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A case report published in the Scandinavian Journal of Rheumatology discusses the efficacy of plasma exchange in a 53-year-old female with anti-Ro52 and anti-MDA5 antibody-positive dermatomyositis and progressive interstitial lung disease. The patient presented with skin manifestations and ILD, leading to emergency admission. Treatment with triple therapy and plasma exchange resulted in remission, highlighting the potential benefits of this combination therapy in refractory cases. Further research is needed to validate these findings and explore the role of plasma exchange in similar cases. [Extracted from the article]

Distributed acoustic sensing (DAS) using existing optical fiber cables facilitates high‐density seismic observation. However, few studies have examined the reliability of the seismic waveform amplitude recorded by DAS. In this study, a DAS network was connected to optical fiber cables installed over a distance of 75 km along a high‐speed train (Shinkansen) railway in the Kumamoto prefecture, Japan. We successfully observed strong motions of the Mj6.6 earthquake (approximately 150 km from the fiber) on 22 January 2022, in Hyuga‐nada, in addition to several small local earthquakes. The observed strong motions from the Mj6.6 earthquake, using DAS, exhibited cycle skipping (clipping) issues due to dynamic range limitations at numerous channels. To address this, we estimated the shaking map, representing maximum strain distributions for Mj6.6, by replacing the clipped data with information from nearby unclipped channels and scaling their RMS amplitudes based on S‐coda (unclipped). Furthermore, we verified the reliability of the amplitude information obtained from DAS by estimating the distance attenuation of seismic waves while correcting for the differences in the structure type and coupling as much as possible. The distance attenuation property of local earthquakes was consistent with that of the peak ground velocities obtained from seismometers, indicating that DAS data acquired using fibers installed on infrastructure (various structures) can also be utilized to assess the spatial distribution of the relative amplitude values along the fiber. Obtaining high‐density seismic motion distributions is important for earthquake early warning and accurate damage estimation of strong motions. Plain Language Summary: In the past decade, the use of distributed acoustic sensing (DAS) for seismological purposes has grown rapidly. By utilizing existing dark fibers, such as telecommunication cables, high‐density seismic observation networks can be established in residential areas. In this study, DAS was applied to an existing optical fiber cable installed along a railway line, which recorded strong ground motions of Mj6.6 originating from a subduction zone, as well as numerous regional earthquakes. Although the technique uses optical phase differences for strain measurements and therefore has a poor response to strong ground motions, we resolve this issue using the correct data from neighboring stations as a reference and estimated the shaking distribution every 5 m along 75 km of the railway line. Additionally, when we analyzed the distance attenuation of small regional earthquakes, we found that the attenuation characteristics were similar to those obtained from permanent seismometers. These findings will significantly impact society in the future, particularly as the fiber cables replace conventional seismic observation networks. As a result, ultra‐high‐density observation networks will be capable of issuing more accurate earthquake early warnings and estimating damage following earthquakes. Key Points: We successfully observed strong motion from the Mj6.6 earthquake in Hyuga‐nada using Distributed acoustic sensing (DAS) over 75 km along railwayThe shaking map of the Mj6.6 was estimated by replacing the clipped channels with nearby unclipped channels and scaling their RMS amplitudes of S‐codaDistance attenuation property of local earthquakes of DAS consistent with that of peak ground velocities from continuous seismometers [ABSTRACT FROM AUTHOR]

Prominent excursions in the number of cosmogenic nuclides (e.g., 10Be) around 774 CE/775 document the most severe solar proton event (SPE) throughout the Holocene. Its manifestation in ice cores is valuable for geochronology, but also for solar‐terrestrial physics and climate modeling. Using the ECHAM/MESSy Atmospheric Chemistry (EMAC) climate model in combination with the Warning System for Aviation Exposure to SEP (WASAVIES), we investigate the transport, mixing, and deposition of the cosmogenic nuclide 10Be produced by the 774 CE/775 SPE. By comparing the model results to the reconstructed 10Be time series from four ice core records, we study the atmospheric pathways of 10Be from its stratospheric source to its sink at Earth's surface. The reconstructed post‐SPE evolution of the 10Be surface fluxes at the ice core sites is well captured by the model. The downward transport of the 10Be atoms is controlled by the Brewer‐Dobson circulation in the stratosphere and cross‐tropopause transport via tropopause folds or large‐scale sinking. Clear hemispheric differences in the transport and deposition processes are identified. In both polar regions the 10Be surface fluxes peak in summertime, with a larger influence of wet deposition on the seasonal 10Be surface flux in Greenland than in Antarctica. Differences in the peak 10Be surface flux following the 774 CE/775 SPE at the drilling sites are explained by specific meteorological conditions depending on the geographic locations of the sites. Plain Language Summary: During large solar storms, high energy particles are hurled with enormous force toward Earth by the Sun. As these particles collide with atmospheric constituents (such as oxygen or nitrogen) unique nuclides of cosmogenic origin are formed in the higher atmosphere. From there they are transported downwards and finally precipitate at the surface due to different sink processes. Their imprints can be conserved over thousands of years within natural archives, such as ice cores or tree rings. Analysis of these natural archives around the globe indicates that the strongest solar storm over the last 10.000 years happened around 774 CE/775. This event is estimated to have been up to two orders of magnitude stronger, than the strongest known events documented for the satellite era. In this study, we model and analyze the transport and deposition of the cosmogenic nuclides produced by the extreme 774 CE/775 event, by applying a new experimental setup. Our results might help to interpret the fingerprints of historical extreme events with respect to the prevailing atmospheric conditions. Key Points: The modeled transport and deposition of the cosmogenic nuclide10Be produced by the 774/775 solar proton event was compared to 10Be ice core recordsHemispheric differences in stratospheric and cross‐tropopause transport, and deposition were identified, with polar summertime maxima of 10Be surface fluxDifferences in reconstructed10Be surface fluxes are explained by the local ratio of wet to dry deposition maximizing inthesummertime [ABSTRACT FROM AUTHOR]

This study aimed to explore the intricate relationship between mitochondrial dysfunction, infection, and neuroinflammation, focusing specifically on the impact of pathogenic epitopes of the Epstein-Barr Virus (EBV) nuclear antigen 1 (EBNA1) in a mouse model of mitochondrial dysfunctions. The investigation included female middle-aged PARK2 -/- and C57BL/6J wild-type mice immunized with EBNA1 386-405 or with active experimental autoimmune encephalomyelitis (EAE) induction by the myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide. The PARK2 -/- mice developed more severe EAE than the wild-type mice. Following immunization with EBNA1 386-405 , only PARK2 -/- exhibited symptoms resembling EAE. During the acute phase, PARK2 -/- mice immunized with either MOG 35-55 or EBNA1 386-405 exhibited a similar infiltration of the T cells and macrophages in the spinal cord and decreased glial fibrillary acidic protein (GFAP) expression in the brain. However, the EBNA1 386-405 -immunized PARK2 -/- mice showed significantly increased frequencies of CD8a + T cells and CD11c + B cells, and distinct cytokine profiles in the periphery compared to the wild-type controls. These findings highlight the role of EBV in exacerbating inflammation, particularly in the context of mitochondrial deficiencies.

