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Left ventricular (LV) diastolic dysfunction is increasingly common in heart failure with preserved ejection fraction (HFpEF), and new drug therapy is desired. We recently reported that dantrolene (DAN) attenuates pressure-overload induced hypertrophic signaling through stabilization of tetrameric structure of cardiac ryanodine receptor (RyR2). Because cardiac hypertrophy substantially affects LV diastolic properties, we investigated the effect of DAN on LV diastolic properties in mineralocorticoid-salt–induced hypertensive rat model exhibiting the HFpEF phenotype.Male Sprague-Dawley (SD) rats (8 weeks old) received an uninephrectomy (UNX), subcutaneous implantation of a 200 mg pellet of deoxycorticosterone acetate (DOCA), and 0.9% NaCl water (UNX + DOCA-salt). UNX, a control pellet, and water without NaCl served as controls (UNX control). The effect of oral administration of 100 mg/kg/d DAN was examined in UNX control and UNX + DOCA-salt groups (UNX + DAN and UNX + DOCA-salt + DAN).UNX + DOCA-salt treatment resulted in mild hypertension. Chronic administration of DAN to UNX + DOCA-salt rats (UNX + DOCA-salt + DAN) did not affect blood pressure. DAN treatment increased the mitral annular early relaxation velocity in the UNX + DOCA-salt group. The size of cardiomyocytes increased in the UNX + DOCA-salt group, whereas the increase was suppressed by DAN treatment. LV fibrotic area was significantly smaller in the UNX + DOCA-salt + DAN group than in the UNX + DOCA-salt group (2.0 ± 0.2% vs 4.0 ± 0.4%). The LV chamber stiffness significantly increased in the UNX + DOCA-salt group, whereas the increase was suppressed by DAN treatment. DAN treatment normalized the CaM-RyR2 interaction and inhibited aberrant Ca2+ release.DAN improved left ventricular diastolic properties with respect to both myocardial relaxation and chamber stiffness. DAN may be a new treatment option for HFpEF. more...

ABSTRACT Leptospirosis is a zoonotic disease caused by infection with pathogenic leptospires. Consistent with recent studies by other groups, leptospires were isolated from 89 out of 110 (80.9%) soil or water samples from varied locations in the Philippines in our surveillance study, indicating that leptospires might have a life cycle that does not involve animal hosts. However, despite previous work, it has not been confirmed whether leptospires multiply in the soil environment under various experimental conditions. Given the fact that the case number of leptospirosis is increased after flood, we hypothesized that waterlogged soil, which mimics the postflooding environment, could be a suitable condition for growing leptospires. To verify this hypothesis, pathogenic and saprophytic leptospires were seeded in the bottles containing 2.5 times as much water as soil, and bacterial counts in the bottles were measured over time. Pathogenic and saprophytic leptospires were found to increase their number in waterlogged soil but not in water or soil alone. In addition, leptospires were reisolated from soil in closed tubes for as long as 379 days. These results indicate that leptospires are in a resting state in the soil and are able to proliferate with increased water content in the environment. This notion is strongly supported by observations that the case number of leptospirosis is significantly higher in rainy seasons and increased after flood. Therefore, we reached the following conclusion: environmental soil is a potential reservoir of leptospires. IMPORTANCE Since research on Leptospira has focused on pathogenic leptospires, which are supposed to multiply only in animal hosts, the life cycle of saprophytic leptospires has long been a mystery. This study demonstrates that both pathogenic and saprophytic leptospires multiply in the waterlogged soil, which mimics the postflooding environment. The present results potentially explain why leptospirosis frequently occurs after floods. Therefore, environmental soil is a potential reservoir of leptospires and leptospirosis is considered an environment-borne as well as a zoonotic disease. This is a significant report to reveal that leptospires multiply under environmental conditions, and this finding leads us to reconsider the ecology of leptospires. more...

Disasters such as the magnitude-9 Great East Japan Earthquake occur periodically. We considered this experience while developing measures against a predicted earthquake in the Nankai Trough. This report includes a summary of 10 disastrous infectious diseases for which a countermeasures seminar was held. Thirty-five speakers from twenty-one organizations performed the lectures. Besides infectious diseases, conference topics also included disaster prevention and mitigation methods. In addition, the development of point-of-care tests, biomarkers for diagnosis, and severity assessments for infectious diseases were introduced, along with epidemics of infectious diseases affected by climate. Of the 28 pathogens that became a hot topic, 17 are viruses, and 14 out of these 17 (82%) are RNA viruses. Of the 10 seminars, the last 2 targeted only COVID-19. It was emphasized that COVID-19 is not just a disaster-related infection but a disaster itself. The first seminar on COVID-19 provided immunological and epidemiological knowledge and commentary on clinical practices. During the second COVID-19 seminar, vaccine development, virological characteristics, treatment of respiratory failure, biomarkers, and human genetic susceptibility for infectious diseases were discussed. Conducting continuous seminars is important for general infectious controls. more...

Public transportation is becoming increasingly important in regions where the residential population is decreasing. In Japan, many regional transportation systems are experiencing financial challenges. It is difficult for fixed-route transportation systems to operate at a surplus when serving only local resident users. We consider one of the problems of these regional public transport systems to be the lack of information on the Internet about regional public transportation routes. For people who are unfamiliar with the region, such as inbound tourists, there is no easy way to conduct a route search. In this paper, we describe our efforts to build a fundamental database of the regional public transportation provided by municipalities and to publish this data for those conducting route searches on the Internet. Specifically, we converted fundamental data regarding regional public transportation to the feed of the General Transit Feed Specification-Japan (GTFS-JP), which is based on the Google GTFS, as formulated by the Ministry of Land in Japan. Then we encouraged municipalities to publish these transit data to enable route searches on Google Maps and other domestic-content providers. more...

Hibernating animals show a remarkable decrease in body temperature without accompanying serious organ damage. Active hypometabolism may be involved in the protective mechanisms. Therefore, in the present study, the phosphorylation status of Akt was used to examine whether metabolism is actively reduced during artificial hypothermia in hamsters. Hypothermia induced by activation of the central adenosine A1 receptor (A1AR) resulted in dephosphorylation of Akt in the heart, as in that of hibernating hamsters. Since phosphorylated Akt almost totally disappeared, it is probable that cellular metabolism is actively reduced in A1AR-mediated hypothermia. Surprisingly, phosphorylation of Akt was significantly, but not totally, reduced even when hypothermia was induced by a combination of inhalation anesthesia and cooling. It can thus be considered that active regulation for the reduction of metabolic activity occurs in A1AR-mediated hypothermia as well as in anesthesia-induced hypothermia, though to a lesser extent. In both hypothermic conditions, serious arrhythmias were rarely observed. In anesthesia-induced hypothermia, during which dephosphorylation of Akt occurred only partially, there was no obvious organ damage in histopathological examination. Taken together, our findings suggest that artificial hypothermia causes active hypometabolism and has therapeutically applicable properties. more...

