Analysis Of Interactions Research Articles

TNNT1 accelerates migration, invasion and EMT progression in lung cancer cells.

Clinically, most patients with lung cancer (LC) die from tumor spread and metastasis. Specific metastasis-related molecules can provide reference for clinical prediction of efficacy, evaluation of prognosis, and search for the best treatment plan. Troponin T1 (TNNT1) is highly expressed in various cancer tissues, which affects malignant behavior of tumor cells and is related to patients' survival and prognosis. However, the role and molecular mechanism of TNNT1 in LC invasion and metastasis have not yet been investigated. Gene expression profiling interactive analysis (GEPIA) online analysis was used to analyze TNNT1 expression in LC tissues. Quantitative real-time-polymerase chain reaction (qRT-PCR) or western blot were performed to measure TNNT1 or epithelial-to-mesenchymal transition (EMT)-related and Wnt/β-catenin pathway-related protein expression in LC cells. After TNNT1 knockdown, cell scratch healing and transwell assays were introduced to assess cell migration and invasion, respectively. TNNT1 expression in LC tissues and cells was increased. TNNT1 knockdown notably impaired LC cell migration, invasion and EMT. TNNT1 knockdown inhibited Wnt/β-catenin pathway of LC cells. Lithium chloride (LiCl) addition partially restored the inhibition of TNNT1 knockdown on migration, invasion, EMT and Wnt/β-catenin of LC cells. TNNT1 knockdown attenuated LC migration, invasion and EMT, possibly through Wnt/β-catenin signaling.

The Intertwining of Children’s Interests and Micro-Practices at a Science Museum: Case Study of Three Children

Children’s multiple interests intersect with their participation in informal learning practices in dynamic ways. Using a theoretical framework illustrating interest as a multifaceted construct that has different forms and a range of scope and durability, this study investigates how children’s situational interests and individual interests are developed and reinforced and how they support micro-practices (i.e., any small practices, actions, activities, interactions that occur moment-by-moment) and vice versa. From a larger data set collected from one-time family science learning sessions at a museum, three children (aged 6–10) were strategically sampled to foreground an enhanced understanding of how interest and participation in practice mutually constitute each other. Using video-based interaction analysis, our case study of three children illustrates different patterns where micro-practices intersect with different types of interests at the museum. Even in the same environment with the same exhibits, each child from this case study constructed a unique pathway of forming the collection of micro-practices that was constantly interacting with situational interests and individual interests in specific disciplines, topics, exhibits, or any other various targets. For example, when having a strongly existing individual interest in a specific science discipline, one child’s micro-practices were mainly driven by making choices of exhibits that are related to his science interest, while another child did not actively choose exhibits but found her own creative ways to connect her science interest and other new interests. Our study contributes to a more robust conception of interest that highlights the intertwining of multiple, malleable, and moment-by-moment interests and micro-practices in the museum.

Relationship between dietary fiber intake and chronic diarrhea in adults.

Dietary fiber is essential for human health and can help reduce the symptoms of constipation. However, the relationship between dietary fiber and diarrhea is, poorly understood. To evaluate the relationship between dietary fiber and chronic diarrhea. This retrospective study was conducted using data from the United States National Health and Nutrition Examination Survey, conducted between 2005 and 2010. Participants over the age of 20 were included. To measure dietary fiber consumption, two 24-hour meal recall interviews were conducted. The independent relationship between the total amount of dietary fiber and chronic diarrhea was evaluated with multiple logistic regression and interaction analysis. Data from 12829 participants were analyzed. Participants without chronic diarrhea consumed more dietary fiber than participants with chronic diarrhea (29.7 vs 28.5, P = 0.004). Additionally, in participants with chronic diarrhea, a correlation between sex and dietary fiber intake was present: Women who consume more than 25 g of dietary fiber daily can reduce the occurrence of chronic diarrhea. Dietary fiber can reduce the occurrence of chronic diarrhea.