Premixed calcium silicate-based materials have recently been developed and are recommended for a wide range of endodontic procedures, including vital pulp therapy. This study investigated the in vitro biocompatibility and pro-mineralization effect and in vivo reparative dentin formation of EndoSequence Root Repair Material, EndoSequence BCRRM, Bio-C Repair, and Well-pulp PT. Both fresh and set extracts had no detrimental effect on the growth of human dental pulp stem cells. The fresh extracts had a higher calcium concentration than the set extracts and induced considerably greater mineralized nodule formation. EndoSequence Root Repair Material had the longest setting time, whereas Bio-C Repair had the shortest. When these materials were applied to exposed rat molar pulps, mineralized tissue deposition was found at the exposure sites after 2 weeks. These results indicate that the premixed calcium silicate-based materials tested could have positive benefits for direct pulp capping procedures.

We report a patient in whom a primary high-grade serous carcinoma (HGSC) of the fallopian tube transformed into a carcinosarcoma at the site of peritoneal dissemination, and immunohistological analysis suggested the involvement of an epithelial-mesenchymal transition (EMT). The patient, a 70-year-old woman, had an abdominal mass palpated on admission, and a laparotomy was performed after a close examination. The resected right fallopian tube was cystically dilated, and a solid mass was observed in its lumen. The histological diagnosis was HGSC of the right fallopian tube with a papillary or complex tubular structure composed of tumor cells with marked nuclear irregularities. p53 was overexpressed, and no mesenchymal tumor component was observed. The resected left-sided abdominal mass of the omentum was a solid with a long diameter of 100 mm. Microscopically, the tumor exhibited a mixture of HGSC and high-grade sarcoma with nonspecific differentiation. Furthermore, a heterologous chondrosarcoma was subsequently observed from the high-grade sarcoma. The HGSC component was E-cadherin positive. The high-grade sarcoma component was positive for EMT-related proteins such as zinc finger E-box-binding homeobox 1 (ZEB1) and twist family bHLH transcription factor 1 (TWIST1). The chondrosarcoma component was ZEB1 positive and TWIST1 negative. p53 overexpression was found in all 3 components. The tumor of the omentum suggested that an EMT phenomenon was involved in the tumorigenesis. In this scenario, the primary HGSC of the fallopian tube with obvious invasion demonstrated that the conversion from carcinoma to sarcoma by EMT occurs only with peritoneal dissemination., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This study developed the Japanese version of the Auckland Individualism and Collectivism Scale (J-AICS), examined its reliability and validity, and explored the associations between its factors (compete, unique, responsibility, advice, and harmony) along with variables related to mental health in the Japanese population., Methods: We recruited 476 Japanese participants from the general population. Participants completed the J-AICS along with questionnaires pertaining to culture and mental health., Results: Confirmatory factor analysis indicated the correlated five-factor model showed a good fit to the data. The Cronbach's α and McDonald's ω coefficients were high for the individualism, collectivism, compete, unique, and advice factors, but low for the responsibility and harmony factors. Convergent validity was supported by significant relationships between culture-related variables. A one-way analysis of variance revealed the low individualism/collectivism cluster had higher loneliness and lower satisfaction with life than the high individualism and collectivism clusters. The multiple regression analyses showed that the responsibility factor was significantly and negatively associated with mental health concerning anxiety and depressive symptoms, loneliness, and satisfaction with life. In addition, the harmony factor was significantly and positively associated with the mental health., Conclusion: These findings demonstrate sufficient validity of the J-AICS; however, reliability was insufficient for responsibility and harmony. Further, responsibility was positively associated with mental health and harmony was negatively associated with mental health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Noda, Okawa, Kasch, Vogelbacher, Lindsay, Nishiuchi, Kobayashi and Hofmann.)

Spotted fever group (SFG) rickettsia, the causative agent of SFG rickettsiosis, is predominantly carried by ticks, whereas Orientia tsutusgamushi, the causative agent of scrub typhus, is primarily transmitted by chigger mites in Japan. In this study, we attempted to isolate intracellular eubacteria from Leptotrombidium scutellare, a major vector of O. tsutsugamushi; moreover, we isolated an SFG rickettsia using a mosquito-derived cell line. Draft genome sequences of this unique isolate, by applying criteria for species delimitation, classified this isolate as a novel strain, proposed as "Rickettsia kedanie." Further genetic analysis identified conserved virulence factors, and the isolate successfully propagated in mammalian cells, suggesting its ability to cause diseases in humans. The presence of SFG rickettsia in unfed larvae implies potential dual-pathogen carriage and reflects a symbiotic relationship similar to that between the mites and O. tsutsugamushi, indicating possibility of its transovarial transmission from female adults. Furthermore, conserved genomic similarity of the novel isolate to known SFG rickettsia suggests potential multiple hosts, including chiggers and ticks. In the natural environment, ticks, chigger mites, and wild animals may carry new isolates, complicating the infection cycle and increasing the transmission risks to humans. This discovery challenges the conventional association of SFG rickettsia with ticks, emphasizing its implications for research and disease control. However, this study was confined to a particular species of chigger mites and geographic area, underscoring the necessity for additional studies to comprehend the ecological dynamics, host interactions, and health implications linked to this newly identified SFG rickettsia., (© 2024 The Societies and John Wiley & Sons Australia, Ltd.)

Recent single-cell RNA-sequencing analysis of rheumatoid arthritis (RA) synovial tissues revealed the heterogeneity of RA synovial fibroblasts (SFs) with distinct functions such as high IL-6 production. The molecular mechanisms responsible for high IL-6 production will become a promising drug target of RASFs to treat RA. In this study, we performed siRNA screening of 65 transcription factors (TFs) differentially expressed among RASF subsets to identify TFs involved in IL-6 production. The siRNA screening identified 7 TFs including ARID5B , a RA risk gene, that affected IL-6 production. Both long and short isoforms of ARID5B were expressed and negatively regulated by TNF-α in RASFs. The siRNA knockdown and lentiviral overexpression of long and short isoforms of ARID5B revealed that the long isoform suppressed IL-6 production stimulated with TNF-α. eQTL analysis using 58 SFs demonstrated that RA risk allele, rs10821944, in intron 4 of the ARID5B gene had a trend of eQTL effects to the expression of long isoform of ARID5B in SFs treated with TNF-α. ARID5B was found to be a negative modulator of IL-6 production in RASFs. The RA risk allele of ARID5B intron may cause high IL-6 production, suggesting that ARID5B will become a promising drug target to treat RA.

