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Background: Ants are one of the most serious household pests. White-footed ants in the genus Technomyrmex (Hymenoptera: Formicidae) are invasive species of increasing global importance as evidenced by recent range expansion, nuisance pest status in residential areas and control difficulties driven mainly by lack of effective bait products. The goal for the current study was to develop an effective hydrogel bait and community-wide management program for controlling the invasive T. brunneus in a residential area of Hachijo Island, Japan., Results: In laboratory insecticide screening, hydrogel baits containing thiamethoxam achieved higher T. brunneus mortality than those containing dinotefuran, imidacloprid, boric acid or fipronil at the concentrations tested. Hydrogel baits containing 0.01% and 0.001% thiamethoxam resulted in ≥90% mortality within seven days. However, the horizontal transfer effect was not strong with either concentration. Field experiments confirmed that hydrogel baits containing 10% and 30% sugar are highly attractive to T. brunneus. The community-wide treatment utilizing hydrogel bait containing 0.001% thiamethoxam and 30% sugar significantly suppressed T. brunneus. Town residents were given the opportunity to participate in the program by applying hydrogel baits around their homes, and a follow-up survey revealed that the residents regarded hydrogel baits as easy to apply and highly attractive and effective against T. brunneus., Conclusion: The hydrogel bait and management program developed in this study can be used to suppress T. brunneus. Furthermore, our results demonstrate that a large network of highly motivated and properly trained members of the public can be highly effective in managing invasive ant populations. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

We clarified the specific micrometric arrangement and nanometric structure of the radiolarian crystalline spines that are not a simple single crystal. A body of the celestite (SrSO 4 ) skeleton of acantharian Acanthometra cf. multispina (Acanthometridae) composed of 20 radial spines having four blades was characterized using microfocus X-ray computed tomography. The regular arrangement of three types of spines was clarified with the connection of the blades around the root of each spine. The surface of the spines was covered with a chitin-based organic membrane to prevent from dissolution in seawater. In the nanometric scale, the mesocrystalline structure that consists of nanoscale grains having distorted single-crystal nature was revealed using scanning- and transmission electron microscopies, electron diffraction, and Raman spectroscopy. The acantharian skeletons have a crystallographically controlled architecture that is covered with a protective organic membrane. These facts are important for penetrating the nature of biogenic minerals., (© 2022. The Author(s).)

Objectives:  In this study, we aimed to evaluate the bactericidal effect and cytotoxicity of an ethylenediaminetetra-acetic acid (EDTA)-based root canal irrigant solution capable of efficiently removing both the organic matter and the smear layer. We prepared a strong alkaline EDTA (AE) solution with an acid buffer capacity similar to that of sodium hypochlorite., Materials and Methods:  AE was used at concentrations of 1%, 2%, and 3%. The bactericidal effect of AE on Enterococcus faecalis was evaluated by determining the colony number and biofilm removal rate. Biofilms were visualized using a Live/Dead BacLight bacterial viability kit. Viability of AE-treated cells were determined using a CCK-8 cell counting assay., Statistical Analysis:  One-way analysis of variance followed by a Dunnett's multiple comparison test were used for comparisons among groups., Results:  Significant reduction in cell viability and biofilm formation were observed in case of 3% and 2% AE. AE exerted bactericidal effects in a concentration-dependent manner. Damage of normal human fibroblasts was not observed at any of the AE concentrations., Conclusions:  Our results suggest that the AE solution could be used as an effective canal irrigant for the removal of bacterial biofilm., Competing Interests: None declared., (European Journal of Dentistry. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Introduction: The 2,2-dihydroxymethyl-1-[ 18 F]fluoropropane group, also called 18 F-labelled neopentyl glycol side-chain, is a novel 18 F-labelling group for positron emission tomography (PET) imaging agents. The aim of using this group is to develop simple purification with solid-phase extraction without high-performance liquid chromatography. However, the effects of the neopentyl 18 F-labelling group on the characteristics of brain imaging agents are unknown. Here, we added this side-chain to compounds with an aminostilbene structure to evaluate their effects on the biological properties of aminostilbene as an amyloid-β (Aβ) radioligand., Methods: Biodistributions of four novel 18 F-labelled stilbene compounds with different lengths of polyethylene glycol (PEG) linkers, called [ 18 F]Cpd-0, -1, -2, and -4, (PEG = 0, 1, 2, and 4), and [ 18 F]AV-1 in normal mice were evaluated. Metabolite analysis of [ 18 F]Cpd-0 and -1 was performed with mouse plasma and brain. A competitive binding assay of [ 18 F]AV-1 binding to Aβ 1 - 42 fibrils was performed to determine the binding properties of the compounds., Results: [ 18 F]Cpd-0, -1, and -2 demonstrated moderate initial brain uptake in mice (3.1-4.2% injected dose/g at 2 min post-injection) followed by fast clearance, and in vivo defluorination of these compounds was negligible. [ 18 F]Cpd-4 exhibited low brain uptake and high bone uptake. Compared with [ 18 F]Cpd-1, the percentage of [ 18 F]Cpd-0 in mouse brain was high at 10 min post-injection. A competitive binding assay revealed partial interference effects by the neopentyl glycol side-chain on binding of stilbene compounds to Aβ 1 - 42 fibrils., Conclusions: Aminostilbene compounds with two or fewer PEG linkers containing an 18 F-labelled neopentyl glycol side-chain demonstrated preferable pharmacokinetic properties as a brain imaging radioligand in normal mice. These side-chains can be used as an alternative labelling group for imaging agents targeting the brain., Competing Interests: Declaration of competing interest KH is an employee of NMP Business Support. KI was an employee of NMP Business Support., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: It was shown that mucosal immunity via salivary IgA may be related to the improvement of seasonal allergic rhinitis (SAR) symptoms, and improvement of SAR symptoms through saliva flow increase has been reported in patients using mouthguard (MG) in dental treatment. The purpose of this study was to analyze the effect of MG use on SAR symptom improvement and to clarify the role of saliva on SAR symptom development., Methods: We recruited patients from the Kanagawa Dental University Hospital including 38 and 8 patients with SAR and non-SAR symptoms during two seasons from March 2017 to April 2018. We analyzed the saliva flow rate pre- and post-MG use and measured the amount of IgA and IgG4 in the saliva. We assessed the correlation between SAR symptoms and MG use. SAR symptoms were examined according to a specific clinical score., Results: It was revealed that salivary IgA concentration was significantly lower in SAR patients than in controls. SAR symptoms significantly improved with MG use. The saliva flow rate and IgA levels significantly increased with MG use, although the IgG4 levels did not change., Conclusions: MG use may be beneficial for improving the symptoms of SAR patients by increasing the IgA levels., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR: UMIN000026428) on 6 th March 2017., Competing Interests: Conflicts of interest The authors deny any conflict of interest related to this study., (Copyright © 2020 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.)

