Search

The purpose of this study was to evaluate the diagnostic accuracies of dual-time-point (DTP) 18F-FDG PET/CT for detection of mediastinal lymph node (LN) metastasis in non-small cell lung cancer (NSCLC) patients through a systematic review and meta-analysis.The PubMed, Cochrane database, and EMBASE database, from the earliest available date of indexing through October 31, 2021, were searched for studies evaluating diagnostic performance of DTP 18F-FDG PET/CT for detection of metastatic mediastinal LN in NSCLC patients. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic curves.Ten studies (758 patients) were included in the current study. In patient-based analysis, early image showed a sensitivity of 0.76 and a specificity of 0.75. Delayed image revealed a sensitivity of 0.84 and a specificity of 0.71. In LN-based analysis, early image showed a sensitivity of 0.80 and a specificity of 0.83. Delayed image revealed a sensitivity of 0.84 and a specificity of 0.87. Retention index or %ΔSUVmax is superior to early or delayed images of DTP 18F-FDG PET/CT for detection of mediastinal LN metastasis.Dual-time-point 18F-FDG PET/CT showed a good diagnostic performances for detection of metastatic mediastinal LNs in NSCLC patients. Early and delayed images of DTP 18F-FDG PET/CT revealed similar diagnostic accuracies for LN metastasis. However, retention index or %ΔSUVmax is superior to early or delayed images of DTP 18F-FDG PET/CT for detection of mediastinal LN metastasis in NSCLC patients. Further large multicenter studies would be necessary to substantiate the diagnostic accuracy of DTP 18F-FDG PET/CT for mediastinal LN staging in NSCLC patients.

The phenomena of hydrogen induced cracking (HIC) in 304 stainless steels was considered in a hydrogen pressure and stress corrosive atmosphere. Microstructures with chloride pits and stress corrosion cracks around the HIC were analyzed by SEM/EDS. Abnormal phase transformations induced by the hydrogen were analyzed using TEM and diffraction. In the hydrogen pressure atmosphere, pits and pores were observed on the surface of the 304 stainless steels. In addition, it was determined that Cl, an etchant component, was concentrated at a high concentration in the pits. SCC (stress corrosion cracking) was induced in the Cl atmosphere by stress caused by the abrasive embedded in the pits. It was assumed that the SCC mechanism is similar to HIC in that it occurs in the surface tensile stress and Cl atmosphere and is accompanied by grain boundary cracks similar to IGSCC (inter-granular SCC). The deformation induced phase transformation accompanied by planar slip should be related to the main cause of HIC in the hydrogen pressured atmosphere. Abnormal forbidden spots between the main diffraction spots were induced by the HIC in the hydrogen attacked area, where the microstructure was hardened. Understanding the HIC mechanism related to chloride corrosion can be used to assess the fitness of austenitic stainless steels for uses where there is a possibility of various susceptible cracking in hydrogen and chloride atmospheres.

We report the fabrication of multifunctional theranositic biomaterials via non-covalent, rapid, and effective encapsulation of 1,1′dioctadecyl-3,3,3′,3′-tetrametylindotrucarbocyanine iodide (DIR) onto mesoporous silica nanoparticles by coating the surface of polyethylene glycol (PEG-DIR@MSN). PEG-DIR@MSNs exhibited great stability with excellent biocompatibility and photothermal conversion properties. PEG-DIR@MSN allowed for not only the detection of various types of tumor and ischemic lesions but also photothermal therapy against breast cancer in living mice, suggesting that PEG-DIR@MSN is a valuable multifunctional theranostic platform.