Background: Predictors of neoatherosclerosis in patients who received primary percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear., Objective: The aim of this study is to investigate the frequency and risk factors of neoatherosclerosis 1-year after the onset of ACS., Methods: This study investigated 83 patients who underwent PCI for ACS followed by 1-year follow-up optical coherence tomography. The patients were categorized into the neoatherosclerosis (n = 11) and non-neoatherosclerosis groups (n = 72). Baseline characteristics, PCI procedures, medical therapies, and blood tests at 1-year, including detailed lipid profiles, were compared between the two groups., Results: Diabetes mellitus was more prominent in the neoatherosclerosis than in the non-neoatherosclerosis group (45% vs. 17 %, respectively, p = 0.03). Total cholesterol (171 ± 37 mg/dL vs. 145 ± 25 mg/dL, respectively, p < 0.01), non-high-density lipoprotein cholesterol (HDL-C) (124 ± 36 mg/dL vs. 94 ± 24 mg/dL, respectively, p < 0.01), low-density lipoprotein cholesterol (94 ± 36 mg/dL vs. 72 ± 19 mg/dL, respectively, p < 0.01), and lipoprotein (a) (Lp[a]) (70 [19-112] mg/dL vs. 10 [3-25] mg/dL, respectively, p = 0.03) at follow-up were significantly higher in the neoatherosclerosis group. Multivariate analysis revealed that neoatherosclerosis was associated with high serum non-HDL-C (odds ratio [OR]: 1.075; 95 % confidence interval [CI]: 1.011-1.144; p < 0.01) and high serum Lp(a) levels (>30 mg/dL) (OR: 11.0; 95 % CI: 1.492-81.02; p = 0.02)., Conclusion: Poorly controlled non-HDL-C and Lp(a) would be risk factors of neoatherosclerosis in patients 1-year after ACS., Competing Interests: Declaration of competing interest Sho Torii received research grants from Abbot Vascular Japan, Boston Scientific Japan, Medtronic, and received honoraria from Boston Scientific Japan. Gaku Nakazawa received honoraria from Abbot Medical, Boston Scientific, Terumo Corp., Daiichi-Sankyo, and OrbusNeich. Yuji Ikari received research grants from Boston Scientific, and received honoraria from AstraZeneca, Boston Scientific, Kaneka, Nipro, Novartis, Bayer, and Boehringer Ingelheim. The remaining authors have nothing to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Unlike plants in the field, which experience significant temporal fluctuations in environmental conditions, plants in the laboratory are typically grown in controlled, stable environments. Therefore, signaling pathways evolved for survival in fluctuating environments often remain functionally latent in laboratory settings. Here, we show that TGA1 and TGA4 act as hub transcription factors through which the expression of genes involved in high-affinity nitrate uptake are regulated in response to shoot-derived phloem mobile polypeptides, CEP DOWNSTREAM 1 (CEPD1), CEPD2 and CEPD-like 2 (CEPDL2) as nitrogen (N) deficiency signals, and Glutaredoxin S1 (GrxS1) to GrxS8 as N sufficiency signals. CEPD1/2/CEPDL2 and GrxS1-S8 competitively bind to TGA1/4 in roots, with the former acting as transcription coactivators that enhance the uptake of nitrate, while the latter function as corepressor complexes together with TOPLESS (TPL), TPL-related 1 (TPR1) and TPR4 to limit nitrate uptake. Arabidopsis plants deficient in TGA1/4 maintain basal nitrate uptake and exhibit growth similar to wild-type plants in a stable N environment, but are impaired in regulation of nitrate acquisition in response to shoot N demand, leading to defective growth under fluctuating N environments where rhizosphere nitrate ions switch periodically between deficient and sufficient states. TGA1/4 are crucial transcription factors that enable plants to survive under fluctuating and challenging N environmental conditions., (© 2024. The Author(s).)

The demand for the essential commodity chemical 1,2-propanediol (1,2-PDO) is on the rise, as its microbial production has emerged as a promising method for a sustainable chemical supply. However, the reliance of 1,2-PDO production in Escherichia coli on anaerobic conditions, as enhancing cell growth to augment precursor availability remains a substantial challenge. This study presents glucose-based aerobic production of 1,2-PDO, with xylose utilization facilitating cell growth. An engineered strain was constructed capable of exclusively producing 1,2-PDO from glucose while utilizing xylose to support cell growth. This was accomplished by deleting the gloA, eno, eda, sdaA, sdaB, and tdcG genes for 1,2-PDO production from glucose and introducing the Weimberg pathway for cell growth using xylose. Enhanced 1,2-PDO production was achieved via yagF overexpression and disruption of the ghrA gene involved in the 1,2-PDO-competing pathway. The resultant strain, PD72, produced 2.48 ± 0.15 g L -1 1,2-PDO with a 0.27 ± 0.02 g g -1 -glucose yield after 72 h cultivation. Overall, this study demonstrates aerobic 1,2-PDO synthesis through the isolation of the 1,2-PDO synthetic pathway from the tricarboxylic acid cycle., (© 2024 Wiley‐VCH GmbH.)