We investigated the effects of a centrally penetrant ghrelin agonist, RQ-00538053, on colorectal motility in female rats in comparison with that in male rats. Intravenous administration of RQ-00538053 enhanced colorectal motility in female rats. However, approximately tenfold higher doses were required to induce responses in female rats similar to those in male rats. Higher doses were required even when the agonist was intrathecally administered to the lumbosacral spinal cord in female rats. The results of RT-qPCR showed that the level of ghrelin receptor expression in the lumbosacral spinal cord was lower in female rats than in male rats, suggesting that the lower expression level of the receptor may contribute, at least in part, to the sex differences in the action of RQ-00538053. The sexually dimorphic action of a ghrelin agonist will be important for future works aiming to utilize ghrelin agonists as novel drugs to improve constipation., Competing Interests: Declarations. Ethics approval and consent to participate: All experimental procedures conformed to the “Regulations for Animal Experiments in Gifu University” and were approved by the president of the university after review by the Committee for Animal Research and Welfare of Gifu University (Permission No. 2021-241, 20220050, AG-P-N-20230190). Consent for publication: Not applicable. Competing interests: YS is an editorial board member of the Journal of Physiological Sciences. The other authors have no competing interests., (© 2024. The Author(s).) more...

Background: Previous studies have shown that Japanese dietary patterns are associated with high nutrient density. However, these studies were limited to the Japanese population. We examined this association in the US population., Methods: A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. We included 3138 people aged 20-79 years. Food and nutrient intake data were based on the 24 h recall method. Three Japanese diet indices were used: (1) Japanese Diet Index (JDI, based on 9 food items), (2) modified JDI (mJDI, based on 12 food items), and (3) weighted JDI (wJDI, selected and weighted from mJDI food items). The nutrient density (ND) score was calculated based on the Nutrient-Rich Food Index 9.3. Spearman's rank correlation coefficients were calculated., Results: The correlation coefficients with the ND score were 0.24 ( p < 0.001) for the JDI and 0.38 ( p < 0.001) for the mJDI. The correlation coefficient between the wJDI and ND score was 0.48 ( p < 0.001). The three Japanese diet indices were correlated with the ND score in all racial groups ( p < 0.001)., Conclusions: Even among the US population, higher degrees of Japanese diet defined by the JDI or mJDI were associated with higher nutrient density. more...

While certain human hepatitis B virus-targeting nucleoside analogs (NAs) serve as crucial anti-HBV drugs, HBV yet remains to be a major global health threat. E-CFCP is a 4'-modified and fluoromethylenated NA that exhibits potent antiviral activity against both wild-type and drug-resistant HBVs but less potent against human immunodeficiency virus type-1 (HIV-1). Here, we show that HIV-1 with HBV-associated amino acid substitutions introduced into the RT's dNTP-binding site (N-site) is highly susceptible to E-CFCP. We determined the X-ray structures of HBV-associated HIV-1 RT mutants complexed with DNA:E-CFCP-triphosphate (E-CFCP-TP). The structures revealed that exocyclic fluoromethylene pushes the Met184 sidechain backward, and the resultant enlarged hydrophobic pocket accommodates both the fluoromethylene and 4'-cyano moiety of E-CFCP. Structural comparison with the DNA:dGTP/entecavir-triphosphate complex also indicated that the cyclopentene moiety of the bound E-CFCP-TP is slightly skewed and deviated. This positioning partly corresponds to that of the bound dNTP observed in the HIV-1 RT mutant with drug-resistant mutations F160M/M184V, resulting in the attenuation of the structural effects of F160M/M184V substitutions. These results expand our knowledge of the interactions between NAs and the RT N-site and should help further design antiviral NAs against both HIV-1 and HBV., (© 2024. The Author(s).) more...

Purines such as ATP are regulatory transmitters in motility of the gastrointestinal tract. The aims of this study were to propose functional roles of purinergic regulation of esophageal motility. An isolated segment of the rat esophagus was placed in an organ bath, and mechanical responses were recorded using a force transducer. Exogenous application of ATP (10-100 μM) evoked relaxation of the esophageal smooth muscle in a longitudinal direction under the condition of carbachol (1 μM) -induced precontraction. Pretreatment with a non-selective P2 receptor antagonist, suramin (500 μM), and a P2Y receptor antagonist, cibacron blue F3GA (200 μM), inhibited the ATP (100 μM) -induced relaxation, but a P2X receptor antagonist, pyridoxal phosphate-6-azophenyl-2,4-disulfonic acid (50 μM), did not affect it. A blocker of ATP-dependent potassium channels (K ATP channels), glibenclamide (200 μM), inhibited the ATP-induced relaxation and application of an opener of K ATP channels, nicorandil (50 μM), produced relaxation. The findings suggest that ATP is involved in inhibitory regulation of the longitudinal smooth muscle in the muscularis mucosae of the rat esophagus via activation of P2Y receptors and then opening of K ATP channels., (© 2024. The Author(s).) more...

In tidal flats, which are located at the transition zone between terrestrial and marine ecosystems, environmental factors such as temperature, sediment particle size, and tidal range exhibit geographic variation. Accordingly, the composition and structure of the microbial communities in the tidal flats are likely to vary in geographically different habitats. To clarify these differences with environmental factors causing them, we analyzed microbial communities consisting of bacteria and ciliates in sediments collected from nine tidal flats in geographical diverse region from Hokkaido to Kagoshima, Japan. The results confirmed that the community structures of bacteria and ciliophora in tidal flat sediments differed at the geographical scale of the Japanese archipelago. However, the variation could not be explained by the physical distance between the tidal flats nor by the differences in the trophic conditions among the tidal flats. Instead, the OTU richness of both the bacterial and ciliophoran communities was significantly related to the tidal range. The results also showed that bacteria and ciliophora tended to form similar communities among the tidal flats with similar median particle sizes. Furthermore, ciliophoran communities were similar among the tidal flats with similar bacterial communities. The results suggest that bacteria and ciliophora interact each other through trophic relationships or physical and chemical processes in the sediment habitats. more...

