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1.
Ultrasonics ; 145: 107474, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39378772

RESUMEN

Sparse matrix beamforming (SMB) is a computationally efficient reformulation of delay-and-sum (DAS) beamforming as a single sparse matrix multiplication. This reformulation can potentially dovetail with machine learning platforms like TensorFlow and PyTorch that already support sparse matrix operations. In this work, using SMB principles, we present the development of beamforming-integrated neural networks (BINNs) that can rationally infer ultrasound images directly from pre-beamforming channel-domain radiofrequency (RF) datasets. To demonstrate feasibility, a toy BINN was first designed with two 2D-convolution layers that were respectively placed both before and after an SMB layer. This toy BINN correctly updated kernel weights in all convolution layers, demonstrating efficiency in both training (PyTorch - 133 ms, TensorFlow - 22 ms) and inference (PyTorch - 4 ms, TensorFlow - 5 ms). As an application demonstration, another BINN with two RF-domain convolution layers, an SMB layer, and three image-domain convolution layers was designed to infer high-quality B-mode images in vivo from single-shot plane-wave channel RF data. When trained using 31-angle compounded plane wave images (3000 frames from 22 human volunteers), this BINN showed mean-square logarithmic error improvements of 21.3 % and 431 % in the inferred B-mode image quality respectively comparing to an image-to-image convolutional neural network (CNN) and an RF-to-image CNN with the same number of layers and learnable parameters (3,777). Overall, by including an SMB layer to adopt prior knowledge of DAS beamforming, BINN shows potential as a new type of informed machine learning framework for ultrasound imaging.

2.
Virulence ; : 2418407, 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39420787

RESUMEN

BACKGROUND: Helicobacter pylori (H. pylori) has infected approximately 4.4 billion individuals worldwide. The known virulence genes and the existing H. pylori typing methods have not been shown to have a recognized correlation with its infectivity. The aim of this study was to elucidate the relationships among known important virulence genes, coccoid transformation, and cytotoxicity of H. pylori isolated from individuals with different clinical diseases to provide guidance for the development of new virulence typing methods for H. pylori. METHODS: The known important virulence genes of 35 H. pylori strains were identified by whole-gene next-generation sequencing (WGS) and polymerase chain reaction (PCR). The chronological changes in the proportion of coccoid forms of H. pylori and their ultramicroscopic structures were observed chronologically using transmission electron microscopy. Human gastric mucosal epithelial cells (GES-1) w. RESULTS: There were no significant correlations among the known important virulence genes, coccoid transformation and cytotoxicity of H. pylori isolated from patients with different clinical diseases. We developed a new virulence classification based on the defensive and offensive abilities of H. pylori. CONCLUSIONS: Coccoid transformation and virulence are two independent characteristics of H. pylori that reflect its defensive and offensive abilities, respectively. These two abilities work synergistically, warranting the construction of a new virulence typing method for H. pylori. However, the correlation between the new virulence classification and pathogenic ability still needs to be further ver.

3.
Anaerobe ; : 102913, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39343356

RESUMEN

OBJECTIVES: To comprehensively characterize a new species, named Finegoldia dalianensis sp. nov., isolated from the pus of a skin abscess from a patient and genomic analysis of the strains belonging to Finegoldia genus. METHODS: Strain LY240594T was definitively characterized through phylogenetic, genomic, and biochemical approach. Extensive genomic comparisons, involving the genome of LY240594T and those of 82 Finegoldia strains from GenBank, were instrumental in revealing genetic relationships within the Finegoldia genus. RESULTS: Strain LY240594 was initially identified as F. magna based on MALDI-TOF MS analysis, showing 99.7% 16S rRNA gene sequence similarity with the type strain of F. magna CCUG 17636T. However, there were 68.5% similarity with dDDH method and 90.9% similarity by ANI analysis respectively, between LY240594T and the selected type strain, F. magna DSM 20470T.Biochemical differences were also found between two strains. The ANI and genomic analysis of 82 Finegoldia sp. strains and Strain LY240594 revealed that those strains could be categorized into at least three groups using a 95% ANI threshold. CONCLUSION: Comprehensive characterization supported the proposal of a new species within the genus Finegoldia, named Finegoldia dalianensis sp. nov. The type strain, LY240594T (=GDMCC 1.4375T =KCTC 25838T), features 1,938 genes and a G+C content of 31.8 mol%. Genomic comparisons and ANI studies elucidated substantial heterogeneity within the Finegoldia genus.