2-Phenylethanol, known for its rose-like odor and antibacterial activity, is synthesized via exogenous phenylpyruvate by the sequential reaction of phenylpyruvate decarboxylase (PDC) and aldehyde reductase. We first targeted ARO10, a phenylpyruvate decarboxylase gene from Saccharomyces cerevisiae, and identified a suitable aldehyde reductase gene. Co-expression of ARO10 and yahK in E. coli transformants yielded 1.1 g/L of 2-phenylethanol in batch culture. We hypothesized that there might be a bottleneck in PDC activity. The computer-based enzyme evolution was utilized to enhance production. The introduction of an amino acid substitution in ARO10 (ARO10 I544W) stabilized the aromatic ring of the phenylpyruvate substrate, increasing 2-phenylethanol yield 4.1-fold compared to wild-type ARO10. Cultivation of ARO10 I544W-expressing E. coli produced 2.5 g/L of 2-phenylethanol with a yield from glucose of 0.16 g/g after 72 h. This approach represents a significant advancement, achieving the highest yield of 2-phenylethanol from glucose using microbes to date., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Immune checkpoint inhibitors (ICIs) have been widely used as standard therapies for various cancers. However, in 20-30% of cases, ICIs can lead to immune-related adverse events (irAEs), which sometimes require discontinuation of treatment. Due to the increased risk of irAEs, patients with pre-existing autoimmune diseases (AI) are often advised against receiving ICIs. However, there has not been sufficient objective risk assessment for AI. In our study, we conducted logistic regression analysis to assess the risk of irAEs by analyzing 478 cases that received anti-PD-(L)1 Ab and/or anti-CTLA4 Ab at our hospital between April 3, 2017, and May 24, 2022. Among these cases, 28 (5.9%) had pre-existing AI. We selected several independent factors for analysis: gender, age, performance status (PS), cancer type, type of ICI, type of combined anti-cancer agents, best overall response, and pre-existing AI. The adjusted odds ratio (OR) of AI for irAE occurrence was 2.52 [95% CI: 1.08-5.86] (p = 0.033), and the adjusted OR of AI for ICI discontinuation due to irAE was 3.32 [1.41-7.78] (p = 0.006). Patients with pre-existing AI experienced a significantly shorter irAE-free survival time compared to those without AI (median irAE-free survival: 5.7 months [95% CI: 3.5-7.8] vs 10.4 months [95% CI: 7.9-12.9], respectively, p = 0.035). Frequently observed irAEs in full ICI cohort, such as dermatologic issues (7.5%), pneumonitis (7.1%), hepatitis (4.6%), and hypothyroidism (4.2%), were often accompanied by pre-existing AI. Furthermore, pre-existing AI flared up in 6 cases (37.5% in AI-positive irAE-positive cases). The activity of AI was not related to the occurrence of irAEs. Grade 3 or higher irAEs were observed in 6 out of 20 (30.0%) cases in AI-accompanied patients complicated with irAEs. Although having a complicated AI increases the risk of irAEs, it may not necessarily be a contraindication for ICI treatment if closely monitored. (292<300 characters)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sumimoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The aim of this study is to establish and test an in vitro digestion-in situ absorption model that can mimic in vivo drug flux by employing a physiologically relevant value of the membrane surface area ( S )/volume ( V ) ratio for accurate prediction of oral drug absorption from lipid-based formulations (LBFs). Three different types of LBFs (Type IIIA-MC, Type IIIA-LC, and Type IV) loaded with cinnarizine (CNZ), a lipophilic weak base with borderline permeability, and a control suspension were prepared. Subsequently, a simultaneous in vitro digestion-permeation experiment was conducted using a side-by-side diffusion cell with a dialysis membrane having a low S / V value. During digestion, CNZ partially precipitated for Type IV, while it remained solubilized in the aqueous phase for Type IIIA-MC and Type IIIA-LC in the donor compartment. However, in vitro drug fluxes for Type IIIA-MC and Type IIIA-LC were lower than those for Type IV due to the reduced free fraction of CNZ in the donor compartment. In pharmacokinetic studies, a similar improvement in in vivo oral exposure relative to suspension was observed, regardless of the LBFs used. Consequently, a poor correlation was found between in vitro permeation and areas under the plasma concentration-time curve (AUC oral ) ( R 2 = 0.087). A luminal concentration measurement study revealed that this discrepancy was attributed to the extremely high absorption rate of CNZ in the gastrointestinal tract compared to that across a dialysis membrane evaluated by the in vitro digestion-permeation model, i.e., the absorption of CNZ in vivo was completed regardless of the extent of the free fraction, owing to the rapid removal of CNZ from the intestine. Subsequently, we aimed to predict the oral absorption of CNZ from the same formulations using a model that demonstrated high drug flux by employing the physiologically relevant S / V value and rat jejunum segment as an absorption sink (for replicating in vivo intestinal permeability). Predigested formulations were injected into the rat intestinal loop, and AUC loop values were calculated from the plasma concentration-time profiles. A better correlation was found between AUC loop and AUC oral ( R 2 = 0.72), although AUC loop underestimated AUC oral for Type IV due to the precipitation of CNZ during the predigestion process. However, this result indicated the importance of mimicking the in vivo drug absorption rate in the predictive model. The method presented herein is valuable for the development of LBFs.

A mesonephric-like endometrial adenocarcinoma (ML-EAC) is very rare and has a worse prognosis than other endometrial carcinomas. We describe an ML-EAC and report our endometrial cytological findings. A 76-year-old woman presented with irregular genital bleeding and a uterine mass. Endometrial cytology revealed atypical cylindrical or spindle-shaped cells in the form of small aggregates or solitary cells. The cell aggregates exhibited irregularly stacked papillary structures, small glandular structures, and fenestrated structures. The atypical cells had a nucleus with fine-granular chromatin and a granular cytoplasm, and nuclear grooves and intranuclear pseudo-inclusions were present. Hyaline globules were observed in the glandular lumens and in the background. The presumptive histological type was an adenocarcinoma, but the cytological features were different from those of an endometrioid carcinoma. A histological examination of the endometrial biopsy revealed an adenocarcinoma, and a simple hysterectomy was performed. A grayish-white elevated mass measuring 90 mm × 70 mm × 40 mm was observed on the uterine corpus in the hysterectomy specimen. Histologically, the tumor proliferated as complex tubular structures containing eosinophilic colloid-like materials and trabecular structures. The tumor cells were diffuse and positive for GATA-3 and partially positive for thyroid transcription factor-1. Estrogen and progesterone receptors were negative. An ML-EAC was diagnosed. The tumor was invasive and extended beyond one-half of the muscle layer with a high degree of vascular invasion. In conclusion, we need to focus on the various shapes of the cell aggregate, nuclear grooves, and intranuclear pseudo-inclusions of tumor cells to distinguish an ML-EAC from other endometrial carcinomas in endometrial cytology., (© 2024 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

Plants initiate specific defense responses by recognizing conserved epitope peptides within the flagellin proteins derived from bacteria. Proteolytic cleavage of epitope peptides from flagellin by plant apoplastic proteases is thought to be crucial for the perception of the epitope by the plant receptor. However, the identity of the plant proteases involved in this process remains unknown. Here, we establish an efficient identification system for the target proteases in Arabidopsis apoplastic fluid; the method employs native two-dimensional electrophoresis followed by an in-gel proteolytic assay using a fluorescence-quenching peptide substrate. We designed a substrate to specifically detect proteolytic activity at the C-terminus of the flg22 epitope in flagellin and identified two plant subtilases, SBT5.2 and SBT1.7, as specific proteases responsible for the C-terminal cleavage of flg22. In the apoplastic fluid of Arabidopsis mutant plants deficient in these two proteases, we observe a decrease in the C-terminal cleavage of the flg22 domain from flagellin, leading to a decrease in the efficiency of flg22 epitope liberation. Consequently, defensive reactive oxygen species (ROS) production is delayed in sbt5.2 sbt1.7 double-mutant leaf disks compared to wild type following flagellin exposure., (© 2024. The Author(s).)

