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Background: The fibrosis-4 (FIB4) index, a simple, noninvasive marker used for hepatic diseases, represents adverse outcomes. The aim of the present study was to evaluate whether the FIB4 index can predict adverse outcomes in patients with ST-elevation myocardial infarction (STEMI)., Methods: We investigated patients with STEMI who underwent primary percutaneous coronary intervention (PCI) and were alive at discharge. The cut-off FIB4 index at discharge was investigated using the survival classification and regression tree (CART) model to predict adverse outcomes. The primary outcome was all-cause mortality., Results: Between January 2006 and December 2018, 1354 patients with STEMI (median age, 68 years; men, 76.1%) were investigated. The median value of the FIB4 index was 1.21 (0.84-1.78). The CART model divided the study population into low (FIB4 index <0.945; n = 435), intermediate (0.945 ≤ FIB4 index < 2.185; n = 692), and high (FIB4 index ≥2.185; n = 227) groups based on the significant predictive values for all-cause death. During a median follow-up period of 4.3 years, all-cause death occurred in 208 patients (15.4%). The Kaplan-Meier analysis showed a significant increase in mortality with higher FIB4 index values (log-rank, P < 0.001). The multivariate Cox regression model revealed that the FIB4 index was an independent risk predictor for all-cause death in patients with STEMI [low group as reference vs. intermediate group, hazard ratio: 1.975; 95% confidence interval (CI): 1.166-3.346; P = 0.011 and vs. high group, hazard ratio: 4.633; 95% CI: 2.549-8.418; P < 0.001]., Conclusions: The FIB4 index was associated with the risk of all-cause mortality in patients with STEMI who underwent primary PCI., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The placement of plastic stents (PS), including intraductal PS (IS), is useful in patients with unresectable malignant hilar biliary obstruction (UMHBO) because of patency and ease of endoscopic reintervention (ERI). However, the optimal stent replacement method for PS remains unclear., Methods: This retrospective study included 322 patients with UMHBO. Among them, 146 received PS placement as initial drainage (across-the-papilla PS [aPS], 54; IS, 92), whereas 75 required ERI. Eight bilateral aPS, 21 bilateral IS, and 17 bilateral self-expandable metallic stent (SEMS) placements met the inclusion criteria. Rates of technical and clinical success, adverse events, recurrent biliary obstruction (RBO), time to RBO (TRBO), overall survival, and secondary ERI were compared., Results: There were no significant intergroup differences in rates of technical or clinical success, adverse events, RBO occurrence, or overall survival. The median TRBO was significantly shorter in the aPS group (47 days) than IS (91 days; P = 0.0196) and SEMS (143 days; P < 0.01) groups. Median TRBO did not differ significantly between the IS and SEMS groups (P = 0.44). On Cox multivariate analysis, the aPS group had the shortest stent patency (hazard ratio 2.67 [95% confidence interval 1.05-6.76], P = 0.038). For secondary ERI, the median endoscopic procedure time was significantly shorter in the IS (22 min) vs. SEMS (40 min) group (P = 0.034)., Conclusions: Bilateral IS and SEMS placement featured prolonged patency after first ERI. Because bilateral IS placement is faster than SEMS placement and IS can be removed during secondary ERI, it may be a good option for first ERI., (© 2024 Japan Gastroenterological Endoscopy Society.)