In this era of expanding life expectancy and popularity of aesthetic breast surgeries, more women are likely to live more years with their augmented breasts. Thus, consistent attention to general breast health is crucial, and preoperative ultrasound is helpful to locate suspicious lesions. In this study, we present a combinative procedure of augmentation mammoplasty and vacuum-assisted breast biopsy (VABB). From January of 2018 to December of 2019, a total of 102 patients received simultaneous augmentation mammoplasty and VABB in our institute. Only patients of primary augmentation mammoplasty who received VABB on unilateral breasts were included. We sought to investigate the results of each breast and safety of adding VABB before performing augmentation within the same incision. Among 204 breasts and implants, 28.43% were done via endoscopic transaxillary approach and 71.57% via inframammary approach. The mean implant volume was 329.34 ± 44.79 ml, and the mean follow-up period was 14.23 ± 4.64 months. All of the complication rates exhibited no statistically significant differences between the two groups. Simultaneous augmentation mammoplasty and VABB prevented unnecessary scars and pain, and the complication rates did not statistically differ from those of augmentation only group. This co-operation is a safe and simple method potentially beneficial to many women interested in breast surgery. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Glioblastoma (GBM) is the most prevalent malignant tumour of the central nervous system and carries a poor prognosis; average survival time after diagnosis is 14 months. Because of its unfavourable prognosis, novel therapies are needed. The aim of this study was to assess whether inhibition of GBM and GBM-derived cancer stem cells (CSCs) by a new tyrosine kinase inhibitor (TKI), K905-0266, is possible. To do this, we generated GBM (D54 and U87MG) cells expressing luciferase and characterised the inhibitory effects of the TKI with bioluminescent imaging (BLI) and western blot (WB). The effect of the TKI was then evaluated in CSCs. BLI showed significant inhibition of D54 and U87MG cells by TKI treatment. WB showed that the TKI decreased pERK and Bcl-2 level and increased cleaved caspase-3 level. Sphere formation was significantly reduced by the TKI in CSCs. Our results showed that a new TKI, K905-0266, effectively inhibited GBM and CSCs, making this a candidate for GBM therapy.

Nutraceutical treatments can reduce inflammation and prevent the development of inflammatory diseases. In this study, the anti-inflammatory effects of Smilax guianensis Vitman extract (SGE) were examined. SGE suppressed lipopolysaccharide (LPS)-mediated nitrite production in RAW 264.7 cells. SGE also prevented the LPS-induced expression of inducible nitric oxide synthase (iNOS) but not cyclooxygenase (COX)-2. Western blot analysis showed that SGE attenuated LPS-induced phosphorylation of IκB kinase (IKK), inhibitor of kappa B (IκB), and p65. Additionally, SGE inhibited LPS-induced IκB degradation in RAW 264.7 cells. Western blot analysis of the cytosolic and nuclear fractions, as well as immunofluorescence assay results, revealed that SGE suppressed LPS-induced p65 nuclear translocation in RAW 264.7 cells. Moreover, SGE reduced LPS-induced interleukin (IL)- 1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA expression and IL-1β and IL-6 protein expression in RAW 264.7 cells. Collectively, these results indicate that SGE suppresses the NF-κB signaling pathway and thereby inhibits the production of NO, IL-1β, and IL-6.

BACKGROUND Recently, single-person households have increased in Korea and this trend may have potential public health implications and affect various health behaviors. This study investigated the associations between living alone and health behaviors such as smoking and alcohol consumption among Korean adults. METHODS We used data from the 6th Korea National Health and Nutrition Examination Survey between 2013 and 2015 and a total of 17,088 adults were included. We performed a multivariable logistic regression analysis and calculated odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS Single-person households accounted for about 10% of the total participants. The proportions of currently smoking and heavy alcohol consumption were higher among individuals living alone than those living together among younger women and middle-aged and elderly men and women. In the multivariable logistic regression analysis, living alone was associated with increased odds of currently smoking compared to living together among middle-aged men and women (OR, 7.37; 95% CI, 2.33-23.32 in men and OR, 2.36; 95% CI, 1.04-5.36 in women) after adjusting for confounding variables. CONCLUSION From this nationwide, population-based study, we found that living alone is associated with increased odds of currently smoking, especially in middle-aged people. Public health concerns may be warranted for middle-aged single-person households to reduce health risks related to smoking.

Consumption of anti-inflammatory nutraceuticals may help treat or prevent inflammation-related illnesses such as diabetes, cardiovascular disease, and cancer. This study evaluated the effect of Croton hirtus L'Her extract (CHE) on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and nuclear factor kappa-B (NF-κB) signaling cascades. CHE significantly suppressed LPS-induced NO production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 macrophages, although cyclooxygenase (COX)-2 expression was not affected. CHE also suppressed LPS-induced IκB kinase (IKK), IκB, and p65 phosphorylation in RAW264.7 cells. Western blot and immunofluorescence assays of cytosol and nuclear p65 and the catalytic subunit of NF-κB showed that CHE suppressed LPS-induced p65 translocation from the cytosol to the nucleus. CHE also suppressed LPS-induced Interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in RAW264.7 cells. These results suggest that CHE prevents NO-mediated inflammation by suppressing NF-κB and inflammatory cytokines.