A dynamic analysis of capital, corruption, and labor market interactions

The complex relationship between corruption, economic growth, and labor dynamics has long been a challenge for policymakers. This study sheds new light on these dynamic interactions by constructing a novel economic model with saturation effects that integrate employment considerations. Unlike static or purely empirical models, our approach captures the system’s evolution over time, employing a logistic growth function to realistically reflect economic limitations and distinguishing between employed and unemployed labor segments. By incorporating a Holling type II function, the model captures the nonlinear influence of corruption on economic growth, acknowledging diminishing returns at higher corruption levels. Through advanced theoretical analysis, we establish the existence and stability conditions for three distinct long-term equilibria: stagnation, corruption-free growth with full employment, and a coexistent state where corruption persists alongside some economic activity. Our analysis goes beyond merely identifying these equilibria by revealing the specific conditions under which each state prevails, and we solidify these theoretical predictions with comprehensive numerical simulations depicting the system’s behavior under varying conditions. The findings underscore the importance of robust anti-corruption measures and a labor-intensive economic approach, highlighting that fostering growth outpacing resource depletion is crucial for escaping stagnation and achieving sustainable development. Overall, this research advances the field by integrating employment dynamics, a Holling type II function for corruption, and a focus on stability analysis, providing invaluable insights for policymakers aiming to promote sustainable economic development, combat corruption, and ensure healthy employment conditions.

Impact of Zeeman and hyperfine interactions on the magnetic properties of paramagnetic metal Ions: III. Analysis of the local interactions in a single crystal of 173Yb3+ doped Y5SiO5

The electron spin echo envelope modulation (ESEEM) technique is a direct method to probe the nuclear spin coherences induced by electron spin transitions. Recently, this approach was used to study an isotopically pure Y2SiO5 crystal doped with 173Yb3+ ions, and the presence of the Fermi contact interaction was proposed to explain the frequency comb detected in the two-pulse ESEEM experiment [Solovarov N. K. et al. JETP Letters 115 (6): 362–67]. Here we simulate the Fourier images of the ESEEM data. The numerical analysis shows that the modulation is mainly due to the nuclear spin coherences induced by the dipole–dipole interactions. However, the correlation between the experimental and simulated data is better when the super-hyperfine interactions of the nearby yttrium nuclei have an additional isotropic contribution. The analysis of the rescaled X-band ESEEM spectra shows that for the EPR transitions at magnetic fields > 100 mT, the main contribution to the modulation comes from the oscillations of the individual nuclei and the effect of interference between coherences originating from several nuclei is not strong. Further experiments to distinguish the sources of the echo modulation are discussed.

Numerical Method of Lateral Pipe-Soil Interaction and Sensitivity Analysis Investigation

The pipe-soil interaction force is a crucial load that ensures the on-bottom stability of submarine pipelines and acts as a vital input parameter for the design of controlled pipeline buckling. It is necessary to precise prediction of soil lateral resistance and sensitivity to environmental parameters. This study developed a numerical simulation technique based on the coupled Euler-Lagrange (CEL) method to systematically analyse the deformation of the pipeline and the soil-pipeline forces on the seabed foundation during service. To validate the numerical method for large lateral displacement of pipe-soil interaction, an experimental approach employing parameter variation was utilized to conduct sensitivity analysis on the environmental parameters. The key parameters affecting soil-pipeline interaction were determined through an analysis of relative variation factors. The research findings demonstrate a satisfactory agreement, with an amplitude difference range of within 15%, between the numerical simulation technique using the CEL method and the experimental results. This method resolves the issue of non-convergence due to grid distortion under conditions of large displacement, thereby enhancing computational accuracy. Sensitivity analysis shows that the relative variation factors for soil friction angle, initial burial depth, and soil density exceed 50%, which is notably higher than the elastic modulus, friction coefficient, and Poisson's ratio of the soil. The results of this study enable the prediction of lateral forces in pipe-soil interaction and identification of environmentally sensitive parameters. This study establishes a foundation for calculating pipeline buckling strength in complex environments and holds paramount importance for the design and construction of pipelines to ensure on-bottom stability.