We compared sex-reversal ratios induced by 17α-methyltestosterone (MT) and 17β-estradiol (E2) exposure in two inbred medaka strains: Hd-rR derived from Oryzias latipes and HNI-II from O. sakaizumii . All MT exposures (0.2-25 ng mL -1 ) induced complete XX sex-reversal in HNI-II. Although MT exposure at 0.2 ng mL -1 induced XX sex-reversal at > 95% in Hd-rR, other concentrations tested caused XX sex-reversal at lower frequencies (<50%). MT exposure at 1, 5, and 25 ng mL -1 induced XY sex-reversal in Hd-rR, but not in HNI-II. In Hd-rR, E2 exposure induced XY sex-reversal at > 10 ng mL -1 , and in all fish feminization occurred 500 ng mL -1 . In HNI-II, E2 induced XY sex-reversal at 50 and 250 ng mL -1 , but only at rates below 20%. To clarify whether the strain differences in sex hormone-induced sex-reversal are characteristic of each species, we examined the effects of MT and E2 exposure on sex differentiation in five and two additional strains or wild stocks/populations of O. latipes and O. sakaizumii , respectively. MT exposure induced low XX and high XY sex-reversal rates in O. latipes , except in the Shizuoka population, but the trend was reversed in O. sakaizumii . Furthermore, E2-induced XY sex-reversal rates varied intraspecifically in O. latipes . Our results demonstrated that sensitivity to MT and E2 varied within O. latipes species. To evaluate the ecological impacts of environmental chemicals using medaka, it is important to define not only the species, but the strains, stocks, and populations to obtain accurate results.

Biomass allocation to fine roots often increases under soil nutrient deficiency, but the fine root biomass does not often increase in old stands, even under nutrient limitation. Therefore, in old stands, the morphology, anatomy, branching architecture and mycorrhization of fine roots may compensate efficiently for nutrient acquisition by the low fine root biomass. In this study, changes in the morphology, anatomy and arbuscular mycorrhizal infection at each branching position of fine root clusters were evaluated in relation to stand age. A chronosequence (6–90 years of age) of stands in a Cryptomeria japonica D. Don plantation was used for these analyses. The fine root size parameters, such as length, weight and tip numbers of fine root clusters, increased with stand age. The specific root tip length (SRTL) decreased with increasing stand age, suggesting that the allocation to root active portions decreased with stand age. From the anatomical observation, the ephemeral root tips increased with stand age, suggesting that root tip turnover within a root cluster was high in old stands. The proportions of proto-xylem groups among branching positions indicated that the life cycles in branching hierarchy should be clearer in old stands than that in younger stands. The increasing in the mycorrhizal infection of root tips in old stands should enhance the root tip absorptive functions. The SRTL was correlated with the wood/needle ratio, suggesting that carbon limitation as the stand ages may result in decline of carbon allocation to maintain active root tips. However, increasing of the ephemeral tips and mycorrhizal infection rates may compensate the declines of tip allocation in old stands.

Motivation: Recent studies have suggested that both the genome and the genome with epigenetic modifications, the so-called epigenome, play important roles in various biological functions, such as transcription and DNA replication, repair, and recombination. It is well known that specific combinations of histone modifications (e.g. methylations and acetylations) of nucleosomes induce chromatin states that correspond to specific functions of chromatin. Although the advent of next-generation sequencing (NGS) technologies enables measurement of epigenetic information for entire genomes at high-resolution, the variety of chromatin states has not been completely characterized., Results: In this study, we propose a method to estimate the chromatin states indicated by genome-wide chromatin marks identified by NGS technologies. The proposed method automatically estimates the number of chromatin states and characterize each state on the basis of a hidden Markov model (HMM) in combination with a recently proposed model selection technique, factorized information criteria. The method is expected to provide an unbiased model because it relies on only two adjustable parameters and avoids heuristic procedures as much as possible. Computational experiments with simulated datasets show that our method automatically learns an appropriate model, even in cases where methods that rely on Bayesian information criteria fail to learn the model structures. In addition, we comprehensively compare our method to ChromHMM on three real datasets and show that our method estimates more chromatin states than ChromHMM for those datasets., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Many social insect species build nests, which differ from the surrounding environment and are often occupied by specific organismal communities. These organisms may interact mutualistically or parasitically with the nest‐builders, or simply co‐occur, being able to survive in these microenvironments. In temperate forests, red wood ants (e.g. Formica polyctena) are known to create distinct, highly developed nests, which consist of large, above‐ground mounds, built primarily out of plant matter collected from the forest litter. The microorganismal communities of such mounds remain understudied. As representatives of Mucoromycota fungi commonly engage in the decomposition process of the forest litter, they would be expected to occur in the mounds. However, it is still not known whether the Mucoromycota community of these ants' nests differ from the one of the surrounding forest litter. In order to distinguish mound‐associated taxa, we characterized Mucoromycota communities of Formica polyctena mounds and the surrounding forest litter. We sampled four sites, twice in a season. Sampled material was plated on agar media and emerging Mucoromycota colonies were identified based on their morphology. Fungal identification was further confirmed using DNA barcoding. In order to compare described communities, PERMANOVA test and non‐metric multidimensional scaling ordinations were used. To distinguish taxa associated with the mounds, multilevel pattern analysis was performed. Our results show that the Mucoromycota community of Formica polyctena's mound differs from the community of the surrounding forest litter. While representatives of Entomortierella lignicola and Absidia cylindrospora clade were found to be associated with the mound environment, representatives of Umbelopsis curvata and Podila verticillata‐humilis clade were associated with forest litter, and were rarely present in the mounds. Our findings strongly suggest that the red wood ants' nest is a specific microenvironment in the temperate forest floor, which is a preferred microhabitat for the mound‐associated Mucoromycota, possibly adapted to live in proximity to ants. [ABSTRACT FROM AUTHOR]

