Search

Coherent nonlinear spectroscopies and imaging in the X-ray domain provide direct insight into the coupled motions of electrons and nuclei with resolution on the electronic length scale and timescale. The experimental realization of such techniques will strongly benefit from access to intense, coherent pairs of femtosecond X-ray pulses. We have observed phase-stable X-ray pulse pairs containing more than 3 × 107 photons at 5.9 keV (2.1 Å) with ∼1 fs duration and 2 to 5 fs separation. The highly directional pulse pairs are manifested by interference fringes in the superfluorescent and seeded stimulated manganese Kα emission induced by an X-ray free-electron laser. The fringes constitute the time-frequency X-ray analog of Young’s double-slit interference, allowing for frequency domain X-ray measurements with attosecond time resolution.

Abstract In π-conjugated polymers, the amorphous region absent from π–π stacking order typically limits polymer functions compared to the crystalline region with high π–π stacking order. Here, we show that a benzodithiophene–thiazolothiazole copolymer containing tripropylsilyl groups (PSTz2) has a greater coplanar backbone structure when the π–π stacking order is absent, such as in solution and in a film blended with a nonfullerene acceptor, than when it is present in a neat film. The excitons and charge carriers generated in PSTz2 are more highly delocalized in the blend film than in the neat film, presumably through the backbone. The unconventional structural feature of PSTz2 shows higher photovoltaic performance in nonfullerene-based cells compared to its alkyl-functionalized counterpart. Our results show that it is possible to develop π-conjugated polymers that perform well in amorphous blends due to the ordered backbone structure.

The BL09XU beamline of SPring-8 has been reorganized into a beamline dedicated for hard X-ray photoelectron spectroscopy (HAXPES) to provide advanced capabilities with upgraded optical instruments. The beamline has two HAXPES analyzers to cover a wide range of applications. Two sets of double channel-cut crystal monochromators with the Si(220) and (311) reflections were installed to perform resonant HAXPES analyses with a total energy resolution of less than 300 meV over a wide energy range (4.9–12 keV) while achieving a fixed-exit condition. A double-crystal X-ray phase retarder using diamond crystals controls the polarization state with a high degree of polarization over 0.9 in the wide energy range 5.9–9.5 keV. Each HAXPES analyzer is equipped with a focusing mirror to provide a high-flux microbeam. The design and performance of the upgraded instruments are presented.

COVID-19 remains a global health threat. Compliance with nonpharmaceutical interventions is essential because of limited effectiveness of COVID-19 vaccines, emergence of highly contagious variants, and declining COVID-19 antibody titers over time. We evaluated compliance with 14 nonpharmaceutical intervention–related COVID-19 preventive behaviors, including mask wearing, ventilation, and surface sanitation, in a longitudinal study in Japan using 4 waves of Internet survey data obtained during 2020–2022. Compliance with most preventive behaviors increased or remained stable during the 2-year period, except for surface sanitation and going out behaviors; compliance with ventilation behavior substantially decreased in winter. Compliance patterns identified from latent class analysis showed that the number of persons in the low compliance class decreased, whereas those in the personal hygiene class increased. Our findings reflect the relaxation of mobility restriction policy in Japan, where the COVID-19 pandemic continues. Policymakers should consider behavioral changes caused by new policies to improve COVID-19 prevention strategies.

In spite of emphasis on patient-centered care and promotion of their quality, shortcomings have been seen in psychiatric care due to lack of compassion. To improve the quality of psychiatric caring in nursing, it is important to develop and implement in-service education based on Locsin’s Technological Competency as Caring in Nursing (TCCN) theory. Objectives to determine psychiatric nurse managers' perception and practice status as a preliminary survey to serve as a resource for in-service psychiatric nursing education. This survey was conducted in August 2022 using the Technological Competency as Caring in Nursing Instrument-Revised for Practice (TCCNI-Repract) scale at "A" psychiatric hospital. Descriptive statistics and Wilcoxon's signed-rank tests were used. Eleven head nurses and assistant head nurses participated in this study. Mean values for the perception dimension of each item of the TCCNI-RePract were high, whereas mean values for practice dimension were low. The results indicated that perception dimension was significantly higher than practice dimension in 21 of 26 items of the TCCNI-RePract. Nurse managers demonstrated a high level of perception of the TCCN theory; however, many practical items scored low. Nurse managers suggested developing a current educational program to inform practice based on the TCCN theory.