The ubiquitin kinase-ligase pair PINK1-PRKN recognizes and transiently labels damaged mitochondria with ubiquitin phosphorylated at Ser65 (p-S65-Ub) to mediate their selective degradation (mitophagy). Complete loss of PINK1 or PRKN function unequivocally leads to early-onset Parkinson disease, but it is debated whether impairments in mitophagy contribute to disease later in life. While the pathway has been extensively studied in cell culture upon acute and massive mitochondrial stress, basal levels of activation under endogenous conditions and especially in vivo in the brain remain undetermined. Using rodent samples, patient-derived cells, and isogenic neurons, we here identified age-dependent, brain region-, and cell type-specific effects and determined expression levels and extent of basal and maximal activation of PINK1 and PRKN. Our work highlights the importance of defining critical risk and therapeutically relevant levels of PINK1-PRKN signaling which will further improve diagnosis and prognosis and will lead to better stratification of patients for future clinical trials.

Proton pump inhibitors (PPIs) have recently been reported to be linked with nephrotoxicity. PPIs are metabolized mainly or partly by cytochrome P450 2C19 (CYP2C19). However, the relationship between CYP2C19 genetic polymorphism and PPI-induced nephrotoxicity is unclear. In this study, we aimed to analyze the association between the time of occurrence of renal injury by PPIs, including lansoprazole, esomeprazole, rabeprazole, and vonoprazan, and CYP2C19 metabolizer status classified by CYP2C19 genotypes. Patients prescribed PPIs were reviewed in this retrospective cohort study. The primary outcome was the time to a 30% decrease in estimated glomerular filtration rate (eGFR) from baseline. In patients treated with lansoprazole, the time to a 30% decrease in eGFR for the CYP2C19 poor metabolizer (PM) group was significantly shorter than that for the non-PM group (hazard ratio for PM vs. non-PM, 2.43, 95% confidence interval, 1.21 to 4.87, P = 0.012). In contrast, in patients that received esomeprazole, rabeprazole, or vonoprazan, no significant differences were found in the time to a 30% decrease in eGFR between non-PM and PM groups. The adjusted hazard ratios for the time to a 30% eGFR decrease in patients treated with lansoprazole were significantly higher for CYP2C19 PM, hypertension, and a history of myocardial infarction. In conclusion, this retrospective study showed that CYP2C19 metabolizer status was associated with the time to a 30% eGFR decrease in patients treated with lansoprazole, but not with esomeprazole, rabeprazole, or vonoprazan., (© 2024 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Purpose: To compare the details, oncologists include in discharge letters with what home care physicians need. Although discharge letters are important to share patients' information for home palliative care, few studies have compared the details, especially patients' emotions, regarding what oncologists include in discharge letters and home care physicians' needs., Methods: This cross-sectional study was conducted by sending anonymous, self-administered questionnaires to 500 certified oncologists (OCs) and 500 directors of home care supporting clinics (HCs) in Japan between March and May 2023. The survey considered 20 potential items found in discharge letters, and compared rates of OCs including these items and HCs needs., Results: Of 310 valid responses, 186 were from OCs (average age: 47.7; 29 females) and 124 from HCs (average age: 55.4; 9 females). Major items with lower inclusion rates for OCs included patients' emotions regarding medical conditions (58.4% in OCs vs. 92.6% in HCs, p < 0.001), families' emotions regarding medical conditions (60.0 vs. 92.6%, respectively, p < 0.001), patients' perceptions regarding medical conditions (84.9 vs. 94.3%, respectively, p = 0.011), families' perceptions regarding medical conditions (84.3 vs. 95.1%, respectively, p = 0.004), and potential late-onset treatment-related adverse events (79.3 vs. 92.6%, respectively, p = 0.002). Conversely, OCs included patients' activities of daily living more frequently (96.2 vs. 90.2%, respectively, p = 0.031)., Conclusion: Transitioning to home-based palliative care may necessitate accurate information and consideration of patients' and families' perceptions and emotions regarding medical conditions in discharge letters for continuous provision of high-quality care., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Coping refers to conscious responses to negative circumstances, with the intention of ameliorating these situations. Few studies have compared the differences between psychotherapy and medication treatment for coping strategies for depression. In this study, we investigated the differences in coping strategies between cognitive behavioral therapy (CBT) combined with medication (CBT group) and medication alone (pharmacotherapy group) among outpatients with depression., Methods: A prospective observational study was conducted among 50 patients with major depression (24 and 26 in the CBT and pharmacotherapy groups, respectively). Stress coping strategies (Coping Inventory for Stressful Situations [CISS]) and depression severity (Beck Depression Inventory-Second Edition [BDI-II]) were assessed at baseline and 16 weeks later. Changes in the CISS and BDI-II scores in both groups were tested using repeated analysis of variance. Inverse probability weighting with propensity score analysis was applied to address potential selection bias., Results: At 16 weeks, the CBT group exhibited increased CISS task-oriented coping, distraction, and social diversion scores, which differed from those of the pharmacotherapy group. The CBT group exhibited a significantly greater reduction in depressive symptoms than the pharmacotherapy group., Limitations: This study was not a randomized controlled trial and thus may have selection bias., Conclusion: Gaining adaptive coping skills, including task-oriented coping, distraction, and social diversion skills, by combining CBT with medication may lead to greater improvement in depression symptoms. These findings suggest that clinicians should evaluate coping strategies and facilitate the acquisition of adaptive coping strategies in patients with depression to reduce their symptoms., Competing Interests: The authors report the following conflicts of interest: AN has received speaker and/or consultant fees from Lundbeck, Otsuka, Sumitomo Pharma, Mitsubishi Tanabe Pharma, Viatris, Takeda, and MICIN. NK has received speaker and/or consultant fees from Lundbeck, Sumitomo Pharma, and Takeda. HU has received grants from Daiichi Sankyo, Eisai, Mochida, Otsuka, and Sumitomo Pharma; speaker’s fees from Eisai, Lundbeck, Meiji Seika Pharma, Otsuka, Boehringer Ingelheim Japan, MSD, and Sumitomo Pharma; and advisory board fees from Lundbeck, Sumitomo Pharma, Takeda Pharmaceutical Company, and Boehringer Ingelheim Japan for the past three years. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ihara, Katayama, Nogami, Amano, Noda, Kurata, Kobayashi, Sasaki, Mitsuda, Ozawa, Matsuoka, Takemura, Uchida and Nakagawa.)