Natural compounds are important precursors for the synthesis of new drugs. The development of novel molecules that are useful for various diseases is the main goal of researchers, especially for the diagnosis and treatment of many diseases. Some pathologies need to be treated with radiopharmaceuticals, and, for this reason, radiopharmaceuticals that use the radiolabeling of natural derivates molecules are arousing more and more interest. Radiopharmaceuticals can be used for both diagnostic and therapeutic purposes depending on the radionuclide. β+- and gamma-emitting radionuclides are used for diagnostic use for PET or SPECT imaging techniques, while α- and β−-emitting radionuclides are used for in metabolic radiotherapy. Based on these assumptions, the purpose of this review is to highlight the studies carried out in the last ten years, to search for potentially useful radiopharmaceuticals for nuclear medicine that use molecules of natural origin as lead structures. In this context, the main radiolabeled compounds containing natural products as scaffolds are analyzed, in particular curcumin, stilbene, chalcone, and benzofuran. Studies on structural and chemical modifications are emphasized in order to obtain a collection of potential radiopharmaceuticals that exploit the biological properties of molecules of natural origin. The radionuclides used to label these compounds are 68Ga, 44Sc, 18F, 64Cu, 99mTc, and 125I for diagnostic imaging. [ABSTRACT FROM AUTHOR]

Treatment of fracture of the naso-orbitoethmoid (NOE) complex is difficult. There are not only aesthetic issues but also functional consequences related to the lacrimal system. Because prophylactic lacrimal intubation for such fractures remains controversial, we have assessed the effectiveness of intraoperative lacrimal intubation to prevent epiphora as a result of such injuries. Thirteen patients diagnosed with craniomaxillofacial fractures including fractures of the NOE complex were included in the study; 10 had unilateral fractures and 3 bilateral. Computed tomography (CT) showed all patients had displaced fragments that had the potential to damage the lacrimal duct. In 7 patients the fractures included the canthal region and in 6 they did not. All patients were treated by open reduction and internal fixation under general anaesthesia, followed by intraoperative lacrimal intubation unilaterally or bilaterally as required. Lacrimal intubation with a silicone tube was successful in all 13 patients (16 sides). The tube was removed 2-9 months (mean 3.8) postoperatively and no subsequent epiphora were seen during follow-up (mean (3-29 months) 11.3 months). Lacrimal intubation for at least 2 months may prevent epiphora caused by injury to the nasolacrimal system after fractures of the NOE complex., (Copyright © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Aims/Introduction:  Mutations in hepatocyte nuclear factor-4α (HNF4α) lead to various diseases, among which C-terminal deletions of HNF4α are exclusively responsible for maturity onset diabetes of the young 1 (MODY1). MODY is an autosomal dominant disease characterized by a primary defect in insulin response to glucose, suggesting that the C-terminus of HNF4α is important for pancreatic β-cell function. To clarify the role of the C-terminus of HNF4α, changes in cellular localization and the binding ability to its regulator were examined, specifically in the region containing Q268, which deletion causes MODY1., Materials and Methods:   Cellular localization of mutant HNF4α were examined in monkey kidney 7 (COS7), Chinese hamster ovary, rat insulinoma and mouse insulinoma cells, and their binding activity to other proteins were examined by fluorescence resonance energy transfer (FRET) in COS7 cells., Results:   Although wild-type HNF4α was localized in the nucleoplasm in transfected cultured cells, Q268X-HNF4α was located predominantly in the nucleolus. Deletion analysis of the C-terminus of HNF4α showed that the S337X-HNF4α mutant, and other mutants with shorter amino acid sequences (S337-K194), were mostly localized in the nucleolus. HNF4α mutants with amino acid sequences shorter than the W192X-HNF4α mutant gradually spread to the nucleoplasm in accordance with their lengths. The A250X-HNF4α mutant was capable of causing the accumulation of HNF4α or the small heterodimer partner (SHP), one of the HNF4α regulators, in the nucleolus. However, the R154X-HNF4α mutant did not have binding ability to wild-type HNF4α or SHP, and thus was seen in the nucleus., Conclusions:   The C-terminus sites might play a key role in facilitating the nucleolar and subnucleolar localization of HNF4α. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00210.x, 2012).

