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Quality control of translation is crucial for maintaining cellular and organismal homeostasis. Obstacles in translation elongation induce ribosome collision, which is monitored by multiple sensor mechanisms in eukaryotes. The E3 ubiquitin ligase Znf598 recognizes collided ribosomes, triggering ribosome-associated quality control (RQC) to rescue stalled ribosomes and no-go decay (NGD) to degrade stall-prone mRNAs. However, the impact of RQC and NGD on maintaining the translational homeostasis of endogenous mRNAs has remained unclear. In this study, we investigated the endogenous substrate mRNAs of NGD during the maternal-to-zygotic transition (MZT) of zebrafish development. RNA-Seq analysis of zebrafish znf598 mutant embryos revealed that Znf598 down-regulates mRNAs encoding the C2H2-type zinc finger domain (C2H2-ZF) during the MZT. Reporter assays and disome profiling indicated that ribosomes stall and collide while translating tandem C2H2-ZFs, leading to mRNA degradation by Znf598. Our results suggest that NGD maintains the quality of the translatome by mitigating the risk of ribosome collision at the abundantly present C2H2-ZF sequences in the vertebrate genome., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ishibashi 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.)

Background: Yeast and lactic acid bacteria (LAB) play an important part in the post-harvest fermentation of coffee. This study applied lab-scale fermentation to commercial green coffee beans using dry coffee pulp as the substrate, with the aim of modifying coffee-bean flavor. In addition to spontaneous fermentation, yeast and LAB isolated from coffee beans and dried coffee pulp were added during fermentation., Results: Co-inoculation of yeast and LAB showed a significant effect on the chlorogenic acid content after between 24 and 72 h of fermentation. Acetic, citric, malic, lactic, and quinic acids were shown to be affected significantly (P < 0.05) by fermentation and inoculation. Gas chromatography detected that esters, alcohols, aldehydes, furans, and pyrazines were the primary compounds in the coffee beans. Certain volatile groups were present in greater concentrations and broader varieties within the inoculated beans. The highest cupping scores were given to beans that had been co-inoculated with yeast and LAB., Conclusion: Overall, the use of yeasts and LAB starters showed potential to create coffee beverages with desirable characteristics by standardized fermentation. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Nondestructive spectroscopic analysis is widely used to evaluate food composition. However, distinguishing analytes of interest from other compounds remains challenging. Since most foods are heterogeneous when viewed under a microscope, we hypothesized that spectra measured at microscopic points would be "purer" than spectra acquired from a larger area. By coupling this data with nonnegative matrix factorization (NMF), the analytes of interest can be separated. This preliminary study discusses the quantification of glucose in mixtures of different sugars. Samples were made by mixing glucose with other powders in different ratios and Raman spectra were measured at 200 micro-points for each sample. NMF was applied to factorize the mixed spectra into spectra of pure compounds and their concentrations, leading to the accurate quantification of glucose, while eliminating the effects of other compounds. While this study targets simple powders, separation of analytes using microscale heterogeneity is applicable for measuring more complex foods., 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 Elsevier Ltd. All rights reserved.)

To enhance the pore structure of green coffee beans (GCB) and detect the sorption capacity and extraction characteristics of flavor compounds before roasting, this study employed several methods: hot air drying (HD), freeze-drying (FD), 3-levels short-time heating with puffing (SH 1 P, SH 2 P, and SH 3 P), and 3-levels microwave with puffing (MW 45 P, MW 60 P, and MW 75 P). These methods were applied to GCBs pre-soaked in water for different times. The effects of these treatments on color change, porosity, microstructure, citric acid sorption capacity, and caffeine and chlorogenic acid extraction yield were investigated. Results indicated that, except for GCBs treated with SH 1 P, SH 2 P, SH 3 P, and MW 75 P, all other modified GCBs showed minimal color change. GCBs treated with MW 60 P exhibited favorable pore structures. MW 60 P treatments significantly improved the extraction yield of caffeine and chlorogenic acid. Furthermore, the increased porosity and improved pore size distribution of GCB after MW 60 P resulted in a significant increase in the sorption of citric acid onto modified GCB. The rate of the sorption reaction followed the pseudo-first-order kinetics. In conclusion, MW 60 P are effective treatments for enhancing the microstructure of GCB, improving sorption capacity, and improving the extraction yield of flavor compounds.