Calcium (Ca) is necessary for bone calcification, and Ca deficiency leads to decreased bone mineral density (BMD). Epidemiological studies have reported a correlation between Ca intake and BMD. Although the influences of Ca deficiency on BMD have been reported, the effects of Ca restriction on bone during high-fat diet ingestion remain unclear. Therefore, we hypothesized that high-fat diet ingestion would potentiate the negative effects of Ca restriction on bone. Sprague-Dawley strain male rats (aged 11 weeks) were divided into 4 groups: basic control diet (Cont.) (11% lipid energy rate, 0.5% calcium), basic control diet with Ca restriction (CaR) (11% lipid energy rate, 0.02% calcium), high-fat diet (HF) (40% lipid energy rate, 0.5% calcium), and high-fat diet with Ca restriction (HFCaR) (40% lipid energy rate, 0.02% calcium). At 28 days after starting the experimental diets, body weights were higher in the high-fat diet groups (HF and HFCaR) than in the standard-fat diet groups (Cont. and CaR) on 2-way analysis of variance. The apparent Ca absorption rate in the Ca-restricted groups (CaR and HFCaR) was higher than in the Ca-sufficient groups (Cont. and HF). BMD and bone strength parameters of the femur and lumbar vertebrae in the Ca-restricted groups were markedly lower than in the Ca-sufficient groups, whereas there were no significant differences between the standard-fat diet and HF diet groups. These results suggest that 28 days of Ca restriction increases the risk of bone fracture and osteoporosis., Competing Interests: Declaration of competing interest There are no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We demonstrate high-output-power and high-efficiency operation of 1.3-µm-wavelength InP-based photonic-crystal surface-emitting lasers (PCSELs). By introducing a metal reflector and adjusting the phase of the reflected light via optimization of the thickness of the p-InP cladding layer, we successfully achieve an output power of approximately 400 mW with the slope efficiency of 0.4 W/A and the wall-plug efficiency of 20% under CW conditions. In addition, this PCSEL exhibits a narrow circular beam with a divergence angle below 1.6° even at high output powers under CW conditions at temperatures from 15°C to 50°C. We have also demonstrated an output power of over 12 W under pulsed conditions at room temperature.

In a previous work, we demonstrated a coupled cavity system where photons in one storage cavity can be transferred to another storage cavity at an arbitrary time by applying a voltage pulse to a third cavity placed in a p-i-n junction. In this work, we demonstrate methods to improve the transfer efficiency and photon lifetimes of such a coupled system. Firstly, we designed a photonic-crystal structure that achieves a large coupling coefficient without reducing the radiation quality factor compared to the previously proposed structure: The photonic-crystal design was changed to a more symmetric configuration to suppress radiation losses and then optimized using an automatic structure tuning method based on the Covariance Matrix Adaptive Evolutional Strategy (CMAES). Here we added two improvements to achieve an evolution toward the desired direction in the two-dimensional target parameter space (spanned by the coupling coefficient and the inverse radiation loss). Secondly, to improve the experimental cavity quality factors, we developed a fabrication process that reduces the surface contamination associated with the fabrication of the p-i-n junction: We covered the photonic structure with a SiO 2 mask to avoid the contamination and the electrode material was changed from Al to Au/Cr to enable cleaning by a weak acid. Owing to these improvements of the cavity design and the fabrication process, the obtained system provides coupling strengths that are about three times stronger and photon lifetimes that are about two times longer, compared to the previously reported system.

Background: Cognitive-behavioral therapy (CBT) effectively improves the clinical symptoms of social anxiety disorder. However, there are non-responders who cannot decrease their cost/probability bias significantly; hence, their social anxiety symptoms remain unaddressed. Mindfulness training and cognitive-behavioral approaches promote a reduction in cost/probability bias and social anxiety symptoms. This study examines the effectiveness of a four-session program of mindfulness and CBT (M-CBT) in a non-clinical sample of individuals with high social anxiety., Methods: Participants were 50 Japanese undergraduate students (37 women and 13 men) randomly allocated to an intervention group (n = 27) and a control group (n = 23). The intervention group underwent a four-session M-CBT program, while the control group did not receive any treatment., Results: A group × time analysis of covariances showed significant interactions in the negative cognition generated when paying attention to others in probability bias, fear of negative evaluation by others, dispositional mindfulness, depressive symptoms, and subjective happiness. M-CBT also produced significant pre-post improvements in the above outcomes with moderate to high effect sizes (ds = .51-1.55). Conversely, there were no interactions in social anxiety symptoms and self-focused attention., Conclusions: These results indicate that M-CBT was effective for the negative cognition generated when paying attention to others in probability bias, fear of negative evaluation by others, dispositional mindfulness, depressive symptoms, and subjective happiness. The combination of mindfulness training with cognitive restructuring is proposed as potentially helpful for individuals with probability bias, leading to negative cognition from paying attention to others., Trial Registration: University Hospital Medical Information Network (UMIN CTR) UMIN000036763. Registered May 16, 2019., (© 2024. The Author(s).)

We develop spatial phase plate (SPP)-integrated photonic-crystal surface-emitting lasers featuring double-lattice photonic-crystal structures embedded using a crystal regrowth technique. SPPs possessing eight segmentations per phase rotation number l are fabricated on the top surface to generate optical vortex beams (OVBs) with l = 1-3. The beams exhibit a high output power of ∼5 W and high mode purities of 85%, 78%, and 72% for l = 1-3, respectively. These purity values are comparable with those of a pure Gaussian mode passing through an SPP. The compact, high-power, and high-purity OVB sources can be used in the fields of material processing, optical manipulation, and microscopy.