Application of AMMI and GGE biplot for genotype by environment interaction and yield stability analysis in potato genotypes grown in Dawuro zone, Ethiopia

The performance of most crop genotypes is greatly influenced by the interactions between genotype and environment. Providing information on well-adapted and high-yielding potato genotypes in a given environment is paramount for small-holder farmers to enhance their productivity. The study aimed to understand GEI effect on tuber yield, and identify and select widely or specifically adapted high-yielding potato genotypes for production. Eleven genotypes were evaluated using a randomized complete block design with three replications. The results of the AMMI analysis of variance showed that tuber yield significantly (p ≤ 0.05) influenced genotype-environment interaction. This reveals that genotypes exhibit varying mean performance in tuber yield across different environments. The sum squared results showed that genotype (62.40 %) and environment (26.73 %) were the main contributors to tuber yield variation, while the genotype-environment interaction effect (10.87 %) contributed least to then tuber yield total variation. The AMMI, GGE biplot, and GSI analysis revealed Gudanie and Gorebella as superior genotypes in tuber yield, demonstrating high mean performance across tested environments. Thus, Gudanie and Gorebella have been chosen as the most broadly adaptable genotypes for production in all potato-growing agroecologies in the Dawuro zone. The GGE and AMMI biplot provided the genotype-by-environment interaction association among environments and genotypes.

Art After Syariat: Sebuah Konsep Seni Rupa dalam Perspektif Syariat Agama Islam

The aim of this research is to describe the boundaries of fine art according to Islamic religious law which gives birth to artistic concepts according to Islamic religious guidelines. The methodology used is a descriptive qualitative method with a literature study approach with data sources in the form of books, research journals, the Koran, hadith books and ulama fatwas. The data analysis technique uses interactive model analysis. The results of the study from several literary sources are a new concept in fine arts that is in accordance with the review of Islamic religious law, namely art after sharia, thus triggering the creativity of artists in creating fine arts in accordance with Islamic law.

Identification and validation of potential common biomarkers for papillary thyroid carcinoma and Hashimoto’s thyroiditis through bioinformatics analysis and machine learning

There is a growing body of evidence suggesting that Hashimoto’s thyroiditis (HT) may contribute to an increased risk of papillary thyroid carcinoma (PTC). However, the exact relationship between HT and PTC is still not fully understood. The objective of this study was to identify potential common biomarkers that may be associated with both PTC and HT. Three microarray datasets from the GEO database and RNA-seq dataset from TCGA database were collected to identify shared differentially expressed genes (DEGs) between HT and PTC. A total of 101 genes was identified as common DEGs, primarily enriched inflammation- and immune-related pathways through GO and KEGG analysis. We performed protein–protein interaction analysis and identified six significant modules comprising a total of 29 genes. Subsequently, tree hub genes (CD53, FCER1G, TYROBP) were selected using random forest (RF) algorithms for the development of three diagnostic models. The artificial neural network (ANN) model demonstrates superior performance. Notably, CD53 exerted the greatest influence on the ANN model output. We analyzed the protein expressions of the three genes using the Human Protein Atlas database. Moreover, we observed various dysregulated immune cells that were significantly associated with the hub genes through immune infiltration analysis. Immunofluorescence staining confirmed the differential expression of CD53, FCER1G, and TYROBP, as well as the results of immune infiltration analysis. Lastly, we hypothesise that benzylpenicilloyl polylysine and aspirinmay be effective in the treatment of HT and PTC and may prevent HT carcinogenesis. This study indicates that CD53, FCER1G, and TYROBP play a role in the development of HT and PTC, and may contribute to the progression of HT to PTC. These hub genes could potentially serve as diagnostic markers and therapeutic targets for PTC and HT.

Elevated expression of ECT2 as a diagnostic marker and prognostic indicator in endometrial cancer