4.
BMC Med Educ ; 24(1): 1041, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334234

RESUMEN

BACKGROUND: Nursing literature suggested that patient mistreatment has significant impacts on nurses' emotions and job burnout. Yet, further research is needed to understand the underlying mechanism and the spillover effect on nurses' families. Leveraging the goal progress theory, this study aimed to examine the association between patient mistreatment, nurses' emotional exhaustion, and work-family conflict, as well as the mediating role of social sharing of negative work events and the moderating role of perceived organizational support. METHODS: During the COVID-19 pandemic in China, a cross-sectional study was conducted with a sample of 1627 nurses from the Hematology Specialist Alliance of Chongqing from October to November 2022. Questionnaires were administered to measure patient mistreatment, perceived organizational support, social sharing of negative work events, emotional exhaustion, and work-family conflict. Hierarchical linear regression and conditional processes were used for statistical analyses. RESULTS: Patient mistreatment was positively associated with emotional exhaustion (ß = 0.354, p < 0.001) and work-family conflict (ß = 0.314, p < 0.001). Social sharing of negative work events played a partial mediating role in the relationship between patient mistreatment and emotional exhaustion (effect = 0.067, SE = 0.013), and work-family conflict (effect = 0.077, SE = 0.014). Moderated mediation analysis found that the mediation effect was stronger when the perceived organizational support was high. CONCLUSION: Our findings reveal the amplifying effect of social sharing of negative work events on nurses' emotional exhaustion and work-family conflict. Perceived organizational support strengthens the positive effect of patient mistreatment on the social sharing of negative work events, thus resulting in increased emotional exhaustion and work-family conflict. We also discuss practical implications, limitations, and directions for future research.


Asunto(s)
Agotamiento Profesional , Humanos , Agotamiento Profesional/psicología , Estudios Transversales , Femenino , Adulto , Masculino , China , COVID-19/psicología , COVID-19/epidemiología , Apoyo Social , Personal de Enfermería en Hospital/psicología , Encuestas y Cuestionarios , Cultura Organizacional , Persona de Mediana Edad , SARS-CoV-2 , Agotamiento Emocional
5.
Pharmaceuticals (Basel) ; 17(9)2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39338283

RESUMEN

Lung cancer has the highest fatality rate among malignant tumors in the world. Finding new biomarkers of drug resistance is of great importance in the prognosis of lung cancer patients. We found that the polymorphisms of Adenylate Cyclase 1 (ADCY1) are significantly associated with platinum-based chemotherapy resistance in lung cancer patients in our previous research. In this study, we wanted to identify the mechanism of ADCY1 affecting platinum resistance. We used an MTT assay to find if the expression of ADCY1 is associated with the sensitivity of cisplatin in A549, H1299, and A549-DDP cells. Then, we performed CCK-8 tests to detect the absorbance of these cells stimulated by ADCY1, which can discover the cell proliferation that is affected by ADCY1. We investigated cell apoptosis and cell cycles regulated by ADCY1 through the flow cytometry assay. RNA sequencing was used to find the downstream genes affected by ADCY1 which may be associated with drug resistance in lung cancer patients. ADCY1 has higher expression in lung cancer cells than in normal cells. ADCY1 can affect cisplatin resistance in lung cancer cells by regulating cell proliferation, cell apoptosis, and the cell cycle. It may control cell apoptosis by regulating the classical apoptosis biomarkers Bax and Bcl2. Our study showed that ADCY1 may be a new biomarker in the prognosis of lung cancer patients. Much work remains to be carried out to clarify the mechanism in this important emerging field.