Background: Epicardial adipose tissue (EAT) is closely associated with atrial fibrillation (AF), suggesting that it may be one of the causes of AF progression. However, it is unclear whether AF affects EAT., Objective: This study aimed to demonstrate that sinus rhythm restoration reduces EAT volume (EATV) through left atrial reverse remodeling (LARR)., Methods: We analyzed data from 247 patients who underwent cryoballoon ablation for AF. EATV was assessed by contrast-enhanced computed tomography with a 3-dimensional analysis workstation, evaluating EATV surrounding the entire heart (Total-EATV) and left atrium (LA-EATV) at baseline and 6 months after cryoballoon ablation., Results: At 6 months, all patients but one with persistent AF were in sinus rhythm. Total-EATV and LA-EATV were both significantly decreased in patients with persistent AF (n = 33; Total-EATV: 148.8 ± 53.3 mL to 142.9 ± 53.5 mL [P = .01]; LA-EATV: 26.8 ± 11.3 mL to 25.2 ± 10.7 mL [P = .01]). No changes were observed in patients with paroxysmal AF (n = 214). Persistent AF was more strongly associated with LARR than paroxysmal AF (odds ratio, 2.34; 95% confidence interval, 1.01-5.44; P = .05). LARR showed an independent correlation with both Total-EATV and LA-EATV reduction (odds ratio, 1.78 [P = .04] and 2.80 [P < .001], respectively)., Conclusion: These findings suggest a novel "AF begets EAT" theory, complementing the previously accepted role of EAT as a cause of AF and supporting the "AF begets AF" mechanism., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Benign choledochojejunal anastomotic stricture (CJS) is a complication of pancreaticoduodenectomy and choledochojejunostomy. Typically managed with endoscopic balloon dilatation, CJS has a high recurrence rate. Covered metallic stent (CMS) placement is a potential alternative; however, a comprehensive evaluation is lacking., Objectives: The aim of this study was to evaluate the treatment outcomes of CMS placement in patients with CJS., Methods: We retrospectively analyzed patients who underwent balloon dilation via endoscopic retrograde cholangiopancreatography using a double-balloon endoscope for CJS between October 2010 and October 2023. The study outcomes included technical and clinical success rates, adverse event rates, choledochojejunal anastomotic stricture recurrence rates, and time to recurrence for balloon dilation and CMS treatment for CJS., Results: There were 43 patients, 55 procedures (40 balloon dilation and 15 CMS placement). The technical and clinical success rates were 100% for both treatments. Recurrence of CJS was observed in 35% (14/40) of the patients in the balloon dilation group. The recurrence rate was significantly higher in the balloon dilation group than in the CMS group (35% vs. 0%, p = 0.006). The time to CJS recurrence was significantly shorter in the balloon dilation group than in the covered metallic stent group (NR vs. NR, p = 0.03)., Conclusion: Placement of CMS for treating patients with CJS was demonstrated to be an effective and safe method with a lower recurrence rate than balloon dilation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Pancreatic juice cytology is useful for diagnosing pancreatic duct strictures and cystic lesions. However, some cases cannot be diagnosed using cytology. This study aimed to evaluate the utility of the overnight-stored pancreatic juice cell block (CB) method for diagnosing pancreatic disease., Methods: This retrospective study included 32 patients who presented with pancreatic duct strictures or cystic lesions between 2018 and 2024. The sensitivity, specificity, and accuracy of the CB method and single/multiple pancreatic juice cytology were compared to evaluate the utility of the CB., Result: An endoscopic nasopancreatic drainage tube was placed in the main pancreatic duct, and pancreatic juice was collected to create a CB specimen. The median amount of pancreatic juice collected was 180(30-200) mL, and the median number of cytological examinations was three(2-8). Of the 32 cases, 13 were malignant, and 19 were benign (non-malignant). The sensitivity was significantly higher for the CB method (62 %) than for single cytology(15 %, P = 0.0414), and there was no significant difference between CB and multiple cytology(54 %, P = 1.0). The specificity and accuracy were not significantly different between the CB method and single or multiple cytology. When multiple cytology and CB were combined, sensitivity improved to 77 %. The pathological findings of the CB specimens were similar to the surgical specimens, including immunohistochemistry., Conclusion: The overnight-stored pancreatic juice CB method was more effective than single cytology, with similar sensitivities to multiple cytology and can also be used for immunohistochemistry. The pancreatic juice CB method is useful for pancreatic juice assessment., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: The fibrosis-4 (FIB-4) index is a noninvasive scoring system that is used to assess the progression of liver fibrosis. This study aimed to assess whether the FIB-4 index is associated with recurrent atrial fibrillation (AF) after catheter ablation in patients with and without heart failure (HF)., Methods: We included 1,184 patients who underwent initial AF catheter ablation between 2016 and 2021. The patients were classified into low-risk (< 1.3), intermediate-risk (1.3-2.67), and high-risk (> 2.67) groups based on their FIB-4 indices at baseline. The patients were divided into HF (n = 552) and non-HF groups (n = 632); the HF group was further divided into paroxysmal AF (PAF) and non-PAF groups. AF recurrence after catheter ablation was then compared among the groups., Results: In the non-HF group, no significant differences in recurrence after ablation were observed between the low-(n = 219), intermediate-(n = 364), and high-risk (n = 49) groups. In contrast, in the HF group, the intermediate-(n = 341) and high-risk (n = 112) groups had significantly higher recurrence rates than the low-risk group (n = 99) (log-rank test, p = 0.005). This association remained significant after multivariate analysis (hazard ratio [HR]:1.374; p = 0.027). The FIB-4 index increased incrementally as the brain natriuretic peptide levels and severity of tricuspid regurgitation increased. The FIB-4 index was an independent predictor of recurrence in the non-PAF HF group (HR:1.498; p = 0.007) but not in the PAF group., Conclusions: The FIB-4 index may be a useful predictor of AF recurrence after catheter ablation in patients with HF, particularly in those with non-PAF., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Extraction ability of N,N-dioctylthiodiglycolamic acid (T-DODGAA), a soft-base sulfur donor ligand with an amide group and a carboxylic acid connected by a thioether chain, for 56 metal ions have been comprehensively investigated and compared with that of N,N-dioctyldiglycolamic acid (DODGAA) with an etheric oxygen atom, a hard-base donor. The acid dissociation constant (pK a ) of the thiodiglycolamic acid framework was determined to be 3.71 ± 0.06 in water (0.1 M LiCl, 25 °C) by potentiometric titration, indicating that T-DODGAA is a slightly weaker acid than DODGAA (pK a  = 3.54 ± 0.03). T-DODGAA can quantitatively extract various metal ions from the 56 metal ions into the organic phase (isooctane) through a proton-exchange reaction. T-DODGAA provided higher extraction performance than DODGAA for Hf(IV), Cr(III), Fe(III), Ni(II), Cu(II), Pd(II), Ag(I), Au(III), Hg(II), Al(III), and Ga(III), especially for soft metal ions. Furthermore, to demonstrate the practical feasibility of T-DODGAA for hydrometallurgy and metal recycling, we performed selective separation tests of rare metal ions such as Sc(III), Ni(II), Co(II), Pd(II), Au(III), In(III), and Ga(III) in metal-mixed extraction systems., (© 2024. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Background: Evidence regarding the association between hyperuricemia and arrhythmia recurrence after catheter ablation for paroxysmal atrial fibrillation (AF) is scarce. We investigated whether hyperuricemia predicts arrhythmia recurrence after catheter ablation for paroxysmal AF and the relationship between hyperuricemia and alcohol consumption in AF recurrence., Methods: Patients who underwent catheter ablation for paroxysmal AF were divided into the hyperuricemia (index serum uric acid [UA] >7.0 mg/dL; n  = 114) and control (UA ≤7.0 mg/dL; n  = 609) groups and were followed for a median of 24 (12-48) months after ablation., Results: The hyperuricemia group had more patients with an alcohol intake of ≥20 g/day (33.3% vs. 22.7%, p  = .017) and a lower incidence of AF-free survival ( p  = .019). Similarly, those with an alcohol intake of ≥20 g/day had a lower incidence of AF-free survival than other patients. Multivariate Cox regression analysis revealed the following independent predictors of AF recurrence (adjusted hazard ratio, 95% confidence interval): hyperuricemia (1.64, 1.12-2.40), female gender (1.91, 1.36-2.67), brain natriuretic peptide level >100 pg/mL (1.59, 1.14-2.22), and alcohol consumption ≥20 g/day (1.49, 1.03-2.15) (all p  < .05). In addition, causal mediation analysis revealed that alcohol consumption of ≥20 g/day directly affected AF recurrence, independent of hyperuricemia., Conclusions: Patients with hyperuricemia may be at a high risk of arrhythmia recurrence after catheter ablation for paroxysmal AF. Although high alcohol consumption may contribute to increased UA levels, the presence of hyperuricemia may independently predict AF recurrence., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s). Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Anamorelin, a ghrelin receptor agonist, is used for cancer-related cachexia but can induce life-threatening arrhythmias. A case study illustrates an extremely wide QRS tachycardia, posing diagnostic challenges. Anamorelin cessation led to normalization, highlighting the importance of ECG monitoring, particularly in liver-compromised patients, and hemodynamic support are crucial during suspected toxicity., Competing Interests: Authors declare no conflict of interests for this article., (© 2024 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Bioequivalence (BE) studies are considered the standard for demonstrating that the performance of a generic drug product in the human body is sufficiently similar to that of its comparator product. The objective of this article is to describe the recommendations from participating Bioequivalence Working Group for Generics (BEWGG) members of the International Pharmaceutical Regulators Programme (IPRP) regarding the conduct and acceptance criteria for BE studies of immediate release solid oral dosage forms. A survey was conducted among BEWGG members regarding their BE recommendations and requirements related to study subjects, study design, sample size, single or multiple dose administration, study conditions (fasting or fed), analyte to be measured, selection of product strength, drug content, handling of endogenous substances, BE acceptance criteria, and additional design aspects. All members prefer conducting single dose cross-over designed studies in healthy subjects with a minimum of 12 subjects and utilizing the parent drug data to assess BE. However, differences emerged among the members when the drug's pharmacokinetics and pharmacodynamics become more complex, such that the study design (e.g., fasting versus fed conditions) and BE acceptance criteria (e.g., highly variable drugs, narrow therapeutic index drugs) may be affected. The survey results and discussions were shared with the ICH M13 Expert Working Group (EWG) and played an important role in identifying and analyzing gaps during the harmonization process. The draft ICH M13A guideline developed by the M13 EWG was endorsed by ICH on 20 December 2022, under Step 2 ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fernandes, Oudtshoorn, Tam, González, Aurela, Potthast, Mettke, Kuribayashi, Shimojo, Kasuga, Morales, Rodríguez, Jones, Ahn, Yun, Kim, Rodrigues, Tiong, Crane, Walther, Roost, Chen, Hsu, Braddy, García-Arieta, Abalos, Divinsky, Alsuwyeh, Alzenaidy and Alharf.)

