67 is a well-known biomarker reflecting cell proliferation. We aim to elucidate the predictive role of KI67 in the efficacy of abiraterone for patients with advanced prostate cancer (PCa). METHODS: Clinicopathological data of 152 men with metastatic PCa, who received abiraterone therapy were retrospectively collected. The KI67 positivity was examined by immunohistochemistry using the prostate biopsy specimen. The predictive value of KI67 on the therapeutic efficacy of abiraterone was explored using Kaplan-Meier curve and Cox regression analysis. The endpoints included prostate-specific antigen (PSA) progression-free survival (PSA-PFS), radiographic PFS (rPFS), and overall survival (OS). RESULTS: In total, 85/152 (55.9%) and 67/152 (44.1%) cases, respectively, received abiraterone at metastatic hormone-sensitive (mHSPC) and castration-resistant PCa (mCRPC) stage. The median KI67 positivity was 20% (interquartile range: 10%-30%). Overall, KI67 rate was not correlated with PSA response. Notably, an elevated KI67-positive rate strongly correlated with unfavorable abiraterone efficacy, with KI67 ≥ 30% and KI67 ≥ 20% identified as the optimal cutoffs for prognosis differentiation in mHSPC (median PSA-PFS: 11.43 Mo vs. 26.43 Mo, p < 0.001; median rPFS: 16.63 Mo vs. 31.90 Mo, p = 0.003; median OS: 21.77 Mo vs. not reach, p = 0.005) and mCRPC (median PSA-PFS: 7.17 Mo vs. 12.20 Mo, p = 0.029; median rPFS: 11.67 Mo vs. 16.47 Mo, p = 0.012; median OS: 21.67 Mo vs. not reach, p = 0.073) patients, respectively. Multivariate analysis supported the independent predictive value of KI67 on abiraterone efficacy. In subgroup analysis, an elevated KI67 expression was consistently associated with unfavorable outcomes in the majority of subgroups. Furthermore, data from another cohort of 79 PCa patients with RNA information showed that those with KI67 RNA levels above the median had a significantly shorter OS than those below the median (17.71 vs. 30.72 Mo, p = 0.035). CONCLUSIONS: This study highlights KI67 positivity in prostate biopsy as a strong predictor of abiraterone efficacy in advanced PCa. These insights will assist clinicians in anticipating clinical outcomes and refining treatment decisions for PCa patients.


Asunto(s)
Androstenos , Biomarcadores de Tumor , Antígeno Ki-67 , Neoplasias de la Próstata , Humanos , Masculino , Antígeno Ki-67/análisis , Antígeno Ki-67/metabolismo , Anciano , Androstenos/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Proliferación Celular/efectos de los fármacos , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Resultado del Tratamiento , Valor Predictivo de las Pruebas , Supervivencia sin Progresión , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico
13.
Clin Cancer Res ; 30(11): 2571-2581, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38512114

RESUMEN

PURPOSE: Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. EXPERIMENTAL DESIGN: A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA-sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for patients with metastasis. RESULTS: In the localized setting, we found that a cell-cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS, 17.3 vs. 9.6 months, P = 0.016) and OS (median OS, not reached vs. 25.7 months, P = 0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. CONCLUSIONS: ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T-cell-derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.


Asunto(s)
Carcinoma de Células Renales , Fumarato Hidratasa , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/terapia , Fumarato Hidratasa/deficiencia , Fumarato Hidratasa/genética , Masculino , Femenino , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/inmunología , Neoplasias Renales/mortalidad , Neoplasias Renales/terapia , Persona de Mediana Edad , Anciano , Adulto , Activación de Linfocitos/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Memoria Inmunológica , Pronóstico , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inmunoterapia/métodos , Células T de Memoria/inmunología , Linfocitos T/inmunología
14.
Opt Express ; 32(4): 6658-6671, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38439364