6.
Org Lett ; 26(37): 7976-7980, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39240022

RESUMEN

The use of an earth-abundant and inexpensive iron complex as a catalyst, coupled with near-infrared (NIR) light as the energy source, for radical reactions with alkyl halides has been far less developed. In this study, we report NIR light-mediated iron(I) dimer-catalyzed radical cascade reactions of fluoroalkyl bromides for the synthesis of ring-fused quinazolinones bearing a difluoromethyl group. In this process, the 3-bromo-1,10-phenanthroline ligand facilitates the reactivity of [CpFe(CO)2]2, thereby improving the efficiency of the reaction.

7.
Cell Rep ; 43(10): 114745, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39298317

RESUMEN

The species-rich cosmopolitan genus Rhododendron offers a good system for exploring the genomic mechanisms underlying adaptation to diverse habitats. Here, we report high-quality chromosomal-level genome assemblies of nine species, representing all five subgenera, different altitudinal distributions, and all flower color types of this genus. Further comprehensive genomic analyses indicate diverse adaptive strategies employed by Rhododendron, particularly adaptation to alpine and subalpine habitats by expansion/contraction of gene families involved in pathogen defense and oxidative phosphorylation, genomic convergent evolution, and gene copy-number variation. The convergent adaptation to high altitudes is further shown by population genomic analysis of R. nivale from the Himalaya-Hengduan Mountains. Moreover, we identify the genes involved in the biosynthesis of anthocyanins and carotenoids, which play a crucial role in shaping flower color diversity and environmental adaptation. Our study is significant for comprehending plant adaptive evolution and the uneven distribution of species diversity across different geographical regions.

8.
Transl Vis Sci Technol ; 13(9): 21, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39292467

RESUMEN

Purpose: Using swept-source optical coherence tomography (SS-OCT) to explore the effect of high myopia on superficial retina vascular density (SVD) of the peripheral region and the area of radial peripapillary capillaries (RPCs). Methods: In this cross-sectional study, a total of 91 volunteers (34 male subjects and 57 female subjects) were recruited and 34 individuals in the high myopic group (group A) and 57 individuals in the low myopic group (group B). Using the wide-field OCT-angiography (OCTA; 24 × 20 mm, 120 degrees angular field) compared the peripheral SVD and the area of RPC between the two groups and investigated its correlation with ocular axial length and diopter. Results: Peripheral SVD of group B around the supratemporal (SVD1), supranasal (SVD2), infratemporal (SVD3), and infranasal (SVD4) directions were significantly higher than those of group A (all P < 0.05). The RPC area of group B around the supranasal (RPC2) and infranasal (RPC4) were significantly larger than that of group A (all P < 0.01). Ocular axial length and diopter were significantly correlated with SVD2 and SVD4 (all P < 0.05), and they also have a significant correlation with the supratemporal (RPC1), RPC2, and RPC4 (all P < 0.05). Conclusions: Peripheral SVD was decreased and the RPC area was mainly reduced on the nasal side in the high myopic group. Peripheral SVD and area of RPC are significantly correlated with ocular axial length and diopter. Translational Relevance: The wide-field OCTA can be used for new detection of myopia's impact on the retinal peripheral SVD and area of peripapillary RPC, offering new insights into the progression of myopia.


Asunto(s)
Capilares , Vasos Retinianos , Tomografía de Coherencia Óptica , Humanos , Masculino , Femenino , Estudios Transversales , Tomografía de Coherencia Óptica/métodos , Adulto , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Capilares/diagnóstico por imagen , Capilares/patología , Angiografía con Fluoresceína/métodos , Adulto Joven , Miopía/diagnóstico por imagen , Miopía/patología , Miopía/fisiopatología , Disco Óptico/irrigación sanguínea , Disco Óptico/diagnóstico por imagen , Disco Óptico/patología , Densidad Microvascular , Persona de Mediana Edad , Longitud Axial del Ojo/diagnóstico por imagen , Longitud Axial del Ojo/patología
9.
Artículo en Inglés | MEDLINE | ID: mdl-39259298