Introduction: Zinc deficiency is highly prevalent in HD patients. On the other hand, it remains unknown about the role of zinc in their nutritional status., Methods: We conducted an open-label randomized controlled trial. We investigated (i) the relationship between serum zinc levels and body composition and (ii) the effects of zinc supplementation on the composition of 48 HD patients with zinc deficiency., Results: Serum zinc levels were significantly correlated with body fat weight (p < 0.01), but not with nonfat tissue weight. Multiple regression analyses demonstrated that serum zinc levels were a significant independent predictor of body fat weight (p < 0.001). Furthermore, the weight of body fat significantly increased in the group that received 1-year zinc supplementation (p < 0.05), but not in the group that did not., Conclusion: Our findings indicate that zinc deficiency plays an important role in fat metabolism in HD patients with its deficiency., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Targeted genome editing has made significant advancements; however, safety and ethical issues have not been fully elucidated, resulting in strict control of the technique. We tested genome editing tools on gametes from a genetically humanized mouse model using a phenylketonuria (PKU) mouse model to gain insights into genome editing in human embryos. The human PKU mouse model Pah hR111X mice was generated. The junctional region between exon 3 and intron 3 of Pah was replaced with a 120 bp corresponding human PAH sequence, including the pathogenic common variant c.331C > T in Pah hR111X mice. Pah hR111X mice successfully recapitulated the PKU phenotype and showed cognitive dysfunction and depressive-like behavior, which are observed in human patients with PKU. Genome editing was applied to fertilized eggs of Pah hR111X mice utilizing sgRNA that targets the human sequence. Mice with the corrected allele exhibited normal serum phenylalanine levels. Through genome editing, we validated the utility of sgRNA. The genetically humanized mouse model suggested that germ-line genome editing of the pathogenic variant may be feasible for monogenic disorders by revealing the recovery of the phenotype; however, there are remaining issues with the tool, including its efficiency and accuracy. This genome editing protocol using a genetically humanized mouse model will provide insights for improving current issues and contribute to the establishment of heritable human genome editing protocols., (© 2024 SSIEM.)

Eukaryotic translation initiation factor (eIF)4A-a DEAD-box RNA-binding protein-plays an essential role in translation initiation. Recent reports have suggested helicase-dependent and helicase-independent functions for eIF4A, but the multifaceted roles of eIF4A have not been fully explored. Here we show that eIF4A1 enhances translational repression during the inhibition of mechanistic target of rapamycin complex 1 (mTORC1), an essential kinase complex controlling cell proliferation. RNA pulldown followed by sequencing revealed that eIF4A1 preferentially binds to mRNAs containing terminal oligopyrimidine (TOP) motifs, whose translation is rapidly repressed upon mTORC1 inhibition. This selective interaction depends on a La-related RNA-binding protein, LARP1. Ribosome profiling revealed that deletion of EIF4A1 attenuated the translational repression of TOP mRNAs upon mTORC1 inactivation. Moreover, eIF4A1 increases the interaction between TOP mRNAs and LARP1 and, thus, ensures stronger translational repression upon mTORC1 inhibition. Our data show the multimodality of eIF4A1 in modulating protein synthesis through an inhibitory binding partner and provide a unique example of the repressive role of a universal translational activator., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Current infertility treatment strategies focus on mature gametes, leaving a significant proportion of cases with gamete progenitors that stopped complete differentiation. On the other hand, recent advancements in next-generation sequencing have identified many candidate genes that may promote maturation of germ cells. Although gene therapy has shown success in mice, concerns about the integration of DNA vectors into oocytes hinder clinical applications. Here, we present the restoration of fertility in female mice through Sendai virus (SeV)-mediated RNA delivery. Ovaries lacking Kitl expression exhibit only primordial follicles due to impaired signaling to oocytes expressing the KIT tyrosine kinase. Despite SeVs being immunogenic and larger than the blood-follicle barrier, the administration of Kitl -expressing SeVs reinitiated oogenesis in genetically infertile mice that have only primordial follicles, resulting in the birth of normal offspring through natural mating. This virus also effectively addressed iatrogenic infertility induced by busulfan, a widely used cancer chemotherapy agent. Offspring born through SeV administration and natural mating displayed normal genomic imprinting patterns and fertility. Since SeVs pose no genotoxicity risk, the successful restoration of fertility by SeVs represents a promising approach for treating congenital infertility with somatic cell defects and protecting fertility of cancer patients who may become infertile due to loss of oocytes during cancer therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Ribosome profiling, which is based on deep sequencing of ribosome footprints, has served as a powerful tool for elucidating the regulatory mechanism of protein synthesis. However, the current method has substantial issues: contamination by rRNAs and the lack of appropriate methods to measure ribosome numbers in transcripts. Here, we overcome these hurdles through the development of "Ribo-FilterOut", which is based on the separation of footprints from ribosome subunits by ultrafiltration, and "Ribo-Calibration", which relies on external spike-ins of stoichiometrically defined mRNA-ribosome complexes. A combination of these approaches estimates the number of ribosomes on a transcript, the translation initiation rate, and the overall number of translation events before its decay, all in a genome-wide manner. Moreover, our method reveals the allocation of ribosomes under heat shock stress, during aging, and across cell types. Our strategy of modified ribosome profiling measures kinetic and stoichiometric parameters of cellular translation across the transcriptome., (© 2024. The Author(s).)

Intracytoplasmic sperm injection (ICSI) is clinically used to treat obstructive/nonobstructive azoospermia. This study compared the efficacy of ICSI with cauda epididymal and testicular sperm in Wistar (WI) and Brown-Norway (BN) rats. The transfer of ICSI oocytes with cryopreserved epididymal and testicular WI sperm resulted in offspring production of 26.2% and 3.7%-4.7%, respectively (P < 0.05). Treatments for artificial oocyte activation (AOA) and acrosome removal improved pronuclear formation in BN-ICSI oocytes; however, only AOA treatment was effective in producing offspring (3.7%-6.5%). In the case of ICSI with testicular sperm (TESE-ICSI), one offspring (0.6%) was derived from the BN-TESE-ICSI oocytes. The application of AOA or a hypo-osmotic sperm suspension did not improve the production of TESE-ICSI offspring. Thus, outbred WI rat offspring can be produced by using ICSI and less efficiently by using TESE-ICSI. Challenges in producing offspring by using ICSI/TESE-ICSI in inbred BN strain require further investigation.