Background: Radioactive iodine (RAI) therapy is an important strategy in the treatment of thyroid cancer. However, anaplastic thyroid cancer (ATC), a rare malignancy, exhibits severe dedifferentiat...

3,4-Dichloroaniline (3,4-DCA) is a transformation product of herbicides that is commonly used as a reference in developmental toxicity studies (OECD TG 236) (Bonnet et al. in Environ Toxicol 22:78–91, 2007). However, the mechanisms underlying 3,4-DCA-induced hepatotoxicity are not well known. We exposed zebrafish larvae at 72 hpf to 3,4-DCA for 3 days and observed lipid accumulation in liver treated with 10-μM 3,4-DCA using oil red O staining. Subsequently, we performed qRT-PCR analysis to determine the genes involved in the observed lipid accumulation. We found that genes related to lipogenesis (srebp1, pparγ, lipin1, and scd1) and ER stress (bip, atf4, ddit3, dnajc3, and edem1) were significantly upregulated. In addition, we found that ROS generation increased in the larvae treated with 10-μM 3,4-DCA. Moreover, glutathione-S-transferase activity in these larvae was increased by 3,4-DCA in a dose-dependent manner, and the expression of the inflammation marker il-1β increased. Our results indicated that exposure to 3,4-DCA induced fatty liver in zebrafish larvae and that this, in association with additional factors such as ER stress response, can promote liver damage. We accordingly suggest that 3,4-DCA could be used to induce fatty liver in zebrafish larvae.

Recently, there has been growing interest in replacing severely damaged salivary glands with artificial salivary gland functional units created in vitro by tissue engineering approaches. Although various materials such as poly(lactic-co-glycolic acid), polylactic acid, poly(glycolic acid), and polyethylene glycol hydrogels have been used as scaffolds for salivary gland tissue engineering, none of them is effective enough to closely recapitulate the branched structural complexity and heterogeneous cell population of native salivary glands. Instead of discovering new biomaterial candidates, we synthesized hyaluronic acid-catechol (HACA) conjugates to establish a versatile hyaluronic acid coating platform named "NiCHE (nature-inspired catechol-conjugated hyaluronic acid environment)" for boosting the salivary gland tissue engineering efficacy of the previously reported biomaterials. By mimicking hyaluronic acid-rich niche in the mesenchyme of embryonic submandibular glands (eSMGs) with NiCHE coating on substrates including polycarbonate membrane, stiff agarose hydrogel, and polycaprolactone scaffold, we observed significantly enhanced cell adhesion, vascular endothelial and progenitor cell proliferation, and branching of in vitro-cultured eSMGs. High mechanical stiffness of the substrate is known to inhibit eSMG growth, but the NiCHE coating significantly reduced such stiffness-induced negative effects, leading to successful differentiation of progenitor cells to functional acinar and myoepithelial cells. These enhancement effects of the NiCHE coating were due to the increased proliferation of vascular endothelial cells via interaction between CD44 and surface-immobilized HAs. As such, our NiCHE coating platform renders any kind of material highly effective for salivary gland tissue culture by mimicking in vivo embryonic mesenchymal HA. Based on our results, we expect the NiCHE coating to expand the range of biomaterial candidates for salivary glands and other branching epithelial organs.

Olea europaea is a beneficial edible plant with a number of biological activities like anti-inflammatory, anti-oxidant, antithrombic, antihyperglycemic, and anti-ischemic activities. The mechanisms behind the antiphotoaging and anti-inflammatory effects of Olea europaea are not fully understood. To investigate how an ethanol extract of Olea europaea (Oe-EE) exerts these effects, we explored its activities in human keratinocytes and dermal fibroblasts. We assessed the anti-oxidant effects of Oe-EE via 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2[Formula: see text]-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays and measured the expression levels of matrix metalloproteinases (MMPs), cyclooxygenase-2, interleukin (IL)-6, tumor necrosis factor (TNF)-[Formula: see text], and moisturizing factors. Antiphotoaging and anti-inflammatory mechanisms of Oe-EE were explored by assessing signaling molecule activation via immunoblotting. Oe-EE treatment decreased the mRNA expression level of MMPs, cyclooxygenase-2, IL-6, and TNF-[Formula: see text] and restored type I collagen, filaggrin, and sirtuin 1 expression in UVB-irradiated cells. Furthermore, Oe-EE inhibited the activities of several activator protein 1 regulatory enzymes, including extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK), and inhibited nuclear factor (NF)-[Formula: see text]B pathway signaling proteins. Therefore, our results indicate that Oe-EE has photoaging-protective and anti-inflammatory effects.