RESUMEN

PURPOSE: To explore the abandonment rate and factors influencing the use of rigid gas-permeable contact lenses (RGPCL) among children aged < 6 years. METHODS: This retrospective case series study included 70 children aged < 6 years who were fitted with RGPCL for visual rehabilitation between January 2016 and December 2021. We collected data on indications, discontinuation rates, and reasons for discontinuation from medical records and via telephone calls and investigated the factors influencing contact lens abandonment. RESULTS: The median age of the 70 participants was 5.0 (interquartile range: 4.0-5.9) years. Further, 36 (51.4%) children stopped wearing contact lenses; among them, 17 (47.2%) stopped within 3 months, and the median duration of lens wearing was 4.0 (interquartile range: 1.0-11.5) months. Additionally, there was a correlation between the duration of lens wearing and lens abandonment (r = -0.698, P < 0.001). A high parental education level (hazard ratio [HR] = 0.425; 95% confidence interval [CI] 0.198, 0.913; P = 0.028) was a protective factor against lens abandonment, while parental assessment indicating harder than expected practicality (HR = 4.062; 95% CI 1.204, 13.707; P = 0.024) was a risk factor for abandonment. CONCLUSION: Children aged < 6 years are susceptible to early discontinuation of RGPCL use. Since parents perform daily lens manipulation, they are crucial to the continuity of lens use in these children. To improve RGPCL use continuity, communication and supervision should be strengthened before and after RGPCL fittings.

10.
Poult Sci ; 103(12): 104253, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39278115

RESUMEN

Chicken egg yolk plasma (EYP), the supernatant fraction of egg yolk obtained by water dilution and centrifugation, is a rich source of various bioactive substances and a significant bearer of yolk-emulsifying properties. This study utilized proteomics to conduct a comprehensive and in-depth analysis of both common and modified EYP proteins (phosphorylated proteins and N-glycosylated proteins). Total of 208 proteins were identified in EYP, including 42 phosphorylated proteins with 137 phosphorylation sites and 150 N-glycoproteins with 332 N-glycosylation sites. Among the phosphorylation sites, tyrosine accounted for 80.6%, while the N-glycosylation sites predominantly featured "N-X-T" motifs, accounting for 58.7%. Functional enrichment analysis revealed that most proteins were involved in regulating enzyme activity and inhibition with a particular focus on modulating peptidase activity. Notably, vitellogenins-2 (30 phosphorylation sites, 9 N-glycosylation sites) and apolipoprotein B (10 phosphorylation sites, 56 N-glycosylation sites) were the 2 proteins with the most modification sites. Additionally, EYP was found to contain the highly N-glycosylated complement proteins C3 and C4. These findings provide new insights into the protein composition of EYP and its roles in chicken embryo development and immune defense, offering a theoretical foundation for the application of EYP in various fields.

11.
Cell Host Microbe ; 32(10): 1805-1821.e10, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39293437

RESUMEN

Microbiota and feeding modes influence the susceptibility of premature newborns to necrotizing enterocolitis (NEC) through mechanisms that remain unknown. Here, we show that microbiota colonization facilitated by breastmilk feeding promotes NOD-like receptor family CARD domain containing 5 (Nlrc5) gene expression in mouse intestinal epithelial cells (IECs). Notably, inducible knockout of the Nlrc5 gene in IECs predisposes neonatal mice to NEC-like injury in the small intestine upon viral inflammation in an NK1.1+ cell-dependent manner. By contrast, formula feeding enhances neonatal gut colonization with environment-derived tilivalline-producing Klebsiella spp. Remarkably, tilivalline disrupts microbiota-activated STAT1 signaling that controls Nlrc5 gene expression in IECs through a PPAR-γ-mediated mechanism. Consequently, this dysregulation hinders the resistance of neonatal intestinal epithelium to self-NK1.1+ cell cytotoxicity upon virus infection/colonization, promoting NEC development. Together, we discover the underappreciated role of intestinal microbiota colonization in shaping a disease tolerance program to viral inflammation and elucidate the mechanisms impacting NEC development in neonates.