Herein, we report a case of myocarditis in a 27-year-old male with long-term follow-up using longitudinal peak systolic strain (LPSS) measurements with transthoracic echocardiography (TTE) and late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR). On admission, a predominant decrease was observed in the LPSS in the posterolateral segments of the TTE. After a period of two weeks, the values of the LPSS observed in the posterolateral segments were still slightly reduced, which is consistent with the LGE results in CMR. After a duration of 16 months, an improvement was noted in the LPSS and LGE results in all the segments. Moreover, a time-phase discrepancy was observed in the segmental longitudinal strain curve for a period of two weeks from the onset of myocarditis. However, an improvement in the discrepancy was detected after 16 months., Learning Objective: Longitudinal peak systolic strain (LPSS) on transthoracic echocardiography (TTE) has predominantly focused on diagnosing the acute phase of myocarditis. Herein, LPSS was evaluated not only in the acute phase but also in the chronic phase. Furthermore, the relationship between the results of segmental LPSS and late gadolinium enhancement was documented. We would like to emphasize the usefulness of LPSS on TTE both for identifying myocarditis and as a tool for the long-term follow-up of patients., Competing Interests: None declared., (© 2024 Japanese College of Cardiology. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.) more...

In seed plants, growth of shoots and roots is indeterminate, while leaves are typically determinate organs that cease to grow after a certain developmental stage. This is due to the characteristics of the leaf meristem, where cell proliferation activity is retained only for a limited period. However, several plants exhibit indeterminacy in their leaves, exemplified by the pinnate compound leaves of Guarea and Chisocheton genera in the Meliaceae family. In these plants, the leaf meristem at the tip of the leaf retains meristematic activity and produces leaflets over years, resulting in a single leaf that resembles a twig. The molecular mechanism underlying the indeterminate leaf meristem of these plants has not been examined. In this research, we used Guarea glabra as a model to investigate the development of indeterminate pinnate leaves. Transcriptome analyses revealed that the gene expression profile in leaf apex tissue differed from that in the shoot apex. However, a class 1 KNOTTED-LIKE HOMEOBOX (KNOX1) gene which is lost in Brassicaceae was highly expressed in both tissues. We established an in situ hybridisation system for this species using Technovit 9100 to analyse the spatial expression patterns of genes. We revealed that the leaf meristematic region of G. glabra expresses KNOX1, LEAFY and ANGUSTIFORIA3 simultaneously, suggesting the involvement of these genes in the indeterminacy of the leaf meristem., (© 2024. The Author(s).) more...

The tunica muscularis of mammalian esophagi is composed of striated muscle and smooth muscle. Contraction of the esophageal striated muscle portion is mainly controlled by cholinergic neurons. On the other hand, smooth muscle contraction and relaxation are controlled not only by cholinergic components but also by non-cholinergic components in the esophagus. Adenosine triphosphate (ATP) is known to regulate smooth muscle contraction and relaxation in the gastrointestinal tract via purinergic receptors. However, the precise mechanism of purinergic regulation in the esophagus is still unclear. Therefore, the aim of the present study was to clarify the effects of ATP on the mechanical responses of the esophageal muscle in mice. An isolated segment of the mouse esophagus was placed in a Magnus's tube and longitudinal mechanical responses were recorded. Exogenous application of ATP induced contractile responses in the esophageal preparations. Tetrodotoxin, a blocker of voltage-dependent sodium channels in neurons and striated muscle, did not affect the ATP-induced contraction. The ATP-evoked contraction was blocked by pretreatment with suramin, a purinergic receptor antagonist. RT-PCR revealed the expression of mRNA of purinergic receptor genes in the mouse esophageal tissue. The findings suggest that purinergic signaling might regulate the motor activity of mouse esophageal smooth muscle. more...

Patients with Parkinson's disease (PD) often have constipation. It is assumed that a disorder of the regulatory mechanism of colorectal motility by the central nervous system is involved in the constipation, but this remains unclear. The aim of this study was to investigate whether central neural pathways can modulate colorectal motility in a rat model of PD. PD model rats were generated by injection of 6-hydroxydopamine into a unilateral medial forebrain bundle and destruction of dopaminergic neurons in the substantia nigra. Colorectal motility was measured in vivo in anesthetized rats. Intraluminal administration of capsaicin, as a noxious stimulus, induced colorectal motility in sham-operated rats but not in PD rats. Intrathecally administered dopamine (DA) and serotonin (5-HT), which mediate the prokinetic effect of capsaicin, at the L6-S1 levels enhanced colorectal motility in PD rats similarly to that in sham-operated rats. In PD rats, capsaicin enhanced colorectal motility only when a GABA A receptor antagonist was preadministered into the lumbosacral spinal cord. Capsaicin-induced colorectal motility was abolished by intrathecal administration of a D2-like receptor antagonist but not by administration of 5-HT 2 and 5-HT 3 receptor antagonists. These findings demonstrate that the inhibitory GABAergic component becomes operative and the stimulatory serotonergic component is suppressed in PD rats. The alteration of the central regulatory mechanism of colorectal motility is thought to be related to the occurrence of constipation in PD patients. Our findings provide a new insight into the pathogenesis of defecation disorders observed in PD. NEW & NOTEWORTHY In a rat model of Parkinson's disease, the component of descending brain-spinal pathways that regulate colorectal motility through a mediation of the lumbosacral defecation center was altered from stimulatory serotonergic neurons to inhibitory GABAergic neurons. Our findings suggest that chronic constipation in Parkinson's disease patients may be associated with alterations in central regulatory mechanisms of colorectal motility. The plasticity in the descending pathway regulating colorectal motility may contribute to other disease-related defecation abnormalities. more...

We demonstrate decoherence-tolerant transmission of a Bell state through a single-mode fiber (SMF) using the photon frequency degree of freedom. To this end, a slightly non-degenerate polarization-entangled singlet, | Ψ - ⟩=(|HV⟩-|VH⟩)/2, is localized at the SMF as the depolarization channel subject to random noise due to incessant fiber bending. Two-photon beats and quantum state tomography jointly verify the absence of collective decoherence, showing that | Ψ - ⟩ is the sought-after one-dimensional decoherence-free subspace (DFS) pertaining to SMF. Efficient splitting and combining of photon streams in our DFS help outperform the DFS in time domain. This motivates us to attempt DFS-enabled fault-tolerant fiber transmission of biphoton qubits. Two-photon BB84 protocol is implemented in a polarization-maintaining fiber to which dephasing noise is relevant so that a two-dimensional DFS is appropriate. A low bit error rate 5.4% is achieved by encoding one-qubit information onto the biphoton state in spite of significant polarization fluctuation. Our scalable frequency-based DFS has a natural affinity for wavelength division multiplexing in fiber communication by design and as such is extensible to multi-particle entanglement. more...

