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Background: This study aimed to clarify the efficacy and safety of minimally invasive transabdominal surgery (MIS) with transperineal minimal invasive surgery (tpMIS) for sacrectomy in advanced primary and recurrent pelvic malignancies. Methods: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of MIS with tpMIS for sacrectomies. Surgery was performed between February 2019 and May 2023. The median follow-up period was 27 months (5–46 months). Results: Fifteen consecutive patients were included in this analysis. The diagnoses were as follows: recurrent rectal cancer, n = 11 (73%); primary rectal cancer, n = 3 (20%); and recurrent ovarian cancer, n = 1 (7%). Seven patients (47%) underwent pelvic exenteration with sacrectomy, six patients (40%) underwent abdominoperineal resection (APR) with sacrectomy, and two patients (13%) underwent tumor resection with sacrectomy. The median intraoperative blood loss was 235 ml (range 45–1320 ml). The postoperative complications (Clavien–Dindo grade ≥ 3a) were graded as follows: 3a, n = 6 (40%); 3b, n = 1 (7%); and ≥ 4, n = 0 (0%). Pathological examinations demonstrated that R0 was achieved in 13 patients (87%). During the follow-up period, two patients (13%) developed local re-recurrence due to recurrent cancer. The remaining 13 patients (87%) had no local disease. Fourteen patients (93%) survived. Conclusions: Although the patient cohort in this study is heterogeneous, MIS with tpMIS was associated with a very small amount of blood loss, a low incidence of severe postoperative complications, and an acceptable R0 resection rate. Further studies are needed to clarify the long-term oncological feasibility. [ABSTRACT FROM AUTHOR]

In this article, a new type of comparison theorem for some second-order nonlinear parabolic systems with nonlinear boundary conditions is given, which can cover classical linear boundary conditions, such as the homogeneous Dirichlet or Neumann boundary condition. The advantage of our comparison theorem over the classical ones lies in the fact that it enables us to compare two solutions satisfying different types of boundary conditions. As an application of our comparison theorem, we can give some new results on the existence of blow-up solutions of some parabolic equations and systems with nonlinear boundary conditions.

Importin α4, which is encoded by the Kpna4 gene, is a well-characterized nuclear-cytoplasmic transport factor known to mediate transport of transcription factors including NF-κB. Here, we report that Kpna4 knock-out (KO) mice exhibit psychiatric disorder-related behavioral abnormalities such as anxiety-related behaviors, decreased social interaction, and sensorimotor gating deficits. Contrary to a previous study predicting attenuated NF-κB activity as a result of Kpna4 deficiency, we observed a significant increase in expression levels of NF-κB genes and proinflammatory cytokines such as TNFα, Il-1β or Il-6 in the prefrontal cortex or basolateral amygdala of the KO mice. Moreover, examination of inflammatory responses in primary cells revealed that Kpna4 deficient cells have an increased inflammatory response, which was rescued by addition of not only full length, but also a nuclear transport-deficient truncation mutant of importin α4, suggesting contribution of its non-transport functions. Furthermore, RNAseq of sorted adult microglia and astrocytes and subsequent transcription factor analysis suggested increases in polycomb repressor complex 2 (PRC2) activity in Kpna4 KO cells. Taken together, importin α4 deficiency induces psychiatric disorder-related behavioral deficits in mice, along with an increased inflammatory response and possible alteration of PRC2 activity in glial cells., (© 2024. The Author(s).)

