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1.
Sci Rep ; 14(1): 15600, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971916

RESUMO

Binding of Staphylococcus aureus protein A (SPA) to osteoblasts induces apoptosis and inhibits bone formation. Bone marrow-derived mesenchymal stem cells (BMSCs) have the ability to differentiate into bone, fat and cartilage. Therefore, it was important to analyze the molecular mechanism of SPA on osteogenic differentiation. We introduced transcript sequence data to screen out differentially expressed genes (DEGs) related to SPA-interfered BMSC. Protein-protein interaction (PPI) network of DEGs was established to screen biomarkers associated with SPA-interfered BMSC. Receiver operating characteristic (ROC) curve was plotted to evaluate the ability of biomarkers to discriminate between two groups of samples. Finally, we performed GSEA and regulatory analysis based on biomarkers. We identified 321 DEGs. Subsequently, 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap and Kif14) were identified by hubba algorithm in PPI. ROC analysis showed that six biomarkers could clearly discriminate between normal differentiated and SPA-interfered BMSC. Moreover, we found that these biomarkers were mainly enriched in the pyrimidine metabolism pathway. We also constructed '71 circRNAs-14 miRNAs-5 mRNAs' and '10 lncRNAs-5 miRNAs-2 mRNAs' networks. Kntc1 and Asf1b genes were associated with rno-miR-3571. Nek2 and Asf1b genes were associated with rno-miR-497-5p. Finally, we found significantly lower expression of six biomarkers in the SPA-interfered group compared to the normal group by RT-qPCR. Overall, we obtained 6 biomarkers (Cenpf, Kntc1, Nek2, Asf1b, Troap, and Kif14) related to SPA-interfered BMSC, which provided a theoretical basis to explore the key factors of SPA affecting osteogenic differentiation.


Assuntos
Diferenciação Celular , Células-Tronco Mesenquimais , Osteogênese , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Osteogênese/genética , Diferenciação Celular/genética , Humanos , Biomarcadores/metabolismo , Quinases Relacionadas a NIMA/metabolismo , Quinases Relacionadas a NIMA/genética , Mapas de Interação de Proteínas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Células da Medula Óssea/metabolismo , Células da Medula Óssea/citologia , Perfilação da Expressão Gênica , Redes Reguladoras de Genes
2.
Heliyon ; 10(12): e32596, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975185

RESUMO

Objective: This study aims to examine the trends in machine learning application to meningiomas between 2004 and 2023. Methods: Publication data were extracted from the Science Citation Index Expanded (SCI-E) within the Web of Science Core Collection (WOSCC). Using CiteSpace 6.2.R6, a comprehensive analysis of publications, authors, cited authors, countries, institutions, cited journals, references, and keywords was conducted on December 1, 2023. Results: The analysis included a total of 342 articles. Prior to 2007, no publications existed in this field, and the number remained modest until 2017. A significant increase occurred in publications from 2018 onwards. The majority of the top 10 authors hailed from Germany and China, with the USA also exerting substantial international influence, particularly in academic institutions. Journals from the IEEE series contributed significantly to the publications. "Deep learning," "brain tumor," and "classification" emerged as the primary keywords of focus among researchers. The developmental pattern in this field primarily involved a combination of interdisciplinary integration and the refinement of major disciplinary branches. Conclusion: Machine learning has demonstrated significant value in predicting early meningiomas and tailoring treatment plans. Key research focuses involve optimizing detection indicators and selecting superior machine learning algorithms. Future efforts should aim to develop high-performance algorithms to drive further innovation in this field.

