White koji, a solid-state culture of Aspergillus luchuensis mut. kawachii using grains such as rice and barley, is used as a source of amylolytic enzymes and citric acid for the production of shochu, a traditional Japanese distilled spirit. We previously characterized changes in gene expression that affect the properties of white koji during the shochu production process; however, the underlying regulatory mechanisms were not determined. We then characterized the NAD+-dependent histone deacetylase sirtuin, an epigenetic regulator of various biological phenomena, in A. l. mut. kawachii and found that sirtuin SirD is involved in expression of α-amylase activity and citric acid accumulation. In this addendum study, we measured the NAD+/NADH redox state and found that the NAD+ level and NAD+/NADH ratio decrease during koji production, indicating that sirtuin activity declines in the late stages of koji culture. By comparing these results with transcriptomic data obtained in our previous studies, we estimate that approximately 35% of the gene expression changes during white koji production are SirD dependent. This study provides clues to the mechanism of gene expression regulation in A. l. mut. kawachii during the production of white koji.
Background Placental mesenchymal dysplasia (PMD) is a morphological abnormality resembling partial hydatidiform moles. It is often associated with androgenetic/biparental mosaicism (ABM) and complicated by Beckwith–Wiedemann syndrome (BWS), an imprinting disorder. These phenomena suggest an association between PMD and aberrant genomic imprinting, particularly of CDKN1C and IGF2 . The existence of another type of PMD containing the biparental genome has been reported. However, the frequency and etiology of biparental PMD are not yet fully understood. Results We examined 44 placental specimens from 26 patients with PMD: 19 of these were macroscopically normal and 25 exhibited macroscopic PMD. Genotyping by DNA microarray or short tandem repeat analysis revealed that approximately 35% of the macroscopic PMD specimens could be classified as biparental, while the remainder were ABM. We performed a DNA methylation analysis using bisulfite pyrosequencing of 15 placenta-specific imprinted differentially methylated regions (DMRs) and 36 ubiquitous imprinted DMRs. As expected, most DMRs in the macroscopic PMD specimens with ABM exhibited the paternal epigenotype. Importantly, the biparental macroscopic PMD specimens exhibited frequent aberrant hypomethylation at seven of the placenta-specific DMRs. Allelic expression analysis using single-nucleotide polymorphisms revealed that five imprinted genes associated with these aberrantly hypomethylated DMRs were biallelically expressed. Frequent aberrant hypomethylation was observed at five ubiquitous DMRs, including GRB10 but not ICR2 or ICR1, which regulate the expression of CDKN1C and IGF2 , respectively. Whole-exome sequencing performed on four biparental macroscopic PMD specimens did not reveal any pathological genetic abnormalities. Clinical and molecular analyses of babies born from pregnancies with PMD revealed four cases with BWS, each exhibiting different molecular characteristics, and those between BWS and PMD specimens were not always the same. Conclusion These data clarify the prevalence of biparental PMD and ABM-PMD and strongly implicate hypomethylation of DMRs in the pathogenesis of biparental PMD, particularly placenta-specific DMRs and the ubiquitous GRB10 , but not ICR2 or ICR1. Aberrant hypomethylation of DMRs was partial, indicating that it occurs after fertilization. PMD is an imprinting disorder, and it may be a missing link between imprinting disorders and placental disorders incompatible with life, such as complete hydatidiform moles and partial hydatidiform moles.
The recently-developed Dual Self-Directed Humor Scale (DSDHS) is the first instrument for measuring individual differences between two dimensions of self-directed humor (SDH): negative (deleterious SDH) and positive (benign SDH). Thus far, the DSDHS has shown high validity and reliability. However, further validation of the underlying causal relationship between SDH and well-being is required. This study estimated the causal relationship between SDH and several well-being indicators via a two-wave, three-month interval, longitudinal dataset of college students (N = 453). A cross-lagged panel analysis showed that deleterious SDH predicted increased depression over time, while benign SDH predicted decreased depression and anxiety. There was also a two-way causal relationship, with anxiety decreasing benign SDH. These results enhance our understanding of the relationship between SDH and well-being.