Phytoremediation is a cost-effective and eco-friendly alternative method for arsenic (As) contaminated water treatment. This study conducted a two-year year-round field study (cycle1 and cycle2) in a temperate area (Sendai, Japan) using small As-hyperaccumulator Pteris vittata seedlings to reduce pre-cultivation time and associated costs. The number of seedlings was changed from 256 in the cycle1 period to 165 in the cycle2 period to evaluate the As removal efficiency of P. vittata for As-contaminated water in field conditions with different plant densities. Before the winter season, with continuously increasing fronds, rhizomes, and roots growth, this reduction did not affect the plant's As removal efficiency for As-contaminated water to decrease the As concentration from 30 μg/L to the environmental quality standard for As in water, set at 10 μg/L in Japan. During the winter season, we found that cold weather caused P. vittata to wither and release the accumulated As into water without a greenhouse (cycle1). In the meantime, the bioaccumulation factor (BAF) and the translocation factor (TF) values for fronds of P. vittata decreased (BAF for fronds: from 66,089 to 8,460; TF for fronds: from 13.4 to 3.4). On the other hand, with greenhouse protection (cycle2), P. vittata did not severely wither and kept accumulating As. Moreover, BAF and TF values for fronds of P. vittata increased (BAF for fronds: from 24,372 to 36,740; TF for fronds: from 5.2 to 17.2). Maintaining the air temperature inside the greenhouse, particularly around the rhizomes, above 0 °C may be the reason why P. vittata remained alive and functional during the cold winter. These results indicate that a single-layer polyethylene greenhouse was sufficient for the tropical-subtropical As-hyperaccumulator fern P. vittata to survive the cold winter and snow in the temperate area, enabling year-round phytoremediation treatment of As-contaminated water in the open field., 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 Elsevier Ltd. All rights reserved.)

Background and Aim: Neutrophil gelatinase-associated lipocalin (NGAL) is characterized by increased expression before the rise in serum creatinine and has been used as a biomarker for the early prediction of acute kidney injury (AKI). However, there have been no comprehensive analyses of its significance in gastrointestinal diseases. This study aimed to analyze the usefulness of measuring urinary NGAL levels in patients with gastrointestinal diseases., Methods: This study included 171 patients with a wide range of gastrointestinal diseases. Urinary NGAL levels were measured in all patients within 24 h of admission and 72 h later., Results: Urinary NGAL levels were higher in patients with acute pancreatitis and acute cholangitis/cholecystitis than in those with other diseases. Although lower than in these diseases, urinary NGAL tends to be higher in inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, as well as in acute and chronic liver diseases, and is higher in liver cirrhosis as the Child-Pugh grade increases. Furthermore, we found that the group with higher urinary NGAL levels, which continued to increase over time, had worse hospital stays and prognosis., Conclusion: Urinary NGAL could be used as an indicator of infectious diseases rather than an indicator of AKI in inflammatory bowel diseases and cirrhosis, and could predict the prognosis of patients with gastrointestinal diseases., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction and Aims: This study aimed to investigate the effects of a developed school-based online health education programme with a periodontal examination results sheet for high school students on their subjective oral symptoms, knowledge and attitudes regarding oral health, and oral health behaviours., Methods: The participants were first- and second-year students aged 15 to 17 years (n = 847) at a high school in Japan. The students underwent a periodontal examination and were divided into periodontal condition (PC) and nonperiodontal condition (non-PC) groups. The students participated in the online oral health education programme, which included a periodontal examination results sheet after the examination. The data for identifying the effect of the programme were collected via questionnaire surveys at the periodontal examination (baseline), after 3 months, and after 1 year, and they were compared between baseline and 3 months later and between baseline and 1 year later by the chi-square test. Logistic regression analysis was used to determine the associations between the measured variables related to oral health at 3 months or 1 year and the presence/absence of periodontal conditions after adjustment for sex and variables at baseline., Results: A total of 628 students (74.1%) participated in this study. The percentages of individuals with knowledge of how many teeth they had, knowledge of periodontal disease, and experience with toothbrushing instruction increased significantly after 1 year in both groups (p < .05). The awareness of gingival swelling and bleeding and the use of fluoride toothpaste at 3 months were positively associated with the presence of periodontal conditions., Conclusions: This study showed that an online oral health education programme contributed to improving oral health knowledge and behaviours among high school students and that the awareness of periodontal conditions according to the periodontal examination results sheet might improve the awareness of gingival swelling and bleeding at 3 months., Competing Interests: Conflict of interest None disclosed., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Neat1 is an architectural RNA that provides the structural basis for nuclear bodies known as paraspeckles. Although the assembly processes by which Neat1 organizes paraspeckle components are well-documented, the physiological functions of Neat1 are not yet fully understood. This is partly because Neat1 knockout (KO) mice, lacking paraspeckles, do not exhibit overt phenotypes under normal laboratory conditions. During our search for conditions that elicit clear phenotypes in Neat1 KO mice, we discovered that the differentiation of beige adipocytes-inducible thermogenic cells that emerge upon cold exposure-is severely impaired in these mutant mice. Neat1&#95;2 , the architectural isoform of Neat1 , is transiently upregulated during the early stages of beige adipocyte differentiation, coinciding with increased paraspeckle formation. Genes with altered expression during beige adipocyte differentiation typically cluster at specific chromosomal locations, some of which move closer to paraspeckles upon cold exposure. These observations suggest that paraspeckles might coordinate the regulation of these gene clusters by controlling the activity of certain transcriptional condensates that coregulate multiple genes. We propose that our findings highlight a potential role for Neat1 and paraspeckles in modulating chromosomal organization and gene expression, potentially crucial processes for the differentiation of beige adipocytes., (© 2024 Toya et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Multicellular organisms are composed of specialized cell types with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains underinvestigated. By performing RNA-seq and Ribo-seq in genetically defined cells in the Drosophila brain, we here revealed substantial post-transcriptional regulations that augment the cell-type distinctions at the level of protein expression. Specifically, we found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low in glia, leading to their preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias toward the 5' leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open-reading frames in the 5' leader confer selective translational suppression in glia. Overall, these findings underscore the profound impact of translational regulation in shaping the proteomics for cell-type distinction and provide new insights into the molecular mechanisms driving cell-type diversity., Competing Interests: TI, SK, MK, YS, MM, SI No competing interests declared, HT Reviewing editor, eLife, (© 2023, Ichinose et al.)