4.
Chemistry ; : e202401739, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954398

RESUMO

Metal halide materials have recently drawn increasing research interest for their excellent opto-electronic properties and structural diversity, but their resulting rigid structures render them brittle and poor formability during manufacturing. Here we demonstrate a thermoplastic luminant hybrid lead halide solid by integrating lead bromide complex into tri-n-octylphosphine oxide (TOPO) matrix. The construction of the hybrid materials can be achieved by a simple dissolution process, in which TOPO molecules act as the solvents and ligands to yield the monodispersed clusters. The combination of these functional units enables the near-room-temperature melt-processing of the materials into targeted geometry by simple molding or printing techniques, which offer possibilities for fluorescent writing inks with outstanding self-healing capacity to physical damage. The intermarriage between metal halide clusters with functional molecules expands the range of practical applications for hybrid metal halide materials.

5.
J Cancer ; 15(13): 4097-4112, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947389

RESUMO

Ferroptosis has been characterized as non-apoptotic programmed cell death and is considered a novel strategy for antitumor treatment. The factor that binds to inducer of short transcripts-1 (FBI-1) is an important proto-oncogene playing multiple roles in human malignancies and the development of resistance to therapy. However, the roles of FBI-1 in ferroptosis of endocrine independent prostate carcinoma are still unknown. The results of this study showed that FBI-1 inhibited the ferroptosis of prostate carcinoma PC-3 cells (a typical endocrine-independent prostate carcinoma cell line) via the miR-324-3p/glutathione peroxidase 4 (miR-324-3p/GPX4) axis. Overexpression of FBI-1 enhanced the expression levels of GPX4. In contrast, knockdown of FBI-1 decreased the expression of GPX4 and induced the ferroptosis of PC-3 cells. The miR-324-3p decreased the expression of GPX4 by targeting the 3'-untranslated region of GPX4 to induce ferroptosis. Notably, FBI-1 increased the expression of GPX4 by repressing the levels of miR-324-3p. The transcription of miR-324-3p was mediated by specificity protein 1 (SP1), and FBI-1 repressed the expression of miR-324-3p by repressing the activation of SP1. In clinical specimens, the endogenous levels of FBI-1 were positively associated with Glutathione Peroxidase 4 (GPX4) and negatively related with the expression of miR-324-3p. Therefore, the results indicated that the miR-324-3p/GPX4 axis participates in the FBI-1-mediated ferroptosis of prostate carcinoma cells.

6.
Imeta ; 3(1): e160, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38868506

RESUMO

Pig gastrointestinal tracts harbor a heterogeneous and dynamic ecosystem populated with trillions of microbes, enhancing the ability of the host to harvest energy from dietary carbohydrates and contributing to host adipogenesis and fatness. However, the microbial community structure and related mechanisms responsible for the differences between the fatty phenotypes and the lean phenotypes of the pigs remained to be comprehensively elucidated. Herein, we first found significant differences in microbial composition and potential functional capacity among different gut locations in Jinhua pigs with distinct fatness phenotypes. Second, we identified that Jinhua pigs with lower fatness exhibited higher levels of short-chain fatty acids in the colon, highlighting their enhanced carbohydrate fermentation capacity. Third, we explored the differences in expressed carbohydrate-active enzyme (CAZyme) in pigs, indicating their involvement in modulating fat storage. Notably, Clostridium butyricum might be a representative bacterial species from Jinhua pigs with lower fatness, and a significantly higher percentage of its genome was dedicated to CAZyme glycoside hydrolase family 13 (GH13). Finally, a subsequent mouse intervention study substantiated the beneficial effects of C. butyricum isolated from experimental pigs, suggesting that it may possess characteristics that promote the utilization of carbohydrates and hinder fat accumulation. Remarkably, when Jinhua pigs were administered C. butyricum, similar alterations in the gut microbiome and host fatness traits were observed, further supporting the potential role of C. butyricum in modulating fatness. Taken together, our findings reveal previously overlooked links between C. butyricum and CAZyme function, providing insight into the basic mechanisms that connect gut microbiome functions to host fatness.