Early afterdepolarization (EAD) is an aberrant cardiac afterpotential that underlies the development of life-threatening ventricular arrhythmias. It is believed that the development of EAD is caused by the reactivation of L-type Ca2+ current during the period of the action potential plateau; however, the cellular mechanisms that underlie the development of EAD is still controversial. One favorable alternative is the depolarizing reverse-mode operation of the Na+/Ca2+ exchanger, which is activated by aberrant Ca2+ release from the sarcoplasmic reticulum in the process of reverse E–C coupling. Since EADs develop preferentially in damaged heart cells with abnormal Ca2+-signaling, here I studied the causal link between the development of EADs and aberrant intracellular Ca2+ level ([Ca2+]i) dynamics in mouse heart cells using the whole-cell clamp technique. My results show (1) the generation of EADs was preceded by the development of depolarizing membrane potential (Vm) fluctuation, (2) the depolarizing Vm fluctuation is associated with [Ca2+]i elevation, suggesting an involvement of reverse E–C coupling via the Na+/Ca2+ exchanger, and (3) that extending the T-tubules’ length constant by decreasing the extracellular K+ level facilitated the development of the Vm fluctuation and EADs. Taken together, I conclude that EADs are caused by the depolarizing Vm fluctuation, which is induced locally in the T-tubule membrane by aberrant [Ca2+]i elevation and is conducted back electrotonically along the T-tubules.
Bismuth vanadate (BiVO4) has recently received significant attention for photocatalytic CO2 conversion due to its low bandgap and high stability, but low position of the conduction band and high electron-hole recombination rate limit its photocatalytic activity. In this study, to overcome the drawbacks of BiVO4, oxygen vacancies and lattice strain are simultaneously introduced in this oxide using a high-pressure torsion process. The processed material not only shows the low recombination rate and enhanced conduction band level but also exhibits bandgap narrowing. The oxygen-deficient and highly-strained BiVO4 shows a high photocatalytic CO2 conversion rate with an activity comparable to the P25 TiO2 photocatalyst. The enhancement of photocatalytic activity is discussed based on the modification of band structure, enhanced light absorbance, the lifetime of excited electrons, and the role of oxygen vacancies as activation sites for CO2 photoreduction. This work introduces a feasible pathway to develop active photocatalysts for CO2 conversion by lattice strain and defect engineering.
Previous studies have reported that a high neutrophil-to-lymphocyte ratio (NLR) is associated with disease severity and poor prognosis in COVID-19 patients. We aimed to investigate the clinical implications of NLR in patients with COVID-19 complicated with cardiovascular diseases and/or its risk factors (CVDRF). In total, 601 patients with known NLR values were selected from the CLAVIS-COVID registry for analysis. Patients were categorized into quartiles (Q1, Q2, Q3, and Q4) according to baseline NLR values, and demographic and clinical parameters were compared between the groups. Survival analysis was conducted using the Kaplan–Meier method. The diagnostic performance of the baseline and follow-up NLR values was tested using receiver operating characteristic (ROC) curve analysis. Finally, two-dimensional mapping of patient characteristics was conducted using t-stochastic neighborhood embedding (t-SNE). In-hospital mortality significantly increased with an increase in the baseline NLR quartile (Q1 6.3%, Q2 11.0%, Q3 20.5%; and Q4, 26.6%; p < 0.001). The cumulative mortality increased as the quartile of the baseline NLR increased. The paired log-rank test revealed significant differences in survival for Q1 vs. Q3 (p = 0.017), Q1 vs. Q4 (p < 0.001), Q2 vs. Q3 (p = 0.034), and Q2 vs. Q4 (p < 0.001). However, baseline NLR was not identified as an independent prognostic factor using a multivariate Cox proportional hazards regression model. The area under the curve for predicting in-hospital death based on baseline NLR was only 0.682, whereas that of follow-up NLR was 0.893. The two-dimensional patient map with t-SNE showed a cluster characterized by high mortality with high NLR at follow-up, but these did not necessarily overlap with the population with high NLR at baseline. NLR may have prognostic implications in hospitalized COVID-19 patients with CVDRF, but its significance depends on the timing of data collection.