Functional mitral regurgitation (FMR) often coexists with atrial fibrillation (AF) and may have a causal relation with AF persistence and exacerbation of heart failure (HF). The purpose of this study was to investigate the impact of FMR on AF catheter ablation (AFCA) outcomes and improvement in FMR after AFCA in patients with HF with preserved ejection fraction (HFpEF) and nonparoxysmal AF. Excluding patients with primary valve disease or post-mitral valve repair, 280 patients with HFpEF who underwent CA for nonparoxysmal AF were retrospectively included. All patients completed 1-year follow-up and were assessed for FMR, AF recurrence and HF parameters, including echocardiography. At baseline, FMR was present in 153 (54.6%) patients (mild, n = 112; moderate, n = 40; severe, n = 1), and these were decreased to 70 (25%) significantly 1 year after AFCA (mild, n = 64; moderate, n = 6), 119 patients (78%) had improvement in MR (a decrease of ≥1 level in the severity from baseline to 1 year on echocardiography). Overall, 274 patients (97.9%) had sinus rhythm at the 1-year examination, and recurrent AF-free survival did not differ in patients with and without MR improvement (83.2% vs 82.4%, p = 0.908). However, the MR improvement group had a significantly lower cardiothoracic ratio, left atrial diameter, E/e', and B-type natriuretic peptide levels after 1 year than those in the MR nonimprovement group. In conclusion, the majority of the HFpEF patients with nonparoxysmal AF had improvement of FMR after AFCA with the high maintenance of sinus rhythm, leading to a virtuous cycle of cardiac function., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aims: Intraductal plastic stent (IS) placement for unresectable malignant hilar biliary obstruction (UMHBO) is an effective option for biliary drainage. However, the effectiveness of bilateral IS placement compared with bilateral self-expandable metal stent (SEMS) placement remains unclear., Methods: Overall, 301 patients with UMHBO were enrolled; 38 patients underwent bilateral IS placement (IS group) and 38 patients underwent SEMS placement (SEMS group) in the propensity score-based cohort. Both groups were compared for technical and clinical success, adverse events (AEs), recurrent biliary obstruction (RBO), time to RBO (TRBO), overall survival (OS), and endoscopic reintervention (ERI)., Results: No significant differences were observed between the groups regarding technical and clinical success, AEs and RBO occurrence rates, TRBO, or OS. The median initial endoscopic procedure time was significantly shorter in the IS group (23 vs 49 minutes, P < .01). ERI was performed on 20 and 19 patients in the IS and SEMS groups, respectively. The median ERI procedure time was significantly shorter in the IS group (22 vs 35 minutes, P = .04). Median TRBO after ERI with plastic stent placement tended to be longer in the IS group (306 vs 56 days, P = .068). A Cox multivariate analysis showed that the IS group was the significant related factor for TRBO after ERI (hazard ratio, .31; 95% confidence interval, .25-.82; P = .035)., Conclusions: Bilateral IS placement can reduce the duration of the endoscopic procedure and provide sufficient stent patency both initially and after ERI stent placement, and the stents are removable. Bilateral IS placement is considered a good option for initial UMHBO drainage. (Clinical trial registration number: UMIN000050546.)., Competing Interests: Disclosure All authors disclosed no financial relationships. This work was supported by JSPS KAKENHI (grant no. JP23K14646, Mitsuru Okuno)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Clinical outcomes concerning the efficacy of excimer laser coronary angioplasty (ELCA) in real-world cases of acute myocardial infarction (MI) are limited. We evaluated and compared the impact of ELCA with manual aspiration thrombectomy on myocardial salvage and left ventricular (LV) systolic/diastolic function in patients with ST-segment elevation MI (STEMI) using nuclear scintigraphy.  We enrolled 143 consecutive patients with STEMI treated with ELCA (63 patients) or manual aspiration thrombectomy (80 patients) between September 2016 and December 2020 in a single-center hospital. We evaluated the peak creatine kinase (CK)/ creatine kinase-myocardial band (CK-MB) levels and performed single-photon emission computed tomography (SPECT) analyses with Quantitative Gated SPECT and Quantitative Perfusion SPECT (Auto QUANT 7.2) at 3-10 days using 123 I-BMIPP and 3 months following percutaneous coronary intervention using 99m Tc-tetrofosmin to evaluate myocardial salvage and LV systolic/diastolic function. No significant difference was observed in the patient and periprocedural characteristics. Peak CK-MB level was significantly different between the groups (ELCA group, 190.0 [70.5-342.0] IU/L vs. aspiration group, 256.5 [157.0-354.8] IU/L, p = 0.047). Although no significant difference was observed in myocardial salvage, significant improvement in the LV ejection fraction (14.1 [6.2-19.8]% vs. 9.5 [3.9-15.3]%, respectively, p = 0.018) and peak emptying rate (-0.54 [-1.02- (-0.27)] mL/s vs. -0.38 [-0.76- (-0.05)] mL/s, respectively, p = 0.017) were detected. ELCA could suppress the myocardial deviation enzymes and potentially improve systolic function compared to manual aspiration thrombectomy in patients with STEMI., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The atrial defibrillation threshold (ADFT) for internal cardioversion is theoretically related to the critical mass for sustaining atrial fibrillation (AF)., Objective: This study aimed to investigate the association of ADFT for internal cardioversion with the outcome of catheter ablation for non-paroxysmal AF (non-PAF)., Methods: We included 368 consecutive patients who underwent first-time catheter ablation for non-PAF. Based on the degree of ADFT recorded by the internal cardioversion before pulmonary vein isolation, we divided the patients into low ADFT (<20 J) and high ADFT (≥20 J) groups and analysed the association between ADFT and atrial tachyarrhythmia recurrence., Results: There were 234 and 134 patients in the low and high ADFT groups, respectively. Of these, 39 patients (16.7%) and 41 (30.6%) patients, respectively, had atrial tachyarrhythmia recurrence during the 2.6±1.0 year follow-up. The high ADFT group showed a significantly higher atrial tachyarrhythmia recurrence than the low ADFT group (p=0.002). This finding was also noted in patients with long-standing persistent AF (p=0.032) but not in patients with persistent AF (p=0.159). The significant predictors of arrhythmia recurrence on multivariate analysis were high ADFT (p=0.004) and long-standing persistent AF (p=0.011). In multivariate analysis within the long-standing persistent AF group, only ADFT remained a significant risk factor for AF recurrence (p=0.035)., Conclusions: The high ADFT of internal cardioversion was found to be a risk factor for post-catheter ablation recurrence in patients with long-standing persistent AF but not in those with persistent AF., Competing Interests: Conflicts of Interest There are no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier B.V.)