8.
Front Plant Sci ; 15: 1396273, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38882567

RESUMO

Fungal effectors play a crucial role in the interaction between pathogenic fungi and their hosts. These interactions directly influence the invasion and spread of pathogens, and the development of diseases. Common in fungal extracellular membrane (CFEM) effectors are closely associated with the pathogenicity, cell wall stability, and pathogenic processes of pathogenic fungi. The aim of this study was to investigate the role of CFEM proteins in Neostagonosporella sichuanensis in pathogen-host interactions. We retrieved 19 proteins containing CFEM structural domains from the genome of N. sichuanensis. By systematic analysis, five NsCFEM proteins had signal peptides but lacked transmembrane structural domains, and thus were considered as potential effectors. Among them, NsCFEM1 and NsCFEM2 were successfully cloned and their functions were further investigated. The validation results show that NsCFEM1 was localized in the cell membrane and nucleus, whereas NsCFEM2 was exclusively observed in the cell membrane. Both were identified as secreted proteins. Additionally, NsCFEM1 inhibited Bax-induced programmed cell death in Nicotiana benthamiana, whereas NsCFEM2 did not induce or inhibit this response. NsCFEM1 was implicated as a virulence factor that contributes to fungal growth, development, stress response, and pathogenicity. NsCFEM2 was implicated in maintenance of cell wall stability. This study lays a foundation for elucidating the role of CFEM proteins in the pathogen of fishscale bamboo rhombic-spot caused by N. sichuanensis. In particular, the functional studies of NsCFEM1 and NsCFEM2 revealed their potential roles in the interaction between N. sichuanensis and the host Phyllostachys heteroclada.

9.
Plants (Basel) ; 13(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38891344

RESUMO

In this study, our aim is to find an effective method to solve the problem of disease similarity caused by multiple diseases occurring on the same leaf. This study proposes the use of an optimized RegNet model to identify seven common apple leaf diseases. We conducted comparisons and analyses on the impact of various factors, such as training methods, data expansion methods, optimizer selection, image background, and other factors, on model performance. The findings suggest that utilizing offline expansion and transfer learning to fine-tune all layer parameters can enhance the model's classification performance, while complex image backgrounds significantly influence model performance. Additionally, the optimized RegNet network model demonstrates good generalization ability for both datasets, achieving testing accuracies of 93.85% and 99.23%, respectively. These results highlight the potential of the optimized RegNet network model to achieve high-precision identification of different diseases on the same apple leaf under complex field backgrounds. This will be of great significance for intelligent disease identification in apple orchards in the future.

10.
J Int Med Res ; 52(6): 3000605241253786, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38870271

RESUMO

OBJECTIVE: To evaluate the effectiveness of machine learning (ML) models in predicting 5-year type 2 diabetes mellitus (T2DM) risk within the Chinese population by retrospectively analyzing annual health checkup records. METHODS: We included 46,247 patients (32,372 and 13,875 in training and validation sets, respectively) from a national health checkup center database. Univariate and multivariate Cox analyses were performed to identify factors influencing T2DM risk. Extreme Gradient Boosting (XGBoost), support vector machine (SVM), logistic regression (LR), and random forest (RF) models were trained to predict 5-year T2DM risk. Model performances were analyzed using receiver operating characteristic (ROC) curves for discrimination and calibration plots for prediction accuracy. RESULTS: Key variables included fasting plasma glucose, age, and sedentary time. The LR model showed good accuracy with respective areas under the ROC (AUCs) of 0.914 and 0.913 in training and validation sets; the RF model exhibited favorable AUCs of 0.998 and 0.838. In calibration analysis, the LR model displayed good fit for low-risk patients; the RF model exhibited satisfactory fit for low- and high-risk patients. CONCLUSIONS: LR and RF models can effectively predict T2DM risk in the Chinese population. These models may help identify high-risk patients and guide interventions to prevent complications and disabilities.


