The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper ...whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.
Radiotherapy (RT) is a highly effective multimodal nonsurgical treatment that is essential for patients with advanced colorectal cancer (CRC). Nevertheless, cell subpopulations displaying intrinsic ...radioresistance survive after RT. The reactivation of their proliferation and successful colonization at local or distant sites may increase the risk of poor clinical outcomes. Recently, radioresistant cancer cells surviving RT were reported to exhibit a more aggressive phenotype than parental cells, although the underlying mechanisms remain unclear.
By investigating public databases containing CRC patient data, we explored potential radioresistance-associated signaling pathways. Then, their mechanistic roles in radioresistance were investigated through multiple validation steps using patient-derived primary CRC cells, human CRC cell lines, and CRC xenografts.
Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling was activated in radioresistant CRC tissues in correlation with local and distant metastases. JAK2 was preferentially overexpressed in the CRC stem cell subpopulation, which was accompanied by the phosphorylation of STAT proteins, especially STAT3. JAK2/STAT3 signaling played an essential role in promoting tumor initiation and radioresistance by limiting apoptosis and enhancing clonogenic potential. Mechanistically, the direct binding of STAT3 to the cyclin D2 (CCND2) promoter increased CCND2 transcription. CCND2 expression was required for persistent cancer stem cell (CSC) growth via the maintenance of an intact cell cycle and proliferation with low levels of DNA damage accumulation.
Herein, we first identified JAK2/STAT3/CCND2 signaling as a resistance mechanism for the persistent growth of CSCs after RT, suggesting potential biomarkers and regimens for improving outcomes among CRC patients.
The rampant generation of lithium hydroxide and carbonate impurities, commonly known as residual lithium, is a practical obstacle to the mass‐scale synthesis and handling of high‐nickel (>90 %) ...layered oxides and their use as high‐energy‐density cathodes for lithium‐ion batteries. Herein, we suggest a simple in situ method to control the residual lithium chemistry of a high‐nickel lithium layered oxide, Li(Ni0.91Co0.06Mn0.03)O2 (NCM9163), with minimal side effects. Based on thermodynamic considerations of the preferred reactions, we systematically designed a synthesis process that preemptively converts residual Li2O (the origin of LiOH and Li2CO3) into a more stable compound by injecting reactive SO2 gas. The preformed lithium sulfate thin film significantly suppresses the generation of LiOH and Li2CO3 during both synthesis and storage, thereby mitigating slurry gelation and gas evolution and improving the cycle stability.
A simple in situ method to control the residual lithium in high‐nickel lithium layered oxide is designed. Residual Li2O (the origin of LiOH and Li2CO3) is preemptively converted into the Li2SO4 thin film by injecting SO2 gas during calcination. This method suppresses the generation of LiOH and Li2CO3 during both synthesis and storage, thereby mitigating slurry gelation and gas evolution and improving cycle stability.
Dementia is a major concern among growing chronic diseases in the aging society and its association with polypharmacy has not been adequately assessed. The objective of this study was to determine ...the association between polypharmacy and dementia through multiple statistical approaches. We conducted a nested case-control study for newly diagnosed dementia cases using the South Korean National Health Insurance Service sample cohort database (2002-2013, n = 1,025,340). Interactions between polypharmacy (an average use of ≥5 prescription drugs daily) and comorbidities or potentially inappropriate medications (PIMs) were tested. The odds ratios (ORs) for dementia were analyzed according to the presence of comorbidities, PIM uses, the average number of prescribed daily drugs, and significant interactions with polypharmacy using univariate and multiple logistic regression analyses. A higher prevalence of comorbidities, history of PIM use, higher PIM exposure, and higher proportion of polypharmacy were noted among cases than in controls. In the univariate analysis, the OR for dementia increased significantly with the increase in the number of prescribed drugs 1-<5 drugs: 1.72, 95% confidence interval (CI): 1.56-1.88; 5-<10 drugs: 2.64, 95% CI: 2.32-3.05; ≥10 drugs: 3.35, 95% CI: 2.38-4.71; <1 drug used as reference. Polypharmacy was correlated with comorbidities and PIM use, and significant interactions were observed between polypharmacy and anticholinergics; H2-receptor antagonists; and comorbidities such as hypertension, peripheral or cerebrovascular disease, congestive heart failure, hemiplegia, diabetes, depression, all other mental disorders, chronic obstructive pulmonary disease, peptic ulcer disease, and chronic liver disease (p<0.001). In the multiple regression analysis, most cases exhibited increasing ORs for dementia with increasing polypharmacy levels. Moreover, the increase in OR was more evident in the absence of drugs or comorbidities that showed significant interactions with polypharmacy than in their presence. Polypharmacy increases the risk of PIM administration, and as some PIMs may have cognition-impairing effects, prolonged polypharmacy may result in dementia. Therefore, efforts are needed to limit or decrease the prescription of medications that have been associated with risk of dementia in the elderly.