This study investigated how water vapor influences the reaction pathway and kinetics of the multistep thermal dehydration of inorganic hydrates, focusing on CaCl 2 ·2H 2 O (CC-DH) transforming into its anhydride (CC-AH) via an intermediate of its monohydrate (CC-MH). In the presence of atmospheric water vapor, the thermal dehydration of CC-DH stoichiometrically proceeded through two distinct steps, resulting in the formation of CC-AH via CC-MH under isothermal conditions and linear nonisothermal conditions at a lower heating rate ( β ). Irrespective of atmospheric water vapor pressure ( p (H 2 O)), these reaction steps were kinetically characterized by a physico-geometrical consecutive process involving the surface reaction and phase boundary-controlled reaction, which was accompanied by three-dimensional shrinkage of the reaction interface. In addition, a significant induction period was observed for the second reaction step, that is, the thermal dehydration of CC-MH intermediate to form CC-AH. With increasing p (H 2 O), a systematic increase in the apparent Arrhenius parameters was observed for the first reaction step, that is, the thermal dehydration of CC-DH to form CC-MH, whereas the second reaction step exhibited unsystematic variations of the Arrhenius parameters. At a larger β in the presence of atmospheric water vapor, the first and second reaction steps partially overlapped; moreover, an alternative reaction step of the thermal dehydration of CC-MH to form CaCl 2 ·0.3H 2 O was observed between these reaction steps. The physico-geometrical phenomena influencing the reaction pathway and kinetics of the multistep thermal dehydration were elucidated by considering the effects of atmospheric and self-generated water vapor in a geometrically constrained reaction scheme.

Spermatogonial stem cells (SSCs) undergo self-renewal division to sustain spermatogenesis. Although it is possible to derive SSC cultures in most mouse strains, SSCs from a 129 background never proliferate under the same culture conditions, suggesting they have distinct self-renewal requirements. Here, we established long-term culture conditions for SSCs from mice of the 129 background (129 mice). An analysis of 129 testes showed significant reduction of GDNF and CXCL12, whereas FGF2, INHBA and INHBB were higher than in testes of C57BL/6 mice. An analysis of undifferentiated spermatogonia in 129 mice showed higher expression of Chrna4, which encodes an acetylcholine (Ach) receptor component. By supplementing medium with INHBA and Ach, SSC cultures were derived from 129 mice. Following lentivirus transduction for marking donor cells, transplanted cells re-initiated spermatogenesis in infertile mouse testes and produced transgenic offspring. These results suggest that the requirements of SSC self-renewal in mice are diverse, which has important implications for understanding self-renewal mechanisms in various animal species., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

T cell infiltration into tumors is a favorable prognostic feature, but most solid tumors lack productive T cell responses. Mechanisms that coordinate T cell exclusion are incompletely understood. Here we identify hepatocyte activation via interleukin-6/STAT3 and secretion of serum amyloid A (SAA) proteins 1 and 2 as important regulators of T cell surveillance of extrahepatic tumors. Loss of STAT3 in hepatocytes or SAA remodeled the tumor microenvironment with infiltration by CD8 + T cells, while interleukin-6 overexpression in hepatocytes and SAA signaling via Toll-like receptor 2 reduced the number of intratumoral dendritic cells and, in doing so, inhibited T cell tumor infiltration. Genetic ablation of SAA enhanced survival after tumor resection in a T cell-dependent manner. Likewise, in individuals with pancreatic ductal adenocarcinoma, long-term survivors after surgery demonstrated lower serum SAA levels than short-term survivors. Taken together, these data define a fundamental link between liver and tumor immunobiology wherein hepatocytes govern productive T cell surveillance in cancer., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Fluorescence Fingerprint (FF) is a powerful tool for rapid quality assessment of various foods and plant-derived products. However, the conventional utilization of FFs measured at a single dilution level (DL) to substitute chemical analyses is extremely challenging, especially for multicomponent materials like spice extracts because fluorescence intensity and concentration widely differ between components, with complex phenomena like inner filter effects. Here, we proposed a new strategy to use the meta-data comprised of FFs measured at multiple DLs with machine learning to estimate common chemical attributes including total polyphenol and flavonoid contents, and antioxidant abilities. This strategy achieved more consistently satisfactory performance in estimation of all chemical attributes of spice extracts compared to using a single DL. Hence, the workflow employed in this study is expected to serve as an alternative method to quickly evaluate the chemical quality of spice extracts, as well as other plant products and food materials., 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 © 2023 Elsevier Ltd. All rights reserved.)