Radium is refocused from the viewpoint of an environmental pollutant and cancer therapy using alpha particles, where it mainly exists as a hydrated ion. We investigated the radium hydration structure and the dynamics of water molecules by extended X-ray absorption fine structure (EXAFS) spectroscopy and ab initio molecular dynamics (AIMD) simulation. The EXAFS experiment showed that the coordination number and average distance between radium ion and the oxygen atoms in the first hydration shell are 9.2 ± 1.9 and 2.87 ± 0.06 Å, respectively. They are consistent with those obtained from the AIMD simulations, 8.4 and 2.88 Å. The AIMD simulations also revealed that the water molecules in the first hydration shell of radium are less structured and more mobile than those of barium, which is an analogous element of radium. Our results indicate that radium can be more labile than barium in terms of interactions with water., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

Liquid-liquid extraction of lanthanide (Ln) ions was investigated using N,N-dioctylthiodiglycolamic acid (DOTDGAA), which is a sulfur donor ligand with an amide group and a carboxyl group connected by a thioether chain. The extraction performance and selectivity of DOTDGAA for Ln ions were compared with those of N,N-dioctyldiglycolamic acid (DODGAA), which is also an oxygen donor ligand with a similar chemical structure, to assess the effect of the soft/hard donor atom on Ln separation. DOTDGAA quantitatively extracted all Ln ions while being selective toward the light and middle Ln ions, in contrast to the selectivity of DODGAA for heavier Ln ions. Slope analysis demonstrated that the Ln 3+ transfer using DOTDGAA proceeded through a proton-exchange reaction, forming a 1:3 complex, Ln(DOTDGAA) 3 . The back-extraction of Ln ions from the extracting phase was successfully achieved under acidic conditions., (© 2022. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

The specimen collection and subsequent pathological diagnosis of malignant biliary stricture (MBS) are difficult. This study aimed to determine whether the cell block (CB) method using overnight-stored bile is useful in the diagnosis of MBS. This trial was a single-arm prospective study involving a total of 59 patients with suspected MBS. The primary endpoint was cancer detectability and accuracy using the CB method, and a comparison with the detectability and accuracy achieved with bile cytology was made. The immunohistochemical sensitivity for maspin and p53 was also investigated in the CB and surgical specimens. We were able to collect bile from all 59 patients, and 45 of these patients were clinically diagnosed with MBS. The cancer detectability using the CB method (62.2%) was significantly higher than that using cytology (37.8%) ( p = 0.0344). When CB was combined with biopsy, the rates of cancer detectability (75.6%) and accuracy (81.4%) increased. In eight patients who received surgical therapy, maspin- and p53-immunohistochemistry was applied to the surgical and CB specimens, and cancer cells in both specimens showed positive cytoplasmic and nuclear staining for maspin and nuclear staining for p53. The CB method is, thus, useful for detecting malignancy (UMIN000034707).

Precise separation and purification of f-block elements are important and challenging especially for the reduction of nuclear waste and the recycling of rare metals but are practically difficult mainly because of their chemical similarity. A promising way to overcome this difficulty is controlling their oxidation state by nonchemical processes. Here, we show resonance-enhanced multiphoton charge transfer in actinide complexes, which leads to element-specific control of their oxidation states owing to the distinct electronic spectra arising from resonant transitions between f orbitals. We observed oxidation of trivalent americium in nitric acid. In addition, we found that the coordination of nitrates is essential for promoting the oxidation reaction, which is the first finding ever relevant to the primary process of photoexcitation via resonant transitions of f-block elements. The resonance-enhanced photochemical process could be used in the nuclear waste management, as it would facilitate the mutual separation of actinides, such as americium and curium.