Abstract Hyperosmotic stress activates in live cells numerous processes and also promotes intracellular protein/RNA aggregation and phase separation. However, the time course and the extent of these changes remain largely uncharacterized. To investigate dynamic changes in intracellular macromolecular crowding (MMC) induced by hyperosmotic stress in live cells, we used fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy (FCS) to quantify changes in the local environment by measuring the fluorescence lifetime and the diffusion of the monomeric enhanced green fluorescent protein (eGFP), respectively. Real-time monitoring of eGFP fluorescence lifetime showed that a faster response to environmental changes due to MMC is observed than when measuring the acceptor/donor emission ratio using the MMC-sensitive Förster resonance energy transfer sensor (GimRET). This suggests that eGFP molecular electronic states and/or collision frequency are affected by changes in the immediate surroundings due to MMC without requiring conformational changes as is the case for the GimRET sensor. Furthermore, eGFP diffusion assessed by FCS indicated higher intracellular viscosity due to increased MMC during hyperosmotic stress. Our findings reveal that changes in eGFP fluorescence lifetime and diffusion are early indicators of elevated intracellular MMC. Our approach can therefore be used to reveal in live cells short-lived transient states through which MMC builds over time, which could not be observed when measuring changes in other physical properties that occur at slower time scales.

Abstract High sensitivity of the Kβ fluorescence spectrum to electronic state is widely used to investigate spin and oxidation state of first-row transition-metal compounds. However, the complex electronic structure results in overlapping spectral features, and the interpretation may be hampered by ambiguity in resolving the spectrum into components representing different electronic states. Here, we tackle this difficulty with a nonlinear resonant inelastic X-ray scattering (RIXS) scheme, where we leverage sequential two-photon absorption to realize an inverse process of the Kβ emission, and measure the successive Kα emission. The nonlinear RIXS reveals two-dimensional (2D) Kβ-Kα fluorescence spectrum of copper metal, leading to better understanding of the spectral feature. We isolate 3d-related satellite peaks in the 2D spectrum, and find good agreement with our multiplet ligand field calculation. Our work not only advances the fluorescence spectroscopy, but opens the door to extend RIXS into the nonlinear regime.

Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of the DNA aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with the AGE-Apt or control-aptamer for 6 weeks and were then sacrificed. Plasma glucose, testicular AGEs, and Rage gene expression in 4-week-old DM mice and plasma glucose, testicular AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice, the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that AGEs-Apt may improve sperm abnormality by suppressing AGE–RAGE-induced oxidative stress and inflammation in the testes of DM mice.

In recent years, diseases such as age-related macular degeneration and retinal pigment degeneration caused by excessive exposure to short-wavelength visible light have become significant concerns. With the aim of quantitatively evaluating the toxicity of short-wavelength light, proliferating cell nuclear antigen (PCNA) accumulation at the irradiation site was investigated using live cell imaging techniques to irradiate individual living cells with short-wavelength laser light. By examining the dependency of PCNA accumulation on the irradiation site within the cells and their cell cycle, it was observed that PCNA accumulation occurred only when the cell nucleus of cells in the S phase of the cell cycle was irradiated. We investigated the accumulation of PCNA at the laser irradiation site using laser light at wavelengths of 405 nm and 375 nm, with intensities ranging from 0.5 μW to 9.0 μW. The results confirmed an increase in PCNA accumulation with increasing intensity, and a higher accumulation was observed with laser light irradiation at a wavelength of 375 nm compared to 405 nm. By comparing the PCNA accumulation and 24 h cell viability, we demonstrated the feasibility of quantitatively assessing laser light toxicity through the measurement of PCNA accumulation.

Abstract The post-surgical fluid leakage from the tubular tissues is a critical symptom after gastrointestinal or urinary tract surgeries. Elucidating the mechanism for such abnormalities is vital in surgical and medical science. The exposure of the fluid such as peritonitis due to urinary or gastrointestinal perforation has been reported to induce severe inflammation to the surrounding tissue. However, there have been no reports for the tissue responses by fluid extravasation and assessment of post-surgical and injury complication processes is therefore vital. The current model mouse study aims to investigate the effect of the urinary extravasation of the urethral injuries. Analyses on the urinary extravasation affecting both urethral mesenchyme and epithelium and the resultant spongio-fibrosis/urethral stricture were performed. The urine was injected from the lumen of urethra exposing the surrounding mesenchyme after the injury. The wound healing responses with urinary extravasation were shown as severe edematous mesenchymal lesions with the narrow urethral lumen. The epithelial cell proliferation was significantly increased in the wide layers. The mesenchymal spongio-fibrosis was induced by urethral injury with subsequent extravasation. The current report thus offers a novel research tool for surgical sciences on the urinary tract.