ObjectivesThe study aims to investigate genes associated with endometrial cancer (EC) progression to identify new biomarkers for early detection. MethodsDifferentially expressed genes (DEGs), Series test of cluster (STC) and protein–protein interaction analyses identified hub genes in EC. Clinical samples were utilized to examine the expression pattern of ECT2, assess its prognostic value, and evaluate its diagnostic potential. ResultsUpregulated DEGs were significantly enriched in cancer-related processes and pathways. Validations across databases identified ASPM, ATAD2, BUB1B, ECT2, KIF14, NUF2, NCAPG, and SPAG5 as potential hub genes, with ECT2 exhibiting the highest diagnostic efficacy. The expression levels of ECT2 varied significantly across different clinical stages, pathological grades, and metastasis statuses in UCEC. Furthermore, ECT2 mRNA was upregulated in the p53abn group, indicating a poorer prognosis, and downregulated in the MMRd and NSMP groups, suggesting a moderate prognosis. In clinical samples, ECT2 expression increased from normal endometria and endometrial hyperplasia without atypia (EH) to atypical endometrial hyperplasia (AH) and EC, effectively distinguishing between benign and malignant endometria. High ECT2 expression was associated with an unfavourable prognosis. ConclusionsECT2 expression significantly rises in AH and EC, showing high accuracy in distinguishing between benign and malignant endometria. ECT2 emerges as a promising biomarker for diagnosing endometrial neoplasia and as a prognostic indicator in EC.

Fine mapping of candidate effector genes for heart rate.

An elevated resting heart rate (RHR) is associated with increased cardiovascular mortality. Genome-wide association studies (GWAS) have identified > 350 loci. Uniquely, in this study we applied genetic fine-mapping leveraging tissue specific chromatin segmentation and colocalization analyses to identify causal variants and candidate effector genes for RHR. We used RHR GWAS summary statistics from 388,237 individuals of European ancestry from UK Biobank and performed fine mapping using publicly available genomic annotation datasets. High-confidence causal variants (accounting for > 75% posterior probability) were identified, and we collated candidate effector genes using a multi-omics approach that combined evidence from colocalisation with molecular quantitative trait loci (QTLs), and long-range chromatin interaction analyses. Finally, we performed druggability analyses to investigate drug repurposing opportunities. The fine mapping pipeline indicated 442 distinct RHR signals. For 90 signals, a single variant was identified as a high-confidence causal variant, of which 22 were annotated as missense. In trait-relevant tissues, 39 signals colocalised with cis-expression QTLs (eQTLs), 3 with cis-protein QTLs (pQTLs), and 75 had promoter interactions via Hi-C. In total, 262 candidate genes were highlighted (79% had promoter interactions, 15% had a colocalised eQTL, 8% had a missense variant and 1% had a colocalised pQTL), and, for the first time, enrichment in nervous system pathways. Druggability analyses highlighted ACHE, CALCRL, MYT1 and TDP1 as potential targets. Our genetic fine-mapping pipeline prioritised 262 candidate genes for RHR that warrant further investigation in functional studies, and we provide potential therapeutic targets to reduce RHR and cardiovascular mortality.

Investigation of the inhibitory potential of caffeic acid phenethyl ester on prion replication, amplification, and fibril formation in vitro

Objective: To investigate the effects and possible mechanisms of caffeic acid phenethyl ester (CAPE) on the replication, amplification, and fibre formation of prions (PrPSc). Methods: The CCK8 assay was used to detect the cell viability of the prion-infected cell model SMB-S15 after CAPE treatment for 3 days and 7 days and the maximum safe concentration of CAPE for SMB-S15 was obtained. The cells were treated with a concentration within a safe range, and the content of PrPSc in the cells before and after CAPE treatment was analyzed by western blot. Protein misfolding cycle amplification (PMCA) and western blot were used to assess changes in PrPSc level in amplification products following CAPE treatment. Real-time-quaking induced conversion assay (RT-QuIC) technology was employed to explore the changes in fibril formation before and after CAPE treatment. The binding affinity between CAPE and murine recombinant full-length prion protein was determined using a molecular interaction assay. Results: CCK8 cell viability assay results demonstrated that treatment with 1 μmol/L CAPE for 3 and 7 days did not exhibit statistically significant differences in cell viability compared to the control group (all P<0.05). However, when the concentration of CAPE exceeded 1 μmol/L, a significant reduction in cell viability was observed in cells treated with CAPE for 3 and 7 days, compared to the control group (all P<0.05). Thus, 1 μmol/L was determined as the maximum safe concentration of CAPE treatment for SMB-S15 cells. The western blot results revealed that treatment with CAPE for both 3 and 7 days led to a detectable reduction in the levels of PrPSc in SMB-S15 cells (all P<0.05). The products of PMCA experiments were assessed using western blot. The findings revealed a significant decrease in the levels of PrPSc (relative grey value) in the PMCA amplification products of adapted-strains SMB-S15, 139A, and ME7 following treatment with CAPE, as compared to the control group (all P<0.05). The RT-QuIC experimental results demonstrated a reduction in fibril formation (as indicated by ThT peak values) in CAPE-treated mouse-adapted strains 139A, ME7, and SMB-S15, as well as in SMB-S15 cells infected with prions. Furthermore, CAPE exhibited varying degrees of inhibition towards different seed fibrils formation, with statistically significant differences observed (all P<0.05). Notably, CAPE exhibited a more pronounced inhibitory effect on ME7 seed fibrils. Molecular interaction analyses demonstrated significant binding between CAPE and murine recombinant prion protein, and the association constant was (2.92±0.41)×10-6 mol/L. Conclusions: CAPE inhibits PrPSc replication, amplification, and fibril formation in vitro possibly due to specific interactions with the prion protein at the molecular level.