Limited data exist on the prevalence and prognosis of isolated posterior ST-segment elevation acute myocardial infarction (STEMI), revealed with a posterior chest lead. Furthermore, the utility of a synthesized-V 7-9 lead in the diagnosis of STEMI is unclear; therefore, we aimed to evaluate its usefulness. We enrolled 142 consecutive patients with STEMI with the culprit lesion on the left circumflex artery (STEMI-LCx) undergoing percutaneous coronary intervention (PCI) between January 2009 and December 2019. We retrospectively checked the ST-segment change of both standard 12-lead and synthesized-V 7-9 lead in all patients with STEMI-LCx. Based on electrocardiogram (ECG) findings, isolated posterior STEMI that was only revealed in synthesized-V 7-9 lead was classified as "STEMI-LCx-synV 7-9 " and the remaining as "STEMI-LCx-12ECG." The prevalence of STEMI-LCx-synV 7-9 in patients with STEMI-LCx was assessed. The incidence of all-cause death, cardiac death, and mechanical complications within 30 days, 3 months, and 1 year was also assessed according to each STEMI-LCx. STEMI-LCx-synV 7-9 and STEMI-LCx-12ECG occurred in 10 (7.0%) and 132 (93.0%) patients, respectively. No significant difference was found in patients' characteristics between the two groups. The patients with STEMI-LCx-synV 7-9 had significantly higher incidences of cardiac death within 3 months and 1 year (30.0% vs. 6.1%, P = 0.031, 30.0% vs. 7.6%, P = 0.050, respectively) and mechanical complications in each follow-up period (20.0% vs. 1.5%, P = 0.025) than those with STEMI-LCx-12ECG. STEMI-LCx-synV 7-9 was observed in 7.0% of the patients with STEMI-LCx. Our findings suggest that the synthesized-V 7-9 lead helps diagnose isolated posterior STEMI and might improve prognosis in patients with STEMI-LCx., (© 2021. Japanese Association of Cardiovascular Intervention and Therapeutics.)

Background: Although short-term mortality in ST-elevation myocardial infarction (STEMI) has improved, data is limited regarding very long-term mortality and concomitant clinical events in STEMI survivors who undergo primary percutaneous coronary intervention (p-PCI). This study aimed to evaluate these parameters at 15 years and to determine the predictors of 15-year mortality in these patients., Methods: The study endpoints were all-cause mortality and cardiac mortality at 15 years. Independent predictors of all-cause mortality were also analyzed. Furthermore, each thrombotic and bleeding event was evaluated., Results: Between January 2004 and December 2006, 260 STEMI survivors who underwent p-PCI (median follow-up period: 3970 days) were evaluated from the Ogaki Municipal hospital registry. The rates of all-cause mortality (cardiac mortality) at 5, 10, and 15 years were 12.1% (4.9%), 23.4% (9.5%), and 34.9% (12.4%), respectively. The cumulative incidences of recurrent myocardial infarction, target vessel revascularization, ischemic stroke, hemorrhagic bleeding, and gastric bleeding at 15 years were 11.3%, 43.6%, 14.3%, 6.9%, and 10.9%, respectively. Cox regression analysis showed that age ≥ 75 years [adjusted hazard ratio (aHR), 7.074, p < 0.001], chronic kidney disease (aHR, 2.320, p = 0.001), left ventricular ejection fraction <40% (aHR, 2.930, p = 0.001), Killip class ≥II at admission (aHR, 2.639, p = 0.003), untreated chronic total occlusion (aHR, 2.090, p = 0.042), and final TIMI grade ≤ 2 (aHR, 1.736, p = 0.048) were independent predictors of all-cause mortality., Conclusion: This study demonstrated that all-cause and cardiac mortality at 15 years were 34.9% and 12.4%, respectively, in all-comers STEMI survivors after p-PCI, indicating that STEMI survivors might have a benign prognosis., Competing Interests: Declaration of competing interest H.I received lecture fees from Astellas Pharma Inc., Astrazeneca Inc., Daiichi-Sankyo Pharma Inc., and MSD K. K. T.A. received lecture fees from Astellas Pharma, AstraZeneca, Bayer, Daiichi Sankyo, and Bristol-Myers Squibb. T.M received lecture fees from Bayel Pharmaceutical Co., Ltd., Daiichi-Sankyo Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Kowa Co., Ltd., MSD K. K., Mitsubishi Tanabe Pharma Co., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K. K., Pfizer Japan Inc., Sanofi-aventis K. K., and Takeda Pharmaceutical Co., Ltd. T.M received unrestricted research grant for Department of Cardiology, Nagoya University Graduate School of Medicine from Astellas Pharma Inc., Daiichi-Sankyo Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Kowa Co., Ltd., MSD K. K., Mitsubishi Tanabe Pharma Co., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K. K., Otsuka Pharma Ltd., Pfizer Japan Inc., Sanofi-aventis K. K., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Low body mass index (BMI) is a predictor of adverse events in patients with ST-elevated myocardial infarction (STEMI) in Western countries. Because the average BMI of Asians is significantly lower than that of the Western population, the appropriate cut-off BMI value and its role in long-term mortality are unclear in Asian patients. Between January 2006 and December 2017, 1215 patients who underwent percutaneous coronary intervention (PCI) for acute STEMI and were alive at discharge (mean age, 67.7 years; male, 75.4%) were evaluated. The cut-off BMI value, which could predict all-cause mortality within 10 years, was detected using a survival classification and regression tree (CART) model. The causes of death according to the BMI value were evaluated in each group. Based on the CART model, the patients were divided into three groups (BMI < 18 kg/m 2 : 54 patients, 18 kg/m 2  ≤ BMI ≤ 20 kg/m 2 : 109 patients, and BMI > 20 kg/m 2 : 1052 patients). The BMI decreased with age; with an increased BMI, patients with dyslipidemia, diabetes mellitus, and smoking habit increased. During the study period (median, 4.9 years), 194 patients (26.8%) died (cardiac death, 59 patients; non-cardiac death, 135 patients). All-cause mortality was more frequent as the BMI decreased (BMI < 18 kg/m 2 ; 72.8%, 18 kg/m 2  ≤ BMI ≤ 20 kg/m 2 ; 40.5%, and BMI > 20 kg/m 2 ; 22.8%; log-rank p < 0.001). Non-cardiac deaths were more frequent than cardiac deaths in all groups, and the dominance of non-cardiac death was highest in the lowest BMI group. Cut-off BMI values of 18 kg/m 2 and 20 kg/m 2 can predict long-term mortality after PCI in Asian STEMI survivors, whose cut-off value is lower than that in the Western populations. The main causes of death in this cohort differed according to the BMI values., (© 2021. Springer Japan KK, part of Springer Nature.)

After an abdominal injury, a woman in her 20s presented to our hospital with abdominal pain. Pancreatic trauma was discovered on computed tomography, along with a pancreatic duct injury and pancreatic juice leakage. Endoscopic retrograde pancreatography revealed a 10-mm rupture of the pancreatic body's main pancreatic duct (MPD) and intraperitoneal leakage of contrast enzyme from the MPD. The pancreatic injury was treated with the placement of a 5-Fr endoscopic nasopancreatic drainage tube in the ruptured distal side of the pancreatic duct;however, 3 months later, the MPD stenosis occurred. The MPD stenosis was improved using a 7-Fr pancreatic stent, and finally, placement of the pancreatic stent was not required for MPD drainage.