Asunto(s)
Animales Recién Nacidos , Enterocolitis Necrotizante , Microbioma Gastrointestinal , Mucosa Intestinal , Factor de Transcripción STAT1 , Animales , Enterocolitis Necrotizante/microbiología , Enterocolitis Necrotizante/inmunología , Enterocolitis Necrotizante/virología , Factor de Transcripción STAT1/metabolismo , Ratones , Mucosa Intestinal/microbiología , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Ratones Noqueados , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Transducción de Señal , Células Epiteliales/microbiología , Células Epiteliales/virología , Células Epiteliales/inmunología , Humanos , Ratones Endogámicos C57BL
12.
Nutr Metab (Lond) ; 21(1): 75, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39304912

RESUMEN

BACKGROUND: 3-Hydroxybutyrate, also called ß-hydroxybutyrate, is a significant constituent of ketone bodies. Previous observational and experimental studies have suggested that ketogenic diet, especially 3-hydroxybutyrate, may have a protective effect against cardiovascular disease. However, the relationship between ketone bodies, especially 3-hydroxybutyrate, and aortic dissection remains uncertain. MATERIALS AND METHODS: Publicly accessible data from genome-wide association study (GWAS) was utilized to obtain information on ketone bodies, including 3-hydroxybutyrate, acetoacetate and acetone as exposure respectively, while GWAS data on aortic dissection was used as outcome. Subsequently, two-sample Mendelian randomization (MR) analysis was conducted to examine the potential relationship between ketone bodies and aortic dissection. Then, reverse and multivariate Mendelian randomization analyses were performed. Additionally, sensitivity tests were conducted to assess the robustness of MR study. RESULTS: The inverse-variance weighted (IVW) method of Mendelian randomization analysis of gene prediction observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection (OR 0.147, 95% CI 0.053-0.410). Furthermore, consistent findings were obtained through the implementation of the weighted median, simple mode, Mendelian randomization-Egger (MR-Egger), and weighted mode methods. After adjusting acetoacetate (OR 0.143, 95% CI 0.023-0.900) or acetone (OR 0.100, 95% CI 0.025-0.398), MR analysis of gene prediction still observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection. No indications of heterogeneity or pleiotropy among the SNPs were detected. CONCLUSION: The findings from the MR analysis demonstrated that genetically predicted 3-hydroxybutyrate exhibits a protective effect against aortic dissection.

13.
Artículo en Inglés | MEDLINE | ID: mdl-39322652

RESUMEN

Over past two years, a total of 39,918 hematopoietic stem cell transplantation (HSCT) cases were reported, with 18,194 and 21,714 transplants performed in 2022 and 2023, respectively. Autologous HSCT accounted for 6562 cases (31%) in 2022, while allogeneic HSCT comprised 12,632 cases (69%). In 2023, the number of allogeneic HSCTs exceeded 15,000, maintaining a 69% share. Participation in the 2022 and 2023 surveys included 193 and 212 transplantation teams, respectively, from 27 provinces, municipalities, or autonomous regions. The leading indication of HSCT was acute leukemia, including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia, with a total of 17,421 cases. AML was the most common disease (10,339, 38%) for allogeneic HSCT, which was followed by ALL (5925 cases, 21%). Peripheral blood emerged as the primary source of stem cell grafts, utilized in 54% of matched sibling donor transplants and 77% of haploidentical donor transplants. The BuCy-based conditioning regimen was the most prevalent, used in 53% of allogeneic HSCT cases in the past two years. This survey offers a comprehensive overview of the current HSCT landscape and serves as a valuable resource for clinical practice.