The independent and interactive effects of changes in overtime and night shifts during the COVID-19 pandemic on burnout among nurses: a longitudinal study.

This study aimed to evaluate the independent and interactive effects of changes in overtime and night shifts on burnout among nurses during the COVID-19 pandemic. Nurses working in an Italian university hospital (N=317) completed the Maslach Burnout Inventory in September 2019 and again in December 2020. Based on hospital administrative data, changes in overtime and night shifts in the same years were categorized into three groups each. Linear regressions were used to estimate 2020 burnout differences between exposure groups, controlling for 2019 burnout levels, demographic and work-related characteristics, and to test the interaction between the two exposures. Nurses in the onset of high overtime group had higher emotional exhaustion [4.33, 95% confidence interval (CI) 1.74-6.92], depersonalization (2.10, 95% CI 0.49-3.71), and poor personal accomplishment (2.64, 95% CI 0.55-4.74) compared to stable low overtime nurses. Nurses in the increase in night shifts group had lower emotional exhaustion (-4.49, 95% CI -7.46- -1.52) compared to no night shift nurses. Interaction analyses revealed that this apparently paradoxical effect was limited to stable low overtime nurses only. Moreover, increases in night shifts were associated with higher depersonalization and poor personal accomplishment in nurses in the stable high overtime group. Increase in overtime is an independent risk factor for burnout among nurses, highlighting the need for specific regulations and actions to address it. Long-standing guidelines for the assignment of night shifts might have contributed to attenuate the impact of their increase on nurses' mental health.

Pro-apoptotic gene BAX is a pan-cancer predictive biomarker for prognosis and immunotherapy efficacy.

Apoptosis Regulator BCL2 Associated X (BAX) is a pro-apoptotic gene. Apoptosis is one of the important components of immune response and immune regulation. However, there is no systematic pan-cancer analysis of BAX. Original data of this study were downloaded from TCGA databases and GTEX databases. We conducted the gene expression analysis and survival analysis of BAX in 33 types of cancer via Gene Expression Profiling Interactive Analysis (GEPIA) database. Real-time PCR and immunohistochemistry (IHC) were further performed to examine the BAX expression in cancer cells and tissues. Moreover, the relationship between BAX and immune infiltration and gene alteration was studied by the Tumor Immune Estimation Resource (TIMER) and cBioPortal tools. Protein-protein interaction analysis was performed in the STRING database. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were utilized to evaluate the enrichment analysis. BAX was highly expressed in most cancers and was associated with poor prognosis in nine cancer types. In addition, BAX showed significant clinical relevance, and the mRNA expression of BAX was also strongly associated with drug sensitivity of many drugs. Furthermore, BAX may participate in proliferation and metastasis of many cancers and was associated with methylation. Importantly, BAX expression was positively correlated with most immune infiltrating cells. Our findings suggested that BAX can function as an oncogene and may be used as a potential predictive biomarker for prognosis and immunotherapy efficacy of human cancer, which could provide a new approach for cancer therapy.