Introduction: Imeglimin is a novel antidiabetic drug with insulinotropic and insulin-sensitizing effects that targets mitochondrial bioenergetics. We investigated acute effects of add-on therapy with imeglimin to preceding metformin on the 24-h glucose profile and glycemic variability assessed by continuous glucose monitoring (CGM) in patients with type 2 diabetes., Methods: We studied 30 outpatients with type 2 diabetes inadequately controlled with metformin. CGM was used for 14 days straight during the research period. Imeglimin 2,000 mg/day was started on day 7 after initiating CGM. Several CGM parameters were compared between days 4-6 (prior to imeglimin treatment) and 11-13 (following the initiation of imeglimin treatment)., Results: After treatment with imeglimin, 24-h mean glucose was acutely decreased from 161.6 ± 48.0 mg/dL to 138.9 ± 32.2 mg/dL (p < 0.0001), while time in range (i.e., at a glucose level of 70-180 mg/dL) was significantly increased from 69.9 ± 23.9% to 80.6 ± 21.0% (p < 0.0001). Addition of imeglimin to metformin significantly decreased the standard deviation (SD) of 24-h glucose and mean amplitude of glycemic excursions, 2 indexes of glycemic variability. Baseline serum high-density lipoprotein (HDL) cholesterol was negatively correlated with changes in mean 24-h glucose (r = -0.3859, p = 0.0352) and those in SD (r = -0.4015, p = 0.0309)., Conclusions: Imeglimin add-on therapy to metformin acutely lowered 24-h glucose levels and improved glycemic variability in patients with type 2 diabetes on metformin. A higher serum HDL cholesterol at baseline was associated with a better response to acute effects of imeglimin on 24-h glucose levels and glycemic variability., (© 2024 The Author(s). Published by S. Karger AG, Basel.) more...

Japanese diet adherence has been inversely correlated with muscle weakness. In this study, we aimed to validate that association. Longitudinal data from 1699 individuals aged ≥50 years (mean age 62.5 ± 6.9 years, 50.4% female) at two time points (2007 and 2011) were used. Participants without muscle weakness from several regions in Japan were included. The 12-component revised Japanese Diet Index (rJDI12) classified by tertiles assessed adherence to the Japanese dietary pattern. Muscle weakness was defined as a handgrip strength of ˂18 kg for females and ˂28 kg for males based on the Asian Working Group for Sarcopenia criteria 2019. A multivariate logistic approach was used to determine the relationship between rJDI12 tertile and the occurrence of muscle weakness by calculating the odds ratio (OR) and its 95% confidence interval (95% CI) throughout the observation period. Muscle weakness was negatively correlated with the highest rJDI12 tertile (OR [95% CI] 0.891 [0.814, 0.973] for T3). This association was consistent in sensitivity analyses with multiple imputations of missing values. Closely following the Japanese dietary pattern appears to reduce the occurrence of muscle weakness among the aging population in this study, suggesting it may prevent frailty and sarcopenia in the aging population. more...

The entire decaying dynamics of harmonic mode-locking (HML) are studied utilizing the dispersive Fourier transform (DFT) technique in a SESAM-based mode-locked fiber laser. It is unveiled that the harmonic solitons do not disappear directly, but undergo transitional processes from the higher-order HML to the lower-order HML and then to the fundamental mode-locking (FML), and finally vanish. The "big corner" can also exist in the decaying process rather than just in the buildup process of HML, and there is at least one "big corner" during the decaying process between the consecutive multi-pulsing states. The energy stabilization phase (ESP) cannot be observed during every transitional process. A breathing behavior and a vibrating soliton molecule are observed in the decaying process from the 2nd HML to the FML and in the decaying process of the FML, respectively. Our work would enrich the understanding of HML behaviors and may contribute to the laser designs. more...

Broadband supercontinuum laser sources in the mid-infrared region have attracted enormous interest and found significant applications in spectroscopy, imaging, sensing, defense, and security. Despite recent advances in mid-infrared supercontinuum laser sources using infrared fibers, the average power of those laser sources is limited to 10-watt-level, and further power scaling to over 50 W (or hundred-watt-level) remains a significant technological challenge. Here, we report an over 50 W all-fiber mid-infrared supercontinuum laser source with a spectral range from 1220 to 3740 nm, by using low loss (<0.1 dB/m) fluorotellurite fibers we developed as the nonlinear medium and a tilted fusion splicing method for reducing the reflection from the fluorotellurite-silica fiber joint. Furthermore, the scalability of all-fiber mid-infrared supercontinuum laser sources using fluorotellurite fibers is analyzed by considering thermal effects and optical damage, which verifies its potential of power scaling to hundred-watt-level. Our results pave the way for realizing all-fiber hundred-watt-level mid-infrared lasers for real applications. more...

A previous study suggested that inflammatory bowel disease (IBD) patients have low plasma levels of trimethylamine N-oxide (TMAO). In the present study, we examined this hypothesis using Mendelian randomization analysis. We used summary statistics data for single-nucleotide polymorphisms associated with plasma levels of TMAO, and the corresponding data for IBD from a genome-wide association meta-analysis of 59,957 individuals (25,042 diagnosed IBD cases, 34,915 controls). The association between genetically predicted plasma TMAO levels and IBD showed odds ratios (95% confidence interval [CI]) per 1 interquartile range increment (per 2.4 μmol/L) in TMAO levels were 0.91 (0.81-1.01, P = .084) for IBD, 0.88 (0.76-1.02, P = .089) for ulcerative colitis, 0.91 (0.79-1.05, P = .210) for Crohn disease. There was no evidence for pleiotropy based on the Mendelian randomization-Egger regression analyses (P-intercept = 0.669 for IBD). Further investigations would be needed to understand the causal relationship between TMAO and IBD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.) more...

Although the association between household economic affluence and children's obesity has been reported, the association between mothers' time affluence and obesity remains unclear. We conducted a cross-sectional study using Japanese national survey data (2015). The target population was 2-6-year-old preschool children and their mothers. Subjective household economic affluence and mothers' time affluence were divided into "affluent," "neither," "less affluent," and "non-affluent" groups. Obesity was defined based on the International Obesity Task Force. A logistic regression model was conducted to examine the association between household economic affluence, mothers' time affluence, and children's obesity. A total of 2254 respondents were included in the present analysis. The lower household economic affluence was not significantly associated with higher rates of children's obesity (odds ratio (OR) for the "non-affluent" compared with the "affluent" group was 1.68 (95% CI, 0.93-3.03)). A lower mothers' time affluence was not significantly associated with higher rates of children's obesity (OR for the "non-affluent" compared with the "affluent" group was 1.67 (95% CI, 0.92-3.03)). The prevalence of obesity was not synergistically higher when lower household economic affluence and lower mothers' time affluence were combined. more...

We analyzed light confinement in circular step-index cores of tellurite and silica fibers through numerical calculations and also examined crosstalk between the fundamental modes of cores in multicore fibers. Our analysis showed that tellurite fibers have a pixel density about 2.2 times higher and a brightness about 1.4 times brighter than silica fibers. As a result, tellurite multicore image fibers have the potential to provide improved resolution and brightness for near-infrared image transportation compared with silica fibers. more...