Spermatogonial stem cell (SSC) transplantation is a valuable tool for studying stem cell-niche interaction. However, the conventional approach requires the removal of endogenous SSCs, causing damage to the niche. Here we introduce WIN18,446, an ALDH1A2 inhibitor, to enhance SSC colonization in nonablated recipients. Pre-transplantation treatment with WIN18,446 induced abnormal claudin protein expression, which comprises the blood-testis barrier and impedes SSC colonization. Consequently, WIN18,446 increased colonization efficiency by 4.6-fold compared with untreated host. WIN18,446-treated testes remained small despite the cessation of WIN18,446, suggesting its irreversible effect. Offspring were born by microinsemination using donor-derived sperm. While WIN18,446 was lethal to busulfan-treated mice, cyclophosphamide- or radiation-treated animals survived after WIN18,446 treatment. Although WIN18,446 is not applicable to humans due to toxicity, similar ALDH1A2 inhibitors may be useful for SSC transplantation into nonablated testes, shedding light on the role of retinoid metabolism on SSC-niche interactions and advancing SSC research in animal models and humans., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Reduced Lactobacillus occupancy in the uterine microflora has been associated with implantation failure. This study aimed to evaluate a treatment for improving the uterine microflora., Methods: This study included patients diagnosed with repeated implantation failure-defined as failure to achieve pregnancy after two or more transfers of viable embryos-who were classified as non-Lactobacillus dominant. Treatment A comprised oral administration of antibiotics for 1 week, followed by oral probiotic butyrate tablets (3 g/day) for approximately 30 days. Treatment B comprised a 1-week course of oral (750 mg/day) and vaginal (250 mg/day) metronidazole, followed by a 1-week intravaginal administration of probiotic capsules (1 capsule/day) and continued oral administration of probiotics (1 capsule/day). Both treatments were compared in terms of efficacy in improving vaginal flora. Improvement was defined as Lactobacillus occupancy >90% or an increase in Lactobacillus occupancy >20%., Results: Seven (41.2%) of 17 patients in the Treatment A group improved in response to the treatment. Contrastingly, 9 (90.0%) of 10 patients improved in the Treatment B group (p = 0.0127). Following treatment, Lactobacillus occupancy in the Treatment B group (62.9% ± 12.7%) was significantly higher than that in the Treatment A group (5.7% ± 9.8%) (p = 0.0242)., Conclusions: This study demonstrates the effectiveness of combining antibiotics and probiotics in vaginal formulations for treating abnormal uterine microflora. However, its potential impact on in vitro fertilization outcomes remains unclear and warrants further investigation through larger, more comprehensive studies., (© 2024 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Gene expression is known to vary among individuals, and this variability can impact the phenotypic diversity observed in natural populations. While the transcriptome and proteome have been extensively studied, little is known about the translation process itself. Here, we therefore performed ribosome and transcriptomic profiling on a genetically and ecologically diverse set of natural isolates of the Saccharomyces cerevisiae yeast. Interestingly, we found that the Euclidean distances between each profile and the expression fold changes in each pairwise isolate comparison were higher at the transcriptomic level. This observation clearly indicates that the transcriptional variation observed in the different isolates is buffered through a phenomenon known as post-transcriptional buffering at the translation level. Furthermore, this phenomenon seemed to have a specific signature by preferentially affecting essential genes as well as genes involved in complex-forming proteins, and low transcribed genes. We also explored the translation of the S. cerevisiae pangenome and found that the accessory genes related to introgression events displayed similar transcription and translation levels as the core genome. By contrast, genes acquired through horizontal gene transfer events tended to be less efficiently translated. Together, our results highlight both the extent and signature of the post-transcriptional buffering., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Pressure-induced superconductivity often occurs following structural transition under hydrostatic pressure (P HP ) but disappears after the pressure is released. In the alkali-earth metal barium, superconductivity appears after structural transformation from body-centered cubic structure to hexagonal-close-packed (hcp) structure at P HP  = 5 GPa, and the superconducting transition temperature (T c ) reaches a maximum of 5 K at P HP  = 18 GPa. Furthermore, by stabilizing the low-temperature phase at P HP ~ 30 GPa, Tc reached a higher level of 8 K. Herein, we demonstrate a significantly higher T c superconductivity in Ba even at ambient pressure. This was made possible through severe plastic deformation of high-pressure torsion (HPT). In this HPT-processed Ba, we observed superconductivity at T c  = 3 K and T c  = 24 K in the quasi-stabilized hcp and orthorhombic structures, respectively. In particular, the latter T c represents the highest value achieved at ambient pressure among single-element superconducting metals, including intermetallics. The phenomenon is attributed to a strained high-pressure phase, stabilized by residual strains generated from lattice defects such as dislocations and grain boundaries. Significantly, the observed T c far exceeds predictions from DFT calculations under normal hydrostatic compressions. The study demonstrates the importance of utilizing high-pressure strained phases as quasi-stable superconducting states at ambient pressure., (© 2024. The Author(s).)