Assuntos
Diabetes Mellitus Tipo 2 , Aprendizado de Máquina , Curva ROC , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Fatores de Risco , Glicemia/metabolismo , Modelos Logísticos , Máquina de Vetores de Suporte , Povo Asiático/estatística & dados numéricos , Idoso , População do Leste Asiático
11.
Medicine (Baltimore) ; 103(24): e38298, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38875421

RESUMO

INTRODUCTION: Most adrenal tumors are benign and primary adrenal malignancies are relatively rare. Primary adrenal lymphoma (PAL) is a very rare and highly aggressive malignant tumor with unknown etiology, atypical clinical symptoms, nonspecific imaging manifestations, difficult disease diagnosis and poor prognosis. CASE REPORT: This case report details a 42-year-old woman who was admitted to the hospital with a 1-year-old bilateral adrenal mass and 1-month-old left upper abdominal pain. Enhanced CT of the abdomen showed a right adrenal nodule and a large occupying lesion in the left adrenal region, with a high probability of pheochromocytoma. Intraoperatively, a huge tumor measuring about 12*12*10 cm was found in the left adrenal region, infiltrating the left kidney, spleen and pancreatic tail. Postoperative pathology: lymphocytes were found in the renal capsule and subcapsule, lymphocytes were found in the pancreas; lymphocytes were found in the spleen. Consider a tumor of the lymphohematopoietic system, possibly lymphoma. CONCLUSION: This case demonstrates that primary adrenal diffuse large B-cell lymphoma (PADLBCL) is highly aggressive, has a poor prognosis, is prone to recurrence, has poor therapeutic outcomes, and is difficult to diagnose. Clinicians should consider the possibility of PADLBCL when encountering huge adrenal-occupying lesions and consider chemotherapy before surgery. Reducing the tumor size before surgery is a more favorable therapeutic approach, thus prolonging the patient life and improving the quality of survival.


Assuntos
Neoplasias das Glândulas Suprarrenais , Linfoma Difuso de Grandes Células B , Humanos , Feminino , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Tomografia Computadorizada por Raios X , Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/diagnóstico por imagem , Glândulas Suprarrenais/cirurgia
12.
Chin Med ; 19(1): 86, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879549

RESUMO

BACKGROUND: Resident microglia- and peripheric macrophage-mediated neuroinflammation plays a predominant role in the occurrence and development of ischemic stroke. Microglia undergo polarization to M1/M2-like phenotype under stress stimulation, which mediates intracellular inflammatory response. ß-elemene is a natural sesquiterpene and possesses potent anti-inflammatory activity. This study aimed to investigate the anti-inflammatory efficacy and mechanism of ß-elemene in ischemic stroke from the perspective of balancing microglia M1/M2-like polarization. METHODS: The middle cerebral artery occlusion (MCAO) model and photothrombotic stroke model were established to explore the regulation effect of ß-elemene on the cerebral ischemic injury. The LPS and IFN-γ stimulated BV-2 cells were used to demonstrate the anti-inflammatory effects and potential mechanism of ß-elemene regulating M1/M2-like polarization in vitro. RESULTS: In C57BL/6 J mice subjected to MCAO model and photothrombotic stroke model, ß-elemene attenuated neurological deficit, reduced the infarction volume and neuroinflammation, thus improving ischemic stroke injury. ß-elemene promoted the phenotype transformation of microglia from M1-like to M2-like, which prevented neurons from oxygen and glucose deprivation/reoxygenation (OGD/R) injury by inhibiting inflammatory factor release, thereby reducing neuronal apoptosis. Mechanically, ß-elemene prevented the activation of TLR4/NF-κΒ and MAPK signaling pathway and increased AKT/mTOR mediated-autophagy, thereby promoting M2-like polarization of microglia. CONCLUSIONS: These results indicated that ß-elemene improved cerebral ischemic injury and promoted the transformation of microglia phenotype from M1-like to M2-like, at least in part, through AKT/mTOR-mediated autophagy. This study demonstrated that ß-elemene might serve as a promising drug for alleviating ischemic stroke injury.