The safety and efficacy of a generic product are partly based on demonstrating bioequivalence to the innovator product; however, when the innovator product is no longer available as a comparator product, a survey conducted within the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP) indicated that the criteria for selecting an alternative comparator product varies. For most members of the BEWGG, an existing marketed generic that was approved based on a comparison with the locally registered innovator product can be used, contingent on criteria that ranges from allowing any generic to be used, to allowing only specific criteria-defined generics to be used. Notwithstanding the acceptability of a generic as an alternative comparator, it is not always the preferred comparator for several jurisdictions. Some jurisdictions require the use of a locally sourced alternative innovator comparator (e.g., the same medicinal ingredient manufactured by a different company) or a foreign innovator comparator. Unlike the other members of the BEWGG, the European Union (EU) has no such options available, rather mechanisms are in place to allow manufacturers to develop a new comparator. The criteria described herein regarding the use of an alternative comparator product can also be applied to scenarios where a specific strength of a series of strengths or an innovative fixed dose combination are discontinued. The results of the survey demonstrate that while criteria for selecting alternative comparator products are not harmonized among the BEWGG participants, the common concern for all jurisdictions is to select a comparator product that meets the safety and efficacy standards of the original innovator product.

Phenanthroline carboxamide compounds are promising for lanthanide intra-series separation. This paper presents a study on the effect of structure modification of phenanthroline carboxamides on the extraction of the whole lanthanide series. The study consists of theoretical calculations, extraction experiments of the 14 stable lanthanides, and extended X-ray absorption fine structure (EXAFS) analyses of Nd and Dy complexes. Tridentate monocarboxamides and tetradentate dicarboxamides show different trends in series extraction, although both preferentially extract the light lanthanides. The amide substituents, although not directly coordinating the metal ions, were also found to impact the distribution ratio, most probably due to a modification in the internal polarity of the molecules. This latter effect, if extrapolated to other nitrogen-based ligands such as pyridines or triazines, can be used to further fine-tune extractants for a process improvement.

Aims: We aimed to examine the benefits of catheter ablation in patients with non-paroxysmal atrial fibrillation (AF) accompanied by heart failure (HF) with preserved ejection fraction (HFpEF), in comparison with the benefits in patients with AF accompanied by HF with reduced ejection fraction (HFrEF) or patients with no HF., Methods and Results: From 1173 consecutive patients undergoing catheter ablation, 502 with non-paroxysmal AF were divided into three groups: no history of HF [plasma B-type natriuretic peptide (BNP) <100 pg/mL and no HF hospitalization; n = 125], HFpEF [left ventricular (LV) EF ≥50%; n = 293], and HF with midrange EF (HFmrEF) + HFrEF (LVEF <50%; n = 84) groups. The endpoints were AF recurrence at 1 year, changes in symptomatic and image-based functional status, and changes in BNP levels from baseline to 1 year. In the HFpEF group, AF recurred in 48 patients (16.4%) and 278 patients (94.8%) had sinus rhythm at 1 year; these values were comparable with those in the other groups. Significant improvement was observed in the left atrial diameter, LVEF, and New York Heart Association functional class in the HFpEF and HFmrEF + HFrEF groups. The BNP level significantly decreased irrespective of the index rate control status, and freedom from AF recurrence was an independent predictor of HF remission, defined as BNP <100 pg/mL at 1 year, in the HFpEF group., Conclusion: Catheter ablation is highly feasible for restoring sinus rhythm in non-paroxysmal AF with coexisting HFpEF, thereby improving cardiac function and BNP levels. Catheter ablation for AF may be an optional management strategy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Knowledge of the long-term prognosis (>10 years) and mortality predictors of ST-elevation myocardial infarction (STEMI) patients who have undergone primary percutaneous coronary intervention (p-PCI) is scarce. Therefore, this study evaluated the long-term prognosis and determined the predictors of long-term outcomes for STEMI patients after p-PCI. Between January, 2006 and December, 2010, we collected data and analyzed 459 consecutive patients with acute STEMI who underwent p-PCI and were discharged from the hospital (mean age, 66.8 years; male, 75.2%; peak creatine phosphokinase level, 2,292.5 IU/L). The primary endpoint was 10-year all-cause mortality. The cumulative 10-year incidence of all-cause death was 23.8%. The Cox multivariate regression analysis identified age ≥ 65 years (adjusted hazard ratio [aHR], p <0.001), body mass index (aHR, 0.93, p = 0.033), presence of atrial fibrillation (aHR, 1.69, p = 0.038), mineralocorticoid receptor antagonist use (aHR, 1.95, p = 0.008), ejection fraction <40% (aHR, 2.14, p = 0.005), and albumin <3.5 g/dL (aHR, 2.01, p = 0.005) as independent predictors of all-cause mortality. In conclusion, a post-discharge 10-year survival rate of 76.2% was identified for STEMI patients who underwent p-PCI., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To clarify the association of detailed angiographic findings with in-hospital outcome after primary percutaneous coronary intervention (p-PCI) for ST-elevation myocardial infarction (STEMI) in Japan., Background: Data regarding the association of detailed angiographic findings with in-hospital outcome after STEMI are limited in the p-PCI era., Methods: Between January-2004 and December-2018, 1735 patients with STEMI (mean age, 68.5 years; female, 24.6%) who presented to the hospital in the 24-hours after symptom onset and underwent p-PCI were evaluated using the disease registries. The registry is an ongoing, retrospective, single-center hospital-based registry., Results: The 30-day mortality rate and in-hospital mortality rate were 7.7% and 9.2%, respectively. Independent predictors of in-hospital mortality were ejection fraction (EF) < 40% [adjusted Odds Ratio (aOR), 4.446, p < 0.001], culprit lesions in the left coronary artery (LCA) (aOR, 2.940, p < 0.001) compared with those in the right coronary artery, Killip class > II (aOR, 7.438; p < 0.001), chronic kidney disease (CKD) (aOR, 4.056; p < 0.001), final thrombolysis in myocardial infarction (TIMI) grades 0/1/2 (aOR, 1.809; p = 0.03), absence of robust collaterals (aOR, 17.309; p = 0.01) and hypertension (aOR, 0.449; p = 0.01)., Conclusions: Among the consecutive patients with STEMI, the in-hospital mortality rate after p-PCI significantly improved in the second half. Not only CKD, Killip class > II, and EF < 40%, but also the angiographic findings such as culprit lesions in the LCA, absence of very robust collaterals, and final TIMI grades <3 were associated with an increased risk of in-hospital mortality., Competing Interests: H.I received lecture fees from Astellas Pharma Inc., Astrazeneca Inc., Daiichi-Sankyo Pharma Inc., and MSD K. K. T.A. received lecture fees from Astellas Pharma, AstraZeneca, Bayer, Daiichi Sankyo, and Bristol-Myers Squibb. T.M received lecture fees from Bayel Pharmaceutical Co., Ltd., Daiichi-Sankyo Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Kowa Co., Ltd., MSD K. K., Mitsubishi Tanabe Pharma Co., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K. K., Pfizer Japan Inc., Sanofi-aventis K. K., and Takeda Pharmaceutical Co., Ltd. T.M received an unrestricted research grant for Department of Cardiology, Nagoya University Graduate School of Medicine from Astellas Pharma Inc., Daiichi-Sankyo Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., Kowa Co., Ltd., MSD K. K., Mitsubishi Tanabe Pharma Co., Nippon Boehringer Ingelheim Co., Ltd., Novartis Pharma K. K., Otsuka Pharma Ltd., Pfizer Japan Inc., Sanofi-aventis K. K., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objective The popularity of primary percutaneous coronary intervention (p-PCI) for ST-elevation myocardial infarction (STEMI) has increased over the past decades. Despite improvements in in-hospital mortality rates, it is clinically important to investigate the prognoses after discharge. However, data on the mode of death and prognostic factors are limited. We analyzed these factors in a Japanese cohort in the modern p-PCI era. Methods Between January 2004 and December 2017, a total of 1,222 patients who underwent p-PCI within 24 hours from the onset of STEMI and were alive at discharge (mean age, 67.7 years old; men, 75.5%), were evaluated. The two-year mortality was analyzed using a Cox regression model, and the mode of death was evaluated. Results The rate of mortality at 2 years was 5.7%. Non-cardiac death was more frequent than cardiac death (62.6% vs. 37.4%). A Cox multivariate analysis identified the following as independent predictors of the 2-year mortality: hemoglobin (log-transformed) [adjusted hazard ratio (HR), 0.048; 95% confidence interval (CI), 0.008-0.29; p<0.001], age above 80 years old (adjusted HR, 2.26; 95% CI, 1.30-3.91; p=0.004), Killip class ≥II (adjusted HR, 1.99; 95% CI, 1.17-3.39; p=0.011), brain natriuretic peptide level (log-transformed) (adjusted HR, 1.47; 95% CI, 1.09-2.01; p=0.013), and body mass index (log-transformed) (adjusted HR, 0.16; 95% CI, 0.030-0.84; p=0.030). Conclusion This study demonstrated that the 2-year mortality was 5.7% in STEMI survivors after p-PCI. Non-cardiac death was more frequent than cardiac death. Compared to well-known clinical variables, angiographic findings did not have a significant influence on the mid-term mortality.

