214 research outputs found

    Liquid Biopsy in Lung Cancer: Clinical Applications of Circulating Biomarkers (CTCs and ctDNA)

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    Lung cancer is by far the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Recent advances in the understanding of the biology of tumors and in highly sensitive detection technologies for molecular analysis offer targeted therapies, such as epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. However, our understanding of an individual patient’s lung cancer is often limited by tumor accessibility because of the high risk and invasive nature of current tissue biopsy procedures. “Liquid biopsy”, the analysis of circulating biomarkers from peripheral blood, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), offers a new source of cancer-derived materials that may reflect the status of the disease better and thereby contribute to more personalized treatment. In this review, we examined the clinical significance and uniqueness of CTCs and ctDNA from NSCLC patients, isolation and detection methods developed to analyze each type of circulating biomarker, and examples of clinical studies of potential applications for early diagnosis, prognosis, treatment monitoring, and prediction of resistance to therapy. We also discuss challenges that remain to be addressed before such tools are implemented for routine use in clinical settings

    sj-docx-1-jfn-10.1177_10748407231198249 – Supplemental material for Couple-Oriented Interventions for Mental Health: A Scoping Review

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    Supplemental material, sj-docx-1-jfn-10.1177_10748407231198249 for Couple-Oriented Interventions for Mental Health: A Scoping Review by Minji Gil, Suk-Sun Kim, Daeun Kim, Hyunmin Han, Boram Lim and Jennie C. De Gagne in Journal of Family Nursing</p

    Facilitating C-C bond cleavage toward selective electrocatalytic oxidation of glycerol to formic acid: d-p orbital hybridization and adsorption thermodynamics

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    Formic acid (FA) is a high-value product in hydrogen energy systems; hence, its selective production via electrochemical glycerol oxidation reaction (GOR) in an alkaline medium has emerged as an energy-efficient approach. However, the process is hindered by sluggish C-C bond cleavage, limited charge transfer, and competitive adsorption between glycerol and OH* species. In this study, we design La-based perovskite electrocatalysts with dual B-site metal incorporation to address the key challenges of alkaline GOR. Among various transition metal combinations (Ni, Fe, and Co), LaNi0.5Co0.5O3 (LNCO) demonstrates the highest GOR performance due to a synergistic effect between Ni and Co, which has been shown to modulate the electronic structure and optimize adsorption thermodynamics. In particular, LNCO exhibits enhanced charge transfer behavior, driven by metal 3d-oxygen 2p orbital hybridization and by a delocalized electronic structure with negligible band gap. Furthermore, glycerol adsorption is thermodynamically more favorable than OH* species, providing balanced adsorption energy conducive to efficient GOR. Consequently, LNCO promotes C-C bond cleavage kinetics and enhances selective FA production. These findings highlight that LNCO is a promising electrocatalytic platform for value-added chemical synthesis via a sustainable electrochemical route.

    Circulating tumor cell clusters are cloaked with platelets and correlate with poor prognosis in unresectable pancreatic cancer

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    © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Circulating tumor cells (CTCs) are known to be heterogeneous and clustered with tumor-associated cells, such as macrophages, neutrophils, fibroblasts, and platelets. However, their molecular profile and clinical significance remain largely unknown. Thus, we aimed to perform a comprehensive gene expression analysis of single CTCs and CTC clusters in patients with pancreatic cancer and to identify their potential clinical relevance to provide personalized medicine. Epitope-independent, rapid (>3 mL of whole blood/min) isolation of single CTCs and CTC clusters was achieved from a prospective cohort of 16 patients with unresectable pancreatic cancer using a cen-trifugal microfluidic device. Forty-eight mRNA expressions of individual CTCs and CTC clusters were analyzed to identify pancreatic CTC phenotype. CTC clusters had a larger proportion of mes-enchymal expression than single CTCs (p = 0.0004). The presence of CTC clusters positively corre-lated with poor prognosis (progression-free survival, p = 0.0159; overall survival, p = 0.0186). Fur-thermore, we found that most CTCs in these patients (90.7%) were cloaked with platelets and found the presence of a positive correlation between the increase in CTC clusters and rapid disease progression during follow-ups. Efficient CTC cluster isolation and analysis techniques will enhance the understanding of complex tumor metastasis processes and can facilitate personalized disease man-agement.11Nsciescopu

    Deciphering oxygen vacancies and d-band structures as key descriptors for understanding electrocatalytic trend of glycerol oxidation reaction kinetics in alkaline media