The purpose of the current study was to evaluate the diagnostic accuracies of 18F-FDG PET/CT for detection of lymph node (LN) metastasis in penile cancer (PeCA) patients through a systematic review and meta-analysis.The PubMed, Cochrane database, and Embase database, from the earliest available date of indexing through August 31, 2021, were searched for studies evaluating diagnostic performance of 18F-FDG PET/CT for detection of metastatic LN in PeCA patients. We determined the sensitivities and specificities across studies, calculated positive and negative likelihood ratios (LR+ and LR-, respectively), and constructed summary receiver operating characteristic curves.Across 12 studies (479 patients), the pooled sensitivity of 18F-FDG PET/CT was 0.87 (95% confidence interval [CI], 0.79-0.92) and the pooled specificity was 0.88 (95% CI, 0.79-0.93). Likelihood ratio syntheses gave an overall LR+ of 7.2 (95% CI, 3.9-13.1) and LR- of 0.15 (95% CI, 0.1-0.24). The pooled diagnostic odds ratio was 47 (95% CI, 19-116). In meta-regression analysis, no variable was the source of the study heterogeneity.18F-FDG PET/CT showed a good diagnostic performances for detection of metastatic LN in PeCA patients. Also, 18F-FDG PET/CT revealed similar diagnostic accuracy for detection of inguinal and pelvic LN metastasis in PeCA patients.

We aimed to investigate the impact of various factors including radioactive iodine (RAI) activity on the therapeutic response according to the range of serum thyroglobulin (Tg) in patients with papillary thyroid carcinoma (PTC).A total of 2809 patients were retrospectively enrolled from 24 hospitals. They were divided into four subgroups according to their serum Tg (stimulated Tg, sTg) or anti-Tg antibody (TgAb) levels, measured just before RAI therapy: sTg 2 ng/mL, 2 ≤ sTg 10 ng/mL, sTg ≥ 10 ng/mL, and TgAb 100 IU/mL. The clinicopathologic factors for therapeutic responses, which were classified as acceptable response (AR) or non-AR, were compared in each subgroup.Clinical impact of the pN category on therapeutic response was different among subgroups based on sTg levels (subgroups with sTg 2 ng/mL (Risk factors for response prediction could be repositioned based on the serum Tg before RAI therapy. RAI activity should be determined while considering the serum Tg-aided remnant thyroid or malignant tissues as well as conventional factors.The online version contains supplementary material available at 10.1007/s13139-022-00756-4.

Pheochromocytoma (PCC) occurs in 4% of pediatric neurofibromatosis type 1 (NF1) patients and is mostly characterized by epinephrine and norepinephrine secretion. Herein, we report the first case of a dopamine-secreting PCC in a 13-year-old patient with NF1, in whom a left adrenal mass was incidentally found on abdominal computed tomography (CT) during hypertension workup. Fractionated 24-h urine metanephrine excretion was normal but urine dopamine level was elevated. On 123I-metaiodobenzylguanidine (MIBG) single photon emission tomography/CT (SPECT/CT), focal MIBG uptake was observed. Our multidisciplinary team determined that surgery would be difficult to perform because the tumor was small and the symptoms were vague, with only increased dopamine level. After six months, the tumor increased in size on abdominal CT, with focal significant uptake of the lesion on 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) PET/CT. Laparoscopic resection was performed, and the mass was histologically confirmed as PCC. Currently, the vital signs of the patient are stable, urine dopamine levels are normal, and there is no abnormal uptake of 18F-FDOPA PET/CT. This study reports a case of a rare dopamine-secreting PCC. When metanephrine is negative in patients at high risk of PCC, focused examination and multidisciplinary approach are needed.