J Reprod Dev, Vol. 70, No. 4, p. 255 Table 2 have been corrected. For the bottom of Survived (%) row, the Survived value, which read "69", should be replaced with "86".

4.5SH RNA is a highly abundant, small rodent-specific noncoding RNA that localizes to nuclear speckles enriched in pre-mRNA-splicing regulators. To investigate the physiological functions of 4.5SH RNA, we have created mutant mice that lack the expression of 4.5SH RNA. The mutant mice exhibited embryonic lethality, suggesting that 4.5SH RNA is an essential species-specific noncoding RNA in mice. RNA-sequencing analyses revealed that 4.5SH RNA protects the transcriptome from abnormal exonizations of the antisense insertions of the retrotransposon SINE B1 (asB1), which would otherwise introduce deleterious premature stop codons or frameshift mutations. Mechanistically, 4.5SH RNA base pairs with complementary asB1-containing exons via the target recognition region and recruits effector proteins including Hnrnpm via its 5' stem loop region. The modular organization of 4.5SH RNA allows us to engineer a programmable splicing regulator to induce the skipping of target exons of interest. Our results also suggest the general existence of splicing regulatory noncoding RNAs., Competing Interests: Declaration of interests Patent applications (JP21663/2022-076674 and PCT/JP2023/015828) have been submitted by R.Y. and S.N. based on these results., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Spermatogonial stem cells (SSCs) possess a unique ability to recolonize the seminiferous tubules. Upon microinjection into the adluminal compartment of the seminiferous tubules, SSCs transmigrate through the blood-testis barrier (BTB) to the basal compartment of the tubule and reinitiate spermatogenesis. It was recently discovered that inhibiting retinoic acid signaling with WIN18,446 enhances SSC colonization by transiently suppressing spermatogonia differentiation, thereby promoting fertility restoration. In this study, we report that WIN18,446 increases SSC colonization by disrupting the BTB. WIN18,446 altered the expression patterns of tight junction proteins (TJPs) and disrupted the BTB in busulfan-treated mice. WIN18,446 upregulated the expression of FGF2, one of the self-renewal factors for SSCs. While WIN18,446 enhanced SSC colonization in busulfan-treated wild-type mice, it did not increase colonization levels in busulfan-treated Cldn11-deficient mice, which lack the BTB, indicating that the enhancement of SSC colonization in wild-type testes depended on the loss of the BTB. Serial transplantation analysis revealed impaired self-renewal caused by WIN18,446, indicating that WIN18,446-mediated inhibition of retinoic acid signaling impaired SSC self-renewal. Strikingly, WIN18,446 administration resulted in the death of 45% of busulfan-treated recipient mice. These findings suggest that TJP modulation is the primary mechanism behind enhanced SSC homing by WIN18,446 and raise concerns regarding the use of WIN18,446 for human SSC transplantation.

Transfer RNA (tRNA) modifications are critical for protein synthesis. Queuosine (Q), a 7-deaza-guanosine derivative, is present in tRNA anticodons. In vertebrate tRNAs for Tyr and Asp, Q is further glycosylated with galactose and mannose to generate galQ and manQ, respectively. However, biogenesis and physiological relevance of Q-glycosylation remain poorly understood. Here, we biochemically identified two RNA glycosylases, QTGAL and QTMAN, and successfully reconstituted Q-glycosylation of tRNAs using nucleotide diphosphate sugars. Ribosome profiling of knockout cells revealed that Q-glycosylation slowed down elongation at cognate codons, UAC and GAC (GAU), respectively. We also found that galactosylation of Q suppresses stop codon readthrough. Moreover, protein aggregates increased in cells lacking Q-glycosylation, indicating that Q-glycosylation contributes to proteostasis. Cryo-EM of human ribosome-tRNA complex revealed the molecular basis of codon recognition regulated by Q-glycosylations. Furthermore, zebrafish qtgal and qtman knockout lines displayed shortened body length, implying that Q-glycosylation is required for post-embryonic growth in vertebrates., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Slightly acidic electrolyzed water (SAEW) is used as a disinfectant for raw chicken meat. Because its volume for a single immersion exceeds 10 times the weight of meat, a large amount of wastewater is generated. Importantly, a higher frequency of immersion is believed to reduce microbial contamination. The objective of this study was to investigate the effect of SAEW immersion at different frequencies on the disinfection and quality of raw chicken legs, thereby possibly limiting the usage of SAEW. Immersion for 1, 3, and 5 times, with a 7:1 SAEW:meat ratio, and duration of 15 min was tested. Meat quality was evaluated based on total aerobic bacteria, Enterobactericeae , total volatile basic nitrogen, thiobarbituric acid reactive substances, and color. A higher immersion frequency lowered the numbers of total aerobic bacteria and Enterobacteriaceae. Moreover, two immersions with a SAEW:meat ratio of 4:1 and a total immersion time of 6 min reduced the bacterial load as effectively as a single 15-min immersion with a SAEW:meat ratio of 7:1. Higher frequencies of SAEW immersion also resulted in lower total volatile basic nitrogen and lipid oxidation after 0 or 3 days of storage. They did, however, magnify the change in color, resulting in brighter meat. Overall, SAEW treatments with two to five immersions can improve the quality of raw chicken legs and reduce wastewater generation., Competing Interests: Conflicts of Interest: Mareto Hamatani and Takashi Soejima are employees of Morinaga Milk Industry Co., Ltd, which manufactured the purester SAEW generator used in this study. Yutaka Kitamura received a research grant from Morinaga Milk Industry Co., Ltd., (2023 Japan Poultry Science Association.)