The supraspinal brain regions controlling defecation reflex remain to be elucidated. The purpose of this study was to determine the roles of the hypothalamic A11 region and the medullary raphe nuclei in regulation of defecation. For chemogenetic manipulation of specific neurons, we used the double virus vector infection method in rats. hM3Dq or hM4Di was expressed in neurons of the A11 region and/or the raphe nuclei that send output to the lumbosacral defecation center. Immunohistological and functional experiments revealed that both the A11 region and the raphe nuclei directly connected with the lumbosacral spinal cord through descending pathways composed of stimulatory monoaminergic neurons. Stimulation of the hM3Dq-expressing neurons in the A11 region or the raphe nuclei enhanced colorectal motility only when GABAergic transmission in the lumbosacral spinal cord was blocked by bicuculline. Experiments using inhibitory hM4Di-expressing rats revealed that enhancement of colorectal motility caused by noxious stimuli in the colon is mediated by both the A11 region and the raphe nuclei. Furthermore, suppression of the A11 region and/or the raphe nuclei significantly inhibited water avoidance stress-induced defecation. These findings demonstrate that the A11 region and the raphe nuclei play an essential role in the regulation of colorectal motility. This is important because brain regions that mediate both intracolonic noxious stimuli-induced defecation and stress-induced defecation have been clarified for the first time. NEW & NOTEWORTHY The A11 region and the raphe nuclei, constituting descending pain inhibitory pathways, are related to both intracolonic noxious stimuli-induced colorectal motility and stress-induced defecation. Our findings may provide an explanation for the concurrent appearance of abdominal pain and defecation disorders in patients with irritable bowel syndrome. Furthermore, overlap of the pathway controlling colorectal motility with the pathway mediating stress responses may explain why stress exacerbates bowel symptoms. more...

Linoleic acid (LA) has a two-sided effect with regard to serum cholesterol-lowering and pro-inflammation, although whether this fatty acid reduces serum cholesterol and the development of atherosclerosis under high-cholesterol conditions has yet to be ascertained. In this study, we examine the effects of dietary LA on reducing serum cholesterol and atherosclerosis development under high-cholesterol conditions. Male and female apoE-deficient (ApoE -/ -) mice were fed AIN-76-based diets containing 10% SFA and 0·04 % cholesterol, 10% LA and 0·04% low cholesterol (LALC), or 10% LA and 0·1% high cholesterol (LAHC) for 9 weeks. The results revealed significant reduction in serum cholesterol levels and aortic lesions with increasing levels of pro-inflammatory biomarkers (urinary isoprostane and aortic MCP-1 mRNA) in male and female LALC groups compared with those in the SFA groups ( P < 0·05). Furthermore, whereas there were significant increases in the serum cholesterol levels and aortic lesions ( P < 0·05), there was no difference in aortic MCP-1 mRNA levels in male and female LAHC groups compared with those in the LALC groups. A high-dietary intake of cholesterol eliminated the serum cholesterol-lowering activity of LA but had no significant effect on aortic inflammation in either male or female ApoE -/ - mice. The inhibitory effect of LA on arteriosclerosis is cancelled by a high-cholesterol diet due to a direct increase in serum cholesterol levels. Accordingly, serum cholesterol levels might represent a more prominent pathogenic factor than aortic inflammation in promoting the development of atherosclerosis. more...

Suppressor of mek1 (Dictyostelium) homolog 2 (Smek2), was identified as one of the responsible genes for diet-induced hypercholesterolemia (DIHC) of exogenously hypercholesterolemic (ExHC) rats. A deletion mutation in Smek2 leads to DIHC via impaired glycolysis in the livers of ExHC rats. The intracellular role of Smek2 remains obscure. We used microarrays to investigate Smek2 functions with ExHC and ExHC.BN-Dihc2 BN congenic rats that harbor a non-pathological Smek2 allele from Brown-Norway rats on an ExHC background. Microarray analysis revealed that Smek2 dysfunction leads to extremely low sarcosine dehydrogenase (Sardh) expression in the liver of ExHC rats. Sarcosine dehydrogenase demethylates sarcosine, a byproduct of homocysteine metabolism. The ExHC rats with dysfunctional Sardh developed hypersarcosinemia and homocysteinemia, a risk factor for atherosclerosis, with or without dietary cholesterol. The mRNA expression of Bhmt, a homocysteine metabolic enzyme and the hepatic content of betaine (trimethylglycine), a methyl donor for homocysteine methylation were low in ExHC rats. Results suggest that homocysteine metabolism rendered fragile by a shortage of betaine results in homocysteinemia, and that Smek2 dysfunction causes abnormalities in sarcosine and homocysteine metabolism., (© 2023. The Author(s).) more...

Distinct sex differences in the prevalence and symptoms of abnormal bowel habits in patients with irritable bowel syndrome (IBS) have been reported. We have elucidated the sex differences in the regulation of colorectal motility via the central nervous system. Noxious stimuli in the colorectum of anesthetized male rats enhance colorectal motility by activating monoaminergic neurons in descending pain inhibitory pathways from the brainstem to the lumbosacral spinal cord. These monoaminergic neurons release serotonin and dopamine into the lumbosacral spinal cord, resulting in the increment of colorectal motility. In female rats, in contrast, noxious stimuli in the colorectum have no effect on colorectal motility. We clarified that GABAergic inhibition in the lumbosacral spinal cord masks the enhancement of colorectal motility induced by monoamines in female animals. Considering that IBS patients often show visceral hypersensitivity and hyperalgesia, our studies suggest that differences in the descending neurons that respond to painful stimuli are involved in various sex differences in abnormal bowel habits. more...

A fiber-based beam shaper to adjust the distribution of spatial modes in a few-mode fiber (FMF) is theoretically and experimentally investigated in this work. A compact and robust device, composed with a single mode fiber-graded index multimode fiber-few mode fiber (SMF-GIMF-FMF), is fabricated by simply fusion splicing of the fibers. Switchable spatial modes and multi-wavelength comb are obtained by the combination of the beam shaper and the few-mode fiber Bragg grating (FM-FBG). This combination acts as a filter to select the wavelength and spatial mode in the laser. A spatial mode switchable fiber laser with high mode purity is extended among LP 01 , LP 11 and cylindrical vector beam (CVB) by adjusting the pressure applied on the beam shaper. Five-discrete wavelengths and their free combination wavelength comb are emitted with a slope efficiency higher than 10%. The fiber laser can be used in the spatial- and wavelength-division multiplexing (SWDM) fiber communication networks requiring particular structure light field. more...