Abstract Aims Risk‐scoring systems for colorectal liver metastasis (CRLM) after hepatectomy allow prognoses to be predicted preoperatively. We investigated the clinical outcomes of neoadjuvant chemotherapy for resectable CRLM according to patient risk status, aiming to determine the subgroup of patients who could benefit from neoadjuvant chemotherapy. Methods In this multi‐institutional retrospective analysis, the preoperative risk score was calculated from six previously reported factors: synchronous metastases, primary lymph node positivity, tumor number, largest tumor diameter, extrahepatic metastasis, and the preoperative carbohydrate antigen 19–9 level. Patients were divided into three groups according to their risk scores: low risk (score = 0), intermediate risk (score 1–10), and high risk (score ≥11). Overall and recurrence‐free survival curves were calculated using the Kaplan–Meier method. After propensity‐score matching in the intermediate‐risk group, we compared clinicopathological features and outcomes. Results There were 318 cases, from 20 institutions. The preoperative risk score could be calculated in 277 cases. There were 34, 192, and 51 patients in the low‐, intermediate‐, and high‐risk groups, respectively. Intermediate‐risk group patients who received neoadjuvant chemotherapy had significantly better recurrence‐free survival than that of patients without neoadjuvant chemotherapy (P = .0453). After propensity‐score matching in the intermediate‐risk group, the recurrence‐free survival rate was better in patients who received neoadjuvant chemotherapy (P = .0261). But the overall survival rate was not improved after the matching. Conclusion Neoadjuvant chemotherapy for resectable CRLM might prolong the recurrence‐free survival period for intermediate‐risk patients with preoperative risk scores in the range of 1–10, but the overall survival was not improved by neoadjuvant chemotherapy.

Abstract The chemical order and disorder of solids have a decisive influence on the material properties. There are numerous materials exhibiting chemical order/disorder of atoms with similar X-ray atomic scattering factors and similar neutron scattering lengths. It is difficult to investigate such order/disorder hidden in the data obtained from conventional diffraction methods. Herein, we quantitatively determined the Mo/Nb order in the high ion conductor Ba7Nb4MoO20 by a technique combining resonant X-ray diffraction, solid-state nuclear magnetic resonance (NMR) and first-principle calculations. NMR provided direct evidence that Mo atoms occupy only the M2 site near the intrinsically oxygen-deficient ion-conducting layer. Resonant X-ray diffraction determined the occupancy factors of Mo atoms at the M2 and other sites to be 0.50 and 0.00, respectively. These findings provide a basis for the development of ion conductors. This combined technique would open a new avenue for in-depth investigation of the hidden chemical order/disorder in materials.

ABSTRACT: Objectives: The association between toothbrushing and coronavirus disease 2019 (COVID-19) infections is unknown. The aim of this study was to test the hypothesis that the change in time and frequency of toothbrushing is associated with having COVID-19 symptoms. Methods: In this 8-month retrospective cohort study, we used the data from the Japan COVID-19 and Society Internet Survey (JACSIS; N = 22,366), which was conducted between August and September 2020. The logistic regression analyses were used to calculate the odds ratios (ORs) of having the 3 main COVID-19 symptoms (high fever, cough, and taste and smell disorder). Confounders were age, sex, educational attainment, equivalised income level, self-rated health, health literacy, and living area. Results: The mean age of the participants was 49 years (SD = ±17.3), and 49.2% were male. Overall 2704 (12.1%) participants changed (increased or decreased) the time and frequency of toothbrushing, whilst 19,662 (87.9%) did not change. Only 60 participants (0.3%) had the 3 main COVID-19 symptoms. All logistic regression models showed that those who had a change in time and frequency of toothbrushing had higher odds of having the 3 main COVID-19 symptoms compared to those who had unchanged time and frequency of toothbrushing. The ORs ranged from 6.00 (95% confidence interval [CI], 3.60–9.99) in the crude model to 4.08 (95% CI, 2.38–6.98) in the fully adjusted model. Conclusions: The change in time and frequency of toothbrushing from before to after the COVID-19 pandemic was associated with having the 3 main COVID-19 symptoms.