In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are 2 major assisted reproductive techniques (ARTs) used widely to treat infertility. Recently, spermatogonial transplantation emerged as a new ART to restore fertility to young patients with cancer after cancer therapy. To examine the influence of germ cell manipulation on behavior of offspring, we produced F1 offspring by a combination of two ARTs, spermatogonial transplantation and ICSI. When these animals were compared with F1 offspring produced by ICSI using fresh wild-type sperm, not only spermatogonial transplantation-ICSI mice but also ICSI-only control mice exhibited behavioral abnormalities, which persisted in the F2 generation. Furthermore, although these F1 offspring appeared normal, F2 offspring produced by IVF using F1 sperm and wild-type oocytes showed various types of congenital abnormalities, including anophthalmia, hydrocephalus, and missing limbs. Therefore, ARTs can induce morphological and functional defects in mice, some of which become evident only after germline transmission.

Despite growing awareness of the importance of monitoring wild crop pollinators worldwide, there are still few reports, especially in East Asia. Considering ongoing global warming may change the distribution range and diurnal activity of pollinators, it is necessary to describe current geographic and diurnal patterns. We clarified pollinators of Cucurbita maxima Duchesne (Cucurbitales: Cucurbitaceae) in three geographically distinct (>350 km, minimum) areas in Japan, focusing on diurnal variation. Apis mellifera L. (Hymenoptera: Apidae) and Halictidae (Hymenoptera) were observed in all of the experimental gardens. Apis cerana japonica Radoszkowski (Hymenoptera: Apidae) were mainly observed in Mie and Kagoshima, while Bombus diversus diversus Smith (Hymenoptera: Apidae) were observed only in Ibaraki. The peak time of flower visits depended both on bee taxa and area, and interestingly, did not necessarily synchronize with the timing of the highest pollen loads and the probability of stigma contact. In particular, visits and probability of contacting stigmas of Halictidae tended to increase as time passed, whereas pollen grains on their bodies sharply decreased with time; only a few individuals of Halictidae that visit early can become effective pollinators. There were no differences in yields between supplementary hand and natural pollination in all areas, and flower-enclosure experiments using different mesh sizes clarified that small insects that can go across an approximately 4-mm mesh may not transport sufficient pollen for fruit set. Our study demonstrated that pollination effectiveness, which is usually regarded as a static value, within a taxon can fluctuate in the space of just several hours. Considering such diurnal patterns can be altered by climate change, we need to carefully monitor the diurnal temporal patterns of pollinators worldwide., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background and Objectives : A relationship between endometrial polypectomy and in vitro fertilization (IVF) pregnancy outcomes has been reported; however, only a few studies have compared polyp removal techniques and pregnancy rates. We investigated whether different polypectomy techniques with endometrial curettage and hysteroscopic polypectomy for endometrial polyps affect subsequent pregnancy outcomes. Materials and Methods : Data from 434 patients who had undergone polypectomy for suspected endometrial polyps using transvaginal ultrasonography before embryo transfer in IVF at four institutions between January 2017 and December 2020 were retrospectively analyzed. Overall, there were 157 and 277 patients in the hysteroscopic (mean age: 35.0 years) and curettage (mean age: 37.3 years) groups, respectively. Single-blastocyst transfer cases were selected from both groups and age-matched to unify background factors. Results : In the single-blastocyst transfer cases, 148 (mean age: 35.0 years) and 196 (mean age: 35.9 years) were in the hysteroscopic and curettage groups, respectively, with the 148 cases matched by age. In these cases, the pregnancy rates for the first embryo transfer were 68.2% (odds ratio (OR): 2.14) and 51.4% (OR: 1.06) in the hysteroscopic and curettage groups, respectively; the resulting OR was 2.03. The pregnancy rates after up to the second transfer were 80.4% (OR: 4.10) and 68.2% (OR: 2.14) in the hysteroscopic and curettage groups, respectively, in which the OR was 1.91. The live birth rates were 66.2% (OR: 1.956) and 53.4% (OR: 1.15) in the hysteroscopic and curettage groups, respectively, in which the odds ratio was 1.71. These results show the effectiveness of hysteroscopic endometrial polypectomy compared to polypectomy with endometrial curettage. No significant difference was found regarding the miscarriage rates between the two groups. Conclusions : Hysteroscopic endometrial polypectomy resulted in a higher pregnancy rate in subsequent embryo transfer than polypectomy with endometrial curettage. Therefore, establishing a facility where polypectomy can be performed hysteroscopically is crucial.