Optics that are capable of merging with biomaterials create a variety of opportunities for sensing disease, for therapeutics, and for augmenting brain-machine interface. The FDA has approved silk devices for sutures and reconstructive surgery. Recently, a silk product made from regenerated silk protein is FDA approved for orthopedic application, as the understanding of structure and processing technologies of silk fibroin has been improved. Here, we report a facile fabrication process to construct silk microlens array. The process includes preparation of regenerated silk solution and casting on a micropatterned poly(dimethylsiloxane) (PDMS) master. Due to the identical surface area of a unit patterned regime, the silk solution exhibits a partial wetting state in the vicinity of the silk solution–PDMS–vapor interface with same contact angle, and after drying, produces consistent radius of curvature within the microlens array. This in turn provides highly uniform focal length, focal spot diameter, and imaging performance of individual lens. Our results provide the foundation for biophotonic microlens adding new capabilities for implantable and degradable devices from regenerated silk protein.

Simple Summary Bone scintigraphy is the most widely used radionuclide technique to investigate bone metastasis, primarily due to its reasonable time and cost factor. However, it is important to recognize that bone scintigraphy to assess treatment response sometimes shows a “flare phenomenon”, which can be misinterpreted as disease progression. Distinction between flare phenomenon and disease progression could help in the decision to continue effective treatments in patients with flare phenomenon and to cease ineffective treatments and consider other salvage treatment plans in patients with disease progression. Despite many methods having been tried to answer this question, there was still no reliable way to differentiate between flare phenomenon and progression of bone metastases. Our results suggest that ALP is a useful serologic marker to differentiate flare phenomenon from disease progression on bone scintigraphy in breast or prostate cancer patients with bone metastasis. Abstract The flare phenomenon (FP) on bone scintigraphy after the initiation of systemic treatment seriously complicates evaluations of therapeutic response in patients with bone metastases. The aim of this study was to evaluate whether serum alkaline phosphatase (ALP) can differentiate FP from disease progression on bone scintigraphy in these patients. Breast or prostate cancer patients with bone metastases who newly underwent systemic therapy were reviewed. Pretreatment baseline and follow-up data, including age, pathologic factors, type of systemic therapy, radiologic and bone scintigraphy findings, and ALP levels, were obtained. Univariate and multivariate analyses of these factors were performed to predict FP. An increased extent and/or new lesions were found in 160 patients on follow-up bone scintigraphy after therapy. Among the 160 patients, 80 (50%) had an improvement on subsequent bone scintigraphy (BS), while subsequent scintigraphy also showed an increased uptake in 80 (50%, progression). Multiple regression analysis revealed that stable or decreased ALP was an independent predictor for FP (p < 0.0001). ALP was an independent predictor for FP on subgroup analysis for breast and prostate cancer (p = 0.001 and p = 0.0223, respectively). Results of the study suggest that ALP is a useful serologic marker to differentiate FP from disease progression on bone scintigraphy in patients with bone metastasis. Clinical interpretation for scintigraphic aggravation can be further improved by the ALP data and it may prevent fruitless changes of therapeutic modality by misdiagnosis of disease progression in cases of FP.

We investigated whether predictive clinicopathologic factors can be affected by different response criteria and how the clinical usefulness of radioactive iodine (RAI) therapy should be evaluated considering variable factors in patients with differentiated thyroid carcinoma (DTC). A total of 1563 patients with DTC who underwent first RAI therapy after total or near total thyroidectomy were retrospectively enrolled from 25 hospitals. Response to therapy was evaluated with two different protocols based on combination of biochemical and imaging studies: (1) serum thyroglobulin (Tg) and neck ultrasonography (US) and (2) serum Tg, neck US, and radioiodine scan. The responses to therapy were classified into excellent and non-excellent or acceptable and non-acceptable to minimize the effect of non-specific imaging findings. We investigated which factors were associated with response to therapy depending on the follow-up protocols as well as response classifications. Multivariate logistic regression analysis was performed to identify factors significantly predicting response to therapy. The proportion of patients in the excellent response group significantly decreased from 76.5 to 59.6% when radioiodine scan was added to the follow-up protocol (P

Background/aim Histone deacetylase 6 (HDAC6) is considered as one of the most promising targets in drug development for cancer therapy. Drug resistance is a major cause of treatment failure in many cancers including glioblastoma (GBM), the most lethal malignant tumor. The role of HDAC6 in GBM resistance and its underlying mechanisms have not been well elucidated. Herein, we investigated the function of HDAC6 in modulating GBM resistance. Materials and methods The anticancer effects of four structurally distinct selective HDAC6 inhibitors were addressed using western blot, flow cytometry, CCK-8 assay, and CI in temozolomide (TMZ)-resistant GBM cells. Results We showed that HDAC6-selecitve inhibitors block activation of the EGFR and p53 pathways in TMZ-resistant GBM cells. Importantly, the inhibition of HDAC6 correlates with increased levels of MSH2 and MSH6, key DNA mismatch repair proteins, in TMZ-resistant GBM cells. In addition to the MSH, HDAC6 inhibitors decrease MGMT expression in TMZ-resistant GBM cells. Furthermore, HDAC6 inhibitors increase TMZ sensitivity and efficiently induce apoptosis in TMZ-resistant GBM cells. Conclusion Selective inhibition of HDAC6 may be a promising strategy for the treatment of TMZ-resistant GBM.