The 2011 magnitude (M) 9.0 Tohoku-oki earthquake was followed by seismicity activation in inland areas throughout Japan. An outstanding case is the M6.2 Northern Nagano earthquake, central Japan, occurred 13-h after the megathrust event, approximately 400 km away from its epicenter. The physical processes relating the occurrence of megathrust earthquakes and subsequent activation of relatively large inland earthquakes are not well understood. Here we use waveform data of a dense local seismic network to reveal with an unprecedented resolution the complex mechanisms leading to the occurrence of the M6.2 earthquake. We show that previously undetected small earthquakes initiated along the Nagano earthquake source fault at relatively short times after the Tohoku-oki megathrust earthquake, and the local seismicity continued intermittently until the occurrence of the M6.2 event, being likely 'modulated' by the arrival of surface waves from large, remote aftershocks off-shore Tohoku. About 1-h before the Nagano earthquake, there was an acceleration of micro-seismicity migrating towards its hypocenter. Migration speeds indicate potential localized slow-slip, culminating with the occurrence of the large inland earthquake, with fluids playing a seismicity-activation role at a regional scale.

The requirements to waive in vivo bioequivalence studies for immediate release solid oral dosage forms based on the Biopharmaceutics Classifications System (BCS) are well known, and biowaivers[1] for other types of oral dosage forms based on pre-defined criteria may also be acceptable. Similarly, biowaivers for dosage forms such as injectable products may also be allowed if certain criteria are met. The current paper summarises the biowaiver requirements for oral solutions and suspensions, soft gelatin capsules and injectable products (intravenous injections, subcutaneous and intramuscular injections, emulsions for injection and micellar solutions for injection) among the participants of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Programme (IPRP). A review of the requirements indicated that there was a trend towards convergence when the dosage form became less complex; however, the most common approach used by each of the jurisdictions was a case-by-case approach given that most jurisdictions do not have well defined guidelines to support all possible scenarios. Even in the simplest case of intravenous solutions, the acceptability of qualitative changes in excipients differ between the IPRP members.  Notwithstanding the differences, the dissemination of the information is a first step towards regulatory convergence regarding biowaivers for certain dosage forms and should be useful for pharmaceutical companies currently developing generic medicinal products for IPRP jurisdictions.

Liquid-liquid extraction for the removal of pertechnetate ( 99 TcO 4 - ) and perrhenate (ReO 4 - ) is reported based on using the tripodal extractant N,N,N',N',N″,N″-hexa-n-octylnitrilotriacetamide (HONTA) composed of three amide groups and a tertiary amine. The extraction behaviors were compared with those using alkyldiamideamines (ADAAM(Oct) and ADAAM(EH)), and the commercial amine-type extractant, trioctylamine (TOA). HONTA quantitatively extracted 99 TcO 4 - and ReO 4 - in the pH range from 1.0 to 2.5 by the co-extraction of protons. The extraction performance of the extractants was improved in the order of HONTA > ADAAM(Oct) > ADAAM(EH) > TOA. 99 TcO 4 - and ReO 4 - in the extracting phase were successfully stripped using neutral aqueous solutions as the receiving phase, and the extraction ability of HONTA was maintained after five repeated uses.