RESUMEN

By effectively controlling the dipole-dipole interaction, we investigate the characteristics of the ground state of bright solitons in a spin-orbit coupled dipolar Bose-Einstein condensate. The dipolar atoms are trapped within a double-lattice which consists of a linear and a nonlinear lattice. We derive the motion equations of the different spin components, taking the controlling mechanisms of the dipole-dipole interaction into account. An analytical expression of dipole-dipole interaction is derived. By adjusting the dipole polarization angle, the dipole interaction can be adjusted from attraction to repulsion. On this basis, we study the generation and manipulation of the bright solitons using both the analytical variational method and numerical imaginary time evolution. The stability of the bright solitons is also analyzed and we map out the stability phase diagram. By adjusting the long-range dipole-dipole interaction, one can achieve manipulation of bright solitons in all aspects, including the existence, width, nodes, and stability. Considering the complexity of our system, our results will have enormous potential applications in quantum simulation of complex systems.

15.
Mol Ecol ; : e17332, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38529738

RESUMEN

Climate change is intensifying the frequency and severity of extreme temperatures. Understanding the molecular mechanisms underlying the ability to cope with acute thermal stress is key for predicting species' responses to extreme temperature events. While many studies have focused on the individual roles of gene expression, post-transcriptional processes and epigenetic modifications in response to acute thermal stress, the relative contribution of these molecular mechanisms remains unclear. The wide range of thermal limits of western mosquitofish (Gambusia affinis) provides an opportunity to explore this interplay. Here, we quantified changes in gene expression, alternative splicing, DNA methylation and microRNA (miRNA) expression in muscle tissue dissected from mosquitofish immediately after reaching high (CTmax) or low thermal limit (CTmin). Although the numbers of genes showing expression and splicing changes in response to acute temperature stress were small, we found a possibly larger and non-redundant role of splicing compared to gene expression, with more genes being differentially spliced (DSGs) than differentially expressed (DEGs), and little overlap between DSGs and DEGs. We also identified a small proportion of CpGs showing significant methylation change (i.e. differentially methylated cytosines, DMCs) in fish at thermal limits; however, there was no overlap between DEGs and genes annotated with DMCs in both CTmax and CTmin experiments. The weak interplay between epigenetic modifications and gene expression was further supported by our discoveries of no differentially expressed miRNAs. These findings provide novel insights into the relative role of different molecular mechanisms underlying immediate responses to extreme temperatures and demonstrate non-concordant responses of epigenetic and transcriptional mechanisms to acute temperature stress.

16.
Thromb Res ; 237: 52-63, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38547695

RESUMEN

The presence of neutrophil extracellular traps (NETs) in thrombotic diseases has been extensively studied. The exact mechanism of NET formation in deep venous thrombosis (DVT) has not been largely studied. This study is aimed to explore the role of NETs and their interaction with platelet factor 4 (PF4) in DVT. In plasma samples from 51 healthy volunteers and 52 DVT patients, NET markers and PF4 were measured using enzyme-linked immunosorbent assays (ELISA). NET generation in blood samples from healthy subjects and DVT patients was analyzed by confocal microscopy and flow cytometry. The plasma levels of NETs were significantly elevated in DVT patients, and neutrophils from patients showed a stronger ability to generate NETs after treatment. PF4 was upregulated in plasma samples from DVT patients and mediated NET formation. NETs enhanced procoagulant (PCA) via tissue factor and activating platelets to induce procoagulant activity. In addition, we established an inferior vena cava ligation (IVC) model to examine the role of NETs in thrombogenicity in DVT. In conclusion, NET formation was mediated by PF4 and enhance the procoagulant activity in DVT.