A spherical green alga, Volvox , achieves phototaxis via a simple on/off switch of flagellar beating in response to changes in light intensity, without the need for complex signal transduction between cells. Moreover, the alga can change its susceptibility to light in order to adapt to its environment. To identify the mechanisms of susceptibility regulation, experiments were conducted at three different levels: population, individual, and cellular. The light intensity dependence of the average velocity at the population level and that of the change in flow speed obtained at the individual level were consistent, indicating that susceptibility regulation occurred in each Volvox colony. Furthermore, by measuring the probability of stopping flagellar beating when the light intensity was changed, susceptibility regulation was found to result from the properties of somatic cells as differential and adaptive photosensors. These photosensing properties deteriorated from the anterior to the posterior regions of the colony. Considering the mechanical motion of a Volvox colony, the position-dependent ability of somatic cells indicates that the anterior cells play the role of a rudder, whereas the posterior cells play the role of a rower. The position-dependent properties of somatic cells imply an early stage of cell differentiation that allows for an efficient response to changes in the circumstances., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Seed dormancy corresponds to a reversible blockage of germination. Primary dormancy is established during seed maturation, while secondary dormancy is set up on the dispersed seed, following an exposure to unfavorable factors. Both dormancies are relieved in response to environmental factors, such as light, nitrate, and coldness. Quantitive Trait Locus (QTL) analyses for preharvest sprouting identified MKK3 kinase in cereals as a player in dormancy control. Here, we showed that MKK3 also plays a role in secondary dormancy in Arabidopsis within a signaling module composed of MAP3K13/14/19/20, MKK3, and clade-C MAPKs. Seeds impaired in this module acquired heat-induced secondary dormancy more rapidly than wild-type (WT) seeds, and this dormancy is less sensitive to nitrate, a signal able to release dormancy. We also demonstrated that MPK7 was strongly activated in the seed during dormancy release, especially in response to light and nitrate. This activation was greatly reduced in map3 k13/14/19/20 and mkk3 mutants. Finally, we showed that the module was not regulated and apparently did not regulate the genes controlling abscisic acid/gibberellin acid hormone balance, one of the crucial mechanisms of seed dormancy control. Overall, our work identified a MAPK module controlling seed germination and enlarged the panel of functions of the MKK3-related modules in plants., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background Patients with chronic kidney disease (CKD) were excluded in most trials that investigated the effects of urate-lowering agents, such as febuxostat and allopurinol, in hyperuricemic patients. This exclusion leads to uncertainty regarding the efficacy of febuxostat in patients with CKD. Due to the high prevalence of hyperuricemia in patients with CKD, we aimed to assess the effect of febuxostat on improving patient outcomes concerning cardiovascular events and survival compared with those treated with allopurinol among patients with CKD. Methods We conducted a retrospective cohort study using Japanese nationwide administrative data from Jan 1, 2013, to Sep 30, 2020. Patients aged over 60 years diagnosed with CKD were included in this study if they were prescribed either febuxostat or allopurinol. The primary outcome was the occurrence of cardiovascular events including myocardial infarction, stroke, unstable angina requiring urgent revascularization, and all-cause deaths. We estimated hazard ratios (HR) and 95% CI using a Cox proportional hazard regression model adjusted for comorbidities, medications, and laboratory data. We also assessed defined starting kidney replacement therapy as a secondary endpoint treating death as a competing risk using the Fine & Gray regression model. Results A total of 21,015 patients included those with febuxostat (n=17,796) and those with allopurinol (n=3,219). The association between the type of drug and the occurrence of cardiovascular events did not show a significant difference (0.107 vs. 0.116 events per patient-year; adjusted HR 0.953, 95% CI: 0.854 to 1.062, P=0.381). Similar results were seen for all-cause deaths (0.060 vs. 0.068 events per patient-year; adjusted HR 0.877, 95% CI: 0.760 to 1.012, P=0.073). Regarding the secondary endpoint, the association between the type of drug and the timing of starting kidney replacement therapy did not show a significant difference (0.118 vs. 0.097 events per patient-year; adjusted HR 0.953, 95% CI: 0.854 to 1.062, P=0.425). Conclusion The use of febuxostat was neither associated with a decreased risk of cardiovascular events or deaths nor with the timing of starting kidney replacement therapy compared to the use of allopurinol in patients with CKD., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Ayumi Shintani is compensated by Kyowa Kirin, and the payment is made to the institution. Financial relationships: Ayumi Shintani declare(s) personal fees from Daiichi Sankyo. Payment was made to her. Ayumi Shintani declare(s) personal fees from Eisai. Payment was made to her. Ayumi Shintani declare(s) personal fees from Maruho. Payment was made to her. Ayumi Shintani declare(s) personal fees from Novo Nordisk Pharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Pfizer. Payment was made to her. Ayumi Shintani declare(s) personal fees from Taisho Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Torii Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Janssen Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Kisei Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Mallinckrodt Pharmaceuticals. Payment was made to her. Ayumi Shintani declare(s) personal fees from Mitsubishi Tanabe Pharma Corporation. Payment was made to her. Ayumi Shintani declare(s) personal fees from Nippon Shinyaku. Payment was made to her. Ayumi Shintani declare(s) personal fees from Ono Pharmaceutical Company Limited. Payment was made to her. Ayumi Shintani declare(s) personal fees from Takeda Pharmaceutical Company Limited. Payment was made to her. Ayumi Shintani declare(s) personal fees from Taisho Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Kyowa Kirin. Payment was made to her. Ayumi Shintani declare(s) personal fees from Merck Biopharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Nipro Corporation. Payment was made to her. Yuta Nonomiya declare(s) a grant from Osaka Metropolitan University. An annual fellowship of 3.9 million yen is paid to the author. Yasutaka Ihara declare(s) employment from Daiichi Sankyo. Yasutaka Ihara is an employee of Daiichi Sankyo. Kazuhiko Tsuruya declare(s) a grant from Teijin. Kazuhiko Tsuruya declare(s) a grant from Mochida. Kazuhiko Tsuruya declare(s) personal fees from Teijin. Kazuhiko Tsuruya declare(s) personal fees from Mochida. Kazuhiko Tsuruya declare(s) personal fees from Sanwa Chemical. Kazuhiko Tsuruya declare(s) personal fees from Fuji. Ayumi Shintani declare(s) personal fees from Chugai Pharmaceutical. Payment was made to the institution. Ayumi Shintani declare(s) personal fees from Daiichi Sankyo. Payment was made to the institution. Ayumi Shintani declare(s) personal fees from Kyowa Kirin. Payment was made to the institution and to her. Ayumi Shintani declare(s) personal fees from Takeda Pharmaceutical Company Limited. Payment was made to the institution. Ayumi Shintani declare(s) personal fees from Shionogi Pharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Abbvie. Payment was made to her. Ayumi Shintani declare(s) personal fees from Asahi Kasei Corporation. Payment was made to her. Ayumi Shintani declare(s) personal fees from AstraZeneca plc. Payment was made to her. Ayumi Shintani declare(s) personal fees from Astellas Pharma. Payment was made to her. Ayumi Shintani declare(s) personal fees from Bayer Yakuhin. Payment was made to her. Ayumi Shintani declare(s) personal fees from Bristol Myers Squibb. Payment was made to her. Ayumi Shintani declare(s) personal fees from Chugai Pharmaceutical. Payment was made to her. Ayumi Shintani declare(s) personal fees from Sanofi K.K. Payment was made to her. Ayumi Shintani declare(s) personal fees from Nippon Kayaku. Payment was made to her. Ayumi Shintani declare(s) personal fees from JCR Pharmaceuticals Co. Payment was made to her. Ayumi Shintani declare(s) personal fees from MSD. Payment was made to her. Hisako Yoshida declare(s) personal fees from Organization for Clinical Medicine Promotion. Other relationships: Febuxostat is sold by the following companies, which I declared in the COI: Teijin, DAIICHI SANKYO ESPHA CO., LTD., and NIPRO CORPORATION. Allopurinol is sold by the following companies, which I declared in the COI: NIPRO ES PHARMA and Shionogi Pharma Co. ., (Copyright © 2024, Otani et al.)

Purpose: The anatomical location of inflammation in and around the ileal pouch affects the pouch survival rate, and diffuse inflammation has poor pouch survival rates. We aimed to clarify the symptoms and histological findings of diffuse inflammation of the pouch., Methods: We evaluated the symptoms, treatment, and histological findings according to the endoscopic phenotypes of diffuse inflammation, focal inflammation, and normal as the pouch body phenotype and afferent limb involvement, inlet involvement, cuffitis, and fistula as the peripheral findings., Results: Of the 318 pouchoscopies, 47 had diffuse inflammation, 201 had focal inflammation, and 70 were normal. Symptomatic patients had diffuse inflammation more frequently (46.8%) than focal inflammation (13.4%) and normal (14.2%), with no difference between focal inflammation and normal. Antibiotics and steroids were higher rate administered in cases of diffuse inflammation, but not in cases of focal inflammation or in normal cases. Histological inflammation, inflammatory bowel disease (IBD)-specific finding, and colonic metaplasia showed severity in the order of diffuse inflammation > focal inflammation > normal. The number of peripheral inflammatory findings overlapped in the following order: diffuse inflammation > focal inflammation > normal. The number of symptomatic patients increased as the number of peripheral inflammatory findings increased., Conclusion: Pouches with diffuse inflammation are more symptomatic, have a higher use of therapeutic agents, and have more severe histological inflammation, IBD-specific finding, and colonic metaplasia accompanying peripheral inflammatory findings than the other groups. The higher the overlap of inflammatory findings in the surrounding tissues, the more symptomatic the patients will appear., (© 2024. The Author(s).)