Mitochondrial pH is a key determinant of mitochondrial energy metabolism. We have developed a new fluorescence-based ratiometric pH biosensor using a chloride-insensitive and hydrogen-sensitive probe for direct, quantitative and bleaching-free measurement in a living cell. Fusing this biosensor with a mitochondrial localization signal (MTpHGV) allowed us to determine mitochondrial pH. This new system was applied to measure mitochondrial pH in pancreatic β-cells, in which mitochondrial function plays a pivotal role in insulin secretion. Rat INS1 cells and mouse MIN6 cells are transfected with MTpHGV stably to monitor mitochondrial pH. While carbonyl cyanide 3-chlorophenylhydrazone (CCCP) treatment rapidly decreased mitochondrial pH in cultured rat MTpHGV-INS-1 cells, MTpHGV-MIN6 cells showed a rapid increase. These data suggest that MTpHGV probe exist in matrix side in INS-1 cells, but on the outer side of mitochondrial inner membrane in MIN6 cells. Moreover, while MTpHGV-INS-1 cells showed a rapid increase of pH by glucose stimulation, mitochondrial pH decreased quickly by glucose stimulation in all MTpHGV-MIN6 cells examined and recovered smoothly. Perfusion study of glucose load in MTpHGV-MIN6 cells under aminooxyacetate (AOA) or 100μM diazoxide showed that this mitochondrial pH acidification was dependent on nicotinamide adenine dinucleotide (NADH) shuttle, but independent from KATP channel. This new system for measuring mitochondrial pH is sensitive across the range of physiologic conditions and may be a useful tool for evaluating mitochondrial function in living cells., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: It is usually suggested that life expectancy of top athletes especially in endurance sports is longer than that of sedentary people. On the other hand, heart rate recovery (HRR) after exercise is an independent risk factor for cardiovascular disease and mortality, but differences in HRR between various top athletes are unclear. We examined HRR in various top athletes to clarify a role of HRR that may affect their life expectancy., Methods: HRR was defined as the difference between the heart rate at peak exercise and that at 2 min after the finish of exercise using symptom-limited maximal graded bicycle ergometer exercise testing. The relationships between HRR with the grade of static and dynamic component of classification of sports, age, and body mass index (BMI) were estimated., Subjects: The subjects were 720 male athletes participating in the National Sports Festival Japan in 2005-2008 and age-matched 28 sedentary controls., Results: HRR was significantly correlated (p<0.0001) with the higher grade of dynamic component of sports, younger age, and lower BMI in both univariate and multivariate analysis., Conclusions: HRR of top athletes is predicted by increased dynamic component of sports, younger age, and lower BMI., (Copyright © 2011 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Objective: Heart rate recovery (HRR) after exercise is an independent risk factor for cardiovascular disease and mortality, and it is well known to be modifiable by weight loss. We investigated whether HRR was mainly improved by better cardiopulmonary function or by alteration of the metabolic profile., Methods: The weight loss program included 2h of group exercise per week and individual dietary instruction by a qualified dietician every week. Clinical assessment (including HRR) was done before and after the 3-month program., Patients: The subjects were 125 obese persons without a past history of stroke, cardiovascular events, or use of medications who participated in and completed our exercise plus weight loss program., Results: HRR (35.61+/-12.83 to 45.34+/-13.6 beats/min, p<0.0001) was significantly faster after the program. The change in HRR was significantly correlated (p<0.05) with the changes in body weight, body mass index, percent body fat, waist circumference, hip circumference, resting heart rate, peak exercise heart rate, exercise time, maximal work load, physical working capacity divided by body weight (PWC75%HRmax/weight), subcutaneous fat area, visceral fat area, low-density lipoprotein cholesterol, and leptin. Multivariate analysis showed that the change in HRR was significantly correlated (p<0.05) with the changes in resting heart rate, peak exercise heart rate, and PWC75%HRmax/weight., Conclusions: Our data demonstrated that HRR can be improved in obese subjects by a 3-month exercise and weight loss program. Improvement in cardiopulmonary function by exercise seems to be the main contributor to the increment of HRR., (Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Recent advances in genome research have enabled the identification of new genomic variations that are associated with type 2 diabetes mellitus (T2DM). Via fine mapping of SNPs in a candidate region of chromosome 21q, the current study identifies potassium inwardly-rectifying channel, subfamily J, member 15 (KCNJ15) as a new T2DM susceptibility gene. KCNJ15 is expressed in the beta cell of the pancreas, and a synonymous SNP, rs3746876, in exon 4 (C566T) of this gene, with T allele frequency among control subjects of 3.1%, showed a significant association with T2DM affecting lean individuals in three independent Japanese sample sets (p = 2.5 x 10(-7), odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.76-3.67) and with unstratified T2DM (p = 6.7 x 10(-6), OR = 1.76, 95% CI = 1.37-2.25). The diabetes risk allele frequency was, however, very low among Europeans in whom no association between this variant and T2DM could be shown. Functional analysis in human embryonic kidney 293 cells demonstrated that the risk allele of the synonymous SNP in exon 4 increased KCNJ15 expression via increased mRNA stability, which resulted in the higher expression of protein as compared to that of the nonrisk allele. We also showed that KCNJ15 is expressed in human pancreatic beta cells. In conclusion, we demonstrated a significant association between a synonymous variant in KCNJ15 and T2DM in lean Japanese patients with T2DM, suggesting that KCNJ15 is a previously unreported susceptibility gene for T2DM among Asians., (2010 The American Society of Human Genetics. Published by Elsevier Inc.)