Burkholderia stabilis strain FERMP-21014 secretes cholesterol esterase (BsChe), which is used in clinical settings to determine serum cholesterol levels. Previously, we constructed an expression plasmid with an endogenous constitutive promoter to enable the production of recombinant BsChe. In this study, we obtained one mutant strain with 13.1-fold higher BsChe activity than the wild type, using N-methyl-N'-nitro-N-nitrosoguanidine as a mutagen. DNA-sequencing analysis revealed that the strain had lost chromosome 3 (∆Chr3), suggesting that the genes hindering BsChe production may be encoded on Chr3. We also identified common mutations in the functionally unknown BSFP&#95;068720/30 genes in the top 10 active strains generated during transposon mutagenesis. As BSFP&#95;068720/30/40 comprised an operon on Chr3, we created the BSFP&#95;068720/30/40 disruption mutant and confirmed that each disruption mutant containing the expression plasmid exhibited ~ 16.1-fold higher BsChe activity than the wild type. Quantitative PCR showed that each disruption mutant and ΔChr3 had a ~ 9.4-fold higher plasmid copy number than the wild type. Structural prediction models indicate that BSFP&#95;068730/40 is structurally homologous to the structural maintenance of chromosomes (SMC) protein MukBE, which is responsible for chromosome segregation during cell division. Conversely, BSFP&#95;068720/30/40 disruption did not lead to a Chr3 drop-out. These results imply that BSFP&#95;068720/30/40 is not a SMC protein but is involved in destabilizing foreign plasmids to prevent the influx of genetic information from the environment. In conclusion, the disruption of BSFP&#95;068720/30/40 improved plasmid stability and copy number, resulting in exceptionally high BsChe production. KEY POINTS: • Disruption of BSFP&#95;068720/30/40 enabled mass production of Burkholderia Che/Lip. • BSFP&#95;068730/40 is an SMC protein homolog not involved in chromosome retention. • BSFP&#95;068720/30/40 is likely responsible for the exclusion of exogenous plasmids., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.) more...

Heart failure (HF) is challenging public medical and healthcare systems. This study aimed to develop and validate a novel deep learning-based prognostic model to predict the risk of all-cause mortality for patients with HF. We also compared the performance of the proposed model with those of classical deep learning- and traditional statistical-based models. The present study enrolled 730 patients with HF hospitalized at Toho University Ohashi Medical Center between April 2016 and March 2020. A recurrent neural network-based model (RNNSurv) involving time-varying covariates was developed and validated. The proposed RNNSurv showed better prediction performance than those of a deep feed-forward neural network-based model (referred as "DeepSurv") and a multivariate Cox proportional hazard model in view of discrimination (C-index: 0.839 vs. 0.755 vs. 0.762, respectively), calibration (better fit with a 45-degree line), and ability of risk stratification, especially identifying patients with high risk of mortality. The proposed RNNSurv demonstrated an improved prediction performance in consideration of temporal information from time-varying covariates that could assist clinical decision-making. Additionally, this study found that significant risk and protective factors of mortality were specific to risk levels, highlighting the demand for an individual-specific clinical strategy instead of a uniform one for all patients. more...

A four-hole birefringence tellurite microstructured optical fiber (BTMOF) was designed and fabricated based on 76.5 T e O 2 -6 Z n O -11.5 L i 2 O -6 B i 2 O 3 glass, and its core (slow and fast axes were) measured to be approximately 4.74 µm and 4.29 µm, respectively. The experimentally measured results demonstrated that the maximum supercontinuum (SC) spectra extended from ∼914.1 n m to ∼1885.1 n m when the polarization state of the pump pulse was parallel to the fast axis at 1400 nm with an average power of 460 mW. We performed numerical simulations based on the nonlinear Schrödinger equation, which support the experimentally measured results. The SC generation in birefringent silica microstructured fiber with the same geometric parameters was simulated, and the results showed that the enhanced nonlinear refractive index of the BTMOF yielded a spectrum with a significantly larger bandwidth. Furthermore, the two polarization states along the fast axis and slow axis exhibit different dispersion characteristics, which provide a convenient way of tuning the properties of the generated SC. This work highlights BTMOF as a promising platform for the development of a SC light source, which can be widely used in food quality inspection, early cancer diagnostics, gas sensing, and high-spatial-resolution imaging. more...

In our previous study, enterohepatic 12α-hydroxylated (12α) bile acid (BA) levels were found to be correlated with hepatic triacylglycerol concentration in rats fed high-fat (HF) diet. Since BA composition is diverse depending on animal species, we evaluated whether such a relationship is applicable in mice in response to an HF diet. C57BL/6JJmsSLC (B6) male mice were fed HF diet for 13 weeks and analyzed for triacylglycerol, cholesterol, oxysterols, and other metabolites in the liver. The BA composition was determined in the liver, small intestinal contents, portal plasma, aortic plasma, and feces. Neutral sterols were also measured in the feces. The ratio of 12α BA/non-12 BA increased in the liver, portal plasma, small intestinal contents, and feces of HF-fed B6 mice. Moreover, a positive correlation was observed between the ratio of fecal 12α BAs/non-12 BAs and hepatic triacylglycerol concentration. The concentration of 7α-hydroxycholesterol was increased in the liver of HF-fed B6 mice, whereas no increase was observed in the hepatic expression of cytochrome P450 family 7 subfamily A member 1. The present study showed that the ratio of 12α BA/non-12 BA in feces is closely associated with hepatic triacylglycerol accumulation in B6 mice fed HF diet., (© 2022. The Author(s).) more...

The association of Japanese and Mediterranean dietary patterns with muscle weakness in middle-aged and older Japanese individuals is unclear. This cross-sectional study investigated the association between Japanese and Mediterranean dietary patterns and muscle weakness in community-dwelling, middle-aged, and older Japanese individuals (enrolled from 2007 to 2011). Based on the dietary consumption information obtained from the brief self-administered diet history questionnaire, we assessed adherence to the Japanese (12-component revised Japanese diet index (rJDI12)) and Mediterranean (alternate Mediterranean diet (aMed) score) dietary patterns. Muscle weakness was defined as handgrip strength <28 and <18 kg for men and women, respectively. Logistic regression was used to ascertain the relationship between dietary pattern and muscle weakness. In our study, with 6031 participants, the Japanese, but not Mediterranean, dietary pattern was inversely associated with muscle weakness ( p for trend = 0.031 and 0.242, respectively). In the model adjusted for confounders, including energy intake, the highest quartile of rJDI12 scores (9-12 points), and the rJDI12 scores, entered as continuous variables, showed an independent association (odds ratio (95% CI), 0.703 (0.507-0.974), and 0.933 (0.891-0.977), respectively). Our findings showed that adherence to the Japanese dietary pattern is associated with a low prevalence of muscle weakness. more...