Tight junctions (TJs) play an important role in water, ion, and solute transport through the paracellular pathway of epithelial cells, however, their role in diabetes-induced salivary gland dysfunction remains unknown. Here, we found that the TJ proteins claudin-1 and claudin-3 were significantly increased in the submandibular glands (SMGs) of db/db mice and high glucose (HG)-treated human SMGs. HG decreased paracellular permeability and increased claudin-1 and claudin-3 expression in SMG-C6 cells. Knockdown of claudin-1 or claudin-3 reversed the HG-induced decrease in paracellular permeability. MiR-22-3p was significantly downregulated in diabetic SMGs and HG-treated SMG-C6 cells. A miR-22-3p mimic suppressed claudin-1 and claudin-3 expression and abolished the HG-induced increases in claudin-1 and claudin-3 levels in SMG-C6 cells, whereas a miR-22-3p inhibitor produced the opposite effects. Specificity protein-1 (Sp1) was enhanced in diabetic SMGs and HG-treated SMG-C6 cells, which promoted claudin-1 and claudin-3 transcription through binding to the corresponding promoters. A luciferase reporter assay confirmed that miR-22-3p repressed Sp1 by directly targeting the Sp1 mRNA 3′-untranslated region (3′-UTR). Consistently, the miR-22-3p mimic suppressed, whereas the miR-22-3p inhibitor enhanced, the effects of HG on Sp1 expression. Taken together, our results demonstrate a new regulatory pathway through which HG decreases the paracellular permeability of SMG cells by inhibiting miR-22-3p/Sp1-mediated claudin-1 and claudin-3 expression.

Protons may have contributed to the evolution of plants as a major component of cosmic-rays and also have been used for mutagenesis in plants. Although the mutagenic effect of protons has been well-characterized in animals, no comprehensive phenotypic and genomic analyses has been reported in plants. Here, we investigated the phenotypes and whole genome sequences of Arabidopsis M2 lines derived by irradiation with proton beams and gamma-rays, to determine unique characteristics of proton beams in mutagenesis. We found that mutation frequency was dependent on the irradiation doses of both proton beams and gamma-rays. On the basis of the relationship between survival and mutation rates, we hypothesized that there may be a mutation rate threshold for survived individuals after irradiation. There were no significant differences between the total mutation rates in groups derived using proton beam or gamma-ray irradiation at doses that had similar impacts on survival rate. However, proton beam irradiation resulted in a broader mutant phenotype spectrum than gamma-ray irradiation, and proton beams generated more DNA structural variations (SVs) than gamma-rays. The most frequent SV was inversion. Most of the inversion junctions contained sequences with microhomology and were associated with the deletion of only a few nucleotides, which implies that preferential use of microhomology in non-homologous end joining was likely to be responsible for the SVs. These results show that protons, as particles with low linear energy transfer (LET), have unique characteristics in mutagenesis that partially overlap with those of low-LET gamma-rays and high-LET heavy ions in different respects.

In the last two decades, methods to incorporate non-canonical amino acids (ncAAs) into specific positions of a protein have advanced significantly; these methods have become general tools for engineering proteins. However, almost all these methods depend on the translation elongation process, and strategies leveraging the initiation process have rarely been reported. The incorporation of a ncAA specifically at the translation initiation site enables the installation of reactive groups for modification at the N-termini of proteins, which are attractive positions for introducing abiological groups with minimal structural perturbations. In this study, we attempted to engineer an orthogonal protein translation initiation system. Introduction of the identity elements of Escherichia coli initiator tRNA converted an engineered Methanococcus jannaschii tRNATyr into an initiator tRNA. The engineered tRNA enabled the site-specific incorporation of O-propargyl-l-tyrosine (OpgY) into the amber (TAG) codon at the translation initiation position but was inactive toward the elongational TAG codon. Misincorporation of Gln was detected, and the engineered system was demonstrated only with OpgY. We expect further engineering of the initiator tRNA for improved activity and specificity to generate an orthogonal translation initiation system.