Numerous health concerns, primarily kidney injury, have been reported with the use of Beni-kōji CholesteHelp, a functional food containing red yeast rice. Here, we describe 2 cases of kidney injury caused by beni-kōji. The first case had normal kidney function before consuming the product. After several months of use, she developed hypertension. After 6 months of supplement consumption, her estimated glomerular filtration rate (eGFR) dropped to 22.5 mL/min/1.73 m 2 . A spot urine sample showed a urinary protein-to-creatinine ratio of 2.03 g/g, leading to the diagnosis of Fanconi syndrome. Kidney biopsy showed tubular degeneration. Thirty-five days after discontinuing the supplement, proteinuria resolved and the eGFR returned to baseline level. The second case, who had diabetes and normal kidney function, experienced severe kidney injury (eGFR, 3.5 mL/min/1.73 m 2 ) after 4 months of Beni-kōji CholesteHelp use. He required hemodialysis for >2 weeks but recovered kidney function after the product was discontinued. Kidney biopsy showed tubular injury similar to the first case and glomeruli changes consistent with diabetic nephropathy. These cases indicate that beni-kōji use is associated with tubular toxicity. Further studies are required to identify the precise etiology and mechanism of kidney injury., (© 2024 The Authors.)

Video summarization aims to select the most informative subset of frames in a video to facilitate efficient video browsing. Past efforts have invariantly involved training summarization models with annotated summaries or heuristic objectives. In this work, we reveal that features pre-trained on image-level tasks contain rich semantic information that can be readily leveraged to quantify frame-level importance for zero-shot video summarization. Leveraging pre-trained features and contrastive learning, we propose three metrics featuring a desirable keyframe: local dissimilarity, global consistency, and uniqueness. We show that the metrics can well-capture the diversity and representativeness of frames commonly used for the unsupervised generation of video summaries, demonstrating competitive or better performance compared to past methods when no training is needed. We further propose a contrastive learning-based pre-training strategy on unlabeled videos to enhance the quality of the proposed metrics and, thus, improve the evaluated performance on the public benchmarks TVSum and SumMe.

Phtheirospermum japonicum, a member of the Orobanchaceae family, is a facultative root parasitic plant that can survive without parasitizing the host. In contrast, obligate root parasitic plants such as Striga and Orobanche, which are also members of the Orobanchaceae family, cannot survive in the absence of the host. The germination of obligate root parasitic plants is typically induced by host root-derived strigolactones (SLs) at very low concentrations. The KAI2/HTL family proteins have been found to be involved in the perception of karrikin (KAR), a smoke-derived germination inducer and unidentified endogenous ligand, in non-parasitic plants. Obligate root parasitic plants possess uniquely diverged KAI2 clade genes, which are collectively referred to as KAI2d. Many of those have been shown to function as SL receptors. Intriguingly, the KAI2d clade genes are also conserved in P. japonicum, even though this plant does not require SLs for germination. The biochemical and physiological functions of the KAI2d proteins in P. japonicum remain unclear. Here, we report that some of these proteins can function as SL receptors in P. japonicum. Moreover, we found that one of them, PjKAI2d4, is highly sensitive to SLs when expressed in Arabidopsis, and it is similar to the sensitive SL receptors found in Striga and Orobanche. These results suggest that the KAI2d clade SL receptors play a crucial role not only in obligate parasites but also in facultative parasitic plants., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Plant parasitic root-knot nematodes are major agricultural pests worldwide, as they infect plant roots and cause substantial damages to crop plants. Root-knot nematodes induce specialized feeding cells known as giant cells (GCs) in the root vasculature, which serve as nutrient reservoirs for the infecting nematodes. Here, we show that the cell walls of GCs thicken to form pitted patterns that superficially resemble metaxylem cells. Interestingly, VASCULAR-RELATED NAC-DOMAIN1 (VND1) was found to be upregulated, while the xylem-type programmed cell death marker XYLEM CYSTEINE PEPTIDASE 1 was downregulated upon nematode infection. The vnd2 and vnd3 mutants showed reduced secondary cell wall pore size, while the vnd1 vnd2 vnd3 triple mutant produced significantly fewer nematode egg masses when compared with the wild type. These results suggest that the GC development pathway likely shares common signaling modules with the metaxylem differentiation pathway and VND1, VND2, and VND3 redundantly regulate plant-nematode interaction through secondary cell wall formation., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Cystinosis is a lysosomal storage disorder characterized by an autosomal recessive phenotype. Intermediate cystinosis, which progresses slowly and causes renal failure, accounts for approximately 5% of all cystinosis cases. Patients with intermediate cystinosis may not exhibit the typical symptoms of cystinosis, such as Fanconi syndrome and ocular symptoms. Because of its diverse clinical presentation and rarity, intermediate cystinosis can be difficult to diagnose. Additionally, few patients can tolerate cystine-depleting drugs, such as cysteamine, because of their complicated administration schedules and side effects. We report a case of intermediate cystinosis that was treated with cysteamine for 10 years., Case Presentation: Urinary abnormalities were first diagnosed when the patient was 3 years of age during a health examination specifically for 3-year-old children, which is unique to Japan. Cystinosis was diagnosed when the patient was 12 years of age. Cysteamine therapy was initiated and regular cystine concentration measurements were performed. Although proteinuria persisted, the patient's renal function progressed slowly. Two renal biopsies were performed, and multinucleated podocytes and cystine crystals without focal segmental glomerulosclerosis lesions were observed in the biopsy specimens. The patient's renal function remained stable., Conclusions: This case of intermediate cystinosis was treated with cysteamine over the course of 10 years. Intermediate cystinosis requires an appropriate diagnosis and long-term treatment., (© 2024. The Author(s).)

Mosses are distributed all over the world including Antarctica. Although Antarctic mosses show active growth in a short summer season under harsh environments such as low temperature, drought and high levels of UV radiation, survival mechanisms for such multiple environmental stresses of Antarctic mosses have not yet been clarified. In the present study, transcriptome analyses were performed using one of the common mosses Bryum pseudotriquetrum grown under an Antarctic field and artificial cultivation conditions. Totally 88 205 contigs were generated by de novo assembly, among which 1377 and 435 genes were significantly up and downregulated, respectively, under Antarctic field conditions compared with artificial cultivation conditions at 15°C. Among the upregulated genes, a number of lipid metabolism-related and oil body formation-related genes were identified. Expression levels of these genes were increased by artificial environmental stress treatments such as low temperature, salt and osmic stress treatments. Consistent with these results, B . pseudotriquetrum grown under Antarctic field conditions contained large amounts of fatty acids, especially α-linolenic acid, linolenic acid and arachidonic acid. In addition, proportion of unsaturated fatty acids, which enhance membrane fluidity, to the total fatty acids was also higher in B . pseudotriquetrum grown under Antarctic field conditions. Since lipid accumulation and unsaturation of fatty acids are generally important factors for the acquisition of various environmental stress tolerance in plants, these intracellular physiological and metabolic changes may be responsible for the survival of B . pseudotriquetrum under Antarctic harsh environments., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company.)