14.
Cell Host Microbe ; 32(9): 1488-1501.e5, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39214086

RESUMEN

The pathogenic outcome of enteric virus infections is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors, with metabolites serving as a key mediator. Noroviruses bind bile acid metabolites, which are produced by the host and then modified by commensal bacteria. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Working in an infant mouse model of norovirus infection, we demonstrate that microbiota and their bile acid metabolites protect from norovirus diarrhea, whereas host bile acids promote disease. We also find that maternal bile acid metabolism determines the susceptibility of newborn mice to norovirus diarrhea during breastfeeding. Finally, targeting maternal and neonatal bile acid metabolism can protect newborn mice from norovirus disease. In summary, neonatal metabolic immaturity and breastmilk bile acids are central determinants of heightened newborn vulnerability to norovirus disease.


Asunto(s)
Animales Recién Nacidos , Ácidos y Sales Biliares , Infecciones por Caliciviridae , Diarrea , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Leche Humana , Norovirus , Animales , Ratones , Ácidos y Sales Biliares/metabolismo , Infecciones por Caliciviridae/metabolismo , Infecciones por Caliciviridae/virología , Leche Humana/virología , Leche Humana/metabolismo , Diarrea/virología , Diarrea/metabolismo , Femenino , Humanos , Ratones Endogámicos C57BL
15.
Mol Divers ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39141208

RESUMEN

A series of novel sulfonyl hydrazide based ß-carboline derivatives (SX1-SX32) were designed and synthesized, and their structures were characterized on NMR and HRMS. Their α-glucosidase inhibitory screening results found that compounds (SX1-SX32) presented potential α-glucosidase inhibitory: IC50 values being 2.12 ± 0.33-19.37 ± 1.49 µM. Compound SX29 with a para-phenyl (IC50: 2.12 ± 0.33 µM) presented the strongest activity and was confirmed as a noncompetitive inhibitor. Fluorescence spectra, CD spectra and molecular docking were conducted to describe the inhibition mechanism of SX29 against α-glucosidase. Cells cytotoxicity indicated SX29 (0-32 µM) had no cytotoxicity on 293T cells. In particular, in vivo experiments revealed that oral administration of SX29 could regulate hyperglycemia and glucose tolerance of diabetic mice. These achieved findings indicated that sulfonyl hydrazide based ß-carboline derivatives bore promising potential for discovering new α-glucosidase inhibitors with hypoglycemic activity.

16.
Front Oncol ; 14: 1441222, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39156700

RESUMEN

Genomic instability stands out as a pivotal hallmark of cancer, and PARP inhibitors (PARPi) emerging as a groundbreaking class of targeted therapy drugs meticulously crafted to inhibit the repair of DNA single-strand breaks(SSB) in tumor cells. Currently, PARPi have been approved for the treatment of ovarian cancer, pancreatic cancer, breast cancer, and prostate cancer characterized by homologous recombination(HR) repair deficiencies due to mutations in BRCA1/2 or other DNA repair associated genes and acquiring the designation of breakthrough therapy. Nonetheless, PARPi exhibit limited efficacy in the majority of HR-proficient BRCA1/2 wild-type cancers. At present, the synergistic approach of combining PARPi with agents that induce HR defects, or with chemotherapy and radiotherapy to induce substantial DNA damage, significantly enhances the efficacy of PARPi in BRCA wild-type or HR-proficient patients, supporting extension the use of PARPi in HR proficient patients. Therefore, we have summarized the effects and mechanisms of the combined use of drugs with PARPi, including the combination of PARPi with HR defect-inducing drugs such as ATRi, CHKi, HR indirectly inducing drugs like VEGFRi, CDKi, immune checkpoint inhibitors and drugs instigating DNA damage such as chemotherapy or radiotherapy. In addition, this review discusses several ongoing clinical trials aimed at analyzing the clinical application potential of these combined treatment strategies.