The hydration behavior of a GCL with polymerized bentonite (PB-GCL) was investigated by laboratory column tests in terms of hydration gravimetric water content (w); apparent degree of saturation (S r *); and air permeability (k air ), and compared with those of a GCL with natural bentonite as the core (NB-GCL). In cases of deionized water (DI water) and 0.1 M NaCl solution as pore water of the subsoil, the PB-GCL had higher final w values than the NB-GCL, but the values of S r * is similar. The values of k air of the PB-GCL are approximately four orders lower than that of the NB-GCL. In addition, k air of the PB-GCL at S r *= 40% is comparable with that of the NB-GCL at S r *= 70%. In the case of the subsoil with 0.6 M NaCl solution, the final value of k air of the PB-GCL is about half of the NB-GCL. These results indicate that cation concentrations in a subsoil has a considerable influence on the hydration behavior of a GCL. It is suggested that the PB-GCL has a better hydration performance than the NB-GCL.
Entamoeba histolytica causes a parasitic infectious disease, amoebiasis. Amoebiasis is a global public health problem with a high occurrence of infection and inadequate clinical options.
Purpose: To report on the long-term outcomes of vesicostomy in elderly patients with chronic urinary retention. Materials and methods: We conducted a study of 16 elderly patients with chronic urinary retention who underwent Blocksom vesicostomy between April 2010 and March 2021. Postoperative follow-up was conducted every 3 months to check for abnormal findings, such as stoma outlet obstruction, infection, bleeding, bladder prolapse, and bladder stones. The incidence of these findings and the time until they occurred, as well as the rate of achieving a catheter-free status and the time until catheter reinsertion, were then calculated using the Kaplan-Meier curve. Results: The mean age (±standard deviation) of patients whose cases were observed was 78.6 (±7.8) years; the oldest patient was 87 years of age. The study population included 14 male patients and 2 female patients, with a higher number of males. The causes of urinary retention included neurogenic bladder in 12 patients (including patients with 3 spinal cord injury), advanced prostate cancer in 2 patients, and iatrogenic urethral stricture in 2 patients. The average follow-up period was 55.7 months. During follow-up, 14 patients (87.5% of the total) achieved a catheter-free status under conditions that required no additional treatment. Complications were observed in 6 cases (37.5%); among them, two cases required reoperation. All complications were observed within 2 years after surgery. Conclusion: Blocksom vesicostomy may become a viable option in the treatment of elderly patients with chronic urinary retention whose symptoms do not improve with medical therapy.