The distribution constants of 4-benzoyl-3-phenyl-5-isoxazolone (HPBI) and deprotonated one (PBI - ) between hydrophobic ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C 1 C 4 im][Tf 2 N]) and aqueous phases were determined, together with the acid-dissociation constant of HPBI. The solvent extraction of three selected lanthanoid ions (La 3+ , Eu 3+ , and Lu 3+ ) with HPBI from aqueous nitrate phase into [C 1 C 4 im][Tf 2 N] has been investigated. Application of the ionic liquid as the extracting phase greatly enhanced the extraction performance of HPBI for lanthanoid ions compared with that in the chloroform system. A slope analysis was conducted in order to compare the results of the solution 4f-ion coordination chemistry in ionic and molecular media. The composition of the extracted species was established to be anionic tetrakis entities, Ln(PBI) 4 - , for light, middle, and heavy lanthanoid ions in an ionic environment (Ln denotes lanthanoid ion). Nevertheless, the typical neutral chelate lanthanoid complexes of the type Ln(PBI) 3 have been detected when the conventional molecular diluent chloroform was applied as an organic phase.

Deprotonative directed ortho cupration of aromatic/heteroaromatic C-H bond and subsequent oxidation with t-BuOOH furnished functionalized phenols in high yields with high regio- and chemoselectivity. DFT calculations revealed that this hydroxylation reaction proceeds via a copper (I → III → I) redox mechanism. Application of this reaction to aromatic C-H amination using BnONH2 efficiently afforded the corresponding primary anilines. These reactions show broad scope and good functional group compatibility. Catalytic versions of these transformations are also demonstrated.

Protozoan parasites of the genus Entamoeba infect many classes of vertebrates and are primarily classified based on morphological criteria. To date, only a few species have been proven to cause disease. Here, we examined the pathology of infected pigs with hemorrhage and detected Entamoeba parasites. Isolates were characterized genetically and ultrastructurally to identify the species. Histopathologically, bleeding and thrombus formation were seen only in the large intestine mucosa, where a large number of trophozoites or some Entamoeba cysts were observed around breakdowns in the lamina propria. No screw-shaped bacteria were detected in the lesions, and no pathogenic bacteria such as Brachyspira spp. were detected in fecal cultures. Interestingly, electron microscopy revealed that the parasites possessed mitochondrial organelles, unlike other Entamoeba spp. The isolates were identified as Entamoeba suis by PCR analysis and sequencing of the small subunit ribosomal RNA (SSU rRNA) gene. In phylogenetic analyses based on the actin gene, the E. suis isolate formed a cluster with Entamoeba histolytica and Entamoeba invadens, as well as with other parasites of the Amoebidae. Whether the pathogenicity of the E. suis isolate is affected by the severity of infection or host health status remains unclear; however, our results suggest that E. suis could cause or exacerbate clinical symptoms such as hemorrhagic colitis or diarrhea.

We report on the acid dissociation constants (Ka) of diglycolamic acid-type ligands together with comprehensive data on the extraction performance of N,N-dioctyldiglycolamic acid (DODGAA) for 54 metal ions. The pKa of the diglycolamic acid framework was determined to be 3.54 ± 0.03 in water (0.1 M LiCl, 25°C) by potentiometric titration, indicating that DODGAA is strongly acidic compared with acetic acid. DODGAA can quantitatively transfer various metal ions among the 54 metal ions through a proton-exchange reaction, and provides excellent extraction performance and separation ability for rare-earth metal ions, In(III), Fe(III), Hg(II), and Pb(II) among the 54 metal ions.

Liquid-liquid extraction of lanthanide ions (Ln(3+)) using N,N-dioctyldiglycolamic acid (DODGAA) was comprehensively investigated, together with fluorescence spectroscopic characterization of the resulting extracted complexes in the organic phase. DODGAA enables the quantitative partitioning of all Ln(3+) ions from moderately acidic solutions, while showing selectivity for heavier lanthanides, and provides remarkably high extraction separation performance for Ln(3+) compared with typical carboxylic acid extractants. Furthermore, the mutual separation abilities of DODGAA for light lanthanides are higher than those of organophosphorus extractants. Slope analysis, loading tests, and electrospray ionization mass spectrometry measurements demonstrated that the transfer of Ln(3+) with DODGAA proceeded through a proton-exchange reaction, forming a 1:3 complex, Ln(DODGAA)3. The stripping of Ln(3+) from the extracting phase was successfully achieved under acidic conditions. Time-resolved laser-induced fluorescence spectroscopy revealed that the extracted Eu(3+) ions were completely dehydrated by complexation with DODGAA.

Here, we report a new approach for the biofabrication of protein-immobilized gold nanoparticles (Au NPs), using oxidoreductase with gold-binding peptide-tagged recombinant proteins. The reduction of Au ions to Au(0) was achieved using a natural electron-donating cofactor, nicotinamide adenine dinucleotide, which was regenerated by the glycerol dehydrogenase (GLD) enzyme. First, we selected the A3 peptide (AYSSGAPPMPPF) as a gold binding moiety. The A3 peptide was introduced to the C-terminus of fusion proteins of immunoglobulin G (IgG)-binding domains of protein G and protein A. In the presence of the recombinant protein, the GLD-catalyzed cofactor reduction resulted in the efficient in situ fabrication of Au NPs immobilized with the fusion protein. Moreover, the protein-immobilized Au NPs were shown to have IgG binding activity. Although the A3 peptide had the ability to stabilize Au NPs, the results suggested that its binding affinity for Au NPs was unexpectedly weaker than that of His-tag. A cysteine residue was thus introduced to a recombinant protein adjacent to the A3 peptide. Finally, an artificial peptide, comprising A3 sequence with the C-terminal single cysteine residue, enabled the stable display of a fusion protein while maintaining its IgG binding activity through the Au-S bond. This enzyme-assisted one-pot methodology for protein-Au NPs conjugation offers one potent route for the facile fabrication of biomolecule-decorated metal NPs.

Selective separation of lead ions (Pb(2+)) from aqueous solutions containing multiple divalent metal ions (Pb(2+), Cu(2+), Cd(2+), Zn(2+), Mn(2+), Co(2+), and Ni(2+)) was investigated using liquid-liquid extraction. N,N-Dioctyldiglycol amic acid (DODGAA) enabled quantitative extraction and efficient separation of Pb(2+) from the metal ion mixture under mildly acidic conditions. Compared with conventional commercial extractants, DODGAA provided better extraction and excellent selectivity for Pb(2+). The extraction of Pb(2+) with DODGAA proceeded through a proton-exchange reaction and formed a 1:2 complex, Pb(DODGAA)(2). The Pb(2+) was readily stripped from the extracting phase under acidic conditions, and the organic solution with DODGAA could be recycled.