Aims: Cardiac resynchronization therapy (CRT) is an established treatment for drug-refractory heart failure (HF) in patients with left bundle branch block (LBBB). Acute haemodynamic improvement after CRT implantation may enable the intensification of HF medication soon thereafter. Immediate pharmacotherapy intensification (IPI) after CRT implantation achieves a synergetic effect, possibly leading to a better prognosis. This study aimed to explore the incidence, characteristics, and impact of IPI on real-world outcomes among CRT recipients with a history of hospitalization for acute HF., Methods and Results: This multicentre retrospective study enrolled CRT recipients with LBBB morphology, a QRS width ≥120 ms, a left ventricular ejection fraction ≤35%, and New York Heart Association II-IV HF symptoms. All patients had previous HF hospitalizations within the previous year and received guideline-directed medical therapy before CRT implantation. Patient baseline characteristics, including HF medication, were collected. IPI was defined as the intensification of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists within 30 days of CRT implantation. The primary endpoint was all-cause death or first hospitalization for HF; the secondary endpoint was all-cause death. We enrolled 194 patients (75% male; mean age, 65 ± 13 years; 78% with non-ischaemic cardiomyopathy). One hundred five (54%) patients received IPI. Patients who received IPI exhibited a significantly shorter QRS duration (159 ± 26 vs. 171 ± 32 ms; P = 0.004), higher estimated glomerular filtration rate (55.2 ± 20.0 vs. 47.8 ± 24.7 mL/min/1.73 m 2 ; P = 0.022), and more dilated cardiomyopathy. During a median follow-up period of 29 months, 70 (36%) patients reached the primary endpoint and 42 (22%) patients died. Patients with IPI showed significantly better outcomes for the primary and secondary endpoints than patients without IPI. The volumetric responder ratio at 6 months after implantation was not significantly different between patients with and without IPI; however, patients who received IPI had reduced mortality even at 6 months after implantation. In the multivariate analysis, IPI was an independent predictor of the primary endpoint (hazard ratio, 0.51; 95% confidence interval, 0.27-0.97; P = 0.043)., Conclusions: Immediate intensification of HF medication was achieved in 54% of CRT recipients and was significantly higher in patients without excessive QRS prolongation, preserved renal function, and dilated cardiomyopathy than others. In patients with LBBB morphology and QRS ≥ 120 ms, IPI was associated with a significantly better prognosis and fewer HF hospitalizations after CRT implantation than others., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The timing of seed germination is controlled by the combination of internal dormancy and external factors. Temperature is a major environmental factor for seed germination. The permissive temperature range for germination is narrow in dormant seeds and expands during after-ripening (AR) (dormancy release). Quantitative trait loci analyses of preharvest sprouting in cereals have revealed that MKK3, a mitogen-activated protein kinase (MAPK) cascade protein, is a negative regulator of grain dormancy. Here, we show that the MAPKKK19/20-MKK3-MPK1/2/7/14 cascade modulates the germination temperature range in Arabidopsis seeds by elevating the germinability of the seeds at sub- and supraoptimal temperatures. The expression of MAPKKK19 and MAPKKK20 is induced around optimal temperature for germination in after-ripened seeds but repressed in dormant seeds. MPK7 activation depends on the expression levels of MAPKKK19/20 , with expression occurring under conditions permissive for germination. Abscisic acid (ABA) and gibberellin (GA) are two major phytohormones which are involved in germination control. Activation of the MKK3 cascade represses ABA biosynthesis enzyme gene expression and induces expression of ABA catabolic enzyme and GA biosynthesis enzyme genes, resulting in expansion of the germinable temperature range. Our data demonstrate that the MKK3 cascade integrates temperature and AR signals to phytohormone metabolism and seed germination., Competing Interests: Competing interests statement:The authors declare no competing interest.

Perfectly diffuse sound fields play an important role in architectural acoustics and there are established theoretical characterizations of perfect diffuseness. Although sound fields in real rooms are diffuse to some extent, they are not perfectly diffuse, and therefore theories are required to describe pseudo-perfectly diffuse sound fields. Here, we aim to spatially characterize pseudo-perfect diffuseness via directional characterization of that, finite-degree spherical harmonic diffuseness. Our results show that finite-degree diffuse sound fields yield local spatial diffuseness, suggesting that spatial pseudo-perfect diffuseness is characterized using the effective radius of diffuseness., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Background: This study describes an outbreak caused by multispecies carbapenemase-producing Enterobacterales (CPE) occurring in a pediatric ward at an academic medical center in Tokyo., Methods: The index case involved a 1-year-old boy with Klebsiella variicola (CPE) detected in anal swabs in June 2016. The second case was Klebsiella quasipneumoniae (CPE) occurred in March 2017 followed by further spread, leading to the declaration of an outbreak in April 2017. Extensive environmental and patient microbiological sampling was performed. The relatedness of the isolates was determined using draft-whole-genome sequencing., Results: CPE surveillance cultures of patients and environments were positive in 19 patients and 9 sinks in the ward. The sinks in hospital rooms uninhabited by CPE patients exhibited no positive CPE-positive specimen during the outbreak. All CPE strains analyzed using draft-whole-genome sequencing harbored bla IMP-1 , except for one harboring bla IMP-11 ; these strains harbored identical bla IMP-1 -carrying IncM1 plasmids. CPE was detected even after sink replacement; infection-control measures focused on sinks were implemented and the CPE outbreak ended after 7 months., Conclusions: Multiple bacterial species can become CPE via bla IMP-1 -carrying IncM1 plasmids of the same origin and spread through sinks in a hospital ward. Thorough infection-control measures implemented as a bundle might be crucial., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: DB is a Commissioner on the Lancet Diabetes & Endocrinology Commission on type 1 diabetes and is the main grant holder for a project supported by the Swiss Agency for Development and Cooperation which contributed to the costs of a workshop on this topic held in Geneva on Sept 17, 2022 (Children Rights And Health—The Case Of Access To Insulin). J-DV is a Member of the Board of the Fondation Brocher. All other authors declare no competing interests. We wish to thank the participants in the aforementioned workshop, which led to the development of the concepts in this Correspondence. The workshop was supported by the Swiss Agency for Development and Cooperation and the Fondation Brocher.