The aim of the present study was to investigate the specific relationship between hepatic steatosis and insulin resistance in the early stage of obesity. Among general health examinees who received an ultrasound scanning, 131 subjects without fatty liver (non-FL group) and 142 subjects with fatty liver (FL group) were selected so that both groups were matched for age, sex, body mass index, and % body fat. The FL group was then subdivided into 2 groups according to the severity of steatosis by ultrasound. Insulin resistance was assessed by homeostasis model assessment for insulin resistance, serum high-molecular-weight (HMW) adiponectin, and insulin-like growth factor binding protein 1 concentrations. Unexpectedly, the non-FL group showed higher waist circumference than the FL group. Nevertheless, homeostasis model assessment for insulin resistance as well as conventional insulin resistance indexes such as serum insulin, free fatty acid, and triglyceride levels demonstrated a stepwise increase, and HMW adiponectin and insulin-like growth factor binding protein 1 demonstrated a stepwise decrease with increasing degree of hepatic steatosis. Overall, insulin resistance markers correlated with obesity indexes, but only HMW adiponectin no longer showed any meaningful correlation in the presence of fatty liver. The prevalence of BP, fasting serum glucose, and high-density lipoprotein cholesterol above or below cutoff points and subjects having 2 or more metabolic syndrome components were higher in the moderate to severe FL group compared to the non-FL group. In conclusion, these results in nondiabetic and relatively normal-body mass index subjects suggest that hepatic steatosis is independently associated with insulin resistance regardless of extrahepatic adiposity and might be the earliest event in pathogenesis of the metabolic syndrome.

This case report describes a patient with elbow contracture due to phlebosclerosis induced by anti-cancer drug infusion. Limitation of elbow extension was completely relieved by surgical excision of the sclerotic vein.

Object: Recently, prothrombin fragment F1+2 was shown to be a sensitive direct marker of thrombin formation. We examined the effect of lifestyle (including physical activity) on prothrombin fragment F1+2 levels., Methods: Using the results of a questionnaire, the subjects were classified into groups on the basis of multiple medications, smoking, exercise, and drinking alcohol. The prothrombin fragment F1+2 levels were compared between each pair of groups and differences were analyzed using the unpaired t-test. Correlations between each parameter and the systolic and diastolic blood pressure, as well as with prothrombin fragment F1+2, were examined by multiple regression analysis. Patients The subjects were 109 patients who had essential hypertension without a past history of thrombotic events, Results: Smokers (1.47 +/- 0.75 vs 0.98 +/- 0.46 nmol/L, p<0.0001), and those without regular exercise (1.22 +/- 0.59 vs 0.68 +/- 0.30 nmol/L, p<0.0001) had higher levels of prothrombin fragment F1+2. Age, lack of exercise, and smoking were significant predictors of a high concentration of prothrombin fragment F1+2. Of the smokers, the patient with a regular exercise had low F1+2 compared with those without regular exercise (0.75 +/- 0.20 vs 2.01 +/- 0.49 nmol/L, p<0.0001., Conclusions: In patients with essential hypertension, age, smoking, and lack of regular exercise may increase the risk of thrombosis. Even in smokers, a regular exercise routine may reduce the tendency towards thrombus formation.

Anthracyclines are chemotherapeutic drugs used to treat solid and hematologic malignancies. However, life‐threatening cardiotoxicity, with cardiac dilation and heart failure, is a drawback. A combination of in vivo for single cell/nucleus RNA sequencing and in vitro approaches is used to elucidate the underlying mechanism. Genetic depletion and pharmacological blocking peptides on phosphatidylinositol binding clathrin assembly (PICALM) are used to evaluate the role of PICALM in doxorubicin‐induced cardiotoxicity in vivo. Human heart tissue samples are used for verification. Patients with end‐stage heart failure and chemotherapy‐induced cardiotoxicity have thinner cell membranes compared to healthy controls do. Using the doxorubicin‐induced cardiotoxicity mice model, it is possible to replicate the corresponding phenotype in patients. Cellular changes in doxorubicin‐induced cardiotoxicity in mice, especially in cardiomyocytes, are identified using single cell/nucleus RNA sequencing. Picalm expression is upregulated only in cardiomyocytes with doxorubicin‐induced cardiotoxicity. Amyloid β‐peptide production is also increased after doxorubicin treatment, which leads to a greater increase in the membrane permeability of cardiomyocytes. Genetic depletion and pharmacological blocking peptides on Picalm reduce the generation of amyloid β‐peptide. This alleviates the doxorubicin‐induced cardiotoxicity in vitro and in vivo. In human heart tissue samples of patients with chemotherapy‐induced cardiotoxicity, PICALM, and amyloid β‐peptide are elevated as well. [ABSTRACT FROM AUTHOR]

Uremic toxins cause bone disorders in patients with chronic kidney disease (CKD). These disorders are characterized by low turnover osteodystrophy and impaired bone formation in the early stages of CKD. Evidence indicates that the aryl hydrocarbon receptor (AhR) mediates signals that suppress early osteogenic differentiation in bone marrow mesenchymal stem cells (BMSCs). However, whether the AhR mediates the effects of indoxyl sulfate (IS), a uremic toxin, on BMSC osteogenesis remains unclear. We investigated whether IS affects osteogenesis through the AhR/Hes1 pathway. Expression levels of osteogenesis genes (Runx2, Bmp2, Alp, and Oc), AhR, and Hes1 were measured in mouse BMSCs (D1 cells). At concentrations of 2–50 μM, IS significantly reduced mineralization, particularly in the early stages of BMSC osteogenesis. Furthermore, IS significantly downregulated the expression of Runx2, Bmp2, Oc, and Alp. Notably, this downregulation could be prevented using an AhR antagonist and through Ahr knockdown. Mechanistically, IS induced the expression of Hes1 through AhR signaling, thereby suppressing the transcription of Runx2 and Bmp2. Our findings suggest that IS inhibits early osteogenesis of BMSCs through the AhR/Hes1 pathway, thus suppressing the transcription of Runx2 and Bmp2. Our findings may guide new therapeutic strategies against CKD-related bone disorders. [ABSTRACT FROM AUTHOR]

