Both simulation and experimental results confirmed the significance of chemical diffusion in the nucleation of calcium carbonate, which was ascribed to the enhancement of unit collision driven by ...diffusion.
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Nucleation widely exists in nature, from cloud formation to haze generation. The classical nucleation theory (CNT) was created to describe the nucleation process, but it fails to predict many experimental phenomena due to the short consideration of nanoscale phenomena and macroscale dynamics. Although the attachment and detachment of monomers are considered in the developed model of nucleation, the diffusion of chemicals in the bulk is not valued as supersaturation in the nucleation process so far. Here we employ simulation and experimental approaches to investigate how the diffusion of ions affects the nucleation of calcium carbonate. The diffusion of ions is regulated by the viscosity of solvents and the sonication imposed on the solution. It is found that the nucleation rates increased exponentially with the diffusion coefficient of ions, which is beyond the prediction of CNT. This abnormal finding might be ascribed to the involvement of cluster aggregation in the nucleation of calcium carbonate. This study highlights the significance of chemical diffusion in the nucleation process, which may help to revise the nucleation theory and develop solutions for the rational synthesis of materials, as well as for the control of air pollution.
Intercellular propagation of aggregated protein inclusions along actin-based tunneling nanotubes (TNTs) has been reported as a means of pathogenic spread in Alzheimer’s, Parkinson’s, and Huntington’s ...diseases. Propagation of oligomeric-structured polyglutamine-expanded ataxin-1 (Atxn1154Q) has been reported in the cerebellum of a Spinocerebellar ataxia type 1 (SCA1) knock-in mouse to correlate with disease propagation. In this study, we investigated whether a physiologically relevant polyglutamine-expanded ATXN1 protein (ATXN182Q) could propagate intercellularly. Using a cerebellar-derived live cell model, we observed ATXN1 aggregates form in the nucleus, subsequently form in the cytoplasm, and finally, propagate to neighboring cells along actin-based intercellular connections. Additionally, we observed the facilitation of aggregate-resistant proteins into aggregates given the presence of aggregation-prone proteins within cells. Taken together, our results support a pathogenic role of intercellular propagation of polyglutamine-expanded ATXN1 inclusions.
Recent studies have shown that increased syndecan-1 (SDC1) expression in human glioma is associated with higher tumor grades and poor prognoses, but its oncogenic functions and the underlying ...molecular mechanisms remain unknown. Here, we examined SDC1 expression in datasets from The Cancer Genome Atlas and the National Center for Biotechnology Information Gene Expression Omnibus. Elevated SDC1 expression in glioma was closely associated with increases in tumor progression and shorter survival. We also examined SDC1 expression and evaluated the effects of stable SDC1 knockdown in glioma cell lines. SDC1 knockdown attenuated proliferation and invasion by glioma cells and markedly decreased PCNA and MMP-9 mRNA and protein expression. In a xenograft model, SDC1 knockdown suppressed the tumorigenic effects of U87 cells in vivo. SDC1 knockdown decreased phosphorylation of the c-src/FAK complex and its downstream signaling molecules, Erk, Akt and p38 MAPK. These results suggest that SDC1 may be a novel therapeutic target in the treatment of glioma.
Patients with sepsis-associated encephalopathy (SAE) have higher mortality rates and longer ICU stays. Predictors of SAE are yet to be identified. We aimed to establish an effective and simple-to-use ...nomogram for the individual prediction of SAE in patients with sepsis admitted to pediatric intensive care unit (PICU) in order to prevent early onset of SAE.
In this retrospective multicenter study, we screened 790 patients with sepsis admitted to the PICU of three hospitals in Shandong, China. Least absolute shrinkage and selection operator regression was used for variable selection and regularization in the training cohort. The selected variables were used to construct a nomogram to predict the risk of SAE in patients with sepsis in the PICU. The nomogram performance was assessed using discrimination and calibration.
From January 2017 to May 2022, 613 patients with sepsis from three centers were eligible for inclusion in the final study. The training cohort consisted of 251 patients, and the two independent validation cohorts consisted of 193 and 169 patients. Overall, 237 (38.7%) patients developed SAE. The morbidity of SAE in patients with sepsis is associated with the respiratory rate, blood urea nitrogen, activated partial thromboplastin time, arterial partial pressure of carbon dioxide, and pediatric critical illness score. We generated a nomogram for the early identification of SAE in the training cohort (area under curve AUC 0.82, 95% confidence interval CI 0.76-0.88, sensitivity 65.6%, specificity 88.8%) and validation cohort (validation cohort 1: AUC 0.80, 95% CI 0.74-0.86, sensitivity 75.0%, specificity 74.3%; validation cohort 2: AUC 0.81, 95% CI 0.73-0.88, sensitivity 69.1%, specificity 83.3%). Calibration plots for the nomogram showed excellent agreement between SAE probabilities of the observed and predicted values. Decision curve analysis indicated that the nomogram conferred a high net clinical benefit.
The novel nomogram and online calculator showed performance in predicting the morbidity of SAE in patients with sepsis admitted to the PICU, thereby potentially assisting clinicians in the early detection and intervention of SAE.
Purpose
Growing evidence has demonstrated an indispensable role for N6‐methyladenosine (m6A) in human diseases, but the copy number variations (CNVs) of m6A regulatory genes in bladder cancer (BLCA) ...remains largely unknown.
Methods
We investigated the CNVs on all known m6A regulatory genes using the Cancer Genome Atlas (TCGA) database. The association between CNV events and clinicopathological as well as molecular characteristics of BLCA patients were explored. Gene set enrichment analysis (GSEA) was implemented to reveal relative cellular processes. Association between m6A regulatory genes and immune infiltrates was analyzed by The Tumor Immune Estimation Resource (TIMER) database.