17.
Front Pharmacol ; 15: 1448381, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39185308

RESUMEN

Background: Artesunate (ART), a natural compound derived from Artemisia annua, has shown promising clinical potentials in the treatment of various tumors, but the exact mechanism is unclear. Choroidal melanoma (CM) is a major malignant ocular tumor in adults, known for its significant malignancy and poor prognosis, with limited efficacy in current treatments. This study explored the anti-CM effects and mechanisms of ART using a combination of network pharmacology, molecular docking and experimental validation. Methods: Potential targets of ART were screened in PubChem, Swiss Target Prediction and Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database Analysis Platform databases, while target genes related to CM prognosis were selected from Online Mendelian Inheritance in Man (OMIM), GeneCards and DisGeNET databases. The intersection of these two groups of datasets yielded the target genes of ART involved in CM. Protein-protein interaction (PPI) network analysis of the intersecting targets, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were conducted to identify core targets and critical pathways. Molecular docking methods were performed to predict the binding interactions between ART and core targets. The effects of ART on CM were evaluated through CCK8, colony formation, transwell, as well as flow cytometry assays to detect apoptosis, cell cycle, reactive oxygen species (ROS). Western blot (WB) assays were conducted to investigate the impact of ART on key proteins and pathways associated with CM. Finally, in vivo assays were conducted to further validate the effects of ART on subcutaneous tumors in nude mice. Results: Research has shown that key pathways and core targets for ART in treating CM were identified through a network pharmacology approach. Molecular docking results verified the strong binding affinity between ART and these core targets. The analysis and predicted results indicated that ART primarily exerted its effects on CM through various tumor-related pathways like apoptosis. The assays in vitro confirmed that ART significantly inhibited the proliferation and migration of CM cells. This was achieved by promoting apoptosis through activation of the p53 signaling pathway, causing cell cycle arrest at the G0/G1 phase by inhibiting the PI3K/AKT/mTOR signaling pathway and increasing the intracellular level of ROS by activating the NRF2/HO-1 signaling pathway. Additionally, the assays in vivo further validated the significant proliferation-inhibitory effect of ART on CM. Conclusion: This study, making the initial exploration, illustrated through network pharmacology combined with molecular docking and in vitro/in vivo assays, confirmed that ART exerted potential anti-cancer effects on CM by promoting apoptosis, inducing cell cycle arrest and increasing intracellular levels of ROS. These findings suggested that ART held significant therapeutic potential for CM.

18.
Nano Lett ; 24(34): 10562-10568, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39159397

RESUMEN

MnBi2Te4 is a magnetic topological insulator with layered A-type antiferromagnetic order. It exhibits a rich layer- and magnetic-state dependent topological phase diagram; however, much about the coupling between spin, charge, and lattice remains to be explored. In this work, we report that MnBi2Te4 is an excellent acoustic phonon cavity by realizing phonon frequency combs using picosecond ultrasonics. With the generated acoustic phonon wavepackets, we demonstrate that the timing and phase of acoustic echoes can be used to detect the presence of stacking faults between van der Waals layers buried deep within the crystal. Furthermore, by implementing this nondestructive ultrafast optical measurement in conjunction with time-resolved magneto-optical Kerr effect experiments, we uncover that out-of-plane vibrations in MnBi2Te4 do not couple to the magnetic order, i.e. there is no appreciable magnetostriction. Our work points out how a well-developed technique can probe the structural defects and phonon pulse engineering in layered topological insulators.

19.
Am J Physiol Gastrointest Liver Physiol ; 327(4): G499-G512, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39104322