Induced pluripotent stem cells (iPSCs) can be generated by introducing several factors into mature somatic cells. Banking of iPSCs can lead to wider application for treatment and research. In an ...economical view, it is important to store cells that can cover a high percentage of the population. Therefore, the use of homozygous human leukocyte antigen‐iPSCs (HLA‐iPSCs) is thought as a potential candidate for effective iPSC banking system for further clinical use. We screened the database stored in the Catholic Hematopoietic Stem Cell Bank of Korea and sorted the most frequent homozygous HLA types of the South Korean population. Blood cells with the selected homozygous HLA types were obtained and transferred to the GMP facility in the Catholic Institute of Cell Therapy. Cells were reprogrammed to iPSCs inside the facility and went through several quality controls. As a result, a total of 13 homozygous GMP‐grade iPSC lines were obtained in the facility. The generated iPSCs showed high pluripotency and normal karyotype after reprogramming. Five HLA‐homozygous iPSCs had the type that was included in the top five most frequent HLA types. Homozygous HLA‐iPSCs can open a new opportunity for further application of iPSCs in clinical research and therapy.
Income inequality is known to have negative impacts on an economic system, thus has been debated for a hundred years past or more. Numerous ideas have been proposed to quantify income inequality, and ...the Gini coefficient is a prevalent index. However, the concept of perfect equality in the Gini coefficient is rather idealistic and cannot provide realistic guidance on whether government interventions are needed to adjust income inequality. In this paper, we first propose the concept of a more realistic and 'feasible' income equality that maximizes total social welfare. Then we show that an optimal income distribution representing the feasible equality could be modeled using the sigmoid welfare function and the Boltzmann income distribution. Finally, we carry out an empirical analysis of four countries and demonstrate how optimal income distributions could be evaluated. Our results show that the feasible income equality could be used as a practical guideline for government policies and interventions.
Quisqualis indica (QI) has been used for treating disorders such as stomach pain, constipation, and digestion problem. This study was aimed to evaluate the therapeutic efficacy of QI extract on ...treating benign prostatic hyperplasia (BPH) in LNCaP human prostate cancer cell line and a testosterone-induced BPH rat model. LNCaP cells were treated with QI plus testosterone propionate (TP), and androgen receptor (AR) and prostate specific antigen (PSA) expression levels were assessed by Western blotting. To induce BPH, the rats were subjected to a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks. The rats in treatment group were orally gavaged with QI (150 mg/kg) together with the TP injection. In-vitro studies showed that TP-induced increases in AR and PSA expression in LNCaP cells were reduced by QI treatment. In BPH-model rats, the prostate weight, testosterone in serum, dihydrotestosterone (DHT) concentration and 5α-reductase type 2 mRNA expression in prostate tissue were significantly reduced following the treatment with QI. TP-induced prostatic hyperplasia and the expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 were significantly attenuated in QI-treated rats. In addition, QI induced apoptosis by up-regulating caspase-3 and -9 activity and decreasing the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio in prostate tissues of BPH rats. Further investigation showed that TP-induced activation of AKT and glycogen synthase kinase 3β (GSK3β) was reduced by QI administration. Therefore, our findings suggest that QI attenuates the BPH state in rats through anti-proliferative and pro-apoptotic activities and might be useful in the clinical treatment of BPH.
Development of miniaturized thin‐film lithium‐ion batteries (TF‐LIBs) using vacuum deposition techniques is crucial for low‐scale applications, but addressing low energy density remains a challenge. ...In this work, structures analogous to SiOx‐based thin‐film electrodes are designed with close resemblance to traditional LIB slurry formulations including active material, conductive agent, and binder. The thin‐film is produced using mid‐frequency sputtering with a single hybrid target consisting of SiOx nanoparticles, carbon nanotubes, and polytetrafluoroethylene. The thin‐film SiOx/PPFC (plasma‐polymerized fluorocarbon) involves a combination of SiOx and conductive carbon within the PPFC matrix. This results in enhanced electronic conductivity and superior elasticity and hardness in comparison to a conventional pure SiOx‐based thin‐film. The electrochemical performance of the half‐cell consisting of thin‐film SiOx/PPFC demonstrates remarkable cycling stability, with a capacity retention of 74.8% up to the 1000th cycle at 0.5 C. In addition, a full cell using the LiNi0.6Co0.2Mn0.2O2 thin‐film as the cathode material exhibits an exceptional initial capacity of ≈120 mAh g−1 at 0.1 C and cycle performance, marked by a capacity retention of 90.8% from the first cycle to the 500th cycle at a 1 C rate. This work will be a stepping stone for the AM/CB/B composite electrodes in TF‐LIBs.