Abstract The domain of psychiatric drug development is currently witnessing a notable transformation, with a paramount emphasis on targeting nonmonoamine receptors and exploring inventive mechanisms of action. This paper presents an overview of the ongoing advancements in antipsychotic and antidepressant drug development. Historically, antipsychotics predominantly targeted dopamine receptors, but there is now an escalating interest in drugs that act on alternative receptors, exemplified by the TAAR1 receptor. One noteworthy candidate is Ulotaront (SEP‐363856), an agent acting as a TAAR1 agonist with 5‐HT1A agonist activity, demonstrating promising outcomes in the treatment of schizophrenia, devoid of extrapyramidal symptoms or metabolic side‐effects. Similarly, MIN‐101 (Roluperidone) and KarXT are currently in development, with its focus on addressing the symptoms in schizophrenia. In the domain of antidepressants, novel therapeutic approaches have surfaced, such as Auvelity, a Food and Drug Administration (FDA)‐approved NMDA receptor antagonist synergistically combined with Bupropion to enhance its effects. Another notable candidate is Zuranolone, operating as a GABA A receptor‐positive allosteric modulator, showcasing efficacy in treating major depressive disorder (MDD) and postpartum depression. Additionally, TAK‐653 (NBI‐1065845) and MJI821 (Onfasprodil) have emerged as potential antidepressants targeting AMPA receptors and NMDA receptor 2B (NR2B) negative allosteric modulation, respectively. This paper underscores the transformative potential of these novel drug candidates in psychiatric treatment and their ability to address cases that were previously treatment‐resistant. By focusing on nonmonoamine receptors and introducing innovative mechanisms, these drugs offer a promising prospect of improved outcomes for individuals suffering from schizophrenia and MDD. Thus, sustained attention and dedication to the development of such drugs are essential to augmenting the therapeutic options available for psychiatric patients.

To investigate the Mo release behavior and its influence on the oxidation of UO2/mixed oxide (MOX) fuel, the oxidation and evaporation (O&E) behaviors of Mo powders and their influencing mechanisms with respect to oxygen partial pressure around powders (pO2s) were researched by using a thermogravimetric analysis technique under Ar-0.1 % O2, Ar-1.0 % O2, and Ar-1.5 % O2 atmospheres in the temperature range from 1473 to 1673 K. The study results reveal that Mo O&E could quickly consume oxygen, substantially decreasing pO2s. This decrease in pO2s facilitates the attainment of an oxygen mass balance by enhancing the diffusion rate of O2(g) towards the powder surfaces and decelerating the O&E rates of the powders. Subsequently, the oxygen consumption rate with respect to Mo release (FO-con) and the potential oxidation rate of UO2 nuclear fuels (FO-ads) under the typical accident conditions created in VERCORS were estimated using the latest analytical model of Mo and the existing fuel oxidation model, respectively. The results demonstrate that, as accident proceeds, FO-con has the potential to surpass FO-ads, thereby retarding the oxidation of nuclear fuel.

Laughter has a protective effect on human health. The spread of coronavirus disease 2019 (COVID-19) has changed opportunities for face-to-face communication and might decrease opportunities for laughter. This cross-sectional study aimed to investigate whether the decrease in face-to-face communication during the COVID-19 pandemic is associated with a decrease in laughter. Additionally, we investigated whether an increase in online communication mitigates this association. Data from the “Japan COVID-19 and Society Internet Survey (JACSIS),” conducted between August and September 2020, were used. Participants aged 15–79 years were included in this study. The outcome was a decrease in laughter before the onset of the COVID-19 pandemic. The explanatory variables were decreased face-to-face communication with friends and increased online communication (text message, telephone, and video contact). Causal mediation analysis was used to calculate prevalence ratios (PRs) and 95 % confidence intervals (CIs) of the controlled direct effects of increased online communication. Furthermore, the proportions eliminated (PEs) by an increase in online communication were calculated. Among the 25,482 participants, 40.4 % had decreased face-to-face communication and 21.4 % had a decreased frequency of laughter. After adjusting for confounders, a decrease in face-to-face communication was significantly associated with a decrease in laughter (PR = 1.62, 95 %CI = 1.55–1.70). PEs for decrease in laughter were 27.2 % (95 %CI = –2.0 to 56.4) for text-based communication, 36.1 % (95 %CI = 12.3–59.8) for telephone-based communication, and 28.6 % (95 %CI = 0.6–56.6) for video-based communication. Although a decrease in face-to-face communication was associated with a decrease in laughter during the COVID-19 pandemic, online communication, particularly telephone-based communication, mitigated this association.