RESUMEN

Apoptosis, inflammation, and wound healing are critical pathophysiological events associated with various liver diseases. Currently, there is a lack of in vivo approaches to study hepatocyte apoptosis-induced liver injury and repair. To address this critical knowledge gap, we developed a unique genetically modified mouse model, namely, 3-Transgene (Tg) with inducible Hepatocyte-Specific Apoptosis Phenotype (3xTg-iHAP) in this study. The 3xTg-iHAP mice possess three transgenes including Alb-Cre, Rosa26-rtTA, and tetO-Fasl on a B6 background. These mice are phenotypically normal, viable, and fertile. After subcutaneous administration of a single dose of doxycycline (5 mg/kg, Dox) to 3xTg-iHAP mice, we observed a complete histological spectrum of sterile liver wound-healing responses: asymptomatic hepatocyte apoptosis at 8 h, necrotic liver injury and sterile inflammation at 48 h, followed by hepatocyte mitosis and regeneration within 7 days. During the injury phase, the mice exhibited an increase in the biomarkers of alanine aminotransferase (ALT), chemokine (C-X-C motif) ligand 1 (CXCL1), and IL-6 in peripheral blood, as well as α-smooth muscle actin (α-SMA) protein in liver tissues. Conversely, the mice displayed a decrease in these markers in the recovery phase. Remarkably, this model shows that the sterile liver injury following elevated hepatocyte apoptosis is associated with an increase in myeloid cells in the liver. Within 7 days post-Dox administration, the liver of Dox-treated 3xTg-iHAP mice displays a normal histological structure, indicating the completion of wound healing. Together, we established a novel mouse model of injury and regeneration induced by hepatocyte apoptosis. This tool provides a robust in vivo platform for studying the pathophysiology of sterile liver inflammation, regeneration, and new therapeutic interventions for liver diseases.NEW & NOTEWORTHY Bu et al. present a triple-transgenic mouse model, namely, 3xTg-iHAP mice that are engineered to explore hepatocyte apoptosis-triggered sterile liver injury and regeneration. This model demonstrates a full spectrum of liver wound-healing responses from asymptomatic apoptosis to injury, myeloid cell-dominant sterile inflammation, and repair after induction of hepatocyte-specific apoptosis. The robust nature of this model makes it an invaluable in vivo tool for studying sterile liver inflammation, regeneration, and new therapeutic strategies.


Asunto(s)
Apoptosis , Modelos Animales de Enfermedad , Hepatocitos , Regeneración Hepática , Ratones Transgénicos , Células Mieloides , Animales , Hepatocitos/metabolismo , Hepatocitos/patología , Ratones , Células Mieloides/metabolismo , Hígado/metabolismo , Hígado/patología , Cicatrización de Heridas , Ratones Endogámicos C57BL , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/genética
20.
Environ Res ; 259: 119576, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38996958

RESUMEN

The interaction between extracellular polymeric substances (EPS) in municipal sludge and antibiotics in wastewater is critical in wastewater treatment, resource recovery, and sludge management. Therefore, it is increasingly urgent to investigate the distribution coefficient (Log K) of sulfonamide antibiotics (SAs) in EPS, particularly in sludge-derived dissolved organic carbon (DOC) and aqueous phase systems. Herein, through balance experiments, the concentrations of SAs were determined using alkaline extraction EPS (AEPS) and alginate-like extracellular polymer (ALE) systems, and the Log KDOC values were determined. The results showed that the Log KDOC of AEPS was higher than that of ALE, which exhibited a negative KDOC value, indicating an inhibitory effect on dissolution. For the three SAs studied, the Log KDOC values were in the following order: sulfamethoxazole > sulfapyridine > sulfadiazine. This order can be attributed to the differing physicochemical properties, such as polarity, of the SAs. Three-dimensional excitation-emission matrix fluorescence spectra and fitting results indicated a lack of aromatic proteins dominated by tryptophan and humus-like substances in ALE. Meanwhile, the hydrophobic interaction of aromatic proteins dominated by tryptophan was the main driving force in the binding process between AEPS and SAs.


Asunto(s)
Antibacterianos , Matriz Extracelular de Sustancias Poliméricas , Aguas del Alcantarillado , Sulfonamidas , Contaminantes Químicos del Agua , Aguas del Alcantarillado/química , Antibacterianos/análisis , Antibacterianos/química , Sulfonamidas/análisis , Sulfonamidas/química , Matriz Extracelular de Sustancias Poliméricas/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Eliminación de Residuos Líquidos/métodos
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