Canopy gaps can result in abiotic heterogeneities and diverse niches from gap borders to centers, potentially affecting fine root decompositions mediated by soil fungal communities. Despite extensive discussions on the relationship between soil fungi and fine root decomposition, the mechanism by which gap locations regulate fine root decomposition through the soil fungal community remains elusive. Here, we conducted an in situ field decomposition experiment of Chinese Toon (Toona sinensis) fine roots in a low-efficiency weeping cypress (Cupressus funebris) plantation forest across three microhabitats: gap centers, gap borders, and closed canopy areas. Soil fungal communities were determined using internal transcribed spacer (ITS) sequencing after two years of field incubation. Results showed that soil properties and nutrient content in residual roots varied across the three microhabitats, with the gap borders exhibiting the highest decomposition rates. While fungal α-diversity remained relatively consistent, taxonomic compositions differed significantly. Decomposition rates did not show significant correlations with soil properties, observed fungal ASVs, or overall community composition. However, they positively correlated with the relative abundance of saprotrophic Sordariomycetes, which in turn positively correlated with soil total nitrogen (with a highest correlation), peaking at the gap borders. Overall community variations were primarily driven by soil temperature and magnesium content in residual roots. Further analysis revealed high fungal community similarities and low dispersal limitations between the gap borders and closed canopy areas, with more phylogenetically clustered communities at the borders. These results demonstrate that the gap borders possess a high decomposition rate, likely due to the centralization of functions driven by soil fungi such as saprotrophs existing in the "microbial seed bank" or migrating from closed canopy areas. These findings highlight the key role of soil fungi, especially saprotrophic fungi, in fine root decomposition at the gap borders, stressing the importance of soil fungi-driven mechanisms in nutrient cycling, and also informing sustainable forest management practices. [ABSTRACT FROM AUTHOR]

Fauna is highly abundant and diverse in soils worldwide, but surprisingly little is known about how it affects soil organic matter stabilization. Here, we review how the ecological strategies of a multitude of soil faunal taxa can affect the formation and persistence of labile (particulate organic matter, POM) and stabilized soil organic matter (mineral-associated organic matter, MAOM). We propose three major mechanisms - transformation, translocation, and grazing on microorganisms - by which soil fauna alters factors deemed essential in the formation of POM and MAOM, including the quantity and decomposability of organic matter, soil mineralogy, and the abundance, location, and composition of the microbial community. Determining the relevance of these mechanisms to POM and MAOM formation in cross-disciplinary studies that cover individual taxa and more complex faunal communities, and employ physical fractionation, isotopic, and microbiological approaches is essential to advance concepts, models, and policies focused on soil organic matter and effectively manage soils as carbon sinks, nutrient stores, and providers of food. In their review, Angst et al. conceptualize how the ecological strategies of a multitude of soil faunal taxa can influence the formation of particulate and mineral-associated organic matter. The authors highlight research gaps and ways forward. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is a common cancer among men worldwide that has a very poor prognosis, especially when it progresses to metastatic castration-resistant prostate cancer (mCRPC). Therefore, novel therapeutic agents for mCRPC are urgently required. Because prostate-specific membrane antigen (PSMA) is overexpressed in mCRPC, targeted alpha therapy (TAT) for PSMA is a promising treatment for mCRPC. Astatine-211 (211At) is a versatile α-emitting radionuclide that can be produced using a cyclotron. Therefore, 211At-labeled PSMA compounds could be useful for TAT; however, 211At-labeled compounds are unstable against deastatination in vivo. In this study, to develop in vivo stable 211At-labeled PSMA derivatives, we designed and synthesized 211At-labeled PSMA derivatives using a neopentyl glycol (NpG) structure that can stably retain 211At in vivo. We also evaluated their biodistribution in normal and tumor-bearing mice. Results: We designed and synthesized 211At-labeled PSMA derivatives containing two glutamic acid (Glu) linkers between the NpG structure and asymmetric urea (NpG-L-PSMA ((L-Glu)2 linker used) and NpG-D-PSMA ((D-Glu)2 linker used)). First, we evaluated the characteristics of 125I-labeled NpG derivatives because 125I was readily available. [125I]I-NpG-L-PSMA and [125I]I-NpG-D-PSMA showed low accumulation in the stomach and thyroid, indicating their high in vivo stability against deiodination. [125I]I-NpG-L-PSMA was excreted in urine as hydrophilic radiometabolites in addition to the intact form. Meanwhile, [125I]I-NpG-D-PSMA was excreted in urine in an intact form. In both cases, no radioactivity was observed in the free iodine fraction. [125I]I-NpG-D-PSMA showed higher tumor accumulation than [125I]I-NpG-L-PSMA. We then developed 211At-labeled PSMA using the NpG-D-PSMA structure. [211At]At-NpG-D-PSMA showed low accumulation in the stomach and thyroid in normal mice, indicating its high stability against deastatination in vivo. Moreover, [211At]At-NpG-D-PSMA showed high accumulation in tumor similar to that of [125I]I-NpG-D-PSMA. Conclusions: [211At]At-NpG-D-PSMA showed high in vivo stability against deastatination and high tumor accumulation. [211At]At-NpG-D-PSMA should be considered as a potential new TAT for mCRPC. [ABSTRACT FROM AUTHOR]