Abstract Background Insulin resistance and hyperinsulinemia in patients with type 2 diabetes (T2D) are adversely associated with the development and worsening of heart failure (HF). Herein, we sought to investigate the effect of canagliflozin on insulin concentrations and the associations of changes in insulin concentrations with HF-related clinical parameters in patients with T2D and HF. Methods This was a post-hoc analysis of the investigator-initiated, multicenter, open-label, randomized, controlled CANDLE trial for patients with T2D and chronic HF (UMIN000017669). The endpoints were the effects of 24 weeks of canagliflozin treatment, relative to glimepiride treatment, on insulin concentrations and the relationship between changes in insulin concentrations and clinical parameters of interest, including New York Heart Association (NYHA) classification. The effects of canagliflozin on those parameters were also analyzed by baseline insulin level. Results Among the participants in the CANDLE trial, a total of 129 patients (canagliflozin, n = 64; glimepiride, n = 65) who were non-insulin users with available serum insulin data both at baseline and week 24 were included in this analysis. Overall, the mean age was 69.0 ± 9.4 years; 75% were male; the mean HbA1c was 6.8 ± 0.7%; and the mean left ventricular ejection fraction was 59.0 ± 14.1%, with parameters roughly balanced between treatment groups. Canagliflozin treatment significantly reduced insulin concentrations at week 24 (p
Background: It is unknown whether beneficial effects of higher-dose statins on cardiovascular events are different according to the thrombotic risk in patients with chronic coronary syndrome (CCS).Methods and Results: The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study is a randomized trial comparing 4 mg and 1 mg pitavastatin in patients with CCS. This study categorized 12,413 patients into 3 strata according to the CREDO-Kyoto thrombotic risk score: low-risk (N=9,434; 4 mg: N=4,742, and 1 mg: N=4,692), intermediate-risk (N=2,415; 4 mg: N=1,188, and 1 mg: N=1,227); and high-risk (N=564; 4 mg: N=269, and 1 mg: N=295). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina. Cumulative 4-year incidence of the primary endpoint was significantly higher in the high-risk stratum than in the intermediate- and low-risk strata (11.0%, 6.3%, and 4.5%, P<0.0001). In the low-risk stratum, the cumulative 4-year incidence of the primary endpoint was significantly lower in the 4 mg than in the 1 mg group (4.0% and 4.9%, P=0.02), whereas in the intermediate- and high-risk strata, it was numerically lower in the 4 mg than in the 1 mg group. There was no significant treatment-by-subgroup interaction for the primary endpoint (P-interaction=0.77). Conclusions: High-dose pitavastatin therapy compared with low-dose pitavastatin therapy was associated with a trend toward lowering the risk for cardiovascular events irrespective of the thrombotic risk in patients with CCS.
CH3NH3SnI3 perovskites, which can be created using printing technology, are environmentally friendly thermoelectric materials, but their applications are limited by unsatisfactory thermoelectric efficiency and structural stability. In this work, CH3NH3SnI3 perovskites are processed by applying high pressure with shear strain for the first time, resulting in better structural stability, enhanced electrical conductivity and the Seebeck coefficient with CH3NH3SnI3 tube structures after processing. First-principles calculations verified the reasonable changes in lattice constants, electronic band structures, electrical conductivity and the Seebeck coefficient. The present study demonstrates a potential strategy to improve the structural and thermoelectric properties of CH3NH3SnI3 and uncovers the possible mechanism.
Full-color emitting materials have always been widely concerned and studied benefiting from their promising application potential in fluorescence imaging and optoelectronic devices. In this paper, four asymmetrically D-A type pyrene-based...
The Japanese pepper (Zanthoxylum piperitum DC.) is an attractive plant that is highly palatable and benefits human health. There are several lineages of pepper plants in Japan. However, the classification of each lineage by analyzing its volatile compounds and studies on the effects of differences in volatile compounds on human flavor perception have not been performed in detail. Herein, we conducted gas chromatography (GC) and GC/mass spectrometry (GC/MS) analysis of volatile compounds and sensory evaluation of flavor by an analytical panel using 10 commercially available dry powdered Japanese pepper products from different regions. GC and GC/MS analysis detected limonene, β-phellandrene, citronellal, and geranyl acetate as the major volatile compounds of Japanese peppers. The composition of volatile compounds showed different characteristics depending on the growing regions, and cluster analysis of composition classified the products into five groups. The sensory evaluation classified the products into four groups, and the results of both classifications were in good agreement. Our results provide an important basis for proposing cooking and utilization methods that take advantage of the unique characteristics of each lineage based on scientific evidence.