Background: The current method for generating an animal model of spinal cord (SC) infarction is highly invasive and permits only short-term observation, typically limited to 28 days., Objective: We aimed to establish a rat model characterised by long-term survival and enduring SC dysfunction by inducing selective ischaemic SC damage., Methods: In 8-week-old male Wistar rats, a convection-enhanced delivery technique was applied to selectively deliver endothelin-1 (ET-1) to the anterior horn of the SC at the Th13 level, leading to SC infarction. The Basso, Beattie and Bresnahan (BBB) locomotor score was assessed for 56 days. The SC was examined by a laser tissue blood flowmeter, MRI, immunohistochemistry, triphenyl tetrazolium chloride (TTC) staining, Western blots and TUNEL staining., Results: The puncture method was used to bilaterally inject 0.7 µL ET-1 (2.5 mg/mL) from the lateral SC into the anterior horns (40° angle, 1.5 mm depth) near the posterior root origin. Animals survived until day 56 and the BBB score was stably maintained (5.5±1.0 at day 14 and 6.2±1.0 at day 56). Rats with BBB scores ≤1 on day 1 showed stable scores of 5-6 after day 14 until day 56 while rats with BBB scores >1 on day 1 exhibited only minor dysfunction with BBB scores >12 after day 14. TTC staining, immunostaining and TUNEL staining revealed selective ischaemia and neuronal cell death in the anterior horn. T2-weighted MR images showed increasing signal intensity at the SC infarction site over time. Western blots revealed apoptosis and subsequent inflammation in SC tissue after ET-1 administration., Conclusions: Selective delivery of ET-1 into the SC allows for more precise localisation of the infarcted area at the targeted site and generates a rat SC infarction model with stable neurological dysfunction lasting 56 days., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The operative field in subclavian vessel surgery is limited by thoracic inlet and outlet structures. Although endovascular therapy for the subclavian artery could be an option, open repair management is occasionally required in cases of large aneurysms, infectious vasculopathy, and trauma. The transmanubrial osteomuscular sparing approach, commonly used in thoracic surgery area to resect superior sulcus tumors, is a simple and safe procedure providing an excellent view of the operative field. Herein, we present three cases that underwent open repair of the subclavian artery using the transmanubrial osteomuscular sparing approach, and we also highlight the utility of the technique along with the procedural details., Case Presentation: Case 1: A 54-year-old man presented with a true aneurysm of the proximal portion of the right subclavian artery. The aneurysm measured 50 × 80 mm and compressed the right lung and trachea. We performed an aneurysm resection and a right subclavian artery reconstruction via the transmanubrial osteomuscular sparing approach under cardiopulmonary bypass support. Case 2: A 72-year-old man who presented with an abscess that formed around the left subclavian artery due to an unremoved guidewire during thoracic endovascular aortic repair for an aortic arch aneurysm in another hospital. After the antibiotics administration, debridement and axillary-axillary bypass were performed, and the guidewire was removed via a transmanubrial osteomuscular sparing approach with a use of cardiopulmonary bypass. Case 3: A 60-year-old man presented with misplacement of an indwelling dialysis catheter inserted for acute renal failure and hyperkalemia. The catheter was placed through the right neck, but had penetrated the right internal jugular vein and was misplaced from the right subclavian artery into the proximal aortic arch. Emergently, we removed the catheter using the transmanubrial osteomuscular sparing approach., Conclusions: The transmanubrial osteomuscular sparing approach to the subclavian artery provides an excellent view and a wide surgical field, even in different pathological situations. This is a simple, safe, and highly useful procedure and could be the standard approach for subclavian artery surgeries., (© 2024. The Author(s).)

Abscisic acid (ABA) is a phytohormone that promotes leaf senescence in response to environmental stress. We previously identified methyl CpG-binding domain 10 (MBD10) as a phosphoprotein that becomes differentially phosphorylated after ABA treatment in Arabidopsis. ABA-induced leaf senescence was delayed in mbd10 knockout plants but accelerated in MBD10-overexpressing plants, suggesting that MBD10 positively regulates ABA-induced leaf senescence. ABA-induced phosphorylation of MBD10 occurs in planta on Thr-89, and our results demonstrated that Thr-89 phosphorylation is essential for MBD10's function in leaf senescence. The in vivo phosphorylation of Thr-89 in MBD10 was significantly downregulated in a quadruple mutant of group C MAPKs (mpk1/2/7/14), and group C MAPKs directly phosphorylated MBD10 in vitro. Furthermore, mpk1/2/7/14 showed a similar phenotype as seen in mbd10 for ABA-induced leaf senescence, suggesting that group C MAPKs are the cognate kinases of MBD10 for Thr-89. Because group C MAPKs have been reported to function downstream of SnRK2s, our results indicate that group C MAPKs and MBD10 constitute a regulatory pathway for ABA-induced leaf senescence., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Between the start of the Russian Federation's invasion of Ukraine on 24 February 2022 and May 2023, more than 8 million individuals have been displaced from Ukraine. Ukraine has the second-largest HIV epidemic in the World Health Organization (WHO) European Region. From a humanitarian and public health perspective it is critical that Ukrainian refugees living with or at risk of HIV have access to testing, treatment and healthcare in their destination country. To gain better insight on the number of refugees from Ukraine receiving antiretroviral therapy (ART) in destination countries, the WHO Regional Office for Europe and the European Centre for Disease Prevention and Control conducted three surveys in July 2022, November 2022 and March 2023. Among 39 countries that responded to at least one survey, 31 had information on the number of refugees from Ukraine receiving ART in their country. A total of 6,519 refugees (1.5 per 1,000 refugees) received ART, lower than previous estimates by WHO, ECDC and partners of between 0.16% and 1.0%. This discrepancy may suggest a substantial number of undiagnosed and/or diagnosed but untreated HIV infections. Improving access to healthcare for people living with HIV among refugees from Ukraine is vital to ensure quality care.