Yoon, Y.-K.; Lee, S.-W., and Yoon, J.-J., 2021. Assessment of the degree of contamination in marine sediments at Cheonsu Bay, west coast of Korea. In: Lee, J.L.; Suh, K.-S.; Lee, B.; Shin, S., and Lee, J. (eds.), Crisis and Integrated Management for Coastal and Marine Safety. Journal of Coastal Research, Special Issue No. 114, pp. 31–35. Coconut Creek (Florida), ISSN 0749-0208. In this study, 32 bottom sediments (30 sites on the surface and 2 sites in the core) were sampled to determine thedegree of marine sediment contamination in Cheonsu Bay. Cleanup indexes of eutrophication (CIET) and harmful chemicals (CHIC) were calculated to determine whether remediation of contaminated sediment was necessary. Generally, an area with CIET ≥ 6 or CHIC ≥ 2 requires cleanup. In the case of Cheonsu Bay, its CEIT value was six or higher at six sites located in the northern area of Cheonsu Bay. The analysis revealed that there was a significant level of organic matter pollution in this region. However, its CHIC was lower than 2 at all sites, indicating that the level of contamination caused by heavy metal pollutants was not high. Core samples were collected up to a depth of 60 cm from the surface at two sites in which CIET was assessed to be greater than 6. Analysis of the core samples indicated that organic matter contamination was present up to a depth of 20–30 cm from the surface. It was inferred that the polluted matter originated from Bunam Lake and Ganwol Lake, which are located to the north of Cheonsu Bay and have highly polluted water and bottom sediments. The results of this study prove that organic matter contamination because of these freshwater lakes has a continuous effect on the sediments in the inner Cheonsu Bay region. To mitigate the degree of contamination in the Cheonsu Bay area, fundamental countermeasures should focus on the source of terrestrial pollutants.

In recent years, an interesting biomarker called membrane breakdown voltage has been examined using artificial planar lipid bilayers. Even though they have great potential to identify cell electrical phenotyping for distinguishing similar cell lines or cells under different physiological conditions, the biomarker has not been evaluated in the context of living cell electrical phenotyping. Herein, we present a single-cell analysis platform to continuously measure the electric response in a large number of cells in parallel using electric frequency and voltage variables. Using this platform, we measured the direction of cell displacement and transparent cell image alteration as electric polarization of the cell responds to signal modulation, extracting the dielectrophoretic crossover frequency and membrane breakdown voltage for each cell, and utilizing the measurement results in the same spatiotemporal environment. We developed paired parameters using the dielectrophoretic crossover frequency and membrane breakdown voltage for each cell and evaluated the paired parameter efficiency concerning the identification of two different breast cancer cells and cell drug response. Moreover, we showed that the platform was able to identify cell electrical phenotyping, which was generated by subtle changes in cholesterol depletion-induced cell membrane integrity disruption when the paired parameter was used. Our platform introduced in this paper is extremely useful for facilitating more accurate and efficient evaluation of cell electrical phenotyping in a variety of applications, such as cell biology and drug discovery.

Endoscopic submucosal dissection (ESD) of gastric neoplasm involving the pyloric channel (GNPC) is technically challenging due to difficulty in precise assessment of resection margin and inadequate visualization. The aim of this study was to evaluate the effectiveness and long-term outcome of ESD for GNPC and introduce a noble technique for resection of GNPC.A total of 97 patients with GNPC underwent ESD from January 2007 to October 2017. We divided them into a conventional anterograde resection group and a retrograde resection group according to the method of procedure. We compared their clinical outcomes and investigated risk factors for postprocedural complications.The en bloc resection rate was 87.6%, and complete resection rate was 83.5%. Postprocedure stenosis occurred in 16 cases (16.5%). GNPCs of the retrograde resection group were more frequently located from antrum to bulb, were significantly larger, were related to ≥75% resection of the circumference, and involved significantly longer procedure times than those in the anterograde resection group. Multivariate analysis showed that resection ≥75% of the circumference was the only significant risk factor for postprocedure stenosis.ESD by retrograde resection method is a novel technique to make the procedure easier, depending on the size, location, and circumference of resection.