Results
CNV events of m6A regulatory genes were frequently observed in BLCA. CNVs of METTL3, METTL14, and METTL16 correlated with molecular characteristics of BLCA patients including TP53 mutation. CNVs of METTL3 associated with the overall survival (OS) of BLCA patients. METTL3 was also associated with several cancer‐related cellular processes, including mitotic spindle assembly, G2/M checkpoint, and E2F targets signaling pathway. Besides, the CNVs of m6A regulatory genes were correlated with specific kinds of immune infiltrates.
Conclusions
There are significant correlations between m6A regulatory genes with CNVs and clinicopathological characteristics. METTL3 with CNVs were associated with the immune infiltrates and performed as a prognostic marker in BLCA.
We investigated the CNV events on all known m6A regulatory genes which were obtained from the Cancer Genome Atlas (TCGA) database through bioinformatics analysis of prognosis as well as immune infiltrates of BLCA patients. We found that CNVs of METTL3 associated with the overall survival (OS). Furthermore, RNA methyltransferases may affect the outcome of tumor immunotherapy via regulating immune infiltrates.
This study aims to evaluate the value of a serum metabolomics-based metabolic signature for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, thereby assisting clinical decisions.
...In this retrospective study, a total of 320 LA-NPC patients were randomly divided into a training set (ca. 70%;
= 224) and a validation set (ca. 30%;
= 96). Serum samples were analyzed using widely targeted metabolomics. Univariate and multivariate Cox regression analyses were used to identify candidate metabolites related to progression-free survival (PFS). Patients were categorized into high-risk and low-risk groups based on the median metabolic risk score (Met score), and the PFS difference between the two groups was compared using Kaplan-Meier curves. The predictive performance of the metabolic signature was evaluated using the concordance index (C-index) and the time-dependent receiver operating characteristic (ROC), and a comprehensive nomogram was constructed using the Met score and other clinical factors.
Nine metabolites were screened to build the metabolic signature and generate the Met score, which effectively separated patients into low- and high-risk groups. The C-index in the training and validation sets was 0.71 and 0.73, respectively. The 5-year PFS was 53.7% (95% CI, 45.12-63.86) in the high-risk group and 83.0% (95%CI, 76.31-90.26) in the low-risk group. During the construction of the nomogram, Met score, clinical stage, pre-treatment EBV DNA level, and gender were identified as independent prognostic factors for PFS. The predictive performance of the comprehensive model was better than that of the traditional model.
The metabolic signature developed through serum metabolomics is a reliable prognostic indicator of PFS in LA-NPC patients and has important clinical significance.
Two cycles of induction chemotherapy (IC) followed by 2 cycles of platinum-based concurrent chemoradiotherapy (CCRT) (2IC+2CCRT) for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) is ...widely adopted but not evidence-confirmed. This study aimed to determine the clinical value of 2IC+2CCRT regarding efficacy, toxicity and cost-effectiveness.
This real-world study from two epidemic centers used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) analyses. The enrolled patients were divided into three groups based on treatment modality: Group A (2IC+2CCRT), Group B (3IC+2CCRT or 2IC+3CCRT) and Group C (3IC+3CCRT). Long-term survival, acute toxicities and cost-effectiveness were compared among the groups. We developed a prognostic model dividing the population into high- and low-risk cohorts, and survivals including overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were compared among the three groups according to certain risk stratifications.
Of 4,042 patients, 1,175 were enrolled, with 660, 419, and 96 included in Groups A, B and C, respectively. Five-year survivals were similar among the three groups after PSM and confirmed by IPTW. Grade 3-4 neutropenia and leukocytopenia were significantly higher in Groups C and B than in Group A (52.1%
41.5%
25.2%; 41.7%
32.7%
25.0%) as were grade 3-4 nausea/vomiting and oral mucositis (29.2%
15.0%
6.1%; 32.3%
25.3%
18.0%). Cost-effective analysis suggested that 2IC+2CCRT was the least expensive, while the health benefits were similar to those of the other groups. Further exploration showed that 2IC+2CCRT tended to be associated with a shorter PFS in high-risk patients, while 3IC+3CCRT potentially contributed to poor PFS in low-risk individuals, mainly reflected by LRRFS.
In LA-NPC patients, 2IC+2CCRT was the optimal choice regarding efficacy, toxicity and cost-effectiveness; however, 2IC+2CCRT and 3IC+3CCRT probably shortened LRRFS in high- and low-risk populations, respectively.
The growth of materials is directly driven by the interface environment, where mass and energy transfer occurs. To some extent, the heterogeneous interface determines the diversity of material ...structures. Owing to the nanoscale and time dependence of the interface environment, it is a challenging issue to describe the interface quantitatively. Here, we propose to use chemical potential difference (Δμ) to quantify the interface environment in the synthesis of silver particles. Silver particles are synthesized by an electrodeposition approach at the interface of electrodes. The interface chemical distribution, which is regulated by the reaction rate, diffusion rate, and forced convection, is quantified by the chemical potential difference. It is found that the morphologies of silver particles are closely dependent on the chemical potential difference. At a low chemical potential difference, polyhedron-like silver particles form. A high chemical potential difference leads to the formation of silver dendrites, and an extremely high value switches the growth domination to nucleation domination, forming silver nanoparticles. This study shows that the chemical potential difference is a valuable factor to quantify the interface environment, which may be used to discover the significance of the interface in energy and mass transfer.
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