In this paper, a no-core tellurite optical fiber (NCTOF)-based sensor was proposed for cryogenic temperature detection in refrigeration process. The ultraviolet adhesive (UVA) dual-curing method was operated to stablish a sandwich-like composite structure, in which a section of NCTOF was compactly sandwiched between two segments of silica fiber to form multimode interference. The temperature sensing characteristics in cryogenic range were experimentally investigated by monitoring the transmission spectral movement, where a high sensitivity of 105.6 pm/°C was achieved in the range of -20-0 °C and 51.6 pm/°C in the range of -20-25 °C. The excellent performance was consistent with the simulation analysis. The maximum repeatability standard deviation and stability wavelength error of the sensor are 0.9799 pm/°C and 0.1676 nm, respectively. To the best of our knowledge, this is the first report on using tellurite optical fibers for cryogenic temperature detection, and the UVA dual-curing method provides a reliable solution for the integration and practical application of tellurite optical fiber. The proposed sensor is simple in structure, easy in fabrication, low in cost and excellent in performance. It can be expected to be used in food refrigeration, air-conditioning engineering, medical and health, industrial production, etc. more...

In this paper, we report a successful fabrication of a highly nonlinear chalcogenide all-solid hybrid microstructured optical fiber with polarization maintaining properties and a mid-infrared SC generation. Up to 4.5 × 10 -4 at 10 µm of the fiber birefringence can be realized by employing a single As 2 Se 3 core and two As 2 S 5 rods horizontally aligned in the AsSe 2 cladding. The fiber possesses a near-zero and flattened all-normal chromatic dispersion profile over the wavelength range from 5 to 10 µm. The polarization maintaining properties of the fiber is experimentally confirmed and a broadband supercontinuum spectrum from 2 to 10 µm in the mid-infrared window was experimentally demonstrated. more...

Noxious stimuli on the colorectum cause colorectal contractions through activation of descending monoaminergic pathways projecting from the supraspinal defecation center to the spinal defecation center. Since it is known that substance P is involved in the response to peripheral noxious stimuli in the spinal cord, we investigated the effects of intrathecally administered substance P at L6-S1 levels on colorectal motility in rats that were anesthetized with α-chloralose and ketamine. Intrathecally administered substance P enhanced colorectal motility, even after transection of the thoracic spinal cord at the T4 level. Severing the pelvic nerves, but not the colonic nerves, abolished substance P enhanced colorectal motility. In the spinal cord at L6-S1 levels, expression of mRNA coding neurokinin (NK) 1-3 receptors was detected by RT-PCR. Immunohistological experiments revealed that preganglionic neurons of the pelvic nerves express NK1 receptors, whereas expression of NK2 receptors was not found. In addition, substance P-containing fibers densely innervated around the preganglionic neurons expressing NK1 receptors. An intrathecally administered NK1 receptor antagonist (spantide) attenuated capsaicin-induced colorectal contractions. These results suggest that the colokinetic action of substance P is mediated by the NK1 receptor in the spinal defecation center. Our findings indicate that substance P may function as a neurotransmitter in the spinal defecation center. NEW & NOTEWORTHY We found that intrathecally administered substance P enhanced colorectal motility in anesthetized rats. Neurokinin (NK) 1 receptors, but not NK2 receptors, were detected in preganglionic neurons of the pelvic nerves. Blockade of NK1 receptors in the spinal cord attenuated the enhanced colorectal motility in response to intracolonic noxious stimuli. The findings indicate that substance P may function as a neurotransmitter in the spinal reflex pathway controlling defecation. more...

Our recent studies have shown that noxious stimuli in the colorectum enhance colorectal motility via the brain and spinal defecation centers in male rats. In female rats, however, noxious stimuli have no effect on colorectal motility. The purpose of this study was to determine whether sex hormones are major contributing factors for sex-dependent differences in neural components of the spinal defecation center. Colorectal motility was measured using an in vivo method under ketamine and α-chloralose anesthesia in rats. Capsaicin was administered into the colorectal lumen as noxious stimuli. Orchiectomy in male rats had no effect on the capsaicin-induced response of colorectal motility. However, in ovariectomized female rats, capsaicin administration enhanced colorectal motility, though intact female animals did not show enhanced motility. When estradiol was administered by using a sustained-release preparation in ovariectomized female rats, capsaicin administration did not enhance colorectal motility unless a GABA A receptor antagonist was intrathecally administered to the lumbosacral spinal cord. These findings suggest that estradiol allowed the GABAergic neurons to operate in response to intracolonic administration of capsaicin. The operation of GABAergic inhibition by the action of estradiol could be manifested in male rats only when the effects of male sex hormones were removed by orchiectomy. Taken together, our results indicate that sex hormones contribute to the sexually dimorphic response in colorectal motility enhancement in response to noxious stimuli through modulating GABAergic pathways. NEW & NOTEWORTHY This study demonstrated that estradiol permits inhibitory regulation in the spinal defecation center not only in female rats but also in orchiectomized male rats. GABAergic pathways are likely involved in the effect of estradiol. This is the first report showing that sex hormones affect colorectal motility through the alteration of neural components of the regulatory pathways. Our findings provide a novel insight into pathophysiological mechanisms of defecation disorders related to changes in sex hormones. more...

Identifying patient prognostic phenotypes facilitates precision medicine. This study aimed to explore phenotypes of patients with heart failure (HF) corresponding to prognostic condition (risk of mortality) and identify the phenotype of new patients by machine learning (ML). A unsupervised ML was applied to explore phenotypes of patients in a derivation dataset (n = 562) based on their medical records. Thereafter, supervised ML models were trained on the derivation dataset to classify these identified phenotypes. Then, the trained classifiers were further validated on an independent validation dataset (n = 168). Finally, Shapley additive explanations were used to interpret decision making of phenotype classification. Three patient phenotypes corresponding to stratified mortality risk (high, low, and intermediate) were identified. Kaplan−Meier survival curves among the three phenotypes had significant difference (pairwise comparison p < 0.05). Hazard ratio of all-cause mortality between patients in phenotype 1 (n = 91; high risk) and phenotype 3 (n = 329; intermediate risk) was 2.08 (95%CI 1.29−3.37, p = 0.003), and 0.26 (95%CI 0.11−0.61, p = 0.002) between phenotype 2 (n = 142; low risk) and phenotype 3. For phenotypes classification by random forest, AUCs of phenotypes 1, 2, and 3 were 0.736 ± 0.038, 0.815 ± 0.035, and 0.721 ± 0.03, respectively, slightly better than the decision tree. Then, the classifier effectively identified the phenotypes for new patients in the validation dataset with significant difference on survival curves and hazard ratios. Finally, age and creatinine clearance rate were identified as the top two most important predictors. ML could effectively identify patient prognostic phenotypes, facilitating reasonable management and treatment considering prognostic condition. more...