Proteomic profiling of laser capture microdissection kidneys from diabetic nephropathy patients

Diabetic nephropathy (DN) remains the primary cause of end-stage renal disease (ESRD), warranting equal attention and separate analysis of glomerular, tubular, and interstitial lesions in its diagnosis and intervention. This study aims to identify the specific proteomics characteristics of DN, and assess changes in the biological processes associated with DN. 5 patients with DN and 5 healthy kidney transplant donor control individuals were selected for analysis. The proteomic characteristics of glomeruli, renal tubules, and renal interstitial tissue obtained through laser capture microscopy (LCM) were studied using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Significantly, the expression of multiple heat shock proteins (HSPs), tubulins, and heterogeneous nuclear ribonucleoproteins (hnRNPs) in glomeruli and tubules was significantly reduced. Differentially expressed proteins (DEPs) in the glomerulus showed significant enrichment in pathways related to cell junctions and cell movement, including the regulation of actin cytoskeleton and tight junction. DEPs in renal tubules were significantly enriched in glucose metabolism-related pathways, such as glucose metabolism, glycolysis/gluconeogenesis, and the citric acid cycle. Moreover, the glycolysis/gluconeogenesis pathway was a co-enrichment pathway in both DN glomeruli and tubules. Notably, ACTB emerged as the most crucial protein in the protein–protein interaction (PPI) analysis of DEPs in both glomeruli and renal tubules. In this study, we delve into the unique proteomic characteristics of each sub-region of renal tissue. This enhances our understanding of the potential pathophysiological changes in DN, particularly the potential involvement of glycolysis metabolic disorder, glomerular cytoskeleton and cell junctions. These insights are crucial for further research into the identification of disease biomarkers and the pathogenesis of DN.

Important Factors in the Development of Young Entrepreneurial Groups in Forest Honeybee Cultivation and Products

The younger generation emerges as a pivotal subject in perpetuating sustainable development, with an expectation to also play a role in rural areas to optimize the potential of local resources, thereby mitigating the negative impacts of urbanization and reducing labor migration. Thus, the research aims to analyze the crucial factors supporting the role of youth in the development of socio-economic institutions in rural areas. The study employs the Participatory Learning and Action method to construct community learning experiences through interviews, Focus Group Discussions, documentation analysis, and observation. The research informants consist of the Young Farmer Group "Prawita Garden", which has successfully cultivated forest honeybees and developed rural tourism destinations. Interactive research analysis is utilized for data reduction, verification, and triangulation, complemented by modeling using the Vensin application. The research findings indicate that the "Prawita Garden" young farmer group has emerged as a pioneer and inspirator in honeybee cultivation and production, particularly of unique honey types such as Klanceng Honeybee, imported European Honeybee, and local Honeybee. Crucial factors in the development of young farmer institutionalization include entrepreneurial motivation and group formation, local indigenous practices passed down through generations or integrated into traditions intertwined with the social capital prevalent in rural communities.

Neural progenitor-derived Apelin controls tip cell behavior and vascular patterning.

During angiogenesis, vascular tip cells guide nascent vascular sprouts to form a vascular network. Apelin, an agonist of the G protein-coupled receptor Aplnr, is enriched in vascular tip cells, and it is hypothesized that vascular-derived Apelin regulates sprouting angiogenesis. We identify an apelin-expressing neural progenitor cell population in the dorsal neural tube. Vascular tip cells exhibit directed elongation and migration toward and along the apelin-expressing neural progenitor cells. Notably, restoration of neural but not vascular apelin expression in apelin mutants remedies the angiogenic defects of mutants. By functional analyses, we show the requirement of Apelin signaling for tip cell behaviors, like filopodia formation and cell elongation. Through genetic interaction studies and analysis of transgenic activity reporters, we identify Apelin signaling as a modulator of phosphoinositide 3-kinase and extracellular signal-regulated kinase signaling in tip cells in vivo. Our results suggest a previously unidentified neurovascular cross-talk mediated by Apelin signaling that is important for tip cell function during sprouting angiogenesis.