SiOx‐based thin‐film electrodes are designed similar to traditional lithium‐ion battery (LIB) slurry formulations, including active material, conductive agent, and binder. Using mid‐frequency sputtering with a hybrid target containing SiOx nanoparticles, carbon nanotubes, and polytetrafluoroethylene, a thin‐film SiOx‐based composite electrode is successfully fabricated within plasma‐polymerized fluorocarbon (PPFC). The SiOx/PPFC composite thin‐film exhibits improved electronic conductivity, elasticity, and hardness compared to pure SiOx‐based thin‐film. The electrochemical performance of the SiOx/PPFC composite thin‐film shows remarkable cycling stability.
Background
Inactivation of
TP53
, a tumor suppressor gene, is associated with the development of several malignancies, including gastric cancer (GC). The present study aimed to evaluate the ...correlation between the overexpression of p53 and survival in different Lauren-type GCs.
Methods
From May 2003 to December 2019, 3608 GC patients treated endoscopically or surgically at the Seoul National University Bundang Hospital were enrolled for the study. Immunohistochemical staining for p53 was performed on all endoscopic and surgical gastric specimens. Clinicopathologic characteristics with Lauren classification, survival rate, and cancer recurrence were analyzed according to p53 overexpression.
Results
Among 3608 GC patients, p53 overexpression was seen in 1334 patients (37%). p53 overexpression was associated with lower depth of invasion (
P
= 0.026) and Early gastric cancer (
P
= 0.044) in intestinal-type GC, and with advanced TNM stage (
P
< 0.001) and Advanced gastric cancer (
P
< 0.001) in diffuse-type GC. The overall survival (OS) and GC-specific survival (GCSS) were significantly lower in p53 overexpression positive patients. This significance was more pronounced and enhanced in the diffuse-type GC and was absent in the intestinal-type GC. In multivariate analyses, p53 overexpression was associated with poor OS in both subtypes of GC and cancer recurrence in diffuse-type GC. (OS in intestinal-type: adjusted hazard ratio aHR = 1.423,
P
= 0.022; OS in diffuse-type: aHR = 1.401
P
= 0.035; cancer recurrence in diffuse-type: aHR = 1.502,
P
= 0.039).
Conclusion
p53 overexpression was associated with poor prognosis in GC, especially in diffuse-type. In addition, p53 overexpression was associated with early stage disease in intestinal-type GC and with advanced stage disease in diffuse-type GC.
•Electron beam (EB) technology is a very useful process to control simultaneously SO2 and NOx.•This review paper is study of EB flue gas treatment technology around the world.•Limitations of ...stand-alone EB technology such as high power costs.•To overcome this, introduction of various hybrid technologies.
Despite worldwide effort, most electric power is still generated by the combustion of fossil fuel. Among the various combustion exhaust gases, SO2 and NOx can exert adverse effects on the human health and environment in both direct and indirect ways. However, their conventional removal technologies (e.g., flue gas desulfurization (FGD: wet, semi-dry, dry), selective catalytic reduction (SCR), and selective non-catalytic reduction (SNCR)) are often restricted to treat only a single target due to several disadvantages (e.g., high capital cost, low efficiency, and waste by-products (including acidic pollutant)). As a means to overcome these drawbacks, electron beam (EB) technology has been developed over the past four decades. A wide range of EB-related research has been undertaken from laboratory to pilot plant scale in Japan, Germany, US, Saudi Arabia, and Bulgaria, while EB flue gas treatment technology has been developed into industrial scale plant in China, Japan, and Poland. EB is well-known for simultaneous removal of SO2 and NOx while producing useful by-products (e.g., fertilizer). In this review, the theoretical background of EB technology is described with respect to the removal of SO2 and NOx from the flue gas based on the lab, pilot plant, and industrial plant. We also discuss the new EB hybrid technology proposed to overcome the problems associated with the stand-alone EB process. Finally, this review addresses the current status and limitations of EB technology along with its prospects.
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