13.
ACS Nano ; 18(26): 16658-16673, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38907726

RESUMO

Current therapies primarily targeting inflammation often fail to address the root relationship between intestinal mucosal integrity and the resulting dysregulated cell death and ensuing inflammation in ulcerative colitis (UC). First, UC tissues from human and mice models in this article both emphasize the crucial role of Gasdermin E (GSDME)-mediated pyroptosis in intestinal epithelial cells (IECs) as it contributes to colitis by releasing proinflammatory cytokines, thereby compromising the intestinal barrier. Then, 4-octyl-itaconate (4-OI), exhibiting potential for anti-inflammatory activity in inhibiting pyroptosis, was encapsulated by butyrate-modified liposome (4-OI/BLipo) to target delivery for IECs. In brief, 4-OI/BLipo exhibited preferential accumulation in inflamed colonic epithelium, attributed to over 95% of butyrate being produced and absorbed in the colon. As expected, epithelium barriers were restored significantly by alleviating GSDME-mediated pyroptosis in colitis. Accordingly, the permeability of IECs was restored, and the resulting inflammation, mucosal epithelium, and balance of gut flora were reprogrammed, which offers a hopeful approach to the effective management of UC.


Assuntos
Colite Ulcerativa , Células Epiteliais , Mucosa Intestinal , Piroptose , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Piroptose/efeitos dos fármacos , Animais , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Camundongos , Humanos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Células Epiteliais/metabolismo , Lipossomos/química , Camundongos Endogâmicos C57BL , Sistemas de Liberação de Medicamentos
14.
Dalton Trans ; 53(26): 10866-10874, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38873998

RESUMO

Vanadate electrodes are potential candidates for lithium-ion batteries (LIBs) due to their large theoretical specific capacity. However, their easy dissolution in the electrolyte, large structural changes, low conductivity and capacity decay during cycling hinder their further application. Herein, a lithium-ion battery electrode of Na5V12O32 (NVO) nanowires covered with a carbon film and formed by the reconstruction of carbon quantum dots (CDs) was obtained using an in situ capping strategy. Remarkably, the carbon film could prevent direct contact between the NVO nanowires and the electrolyte, thus slowing down the occurrence of side reactions and avoiding the dissolution of the NVO nanowires. Among the electrodes treated at different temperatures, the C@NVO-400 electrode exhibits high capacity and excellent cycling stability as the electrode of LIBs, with a discharge specific capacity of 779.1 and 315.5 mAh g-1 after 400 and 1000 cycles at a current density of 0.1 and 2 A g-1, respectively. An in situ coating strategy is proposed here to contribute to the further development of coated vanadate electrodes for high-performance LIBs.

15.
Materials (Basel) ; 17(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38893978

RESUMO

Manufactured sand (MS) is a promising alternative aggregate to quartz sand (QS) in ultra-high-performance concrete (UHPC) in the preparation of ultra-high-performance manufactured sand concrete (UHPMC), which possesses the characteristics of high strength, low cost, and environmental friendliness. In this study, the effects of variable compositional characteristics including the water-binder ratio, the stone powder (SP) content, and the MS replacement ratio on the mechanical and flexural strength of UHPMC were compared and analyzed based on response surface methodology (RSM). Meanwhile, the damage characteristics of UHPMC during compressive and flexural stress were monitored and evaluated using acoustic emission (AE) technology. The results reveal that the compressive and flexural strengths of UHPMC are both negatively correlated with the water-binder ratio, while they are positively correlated with the MS replacement rate. They tend to firstly increase and subsequently decrease with the increase in the stone powder content. In the load-displacement curve of concrete with a high MS replacement ratio and a low water-binder ratio, the slope in the elastic stage is steeper, the stiffness is higher, and the bending toughness and ductility are also better. The specimens with a 10% to 0% stone powder content present a steeper elastic phase slope, a slightly higher stiffness, and superior ductility. The specimens with a low MS replacement ratio and a high water-binder ratio display earlier cracking and weaker resistance, and the destruction process is complex and very unstable. The damage mode analysis based on RA-AF shows that an increase in the MS replacement ratio and a decrease in the water-binder ratio can both reduce the tensile cracking of UHPMC specimens under a four-point bending test. Although 10% stone powder can marginally slow down crack growth, the failure mode is not significantly affected.