Purpose The objective of this study was to estimate the incidence of secondary cancers and the factors associated with their development among patients who underwent radioiodine therapy (RIT) with differentiated thyroid cancer. Methods We retrospectively collected medical records for patients who underwent first RIT between January 1, 2000 and December 31, 2005 from seven tertiary hospitals in South Korea after total thyroidectomy for differentiated thyroid cancer. Cancer incidence and calculated standardized rate ratio was compared with Korean cancer incidence data. The association between the development of secondary cancers and various parameters was analyzed by Cox-proportional hazard regression. Results A total of 3106 patients were included in this study. Mean age at the time of diagnosis of thyroid cancer was 45.7 ± 13.3 years old, and 2669 (85.9%) patients were female. The follow-up period was 11.9 ± 4.6 (range, 1.2–19.6) years. A total of 183 secondary cancers (5.6%), which included 162 solid and 21 hematologic cancers occurred in 173 patients. There was no significant difference between solid cancer incidence in our study population who underwent RIT and the overall Korean population, but the incidence of hematologic cancers and total cancer in our study was significantly higher compared with that of the Korean population. A multivariate analysis identified independent prognostic factors for the development of secondary cancer including age at 1st RIT, male, and total cumulative dose over 200 mCi. Conclusion We need to assess the risk benefit for patients who receive over 200 mCi of a total cumulative dose.

Background Chronic cerebral hypoperfusion (CCH) is known to induce Alzheimer’s disease (AD) pathology, but its mechanism remains unclear. The purpose of this study was to identify the cerebral regions that are affected by CCH, and to evaluate the development of AD pathology in a rat model of CCH. Methods A rat model of CCH was established by bilaterally ligating the common carotid arteries in adult male rats (CCH group). The identical operations were performed on sham rats without arteries ligation (control group). Regional cerebral glucose metabolism was evaluated at 1 and 3 months after bilateral CCA ligation using positron emission tomography with F-18 fluorodeoxyglucose. The expression levels of amyloid β40 (Aβ40), amyloid β42 (Aβ42), and hyperphosphorylated tau were evaluated using western blots at 3 months after the ligation. Cognitive function was evaluated using the Y-maze test at 3 months after the ligation. Results At 1 month after the ligation, cerebral glucose metabolism in the entorhinal, frontal association, motor, and somatosensory cortices were significantly decreased in the CCH group compared with those in the control group. At 3 months after the ligation, cerebral glucose metabolism was normalized in all regions except for the anterodorsal hippocampus, which was significantly decreased compared with that of the control group. The expression of Aβ42 and the Aβ42/40 ratio were significantly higher in the CCH group than those in the control group. The phosphorylated-tau levels of the hippocampus in the CCH group were significantly lower than those in the control group. Cognitive function was more impaired in the CCH group than that in the control group. Conclusion Our findings suggest that CCH causes selective neurodegeneration of the anterodorsal hippocampus, which may be a trigger point for the development of AD pathology.

Recent technological advances in high-resolution imaging and artificial modulation of genetic functions at different times and regions have enabled direct observations of the formation and elimination of abnormal cell populations. A recent trend in cell competition research is the incorporation of cell mechanics. In different tissues and species, abnormal cells developing in epithelial tissues are mechanically eliminated by cell contraction via actomyosin accumulation at the interface between normal and abnormal cells. This mechanical cell elimination process has attracted attention as a potential universal defense mechanism. Here, we theoretically examined the conditions for mechanical elimination of growing abnormal cell populations. Simulations and mathematical analyses using a vertex dynamics model revealed two types of critical cell density associated with mechanical elimination of abnormal cell clusters. One is a subtype of homeostatic density, in which the frequencies of spontaneous mechanical cell elimination and proliferation are balanced, even if no explicit dependence of proliferation or apoptosis on the cell density is assumed. This density is related to the mechanical stability of a single cell. The other is density related to mechanical stability as a cell population under external pressure. Both density types are determined by tissue mechanical properties. In solid tissues, the former type is reached first as the intensity of interfacial contraction increases, and it functions as a critical density. On the other hand, the latter type becomes critical when tissues are highly fluid. The derived analytical solution explicitly reveals the dependence of critical contractile force and density on different parameters. We also found a negative correlation between the proliferation rate of abnormal cells and the likelihood of the abnormal cell population expanding by escaping elimination. This is counterintuitive because in the context of cell competition, fast-growing cell populations generally win. These findings provide new insight into, and interpretation of, the results from experimental studies.