The Japanese dietary pattern has long been discussed as one of the factors behind the longevity of Japanese people. However, the health benefits of the Japanese dietary pattern have not been fully elucidated. We published the first report in the world regarding the relation between the Japanese dietary pattern and cardiovascular disease mortality in 2007 using cohort studies including Japanese residents of Ohsaki City, Miyagi Prefecture, Japan. Since then, we have developed the Japanese Diet Index (JDI) that was based on previous findings to assess the degree of the Japanese dietary pattern and to advance the evidence on the health effects of the Japanese dietary pattern. So far, we have explored the associations between the JDI score (in quartiles) and various outcomes. For all-cause mortality, in comparison to Q1 (the lowest), the multivariable hazard ratios (HRs) and 95% confidence intervals (95%CIs) were 0.92 (0.85-1.00) for Q2, 0.91 (0.83-0.99) for Q3, and 0.91 (0.83-0.99) for Q4 (the highest). For functional disability, the multivariable HRs (95%CIs) were 0.94 (0.81-1.09) for Q2, 0.90 (0.77-1.05) for Q3, and 0.79 (0.68-0.92) for Q4. For dementia, the multivariable HRs (95%CIs) were 0.88 (0.74-1.05) for Q2, 0.87 (0.73-1.04) for Q3, 0.79 (0.66-0.95) for Q4. In addition, people with higher adherence to the Japanese dietary pattern also showed decreases in disability and dementia risks. The purpose of this article was to review all six papers, summarize the health effects of the Japanese dietary pattern, and discuss implications for future research. more...

Background: Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations., Methods: We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model., Results: In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption., Conclusions: In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD., (© The Author(s) 2021; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.) more...

The outer membrane of Gram-negative bacteria functions as an impermeable barrier to foreign compounds. Thus, modulating membrane transport can contribute to improving susceptibility to antibiotics and efficiency of bioproduction reactions. In this study, the cellular uptake of hydrophobic and large-scaffold antibiotics and other compounds in Gram-negative bacteria was investigated by modulating the homolog expression of bamB encoding an outer membrane lipoprotein and tolC encoding an outer membrane efflux protein via gene deletion and gene silencing. The potential of deletion mutants for biotechnological applications, such as drug screening and bioproduction, was also demonstrated. Instead of being subjected to gene deletion, wild-type bacterial cells were treated with cell-penetrating peptide conjugates of a peptide nucleic acid (CPP-PNA) against bamB and tolC homologs as antisense agents. Results revealed that the single deletion of bamB and tolC in Escherichia coli increased the uptake of large- and small-scaffold hydrophobic compounds, respectively. A bamB-and-tolC double deletion mutant had a higher uptake efficiency for certain antibiotics and other compounds with high hydrophobicity than each single deletion mutant. The CPP-PNA treated E. coli and Pseudomonas aeruginosa cells showed high sensitivity to various antibiotics. Therefore, these gene deletion and silencing approaches can be utilized in therapeutic and biotechnological fields., (© 2022. The Author(s).) more...

Background: NIRO-Pulse is a novel mode of near-infrared spectroscopy that can be used to visually evaluate cerebral perfusion during cardiopulmonary resuscitation (CPR), providing real-time feedback as to the quality of the CPR. The aim of this report was to describe the several representative cases of NIRO-Pulse for physiological monitoring during CPR., Methods: We present several cases from out-of-hospital cardiac arrest (OHCA) patients for whom NIRO-Pulse was attached to the forehead after hospital arrival. Patients were subjected to continuous brain monitoring during CPR using NIRO-Pulse, which allows for the visualisation of ΔHb (Hb pulsation). NIRO-Pulse is capable of simultaneously measuring and displaying cerebral tissue oxygen saturation (SctO2) and Hb pulsation, providing real-time feedback during CPR in the form of physiological indicators, and assessing changes in SctO2 throughout the CPR procedure by post-mortem analysis., Results: We observed several representative cases that provided the following insights: (1) SctO2 increased after a change in the quality of chest compression, (2) SctO2 decreased during the ventilation phase of synchronised CPR, (3) SctO2 decreased during the interruption of chest compressions for the preparation of defibrillation, and (4) SctO2 gradually and continuously increased after return of spontaneous circulation., Conclusion: Displaying Hb pulsation in conjunction with SctO2 during CPR may be helpful for evaluating the quality of and patient responsiveness to CPR. Further studies investigating the association between the use of NIRO-Pulse during CPR and subsequent outcomes should be conducted. more...

The influence of public health measures against COVID-19 in Japan on child mental health by household type is unknown. This study aimed to investigate whether COVID-19 and the declaration of a state of emergency in Japan affected children's mental health between single-parent and two-parent households disproportionately. A large cross-sectional online survey was conducted from August to September 2020. The study included 3365 parents with children aged 0-14 years old who reported their children's mental status during the declared state of emergency. Emotional instability was reported dichotomously by parents. As the primary result, the probability of emotional instability was higher in single-parent households compared with that in two-parent households after adjustments for potential covariates; the adjusted prevalence ratio (95% CI) was 1.26 (1.07-1.49). Our findings suggest a disproportionate impact on children's mental health due to the pandemic. more...

Hereditary (variant) transthyretin amyloidosis (ATTRv amyloidosis), which is caused by variants in the transthyretin (TTR) gene, leads to TTR amyloid deposits in multiple organs and various symptoms such as limb ataxia, muscle weakness, and cardiac failure. Interaction between amyloid proteins and extracellular vesicles (EVs), which are secreted by various cells, is known to promote the clearance of the proteins, but it is unclear whether EVs are involved in the formation and deposition of TTR amyloid in ATTRv amyloidosis. To clarify the relationship between ATTRv amyloidosis and EVs, serum-derived EVs were analyzed. In this study, we showed that cell-derived EVs are involved in the formation of TTR amyloid deposits on the membrane of small EVs, as well as the deposition of TTR amyloid in cells. Human serum-derived small EVs also altered the degree of aggregation and deposition of TTR. Furthermore, the amount of TTR aggregates in serum-derived small EVs in patients with ATTRv amyloidosis was lower than that in healthy controls. These results indicate that EVs contribute to the metabolism of TTR amyloid, and suggest that TTR in serum-derived small EVs is a potential target for future ATTRv amyloidosis diagnosis and therapy., 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 © 2022 Yamaguchi, Kawahara, Kodera, Kumaki, Tada, Tang, Sakai, Ono, Yamada and Hanayama.) more...

We successfully fabricate a transversely disordered optical fiber made of AsSe 2 and As 2 S 5 glasses for high-resolution mid-infrared image transport. By using the fabricated fiber, we experimentally observe transverse Anderson localization of mid-infrared light at the wavelength of 3 µm. Moreover, we numerically evaluate the localization in the fiber by using a cross-sectional image of the fiber. more...