Dimesulfazet can control annual and perennial sedges in rice paddies. Here we assessed its mode of action. We performed a phenotype assay of Arabidopsis , conducted a metabolomic analysis of Echinochloa crus-galli , and analyzed the endogenous concentration of very long-chain fatty acids (VLCFAs) in Schoenoplectiella juncoides . Dimesulfazet treatment caused curling and greening symptoms in the leaves and fiddlehead -like symptoms in the inflorescences of Arabidopsis . These symptoms were visually indistinguishable from those caused by flufenacet and benfuresate, which belong to Herbicide Resistance Action Committee (HRAC) Group 15. We performed GC-MS/MS analysis of primary metabolites and LC-MS analysis of lipids in the herbicide-treated E. crus-galli , followed by Orthogonal Partial Least Squares Discriminant Analysis clustering. The results showed that dimesulfazet belongs to the HRAC Group 15 cluster. The endogenous concentrations of C24:0, C26:0, and C28:0 decreased in dimesulfazet-treated plants as compared to those in the control. Overall, the mode of action of dimesulfazet involves the inhibition of VLCFA biosynthesis., Competing Interests: Declarations of interestNone, (© 2024 Pesticide Science Society of Japan.)

Tertiary lymphoid tissue (TLT) develops at sites of chronic immune stimulation, including infection, autoimmune disease, transplant rejection, and cancer. Recently, TLT has been focused on an indicator for poor renal prognosis in various kidney diseases. In cryoglobulinemic vasculitis (CV), specific glomerular and vascular lesions are seen; however, tubulointerstitial lesions are usually nonspecific. We herein report the case of a 74-year-old man with idiopathic CV with rare tubulointerstitial lesions, such as tubulointerstitial nephritis (TIN) with IgG4-positive plasma cell infiltration and TLT. To our knowledge, this is the first report identifying TLT in the kidney biopsy in a patient with CV. Glucocorticoid improved the renal outcome. The association between CV and TIN with TLT remains unknown., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

We present three cases of bilateral metachronous testicular tumors. The patient in case 1 had a history of left orchiectomy for undescended testis at the age of 19. The pathological findings revealed germ cell neoplasia in situ. Twenty-four years later (age＝43), he was diagnosed with right testicular tumor with lymph node and lung metastasis (stage IIIc). Right orchiectomy was performed, and the pathological finding showed nonseminomatous germ cell tumor. He underwent chemotherapy, followed by lymph node dissection and lung metastasectomy. The patient in case 2 had a history of left orchiectomy for testicular tumor at the age of 41. The pathological finding of the left testis revealed seminoma (stage IA). Nineteen years later (age＝60), he was diagnosed with right testicular tumor and underwent right orchiectomy. Herein, the pathological finding showed seminoma (stage IA). The patient in case 3 had a history of right orchiectomy for testicular tumor at the age of 25. The pathological findings revealed seminoma (stage IS), and he underwent adjuvant radiation of the para-aortic field without subsequent recurrence. Fourteen years later (age＝39), he was diagnosed with left testicular tumor and underwent left orchiectomy. The pathological finding revealed seminoma (stage IB). The patient underwent adjuvant carboplatin monotherapy to prevent recurrence. Due to the long interval between the occurrence of bilateral metachronous testicular tumors (mean＝19 years ; three cases), long-term observation is necessary to detect the possible occurrence of contralateral testicular tumors. Contralateral testicular biopsy might be considered at the time of orchiectomy for unilateral testicular tumor if associated with testicular atrophy and/or a history of undescended testis.

XK-related 8 (XKR8), in complex with the transmembrane glycoprotein basigin, functions as a phospholipid scramblase activated by the caspase-mediated cleavage or phosphorylation of its C-terminal tail. It carries a putative phospholipid translocation path of multiple hydrophobic and charged residues in the transmembrane region. It also has a crucial tryptophan at the exoplasmic end of the path that regulates its scrambling activity. We herein investigated the tertiary structure of the human XKR8-basigin complex embedded in lipid nanodiscs at an overall resolution of 3.66 Å. We found that the C-terminal tail engaged in intricate polar and van der Waals interactions with a groove at the cytoplasmic surface of XKR8. These interactions maintained the inactive state of XKR8. Point mutations to disrupt these interactions strongly enhanced the scrambling activity of XKR8, suggesting that the activation of XKR8 is mediated by releasing the C-terminal tail from the cytoplasmic groove. We speculate that the cytoplasmic tail region of XKR8 functions as a plug to prevent the scrambling of phospholipids., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

BACKGROUND  : Cystinosis is a rare autosomal recessive lysosomal disorder that mainly affects the kidney and eye. Early treatment with cysteamine significantly improves the prognosis. However, early diagnosis of cystinosis, especially the juvenile nephropathic form, remains challenging because typical symptoms only become apparent in adulthood. We herein describe a 13-year-old girl who presented with proteinuria only but was diagnosed with juvenile nephropathic cystinosis based on multinucleated podocytes in her kidney biopsy specimen. We also studied the nephropathology of another case to determine the features of the multinucleated podocytes. CASE DIAGNOSIS: A previously healthy 13-year-old girl presented to our hospital because proteinuria had been detected in her school urine screening. She had been noted to have proteinuria on her school urine screening when she was 11 years of age but there was no consultation with her physician at that time. She was asymptomatic and had no other abnormalities on examination other than a relatively high urinary β-2 microglobulin level. Her kidney biopsy showed 15 multinucleated podocytes in 34 glomeruli, and the mean number of nuclei per multinucleated podocyte was 4.4. Ophthalmological examination showed cystine crystals in her cornea. Her white blood cell cystine level was high, and she was diagnosed with juvenile nephropathic cystinosis. She started oral cysteamine treatment and showed almost no progression of the disease after 2 years. In another patient with juvenile nephropathic cystinosis, there were 25 multinucleated podocytes in 63 glomeruli, and the mean number of nuclei per multinucleated podocyte was 2.9. CONCLUSION: Early diagnosis is crucial to improve the prognosis of patients with cystinosis. This report emphasizes the importance of recognizing the unique pathological feature of multinucleated podocytes as an essential clue to the diagnosis of cystinosis., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Seed germination is controlled by a combination of the seed dormancy level and environmental conditions such as light, temperature, moisture, and nitrate levels. Seed dormancy is programed genetically, but it is also sensitive to maternal environmental conditions before and after anthesis. Recent developments in molecular genetics and bioinformatics have greatly enhanced our understanding of the molecular mechanisms of seed dormancy and germination in model plants and economically important crop species. This chapter focuses on temperature as an environmental factor and discusses the genetic and epigenetic mechanisms of dormancy and germination., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Germination test is fundamental and commonly used technique for seed dormancy and germination studies, and proper assessment of dormancy level and germination ability of a given set of seeds is prerequisite for most of the studies. However, germination is very sensitive to imbibition conditions, and dormancy development is also sensitive to growth conditions of the mother plants. In this chapter, we describe tips for plant growth and germination test mainly for physiological and molecular genetic studies with Arabidopsis. This protocol can be applied for other plant species with relatively small seeds and for various studies to analyze the effect of light, phytohormones, and other chemicals in seed germination., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Endoscopic monitoring of disease activity in patients with ulcerative colitis (UC) is important. However, frequent colonoscopic examinations are difficult to perform because of their invasiveness, especially in children. Bowel wall thickness (BWT) measurement using intestinal ultrasonography and fecal calprotectin (FC) measurement are useful noninvasive evaluation methods., Methods: We retrospectively analyzed BWT and FC levels and evaluated the Mayo endoscopic subscore (MES) using colonoscopy in pediatric patients with UC during the same period. The BWT was evaluated using the maximum BWT (mBWT), which was the maximum value of each colonic BWT; the sum of BWT (sBWT), which was the sum of each colonic BWT; and the sum of the adjusted BWT (saBWT), which was corrected using sBWT., Results: In 54 procedures from 40 patients, FC, mBWT, sBWT, and saBWT were significantly different between MES 0-1 and MES 2. The agreement between BWT and MES 2 was 193 out of 216 segments (89.4%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FC were 68.8%, 84.2%, 64.7%, 86.5%, and 79.6% respectively, while those of saBWT were 81.2%, 89.5%, 76.5%, 91.9%, 87.0%, respectively., Conclusions: BWT in each colonic segment, particularly saBWT, was more useful than FC for detecting moderate colonic inflammation (MES 2) in pediatric patients with UC. Therefore, intestinal ultrasonography may be helpful in the less invasive management of pediatric patients with UC., (© 2024 Japan Pediatric Society.)