Investigation of coagulation and proteomics profiles in symptomatic feline hypertrophic cardiomyopathy and healthy control cats

BackgroundHypertrophic cardiomyopathy (HCM) is a crucial heart disease in cats. The clinical manifestations of HCM comprise pulmonary edema, dyspnea, syncope, arterial thromboembolism (ATE), and sudden cardiac death. D-dimer and prothrombin time (PT) are powerful biomarkers used to assess coagulation function. Dysregulation in these two biomarkers may be associated with HCM in cats. This study aims to assess D-dimer levels, PT, and proteomic profiling in healthy cats in comparison to cats with symptomatic HCM.ResultsTwenty-nine client-owned cats with HCM were enrolled, including 15 healthy control and 14 symptomatic HCM cats. The D-dimer concentration and PT were examined. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In symptomatic cats, D-dimer levels were statistically significantly higher (mean ± SEM: 372.19 ng/ml ± 58.28) than in healthy cats (mean ± SEM: 208.54 ng/ml ± 10.92) with P-value of less than 0.01, while PT was statistically significantly lower in symptomatic cats (mean ± SEM: 9.8 s ± 0.15) compared to healthy cats (mean ± SEM: 11.08 s ± 0.23) with P-value of less than 0.0001. The proteomics analysis revealed upregulation of integrin subunit alpha M (ITGAM), elongin B (ELOB), and fibrillin 2 (FBN2) and downregulation of zinc finger protein 316 (ZNF316) and ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in symptomatic HCM cats. In addition, protein-drug interaction analysis identified the Ras signaling pathway and PI3K-Akt signaling pathway.ConclusionsCats with symptomatic HCM have higher D-dimer and lower PT than healthy cats. Proteomic profiles may be used as potential biomarkers for the detection and management of HCM in cats. The use of D-dimer as a biomarker for HCM detection and the use of proteomic profiling for a better understanding of disease mechanisms remain to be further studied in cats.

The prognostic value and its relationship with immune infiltration of ACLY in clear cell renal cell carcinoma

ATP citrate lyase (ACLY) is activated in various cancers, but its role in clear cell renal cell carcinoma (ccRCC) remains poorly understood. Herein, we investigated the prognostic role and potential mechanism of ACLY in ccRCC. The expression profile of ACLY in ccRCC was explored using Gene Expression Profiling Interactive Analysis 2 (GEPIA2), Gene Expression Omnibus (GEO), UALCAN and western blotting assays. The prognosis was investigated using immunohistochemistry (IHC) and Kaplan–Meier plotter assays. The relationship with immune infiltration was further evaluated using Tumor Immune Estimation Resource 2 (TIMER2) and Tumor Immune System Interactions and DrugBank (TISIDB) databases, respectively. Further biological function of ACLY in ccRCC pathogenesis was explored using in vitro experiments. ACLY level was higher in ccRCC than adjacent kidney tissues, and Kaplan–Meier survival analysis showed ACLY mRNA or protein were predictors of poor prognosis in ccRCC patients. Importantly, we reported for the first time that ACLY gene expression was significantly correlated with numerous immune cells and immune inhibitors in ccRCC. ACLY inhibition significantly impaired cell proliferation, induced cell apoptosis, attenuated cell migration, decreased lipid droplets formation, and suppressed epithelial-mesenchymal transition (EMT) of ccRCC. Moreover, these effects might be acted through mammalian target of rapamycin complex 1 (mTORC1) pathway. Collectively, ACLY was not only implicated in ccRCC tumorigenesis and progression, but also potentially interacted with immune infiltration and mTORC1 pathway. Our findings may provide a novel therapeutic strategy by targeting ACLY for ccRCC treatment.

Children’s agency as a relational concept in bilingual family language practices

ABSTRACT This paper reports the study of the agency of children aged 10–14 in their language practices as they interacted with their family members. The study was located in a Vietnamese migrant community in Victoria, Australia. In using a thematic, interactional analysis combined with a relational approach to agency, it was found that children’s agency emerged on a continuum which ranged from a more negative end of the continuum – manifested through the children’s explicit resistance to parental requests for home language use – to a more positive end of the continuum – manifested through their flexible linguistic repertoire in accommodating their interlocutors’ needs. Findings also suggest that the linguistic practices in the family domain surfaced as dynamic co-constructions to reflect the adults’ and children’s constant (re)negotiation in their everyday language practices in the home, which was also influenced by other factors such as children’s linguistic competence and the families’ linguistic norms. The study builds on previous findings on the relational nature of children’s agency by bringing attention to the different manifestations of children’s agency that arise in situ as they interact.