16.
Org Lett ; 26(24): 5196-5201, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38858221

RESUMO

A novel strategy for incorporating a trifluoroacetyl functionality into a range of structurally varied unsaturated bonds was developed by using PhI(OCOMe)2 as an oxidant with a masked trifluoroacyl reagent as a trifluoroacetyl radical precursor. The oxidative decarboxylation of the masked trifluoroacyl precursor followed by a tandem radical process provides versatile access to 5-exo-trig cyclization of N-arylacrylamides, direct C(sp2)-H trifluoroacetylation of quinolines, isoquinoline, 2H-indazole, and quinoxalin-2(1H)-ones, and C(sp)-H trifluoroacetylation of alkynes. This protocol is characterized by mild reaction conditions, operational simplicity, and broad functional group compatibility.

17.
BMC Med Genomics ; 17(1): 162, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890701

RESUMO

BACKGROUND: The present study aims to identify the differential miRNA expression profile in middle ear cholesteatoma and explore their potential roles in its pathogenesis. METHODS: Cholesteatoma and matched normal retroauricular skin tissue samples were collected from patients diagnosed with acquired middle ear cholesteatoma. The miRNA expression profiling was performed using small RNA sequencing, which further validated by quantitative real-time PCR (qRT-PCR). Target genes of differentially expressed miRNAs in cholesteatoma were predicted. The interaction network of 5 most significantly differentially expressed miRNAs was visualized using Cytoscape. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses were processed to investigate the biological functions of miRNAs in cholesteatoma. RESULTS: The miRNA expression profile revealed 121 significantly differentially expressed miRNAs in cholesteatoma compared to normal skin tissues, with 56 upregulated and 65 downregulated. GO and KEGG pathway enrichment analyses suggested their significant roles in the pathogenesis of cholesteatoma. The interaction network of the the 2 most upregulated (hsa-miR-21-5p and hsa-miR-142-5p) and 3 most downregulated (hsa-miR-508-3p, hsa-miR-509-3p and hsa-miR-211-5p) miRNAs identified TGFBR2, MBNL1, and NFAT5 as potential key target genes in middle ear cholesteatoma. CONCLUSIONS: This study provides a comprehensive miRNA expression profile in middle ear cholesteatoma, which may aid in identifying therapeutic targets for its management.


Assuntos
Colesteatoma da Orelha Média , Perfilação da Expressão Gênica , MicroRNAs , Humanos , MicroRNAs/genética , Colesteatoma da Orelha Média/genética , Colesteatoma da Orelha Média/patologia , Redes Reguladoras de Genes , Análise de Sequência de RNA , Masculino , Feminino , Ontologia Genética , Adulto , Pessoa de Meia-Idade , Transcriptoma , Receptor do Fator de Crescimento Transformador beta Tipo II/genética
18.
Eur J Med Chem ; 275: 116611, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901104

RESUMO

The identification of chemically different inhibitors that target the colchicine site of tubulin is still of great value for cancer treatment. Combretastatin A-4(CA-4), a naturally occurring colchicine-site binder characterized by its structural simplicity and biological activity, has served as a structural blueprint for the development of novel analogues with improved safety and therapeutic efficacy. In this study, a library of forty-eight 4-phenyl-5-quinolinyl substituted triazole, pyrazole or isoxazole analouges of CA-4, were synthesized and evaluated for their cytotoxicity against Esophageal Squamous Cell Carcinoma (ESCC) cell lines. Compound C11, which features a 2-methyl substitution at the quinoline and carries an isoxazole ring, emerged as the most promising, with 48 h IC50s of less than 20 nmol/L against two ESCC cell lines. The findings from EBI competitive assay, CETA, and in vitro tubulin polymerization assay of C11 are consistent with those of the positive control colchicine, demonstrating the clear affinity of compound C11 to the colchicine binding site. The subsequent cellular-based mechanism studies revealed that C11 significantly inhibited ESCC cell proliferation, arrested cell cycle at the M phase, induced apoptosis, and impeded migration. Experiments conducted in vivo further confirmed that C11 effectively suppressed the growth of ESCC without showing any toxicity towards the selected animal species. Overall, our research suggests that the tubulin polymerization inhibitor incorporating quinoline and the isoxazole ring may deserve consideration for cancer therapy.