The Internet of Things (IoT) integrates more than billions of intelligent devices over the globe with the capability of communicating with other connected devices with little to no human intervention. IoT enables data aggregation and analysis on a large scale to improve life quality in many domains. In particular, data collected by IoT contain a tremendous amount of information for anomaly detection. The heterogeneous nature of IoT is both a challenge and an opportunity for cybersecurity. Traditional approaches in cybersecurity monitoring often require different kinds of data pre-processing and handling for various data types, which might be problematic for datasets that contain heterogeneous features. However, heterogeneous types of network devices can often capture a more diverse set of signals than a single type of device readings, which is particularly useful for anomaly detection. In this paper, we present a comprehensive study on using ensemble machine learning methods for enhancing IoT cybersecurity via anomaly detection. Rather than using one single machine learning model, ensemble learning combines the predictive power from multiple models, enhancing their predictive accuracy in heterogeneous datasets rather than using one single machine learning model. We propose a unified framework with ensemble learning that utilises Bayesian hyperparameter optimisation to adapt to a network environment that contains multiple IoT sensor readings. Experimentally, we illustrate their high predictive power when compared to traditional methods. [ABSTRACT FROM AUTHOR]

Simple Summary: Interactions among soil organisms are crucial for food webs and ecological functions. However, the effects of millipedes, which play a key role as decomposers in the soil, on soil microarthropods remain unclear. This study demonstrates that millipede activity in the soil decreased the abundance and diversity of Collembola in the soil while increasing their abundance and diversity in the litter layer. Consequently, this led to an increase in the abundance and diversity of Acari in the soil. The dominant species of both Acari and Collembola were most notably affected by the experiment. Millipede activity significantly altered the community structure of Acari and Collembola and strengthened the correlation between these two groups. These findings enhance our understanding of the ecological role of millipedes. Ecosystem engineers influence the structure and function of soil food webs through non-trophic interactions. The activity of large soil animals, such as earthworms, has a significant impact on the soil microarthropod community. However, the influence of millipedes on soil microarthropod communities remains largely unknown. In this microcosm experiment, we examined the effects of adding, removing, and restricting millipede activity on Acari and Collembola communities in litter and soil by conducting two destructive sampling sessions on days 10 and 30, respectively. At the time of the first sampling event (10 d), Acari and Collembola abundance was shown to increase and the alpha diversity went higher in the treatments with millipedes. At the time of the second sampling event (30 d), millipedes significantly reduced the Collembola abundance and alpha diversity. The results were even more pronounced as the millipedes moved through the soil, which caused the collembolans to be more inclined to inhabit the litter, which in turn resulted in the increase in the abundance and diversity of Acari in the soil. The rapid growth of Collembola in the absence of millipedes significantly inhibited the abundance of Acari. The presence of millipedes altered the community structure of Acari and Collembola, leading to a stronger correlation between the two communities. Changes in these communities were driven by the dominant taxa of Acari and Collembola. These findings suggest that millipedes, as key ecosystem engineers, have varying impacts on different soil microarthropods. This study enhances our understanding of biological interactions and offers a theoretical foundation for soil biodiversity conservation. [ABSTRACT FROM AUTHOR]

Eucalyptus roots form symbiotic relationships with arbuscular mycorrhizal (AM) fungi in soil to enhance adaptation in challenging environments. However, the evolution of the AM fungal community along a chronosequence of eucalypt plantations and its relationship with soil properties remain unclear. In this study, we evaluated the tree growth, soil properties, and root AM fungal colonization of Eucalyptus grandis W. Hill ex Maiden plantations at different ages, identified the AM fungal community composition by high-throughput sequencing, and developed a structural equation model among trees, soil, and AM fungi. Key findings include the following: (1) The total phosphorus (P) and total potassium (K) in the soil underwent an initial reduction followed by a rise with different stand ages. (2) The rate of AM colonization decreased first and then increased. (3) The composition of the AM fungal community changed significantly with different stand ages, but there was no significant change in diversity. (4) Paraglomus and Glomus were the dominant genera, accounting for 70.1% and 21.8% of the relative abundance, respectively. (5) The dominant genera were mainly influenced by soil P, the N content, and bulk density, but the main factors were different with stand ages. The results can provide a reference for fertilizer management and microbial formulation manufacture for eucalyptus plantations. [ABSTRACT FROM AUTHOR]

Stable isotopes of cerium (Ce) and neodymium (Nd), two rare earth elements (REEs), have emerged recently as useful tracers for a range of geological and environmental processes, such as redox changes in environments or continental weathering. However, the coupled use of stable isotopes of two (or more) rare earth elements is often hampered by difficulties in sequential separation of individual REEs and analysis of their stable isotope ratios at high precision. Here, we report a new three-stage chromatographic procedure that allows for simultaneous separation of Ce and Nd from geological samples for high-precision analysis of their stable isotope ratios on MC-ICP-MS. This approach also allows for analysis of radiogenic 143Nd/144Nd ratios at high precision. Sequential separation of Nd and Ce in our procedure was achieved and optimized using α-hydroxyisobutyric acid (α-HIBA) as an eluent. Possible Ce and Nd stable isotope fractionations induced by the α-HIBA column were quantified. Total procedural blanks of our three-stage separation are low for Ce (∼46 pg) and Nd (∼2 pg). Extensive tests were conducted on MC-ICP-MS under dry plasma conditions to evaluate matrix effects associated with common cationic impurities, acid concentration, analyte/dopant ratio, and concentration mismatch between the sample and the bracketing standards. The presence of α-HIBA, and, occasionally, aluminum (Al) can affect measurements of both stable Ce and Nd isotopes, and acid concentration mismatch may affect stable Nd isotope measurements. An iterative correction method was developed to considerably increase the tolerance of stable Ce isotope analysis to Nd isobaric interferences, thereby improving the robustness of our measurement. Based on the analysis of various reference materials, we demonstrate that our new method is suitable for routine high-precision stable Ce and Nd isotope measurements on geological samples with a wide range of matrix compositions, yielding a long-term precision of ≤0.04‰ (2SD) for 142Ce/140Ce and ≤0.03‰ (2SD) for 146Nd/144Nd. This method also permits accurate radiogenic 143Nd/144Nd measurement with an external precision of ≤15 ppm (2SD). Because the α-HIBA column is known for its capability of separating individual REEs, our approach can be adapted to separate other REEs for high-precision stable and radiogenic isotope analysis with minor modifications. [ABSTRACT FROM AUTHOR]

Notch is a signaling molecule which plays a critical role in the determination of multiple cellular differentiation pathways and morphogenesis in various biological systems, such as neurogenesis, immune system, and hematopoiesis. However, roles of Notch signaling in osteo/chondrogenesis have not been well studied. We will present our recent progress in investigating roles of Notch signaling in chondrogenesis using in vitro chondrogenic system. We will also discuss about the recent reports which used conditional knockout mice to investigate roles of Notch signaling molecules in vivo .