Background and Objective: Chronic graft versus host disease (GVHD)-associated myositis targeting skeletal muscle is a relatively rare but potentially debilitating complication following allogeneic hematopoietic stem cell transplantation (HSCT). We reviewed the clinicopathological features of GVHD-associated myositis among patients receiving allogeneic HSCT to elucidate the cellular pathogenesis., Methods: We retrospectively reviewed clinical data and muscle biopsy results from 17 consecutive patients diagnosed with GVHD-associated myositis at our institution between 1995 and 2019. Immunostaining findings of GVHD-associated myositis were compared to those of patients with anti-tRNA-synthetase antibody-associated myopathy (ASM) (n = 13) and dermatomyositis (DM) (n = 12)., Results: The majority of patients with GVHD-associated myositis showed subacute or chronic progression of mild to moderate limb weakness together with elevated serum creatine kinase. These patients also exhibited mild C-reactive protein elevation but were negative for myositis-related autoantibodies. Programmed death-1 (PD-1)-positive cells were observed in muscle interstitium adjacent to myofibers expressing human leukocyte antigen (HLA)-DR. The interstitium was also HLA-DR-positive, similar to biopsy samples from ASM patients but not DM patients. The proportions of HLA-DR-positive muscle fibers and PD-1-positive interstitial cells were significantly higher in GVHD and ASM samples than DM samples. The PD-1-positive cells were mostly CD-8-positive lymphocytes., Discussion: GVHD-associated myositis is characterized by HLA-DR-positive myofibers and infiltration of PD-1-positive lymphocytes. These features distinguish GVHD-associated myositis from DM but not from ASM., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Spinal and bulbar muscular atrophy (SBMA) is a hereditary neuromuscular disorder caused by the expansion of trinucleotide cytosine-adenine-guanine (CAG) repeats, which encodes a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. Recent evidence suggests that, in addition to motor neuron degeneration, defective skeletal muscles are also the primary contributors to the pathogenesis in SBMA. While benefits of physical exercise have been suggested in SBMA, underlying mechanism remains elusive., Methods: We investigated the effect of running exercise in a transgenic mouse model of SBMA carrying human AR with 97 expanded CAGs (AR97Q). We assigned AR97Q mice to exercise and sedentary control groups, and mice in the exercise group received 1-h forced running wheel (5 m/min) 5 days a week for 4 weeks during the early stage of the disease. Motor function (grip strength and rotarod performance) and survival of each group were analysed, and histopathological and biological features in skeletal muscles and motor neurons were evaluated., Results: AR97Q mice in the exercise group showed improvement in motor function (~40% and ~50% increase in grip strength and rotarod performance, respectively, P < 0.05) and survival (median survival 23.6 vs. 16.7 weeks, P < 0.05) with amelioration of neuronal and muscular histopathology (~1.4-fold and ~2.8-fold increase in motor neuron and muscle fibre size, respectively, P < 0.001) compared to those in the sedentary group. Nuclear accumulation of polyQ-expanded AR in skeletal muscles and motor neurons was suppressed in the mice with exercise compared to the sedentary mice (~50% and ~30% reduction in 1C2-positive cells in skeletal muscles and motor neurons, respectively, P < 0.05). We found that the exercise activated 5'-adenosine monophosphate-activated protein kinase (AMPK) signalling and inhibited mammalian target of rapamycin pathway that regulates protein synthesis in skeletal muscles of SBMA mice. Pharmacological activation of AMPK inhibited protein synthesis and reduced polyQ-expanded AR proteins in C2C12 muscle cells., Conclusions: Our findings suggest the therapeutic potential of exercise-induced effect via AMPK activation in SBMA., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Styrene is an important industrial chemical. Although several studies have reported microbial styrene production, the amount of styrene produced in batch cultures can be increased. In this study, styrene was produced using genetically engineered Escherichia coli . First, we evaluated five types of phenylalanine ammonia lyases (PALs) from Arabidopsis thaliana (AtPAL) and Brachypodium distachyon (BdPAL) for their ability to produce trans -cinnamic acid (Cin), a styrene precursor. AtPAL2-expressing E. coli produced approximately 700 mg/L of Cin and we found that BdPALs could convert Cin into styrene. To assess styrene production, we constructed an E. coli strain that co-expressed AtPAL2 and ferulic acid decarboxylase from Saccharomyces cerevisiae . After a biphasic culture with oleyl alcohol, styrene production and yield from glucose were 3.1 g/L and 26.7% (mol/mol), respectively, which, to the best of our knowledge, are the highest values obtained in batch cultivation. Thus, this strain can be applied to the large-scale industrial production of styrene.

In perioperative chemotherapy for breast cancer, dexamethasone (DEX) is administered at high dose to prevent adverse effects. Abrupt cessation of high-dose DEX treatment induces fatigue, but the incidence of the fatigue is uncertain. In this study, we retrospectively evaluated the incidence of fatigue following DEX administration for supportive therapy and the improvement of fatigue with DEX tapering, a gradual reduction of the daily dose, in breast cancer patients. The subjects were 124 patients with breast cancer receiving epirubicin- or docetaxel-based regimens as perioperative chemotherapy. Of all patients, 16.1% of patients experienced fatigue after cessation of DEX administration. The severity of fatigue was grade 1 in 6.5% of patients, grade 2 in 8.1% of patients, and grade 3 in 1.6% of patients. There were no significant differences in dose and duration of DEX administration between the group with fatigue and the group without fatigue. In almost all patients with fatigue, DEX tapering was performed from the next cycle. The efficacy of DEX tapering was evaluated by comparing the grade and subjective symptoms. Following DEX tapering, the severity of fatigue was significantly reduced (p < 0.05), and the subjective symptom was improved in 94.7% of patients. Therefore, fatigue is occasionally induced after the cessation of DEX administration for supportive therapy in breast cancer patients. The tapering of DEX may be effective for fatigue.

In the implementation of the policy for the elderly, the nurses who have the competency to pull out their potential power to continue living with several stakeholders' support are required to provide care in the community. Community nurse in Thailand has the responsibility to deliver adequate medical care and also social care for the elderly. The study aimed to identify the role of community nurse in the implementation of Thai health policy for the elderly. Codes regarding the role of community nurse in the implementation of Thai health policy for the elderly were extracted from descriptive data interviewed with 15 policy implementors in Thailand. The codes were categorized by similarities using thematic analysis. The role of community nurse was 16 categories and 102 codes out of factors promoting implementation of Thai health policy for the elderly, with 27 categories and 416 codes. The main roles were Coordination, Service delivery, and Monitoring and evaluation, composing seven categories and 45 codes, eight categories and 51 codes, and one category and six codes, respectively. It was conspicuous in coordination mechanisms, especially between the organizations and disciplines in providing Primary Health Care. Both health promotion activities and medical treatment were crucial roles for community nurses. The role of community nurse was one of promoting factors of Thai health policy for the elderly. The community nurse acts as a lubricant between the hospital and the community, which means that the community nurse implements seamless service delivery for the elderly integrating medical care and welfare., Competing Interests: The authors have no conflicts of interest to disclose., (2023, National Center for Global Health and Medicine.)