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    Despite the advantages of employing electrocatalytic glycerol oxidation reaction (EGOR) as the anode reaction for hydrogen production, the limited understanding of how electrocatalytic activity trends relate to the intrinsic properties of electrocatalysts leads to frequent trial and error in designing high-performance electrocatalyst materials. Herein, we report systematic studies to decipher the correlation between the kinetics of EGOR under alkaline conditions and the concentration of oxygen vacancy (Vo) and d-band filling (fd) of electrocatalysts using a perovskite-based model system. The modulation of transition metal species in the B-site of LaMO3 (M = transition metal species such as Mn, Fe, Co, and Ni) electrocatalysts allows the systematic control of the density of Vo and fd of electrocatalysts. Our results, based on the experimental and computational calculation analyses, show that LaNiO3 (LNO) with the highest contents of Vo and fd exhibits the most enhanced intrinsic kinetics of EGOR. This is because accelerated charge transfer between LNO and glycolate species by high contents of Vo and fd weakens the strength of C-C bond in glycolate. In particular, the contents of Vo and fd have a proportional relationship with the specific electrocatalytic activity of LaMO3, indicating that Vo and fd can be used as descriptors to predict the specific activity of electrocatalysts. This work highlights the importance of controlling Vo and fd of electrocatalysts to achieve high performance EGOR.

    A lab-on-a-disc platform enables serial monitoring of individual CTCs associated with tumor progression during EGFR-targeted therapy for patients with NSCLC

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    Rationale: Unlike traditional biopsy, liquid biopsy, which is a largely non-invasive diagnostic and monitoring tool, can be performed more frequently to better track tumors and mutations over time and to validate the efficiency of a cancer treatment. Circulating tumor cells (CTCs) are considered promising liquid biopsy biomarkers; however, their use in clinical settings is limited by high costs and a low throughput of standard platforms for CTC enumeration and analysis. In this study, we used a label-free, high-throughput method for CTC isolation directly from whole blood of patients using a standalone, clinical setting-friendly platform. Methods: A CTC-based liquid biopsy approach was used to examine the efficacy of therapy and emergent drug resistance via longitudinal monitoring of CTC counts, DNA mutations, and single-cell-level gene expression in a prospective cohort of 40 patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Results: The change ratio of the CTC counts was associated with tumor response, detected by CT scan, while the baseline CTC counts did not show association with progression-free survival or overall survival. We achieved a 100% concordance rate for the detection of EGFR mutation, including emergence of T790M, between tumor tissue and CTCs. More importantly, our data revealed the importance of the analysis of the epithelial/mesenchymal signature of individual pretreatment CTCs to predict drug responsiveness in patients. Conclusion: The fluid-assisted separation technology disc platform enables serial monitoring of CTC counts, DNA mutations, as well as unbiased molecular characterization of individual CTCs associated with tumor progression during targeted therapy

    Optimizing flux distribution between the glyoxylate and TCA cycle for efficient tyrosine production from acetate in Escherichia coli

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    Acetate is one of promising feedstocks owing to its cheap price and great abundance. Here, we engineered a previously reported strain, SCK1, for efficient production of tyrosine from acetate. Initially, the acetate uptake and gluconeogenic pathway were amplified to maximize the flux toward tyrosine. As flux distribution between glyoxylate and TCA cycles is critical for efficient precursor supplementation, the activity of the glyoxylate cycle was precisely controlled by expression of isocitrate lyase gene under different-strength promoters. Consequently, the engineered strain with optimal flux distribution produced 0.70 g/L tyrosine with 20% of the theoretical maximum yield which are 60% and 80% increased values of the parental strain. Our strategies would be applicable to the production of various chemicals from acetate in future.​ Keywords: Flux optimization, metabolic engineering, tyrosine, acetate2

    Correlation of dynamic membrane fluctuations in red blood cells with diabetes mellitus and cardiovascular risks

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    The rheological and physiological properties of red blood cells (RBCs) are affected by many factors in the vascular environment. Among them, membrane fluctuations (MFs), particularly dynamic fluctuations in RBC cell membrane thickness (RBC-MFs), are likely to be altered by the level of glycation of haemoglobin in patients with diabetes mellitus (DM). We investigated the associations of RBC-MFs with physiological variables associated with DM and cardiovascular diseases (CVDs). Forty-one healthy control subjects and 59 patients with DM were enrolled. Five-microliter samples of blood were collected and diluted 400 times. To measure the RBC-MFs, holotomography was used, which non-invasively and precisely analyses the optical characteristics of RBCs. Associations between the RBC-MFs and biochemical parameters related to glucose homeostasis and lipid profiles were investigated. Independent associations of the RBC-MFs with the presence of CVDs were also analysed. RBC-MFs were lower in patients with DM than in healthy participants (61.64 +/- 7.49 nm vs 70.65 +/- 6.65 nm, P=1.4x10(-8)). RBC-MFs correlated modestly with glycated haemoglobin level (rho=-0.47) and weakly with age (rho=-0.36), duration of diabetes (rho=-0.36), fasting plasma glucose level (rho=-0.37), and the 10-year Framingham risk score (rho=-0.38) (all P&lt;0.05). Low RBC-MFs were independently associated with the presence of CVDs after adjusting for CVD risk factors. The weak but significant associations of RBC-MFs with cardiometabolic risk factors and CVDs suggest that such deformity of circulating RBCs may be a useful marker of vascular complications of DM.
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