In endochondral ossification, chondrogenesis precedes bone development. Cartilage differentiation is initiated by the formation of chondrogenic cell condensates. Thus, it is essential to investigate genes expressed at the condensation stage for a better understanding of chondrogenesis and ossification. To this end, we constructed a cDNA library from the mRNA fraction derived from a chondrogenic cell line (ATDC5) at the cell condensation stage by using the signal sequence trap by retrovirus-mediated expression (SST-REX) method. We obtained 486 factor (IL-3)-independent clones by screening 5.7 x 10(3) clones. DNA sequencing analysis of the clones identified genes encoding 157 known proteins and 4 novel proteins. These 4 genes encoding novel proteins were expressed not only in chondrogenic ATDC5 cells but also in osteogenic MC3T3-E1 and myogenic C2C12 cells. The mRNA expression level of 1 of the 4 clones increased at the calcification stage of the differentiation of MC3T3-E1 cells. The results demonstrate that the SST-REX method is a useful experimental system to identify genes involved in the complicated mechanisms of bone formation.

Notch signaling is an evolutionarily conserved mechanism that plays a critical role in the determination of multiple cellular differentiation pathways and morphogenesis during embryogenesis. The limb bud high-density culture is an established model that recapitulates mesenchymal condensation and chondrocyte differentiation. Reverse transcription-polymerase chain reaction (RT-PCR) showed that Notch and its related genes were expressed in such cultures on day 1 and reached a peak between day 3 and day 5, when cell condensation and nodule formation were initiated. Immunohistochemical experiments revealed that the expression of Notch1 was initially localized within the nodules and shifted to their peripheral region as the cell differentiation progressed. We disrupted Notch signaling by using a gamma-secretase inhibitor, N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), to analyze the function of Notch signaling in the culture system. The blocking of Notch signaling by DAPT apparently promoted the initiation of prechondrogenic condensation and fusion of the nodules, and such an effect was reversed by exogenous expression of the Notch cytoplasmic domain. DAPT treatment also induced chondrogenic markers and bone morphogenetic protein (BMP)-related molecules, including type II collagen, Sox9, GDF5, and Id1. These observations imply that the Notch signal may have an important role in chondrogenic differentiation by negatively regulating the initiation of prechondrogenic condensation and nodule formation.

Notch is a transmembrane protein involved in cell fate determination. In the present study, we observed temporally and spatially restricted expression of Notch1 in developing cartilage. Notch1 was localized starting from the mesenchymal condensation stage of embryonic mouse forelimbs. Interestingly, although localization could not be detected in the proliferating chondrocytes, obvious immunoreactivity indicating its expression was retained in the perichondrial region. Next, we investigated the expression of Notch1 and related molecules in a chondrogenic cell line, ATDC5 cells. Notch1, Delta-like (Dll)1, Deltex2, and Deltex3 were coexpressed after 6-day insulin treatment. Expression of Hairy and Enhancer of split homologue (HES)-1 followed thereafter. These results suggest that Notch may have a role in the early stage of chondrogenesis. To assess the effect of Notch activation, we cultured ATDC5 cells with a myeloma clone constitutively expressing Dll1, a ligand of Notch. We also used an adenovirus vector to express the constitutively active Notch1 intracellular domain (NIC). Activating either the endogenous or exogenous Notch receptor dramatically inhibited chondrogenic cell differentiation of ATDC5 cells, as assessed by Alcian blue staining of the cells and chondrocyte differentiation markers. Last, we investigated the effect of NIC on the proliferation of the ATDC5 cells. Expression of NIC by the adenovirus strongly suppressed thymidine incorporation. These results indicate that Notch is expressed in the initial stage of chondrogenic cell differentiation and has a strong inhibitory effect on both differentiation and proliferation of the cells when activated. The expression of Notch decreases as chondrogenic differentiation proceeds; however, a population of the cells with sustained expression of Notch1 become perichondrial cells. Considering that the perichondrium acts as a stem cell source of osteoblasts and chondrocytes, Notch1 may have a role in the formation of these cells by suppressing both differentiation and proliferation.

The purpose of this study was to assess the clinical significance of spatial and temporal analysis of left ventricular (LV) filling-flow propagation using color M-mode Doppler echocardiography before and after regression of LV hypertrophy in patients with hypertension. Seven patients with hypertensive LV hypertrophy were studied. Echocardiographic and Doppler examinations were performed both before and after 6 months administration of alacepril. LV mass index (LVMI), LV flow propagation velocity (FPV), and the maximal early transmitral flow velocity (E) were measured. LVMI, FPV, and FPV/E ratio were compared to before and after administration of alacepril. In addition, the correlation between LVMI and FPV/E ratio was evaluated. Results showed that LVMI was significantly decreased (P < 0.05) and the FPV/E ratio was significantly increased (P < 0.05) after treatment with alacepril. There was no significant change in FPV. In addition, there was a significant negative correlation between LVMI and the FPV/E ratio (r = -0.662, P < 0.001). The present study indicates that the FPV/E ratio could be a useful noninvasive parameter to assess the diastolic dysfunction associated with LV hypertrophy in patients with hypertension.