Introduction: This study aimed to identify immune mediators, including cytokines, chemokines, and growth factors, in the plasma for predicting treatment efficacy and immune-related adverse events (irAEs) in advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICIs).Methods: We enrolled 57 patients with aUC who were treated with the anti-programmed cell death protein 1 (PD-1) antibody pembrolizumab after the failure of platinum-based chemotherapy between February 2018 and December 2020. Plasma levels of 73 soluble immune mediators were measured before and 6 weeks after initiating pembrolizumab therapy. The association of estimated soluble immune mediators with clinical outcomes, including overall survival (OS), progression-free survival (PFS), anti-tumor responses, and irAEs, were statistically evaluated.Results: In the multivariate analysis, levels of 18 factors at baseline and 12 factors during treatment were significantly associated with OS. Regarding PFS, baseline levels of 17 factors were significantly associated with PFS. Higher levels of interleukin (IL)-6, IL-8, soluble tumor necrosis factor receptor 1 (sTNF-R1), and IL-12 (p40), both at baseline and post-treatment, were significantly associated with worse OS. Conversely, low IL-6 and high TWEAK levels at baseline were associated with irAEs. Among identified factors, interferon (IFN) γ and IL-12 (p40) were repeatedly identified; high baseline levels of these factors were risk factors for worse OS and PFS, as well as progressive disease. Notably, using correlation and principal component analysis, factors significantly associated with clinical outcomes were broadly classified into three groups exhibiting similar expression patterns.Discussion: Measuring plasma levels of soluble immune mediators, such as IL-6, IL-8, sTNF-R1, IFNγ, and IL-12 (p40), could be recommended for predicting prognosis and irAEs in ICI-treated patients with aUC.

This study investigates the impact of different control strategies on the performance of a single desiccant wheel dehumidifier with a heat recovery in real-world applications. A method to minimize the performance fluctuation as an effect of dynamic system performance response is proposed. First, the effect of regeneration heat input (Qin) changes on the system performance of the above dehumidifier was clarified. Second, the performance behavior was examined in response to transient conditions for different operation modes and was used to determine the most effective operation mode. Qin was assumed to change over time, which would influence the regeneration temperature and airflow velocity. The results showed that fluctuating Qin reduces the dehumidification capacity (ΔX) and coefficient of regeneration performance (COPreg). Therefore, a rotational control speed was implemented in the optimum operation mode, which was effective in preventing the system performance decline and accelerated the emergence of the rotational speed control effect.

Non-aqueous Li–O2 batteries offer an extremely high energy density, but suffer from high overvoltage on charge and poor cycle characteristics. In the past decade, soluble redox mediators (RMs) have been utilized to reduce the charge overvoltage. However, the use of RMs inhibits the effective decomposition of Li2O2 due to the shuttling of RMs between the cathode and anode. In this study, 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO), which was previously proposed as an RM, was immobilized on the electrode surface by immersing carbon paper in a solution of the synthesized 4-(N-(3-triethoxysilyl-propyl) carbamoyloxy)-2,2,6,6-tetramethyl-1-piperidinoxyl (TESPCP), followed by a heat treatment. Charge–discharge testing of Li–O2 batteries using the TEMPO-immobilized cathode with a Li anode exhibited a charge plateau of about 3.7 V, indicating that the immobilized TEMPO could react electrochemically as a redox mediator. No overcharge behavior was observed in the cell, suggesting the RM shuttling effect was suppressed. Furthermore, SEM and XPS analyses of the cathode surface confirmed that no Li2O2 residues remained on the cathode after charging, unlike the control sample that utilized soluble RMs. These results indicate that a TEMPO-immobilized cathode can successfully mitigate RM shuttling while maintaining the benefits of RMs, allowing effective decomposition of Li2O2, during charging without leading to overcharging.

Abstract Peptidoglycan for elongation in Escherichia coli is synthesized by the Rod complex, which includes RodZ. Although various mutant strains of the Rod complex have been isolated, the relationship between the activity of the Rod complex and the overall physical and chemical structures of the peptidoglycan have not been reported. We constructed a RodZ mutant, termed RMR, and analyzed the growth rate, morphology, and other characteristics of cells producing the Rod complexes containing RMR. The growth and morphology of RMR cells were abnormal, and we isolated suppressor mutants from RMR cells. Most of the suppressor mutations were found in components of the Rod complex, suggesting that these suppressor mutations increase the integrity and/or the activity of the Rod complex. We purified peptidoglycan from wild‐type, RMR, and suppressor mutant cells and observed their structures in detail. We found that the peptidoglycan purified from RMR cells had many large holes and different compositions of muropeptides from those of WT cells. The Rod complex may be a determinant not only for the whole shape of peptidoglycan but also for its highly dense structure to support the mechanical strength of the cell wall.