19.
Phys Med Biol ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38925140

RESUMO

Objective.225Ac radiopharmaceuticals have tremendous potential for targeted alpha therapy (TAT), however,225Ac (t1/2= 9.9 d) lacks direct gamma emissions forin vivoimaging.226Ac (t1/2= 29.4 h) is a promising element-equivalent matched diagnostic radionuclide for preclinical evaluation of225Ac radiopharmaceuticals.226Ac has two gamma emissions (158 keV and 230 keV) suitable for SPECT imaging. This work is the first feasibility study forin vivoquantitative226Ac SPECT imaging and validation of activity estimation.Approach.226Ac was produced at TRIUMF (Vancouver, Canada) with its Isotope Separator and Accelerator (ISAC) facility. [226Ac]Ac3+was radiolabelled with the bioconjugate crown-TATE developed for therapeutic targeting of neuroendocrine tumours (NET). Mice with AR42J tumour xenografts were injected with either 2 MBq of [226Ac]Ac-crown-TATE or 4 MBq of free [226Ac]Ac3+activity and were scanned at 1, 2.5, 5, and 24 h post injection in a preclinical microSPECT/CT. Quantitative SPECT images were reconstructed from the 158 keV and 230 keV photopeaks with attenuation, background, and scatter corrections. Image-based226Ac activity measurements were assessed from volumes of interest (VOIs) within tumours and organs of interest. Imaging data was compared withex vivobiodistribution measured via gamma counter.Main Results. We present, to the best of our knowledge, the first everin vivoquantitative SPECT images of226Ac activity distributions. Time-activity curves derived from SPECT images quantify thein vivobiodistribution of [226Ac]Ac-crown-TATE and free [226Ac]Ac3+activity. Image-based activity measurements in the tumours and organs of interest corresponded well withex vivobiodistribution measurements.Significance. Here in, we established the feasibility ofin vivo226Ac quantitative SPECT imaging for accurate measurement of actinium biodistribution in a preclinical model. This imaging method could quantitativein vivopharmacokinetic information essential for estimating toxicities, dosimetry, and therapeutic potency.

20.
Biomimetics (Basel) ; 9(6)2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38921216

RESUMO

The vibrissae of harbor seals exhibit a distinct three-dimensional structure compared to circular cylinders, resulting in a wave-shaped configuration that effectively reduces drag and suppresses vortex shedding in the wake. However, this unique cylinder design has not yet been applied to wind power technologies. Therefore, this study applies this concept to the design of downwind wind turbines and employs wind tunnel testing to compare the wake flow characteristics of a single-cylinder model while also investigating the output power and wake performance of the model wind turbine. Herein, we demonstrate that in the single-cylinder test, the bionic case shows reduced turbulence intensity in its wake compared to that observed with the circular cylinder case. The difference in the energy distribution in the frequency domain behind the cylinder was mainly manifested in the near-wake region. Moreover, our findings indicate that differences in power coefficient are predominantly noticeable with high tip speed ratios. Furthermore, as output power increases, this bionic cylindrical structure induces greater velocity deficit and higher turbulence intensity behind the rotor. These results provide valuable insights for optimizing aerodynamic designs of wind turbines towards achieving enhanced efficiency for converting wind energy.

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