The COVID-19 pandemic has caused serious disruptions to health systems across the world. While the pandemic has not ended, it is important to better understand the resilience of health systems by looking at the response to COVID-19 by hospitals and hospital staff. Part of a multi-country study, this study looks at the first and second waves of the pandemic in Japan and examines disruptions experienced by hospitals because of COVID-19 and the processes through which they overcame those disruptions. A holistic multiple case study design was employed, and two public hospitals were selected for the study. A total of 57 interviews were undertaken with purposively selected participants. A thematic approach was used in the analysis. The study found that in the early stages of the pandemic, faced with a previously unknown infectious disease, to facilitate the delivery of care to COVID-19 patients while also providing limited non-COVID-19 health care services, the case study hospitals undertook absorptive, adaptive, and transformative actions in the areas of hospital governance, human resources, nosocomial infection control, space and infrastructure management, and management of supplies. The process of overcoming the disruptions caused by the pandemic was complex, and the solution to one issue often caused other problems. To inform preparations for future health shocks and promote resilience, it is imperative to further investigate both organizational and broader health system factors that build absorptive, adaptive, and transformative capacity in hospitals.

In this study, we investigated the changes in composition, microstructure, and starch molecular structure of shochu koji during preparation. We observed that the gelatinized and outer part of starch was decomposed in priority during the early and middle preparation stages. The gap between the starch granules increased with the delayed time. Finally, the koji microstructure became spongy. Shochu koji mold produced two α-amylases in different expression manners. Acid-labile α-amylase was produced in the early and middle preparation stages. Acid-stable α-amylase and saccharification power were produced in the middle and late stages. Throughout the koji preparation, reducing sugars content reached approximately 13-20 % of the total sugar content, with glucose representing over 70 % of the reducing sugars. α-Glucan fragments with C chains of degree of polymerization (DP) 4-73 were observed in the early and middle stages (<23 h), indicating the degradation of amylopectin at long B chains. In the latter stage, the amount of C chains of DP 6-30 decreased, while the longer C chains (DP 30<) did not change. These results showed that acid-labile α-amylase, acid-stable α-amylase, and saccharification enzymes including glucoamylase and α-glucosidase work preferentially on the amorphous regions of starch granules, and cooperative action of these enzymes during koji preparation contributes to the formation of the observed microstructure. Our study is the first report on the decomposition schemes of starch and the microstructure forming process in shochu koji., Competing Interests: The authors declare that they have no conflict of interest., (2023 by The Japanese Society of Applied Glycoscience.)

An 84-year-old man was diagnosed with anti-acetylcholine receptor (AChR) antibody-positive ocular myasthenia gravis (OMG) at the age of 77 and received treatment. The patient was referred to our department with swelling and pain in his right upper arm, which had spread to other limbs. His serum anti-AChR antibody and creatine kinase levels were elevated, and MRI of the limbs displayed signal changes suggesting inflammation in the several muscles. Despite showing no sign of thymoma, he was positive for serum anti-titin and anti-Kv1.4 antibodies. We performed a muscle biopsy, which led to a diagnosis of inflammatory myopathy (IM). IM associated with OMG is relatively mild. Age-related immune dysregulation may cause both OMG and IM. Evaluation of disease activity with serum anti-AChR antibody levels, and assessment of prognosis with examining anti-striational antibodies are necessary for appropriate management of IM associated with MG.

Nitroaromatic compounds are widely used in industry, but their production is associated with issues such as the hazardousness of the process and low regioselectivity. Here, we successfully demonstrated the production of p-nitrobenzoate (PNBA) from glucose by constructing p-aminobenzoate N-oxygenase AurF-expressing E. coli. We generated this strain, which we named PN-1 by disrupting four genes involved in PNBA degradation: nfsA, nfsB, nemA, and azoR. We then expressed AurF from Streptomyces thioluteus in this strain, which resulted in the production of 945 mg/L PNBA in the presence of 1 g/L p-aminobenzoate. Direct production of PNBA from glucose was achieved by co-expressing the pabA, pabB, and pabC, as well as aurF, resulting in the production of 393 mg/L PNBA from 20 g/L glucose. To improve the PNBA titer, we disrupted genes involved in competing pathways: pheA, tyrA, trpE, pykA, and pykF. The resultant strain PN-4Ap produced 975 mg/L PNBA after 72 h of cultivation. These results highlight the potential of using microorganisms to produce other nitroaromatic compounds., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

RecN, a bacterial structural maintenance of chromosomes-like protein, plays an important role in maintaining genomic integrity by facilitating the repair of DNA double-strand breaks (DSBs). However, how RecN-dependent chromosome dynamics are integrated with DSB repair remains unclear. Here, we investigated the dynamics of RecN in response to DNA damage by inducing RecN from the P BAD promoter at different time points. We found that mitomycin C (MMC)-treated ΔrecN cells exhibited nucleoid fragmentation and reduced cell survival; however, when RecN was induced with arabinose in MMC-exposed ΔrecN cells, it increased a level of cell viability to similar extent as WT cells. Furthermore, in MMC-treated ΔrecN cells, arabinose-induced RecN colocalized with RecA in nucleoid gaps between fragmented nucleoids and restored normal nucleoid structures. These results suggest that the aberrant nucleoid structures observed in MMC-treated ΔrecN cells do not represent catastrophic chromosome disruption but rather an interruption of the RecA-mediated process. Thus, RecN can resume DSB repair by stimulating RecA-mediated homologous recombination, even when chromosome integrity is compromised. Our data demonstrate that RecA-mediated presynapsis and synapsis are spatiotemporally separable, wherein RecN is involved in facilitating both processes presumably by orchestrating the dynamics of both RecA and chromosomes, highlighting the essential role of RecN in the repair of DSBs., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Orobanchaceae root parasitic weeds cause significant damage to agriculture and become threats to global food security. Integrated pest management is a key concept in modern agriculture and requires chemicals with various modes of action. Planteose accumulates as a storage carbohydrate in the dry seeds of root parasitic weeds. In Orobanche minor seeds, planteose is hydrolyzed by an α-galactosidase, OmAGAL2, during germination. It was found that the OmAGAL2 inhibitor, PI-28, suppressed the radicle elongation of germinating O . minor seeds. This inhibitory activity against O . minor radicle elongation was evaluated for a series of aryloxyacetylthioureas synthesized based on the structure of PI-28. Compounds with a 3-Cl or 4-Cl substituent on the benzene ring in the phenoxy moiety in PI-28 exhibited more potent activity than the parent PI-28. This is the first report on the effect of aryloxyacetylthioureas on a root parasitic weed and will contribute to the development of control reagents for root parasitic weeds., (© 2023 Pesticide Science Society of Japan.)