Objective: To evaluate the screening of blood samples for infectious disease markers at laboratories and blood banks in Latin America per the findings of an External Quality Assessment Program (EQAP)., Methods: This qualitative analysis used data from the EQAP coordinated by the Fundação Pro Sangue Hemocentro de São Paulo with the support of the Pan American Health Organization to assess the performance of blood screening for infectious diseases from 2014 to 2018 in Latin America. Each participating laboratory or blood bank received an identical blind panel with 24 blood samples with variable reactivity for all the screening parameters. Panels were processed at each participating facility and results were returned to the Fundação Pro Sangue Hemocentro de São Paulo for individual and joint analyses. Two types of discrepant results were potential failures: false positive results (FPRs) and false nonreactive results (FNRRs)., Results: A total of 23 136 samples were evaluated. Global rates of FPR, FNRR, and concordant results were 0.3%, 1.0% and 98.7%, respectively. Seven FNRRs were found for HBsAg (1.0%), 12 for syphilis (2.6%), and 21 for Chagas disease (2.9%). No FNRRs were found for the HIV, HCV, and HTLV viruses. The average accuracy of all the laboratories and blood banks participating in the EQAP during the study period was 99.5% (standard deviation, 0.5%)., Conclusion: The findings of this qualitative analysis are positive for blood safety in Latin America, with an average accuracy of 99.5% among the participating laboratories and blood banks. This report reflects an important improvement in blood bank serological screening EQAP-PAHO report since the 2003.

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) has been reported to reduce patients' quality of life and impair cancer treatment by causing anticancer drug withdrawal or interruption. However, there are currently no effective methods for the prevention of CIPN. Renin-angiotensin-aldosterone system (RAAS) inhibitors may be associated with a reduced risk of developing oxaliplatin-induced peripheral neuropathy, and it would be valuable to examine whether they have the same effect on CIPN caused by other anticancer drugs. Our study explored the potential preventive effects of RAAS inhibitors on preventing paclitaxel-induced peripheral neuropathy (PIPN)., Methods: An exploratory cohort study was conducted using commercially available administrative claims data on lung cancer patients treated with paclitaxel-based chemotherapy. Cumulative paclitaxel doses, RAAS inhibitor prescriptions, and incidences of PIPN were identified using patient medical records. Fine-Gray analyses with death as a competing risk were performed. A propensity score approach was applied to address the problem of confounding., Results: Patients with lung cancer who received paclitaxel-based chemotherapy were classified into users of RAAS inhibitor (n = 1320) and non-users of RAAS inhibitor (n = 4566). The doses of RAAS inhibitors in our study were similar to those commonly used to treat hypertension. The PIPN incidence was significantly lower in users of RAAS inhibitor than in the non-users of RAAS inhibitor (sub-distribution hazard ratio, 0.842; 95% confidence interval, 0.762-0.929). The result was consistent in various sensitivity analyses and important subgroup analyses., Conclusions: RAAS inhibitors at doses commonly used for hypertension were associated with a reduced incidence of PIPN in patients with lung cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The University of Wisconsin (UW) solution is the gold standard for preserving the liver, kidneys, and pancreas. For renal preservation, the addition of the flavonoid, quercetin (QE), to the preservation solution reduces damage to renal tubular cells, and the addition of sucrose (Suc) is also beneficial for preservation. The aim of this study was to investigate the protective effects of QE and Suc on porcine livers in terms of warm and cold injury and to evaluate whether their use improves ischemia-reperfusion (I/R) injury after simple cold storage (CS)., Methods: We tested porcine livers procured after 30 minutes of warm ischemia followed by preservation for 6 hours under the following 2 conditions: group 1, preserved with the CS/UW solution (n = 4); group 2, preserved with the CS/UW solution containing Que 33.1 μM and Suc 0.1 M (n = 6). All livers were evaluated using an ex vivo isolated liver reperfusion model with saline-diluted autologous blood., Results: Aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels in group 2 were significantly lower at 30 minutes of reperfusion than in group 1. Furthermore, histologic evaluation by hematoxylin and eosin staining showed significantly fewer morphologic changes in group 2 than in group 1, as indicated by the total Suzuki score. Group 2 also had significantly better scores for sinusoidal congestion and hepatocyte cytoplasmic vacuolization., Conclusion: Adding Que and Suc to the UW solution can effectively prevent cold injury in livers donated after circulatory death., Competing Interests: Declaration of Competing Interest Masashi Imamura is an employee of Ishihara Sangyo Kaisha, Ltd. The other authors declare no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Rhombohedral boron monosulfide (r-BS) with a layer stacking structure is a promising electrocatalyst for an oxygen evolution reaction (OER) within an alkaline solution. We investigated the catalytic mechanisms at the r-BS electrode/alkaline medium interface for an OER using hybrid solvation theory based on the first-principles method combined with classical solution theory. In this study, we elucidate the activities of the OER at the outermost r-BS sheet with and without various surface defects. The Gibbs free energies along the OER path indicate that the boron vacancies at the first and second layers of the r-BS surface (V B1 and V B2 ) can promote the OER. However, we found that the V B1 is easily occupied by the oxygen atom during the OER, degrading its electrocatalytic performance. In contrast, V B2 is suitable for the active site of the OER due to its structure stability. Next, we applied a bias voltage with the OER potential to the r-BS electrode. The bias voltage incorporates the positive excess surface charge into pristine r-BS and V B2 , which can be understood by the relationship between the OER potential and potentials of zero charge at the r-BS electrode. Because the OH - ions are the starting point of the OER, the positively charged surface is kinetically favorable for the electrocatalyst owing to the attractive interaction with the OH - ions. Finally, we qualitatively discuss the flat-band potential at a semiconductor/alkaline solution interface. It suggests that p-type carrier doping could promote the catalytic performance of r-BS. These results explain the previous measurement of the OER performance with the r-BS-based electrode and provide valuable insights into developing a semiconductor electrode/water interface.