Background Hand and wrist pain can develop during the postpartum period, may be exacerbated by activities during childcare and may continue for several months, leading to chronic upper extremity disability. Little is known about the impact of hand and wrist pain on quality of life in postpartum mothers. Aims This study aimed to explore the relationship between self-assessed hand and wrist pain, upper extremity disability and quality of life among postpartum mothers in Japan. Methods A prospective cohort study was designed for women who had given birth at a general hospital and a clinic in the south of Japan. Participants self-assessed hand and wrist pain using Eichhoff's test and upper extremity disability using the Hand20 questionnaire. General quality of life was assessed with the EQ-5D-5L. Results Self-assessed hand and wrist pain was significantly associated with upper extremity disability. Self-reported subjective and induced pain was associated with lower quality of life. Conclusions Self-assessed hand and wrist pain in postpartum women can significantly lower quality of life. Reporting subjective and self-induced pain helps diagnosis of and may prevent disability, improving a mother's quality of life.
Background/objectives Low-carbohydrate diets (LCD) are useful for weight reduction, and 50–55% carbohydrate consumption is associated with minimal risk. Genetic differences were related to nutritional consumption, food preferences, and dietary patterns, but whether particular genetic differences in individuals influence LCD adherence is unknown. Subjects/methods We conducted a GWAS on adherence to LCD utilizing 14,076 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a previously validated semiquantitative food frequency questionnaire to estimate food consumption. Association of the imputed variants with the LCD score by Halton et al. we used linear regression analysis adjusting for sex, age, total dietary energy consumption, and components 1 to 10 by principal component analysis. We repeated the analysis with adjustment for alcohol consumption (g/day) in addition to the above-described variables. Results Men and women combined analysis without adjustment for alcohol consumption; we found 395 variants on chromosome 12 associated with the LCD score having P values <5 × 10⁻⁸. A conditional analysis with the addition of the dosage data of rs671 on chromosome 12 as a covariate, P values for all 395 SNPs on chromosome 12 turned out to be insignificant. In the analysis with additional adjustment for alcohol consumption, we did not identify any SNPs associated with the LCD score. Conclusion We found rs671 was inversely associated with adherence to LCD, but that was strongly confounded by alcohol consumption.
Vγ6⁺γδ T cells develop in the thymus at the perinatal stage and are exclusive IL‐17A producers among γδ T cells. The loss of MHC class II led to the expansion of IL‐17A⁺Vγ6⁺γδ T cells in the thymus. Thus, MHC class II in the thymus inhibits the generation of IL‐17A⁺Vγ6⁺γδ T cells. image
Consultation by subspecialty experts is the most common mode of rendering diagnosis in challenging cases in pathological practice. Our study aimed to highlight the diagnostic benefits of whole-slide image (WSI)-based remote consultation. We obtained diagnostically challenging cases from two institutions from the years 2010 and 2013, with histological diagnoses that contained keywords “probable,” “suggestive,” “suspicious,” “inconclusive,” and “uncertain.” A total of 270 cases were selected for remote consultation using WSIs scanned at 40 × . The consultation process consisted of three rounds: the first and second rounds each with 12 subspecialty experts and the third round with six multi-expertise senior pathologists. The first consultation yielded 44% concordance, and a change in diagnosis occurred in 56% of cases. The most frequent change was from inconclusive to definite diagnosis (30%), followed by minor discordance (14%), and major discordance (12%). Out of the 70 cases which reached the second round, 31 cases showed discrepancy between the two consultants. For these 31 cases, a consensus diagnosis was provided by six multi-expertise senior pathologists. Combining all WSI-based consultation rounds, the original inconclusive diagnosis was changed in 140 (52%) out of 266 cases. Among these cases, 80 cases (30%) upgraded the inconclusive diagnosis to a definite diagnosis, and 60 cases (22%) changed the diagnosis with major or minor discordance, accounting for 28 cases (10%) and 32 cases (12%), respectively. We observed significant improvement in the pathological diagnosis of difficult cases by remote consultation using WSIs, which can further assist in patient healthcare. A post-study survey highlighted various benefits of WSI-based consults.
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