Asunto(s)
Trampas Extracelulares , Factor Plaquetario 4 , Trombosis de la Vena , Adulto , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Plaquetas/metabolismo , Trampas Extracelulares/metabolismo , Neutrófilos/metabolismo , Factor Plaquetario 4/sangre , Factor Plaquetario 4/metabolismo , Trombosis de la Vena/sangre , Trombosis de la Vena/patología
17.
Cell Death Discov ; 10(1): 76, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38355574

RESUMEN

Long noncoding RNAs (lncRNAs) are a group of noncoding RNAs with transcript lengths of >200 nucleotides. Mounting evidence suggests that lncRNAs are closely associated with tumorigenesis. LncRNA H19 (H19) was the first lncRNA to function as an oncogene in many malignant tumors. Apart from the established role of H19 in promoting cell growth, proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and metastasis, it has been recently discovered that H19 also inhibits programmed cell death (PCD) of cancer cells. In this review, we summarize the mechanisms by which H19 regulates PCD in cancer cells through various signaling pathways, molecular mechanisms, and epigenetic modifications. H19 regulates PCD through the Wnt/ß-catenin pathway and the PI3K-Akt-mTOR pathway. It also acts as a competitive endogenous RNA (ceRNA) in PCD regulation. The interaction between H19 and RNA-binding proteins (RBP) regulates apoptosis in cancer. Moreover, epigenetic modifications, including DNA and RNA methylation and histone modifications, are also involved in H19-associated PCD regulation. In conclusion, we summarize the role of H19 signaling via PCD in cancer chemoresistance, highlighting the promising research significance of H19 as a therapeutic target. We hope that our study will contribute to a broader understanding of H19 in cancer development and treatment.

18.
Sensors (Basel) ; 24(3)2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38339512

RESUMEN

This work investigates wireless covert communication in a multi-sensor asymmetric noise scenario. We adopt KL (Kullback-Leibler) divergence as the covertness constraint metric and mutual information as the transmission rate metric. To accurately approximate KL divergence and mutual information in covert communication, we employ the Taylor series expansion technique. Analytical expressions for KL divergence and mutual information in covert communication are derived, and we optimize the amplitude gain and phase angles based on these analytical expressions. Our findings underscore the importance of phase angle selection in covert communication within asymmetric noise systems. We propose an effective method for optimizing the transmission amplitude gain and phase angles in scenarios with asymmetric noise. Numerical results validate the effectiveness and superiority of our proposed method.

20.
Artículo en Inglés | MEDLINE | ID: mdl-38355915

RESUMEN

AIM: This study aims to utilize machine learning (ML) and logistic regression (LR) models to predict surgical outcomes among patients with traumatic brain injury (TBI) based on admission examination, assisting in making optimal surgical treatment decision for these patients. METHOD: We conducted a retrospective review of patients hospitalized in our department for moderate-to-severe TBI. Patients admitted between October 2011 and October 2022 were assigned to the training set, while patients admitted between November 2022 and May 2023 were designated as the external validation set. Five ML algorithms and LR model were employed to predict the postoperative Glasgow Outcome Scale (GOS) status at discharge using clinical and routine blood data collected upon admission. The Shapley (SHAP) plot was utilized for interpreting the models. RESULTS: A total of 416 patients were included in this study, and they were divided into the training set (n = 396) and the external validation set (n = 47). The ML models, using both clinical and routine blood data, were able to predict postoperative GOS outcomes with area under the curve (AUC) values ranging from 0.860 to 0.900 during the internal cross-validation and from 0.801 to 0.890 during the external validation. In contrast, the LR model had the lowest AUC values during the internal and external validation (0.844 and 0.567, respectively). When blood data was not available, the ML models achieved AUCs of 0.849 to 0.870 during the internal cross-validation and 0.714 to 0.861 during the external validation. Similarly, the LR model had the lowest AUC values (0.821 and 0.638, respectively). Through repeated cross-validation analysis, we found that routine blood data had a significant association with higher mean AUC values in all ML and LR models. The SHAP plot was used to visualize the contributions of all predictors and highlighted the significance of blood data in the lightGBM model. CONCLUSION: The study concluded that ML models could provide rapid and accurate predictions for postoperative GOS outcomes at discharge following moderate-to-severe TBI. The study also highlighted the crucial role of routine blood tests in improving such predictions, and may contribute to the optimization of surgical treatment decision-making for patients with TBI.

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