Objective: Medroxyprogesterone acetate (MPA) may increase the risk of atherosclerosis during hormone replacement therapy (HRT); therefore, the effect of progestogens other than MPA on atherosclerotic lesions requires evaluation. Adhesion of monocytes to vascular endothelial cells is an important early step in atherosclerosis progression. MCP-1 is a key chemokine that promotes monocyte migration and adhesion to vascular endothelial cells. In this study, we investigated the effects of dienogest (DNG), an alternative progestogen, on monocyte adhesion and cytokine expression in human umbilical vein endothelial cells (HUVECs)., Study Design: HUVECs were treated with DNG, natural progesterone, or MPA, followed by interleukin (IL)-1β stimulation. The mRNA expression of adhesion molecules (E-selectin and ICAM-1) and cytokines (MCP-1 and IL-6) was examined using real-time PCR. A flow chamber system was used to examine the effect of DNG on the adhesion of U937 monocytic cells to monolayer HUVECs., Results: Unlike MPA, DNG did not alter the mRNA expression of E-selectin, ICAM-1, MCP-1, and IL-6 in HUVECs. Moreover, it did not increase the number of monocytes adhering to HUVECs in the flow chamber system. However, MPA treatment significantly enhanced monocyte adhesion to HUVECs ( p  < 0.05)., Conclusions: DNG had no effect on the mRNA expression of adhesion molecules and cytokines in HUVECs, as well as the monocyte adhesion to HUVECs, suggesting that DNG can be explored as an alternative to MPA for HRT.

We present a combined simulation method of single-component artificial force induced reaction (SC-AFIR) and effective screening medium combined with the reference interaction site model (ESM-RISM), termed SC-AFIR+ESM-RISM. SC-AFIR automatically and systematically explores the chemical reaction pathway, and ESM-RISM directly simulates the precise electronic structure at the solid-liquid interface. Hence, SC-AFIR+ESM-RISM enables us to explore reliable reaction pathways at the solid-liquid interface. We applied it to explore the dissociation pathway of an H 2 O molecule at the Cu(111)/water interface. The reaction path networks of the whole reaction and the minimum energy paths from H 2 O to H 2 + O depend on the interfacial environment. The qualitative difference in the energy diagrams and the resulting change in the kinematically favored dissociation pathway upon changing the solvation environments are discussed. We believe that SC-AFIR+ESM-RISM will be a powerful tool to reveal the details of chemical reactions in surface catalysis and electrochemistry.

Objective: In subjects with chronic kidney disease (CKD), the effect of low-protein diet (LPD) is expected to alleviate uremic symptoms. However, whether LPD is effective in preventing loss of kidney function is controversial. The aim of this study was to evaluate the association between LPD and renal outcomes., Methods: We conducted a multicenter cohort study of 325 patients who suffered CKD stage 4 and 5 with eGFR ≥10 mL/min/1.73 m, 2 between January 2008 and December 2014. The primary diseases of the patients were chronic glomerulonephritis (47.7%), nephrosclerosis (16.9%), diabetic nephropathy (26.2%), and others (9.2%). The patients were divided into four groups, based on the mean protein intake (PI)/day, group 1 (n = 76): PI < 0.5 g/kg ideal body weight/day, group 2 (n = 56): 0.5 ≤ PI < 0.6 g/kg/day, group 3 (n = 110): 0.6 ≤ PI < 0.8 g/kg/day, group 4 (n = 83): PI ≥ 0.8 g/kg/day. Dietary supplementation with essential amino acids and ketoanalogues was not used. The outcome measure was occurrence of renal replacement therapy (RRT) (hemodialysis, peritoneal dialysis, renal transplantation (excluding preemptive transplantation)) and all-cause mortality until December 2018. Cox regression models were used to examine whether LPD was associated with the risk of outcomes., Results: During a mean follow-up of 4.1 ± 2.2 years. Thirty-three patients (10.2%) died of all causes, 163 patients (50.2%) needed to start RRT, and 6 patients (1.8%) received a renal transplant. LPD therapy of 0.5 g/kg/day or less was significantly related to a lower risk of RRT and all-cause mortality [Hazard ratio = 0.656; 95% confidence interval, 0.438 to 0.984, P = .042]., Conclusions: These results suggest that non-supplemented LPD therapy of 0.5 g/kg/day or less may prolong the initiation of RRT in stage 4 and 5 CKD patients., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

NUP98 and NUP214 form chimeric fusion proteins that assemble into phase-separated nuclear bodies containing CRM1, a nuclear export receptor. However, these nuclear bodies' function in controlling gene expression remains elusive. Here, we demonstrate that the nuclear bodies of NUP98::HOXA9 and SET::NUP214 promote the condensation of mixed lineage leukemia 1 (MLL1), a histone methyltransferase essential for the maintenance of HOX gene expression. These nuclear bodies are robustly associated with MLL1/CRM1 and co-localized on chromatin. Furthermore, whole-genome chromatin-conformation capture analysis reveals that NUP98::HOXA9 induces a drastic alteration in high-order genome structure at target regions concomitant with the generation of chromatin loops and/or rearrangement of topologically associating domains in a phase-separation-dependent manner. Collectively, these results show that the phase-separated nuclear bodies of nucleoporin fusion proteins can enhance the activation of target genes by promoting the condensation of MLL1/CRM1 and rearrangement of the 3D genome structure., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)