The efflorescence of sodium carbonate decahydrate (SC-DH) required to form its monohydrate (SC-MH) was systematically studied under isothermal and linear nonisothermal conditions at different atmospheric water vapor pressures ( p (H 2 O)) using a humidity-controlled thermogravimetry instrument equipped with a cooling circulator. The universal kinetic description at various temperatures ( T ) and p (H 2 O) values was evaluated using the extended kinetic equation with an accommodation function (AF) comprising p (H 2 O) and the equilibrium pressure of the reaction ( P eq ( T )). By optimizing two exponents in the AF, all kinetic data were universally described in terms of the isoconversional kinetic relationship examined at individual degrees of reaction ( α ). This enabled the examination of the isothermal kinetic relationship and the parameterization of the contribution of the self-generated water vapor, allowing the incorporation of kinetic data recorded in a stream of dry N 2 into the universal kinetic description as a function of T , α , and p (H 2 O). The results indicated that the reaction is physico-geometrically controlled by the surface reaction at the hemispherical top surface of SC-DH particles and subsequent advancement of the reaction interface toward the center and bottom of these particles, where the interfacial process is regulated by an elementary step of the consumption of H 2 O vacancies to form the SC-MH building unit. The apparent activation energy ( E a ) of ∼178 kJ mol -1 was determined using the extended kinetic approach considering the effect of p (H 2 O) correlated with the intrinsic E a of the Arrhenius-type temperature dependence (∼63 kJ mol -1 ) by subtracting the contribution of the temperature dependence of P eq ( T ) in the AF.

Reactive oxygen species (ROS) are generated from NADPH oxidases and mitochondria; they are generally harmful for stem cells. Spermatogonial stem cells (SSCs) are unique among tissue-stem cells because they undergo ROS-dependent self-renewal via NOX1 activation. However, the mechanism by which SSCs are protected from ROS remains unknown. Here, we demonstrate a crucial role for Gln in ROS protection using cultured SSCs derived from immature testes. Measurements of amino acids required for SSC cultures revealed the indispensable role of Gln in SSC survival. Gln induced Myc expression to drive SSC self-renewal in vitro, whereas Gln deprivation triggered Trp53-dependent apoptosis and impaired SSC activity. However, apoptosis was attenuated in cultured SSCs that lacked NOX1. In contrast, cultured SSCs lacking Top1mt mitochondria-specific topoisomerase exhibited poor mitochondrial ROS production and underwent apoptosis. Gln deprivation reduced glutathione production; supra-molar Asn supplementation allowed offspring production from SSCs cultured without Gln. Therefore, Gln ensures ROS-dependent SSC-self-renewal by providing protection against NOX1 and inducing Myc., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Background: The progression of liver fibrosis leads to portal hypertension and liver dysfunction. However, no antifibrotic agents have been approved for cirrhosis to date, making them an unmet medical need. Small extracellular vesicles (sEVs) of mesenchymal stem cells (MSCs) are among these candidate agents. In this study, we investigated the effects of sEVs of MSCs, analyzed their distribution in the liver post-administration, whether their effect was dose-dependent, and whether it was possible to collect a large number of sEVs., Methods: sEVs expressing tdTomato were generated, and their uptake into constituent liver cells was observed in vitro, as well as their sites of uptake and cells in the liver using a mouse model of liver cirrhosis. The efficiency of sEV collection using tangential flow filtration (TFF) and changes in the therapeutic effects of sEVs in a volume-dependent manner were examined., Results: The sEVs of MSCs accumulated mostly in macrophages in damaged areas of the liver. In addition, the therapeutic effect of sEVs was not necessarily dose-dependent, and it reached a plateau when the dosage exceeded a certain level. Furthermore, although ultracentrifugation was commonly used to collect sEVs for research purposes, we verified that TFF could be used for efficient sEV collection and that their effectiveness is not reduced., Conclusion: In this study, we identified some unknown aspects regarding the dynamics, collection, and capacity dependence of sEVs. Our results provide important fundamentals for the development of therapies using sEVs and hold potential implications for the therapeutic applications of sEV-based therapies for liver cirrhosis., (© 2023. Japanese Society of Inflammation and Regeneration.)

Purpose: To examine the optimal timing of second ovarian stimulation using the dual stimulation method for good ovarian responders with cancer undergoing oocyte retrieval for fertility preservation., Methods: A retrospective analysis was conducted using data from 69 patients with cancer who underwent oocyte retrieval for fertility preservation at four Japanese institutions during 2010-2021. Twenty-two patients underwent two oocyte retrievals for fertility preservation. We studied the relationship between the initial number of oocytes retrieved via dual stimulation and risk of ovarian enlargement as well as the appropriate waiting interval between the end of the first ovarian stimulation and beginning of the second ovarian stimulation., Results: The risk of ovarian enlargement was high when the initial number of oocytes retrieved via dual stimulation was ≥5. An 8-day waiting interval may be more effective for performing a second ovarian stimulation oocyte retrieval in these cases, although the difference was not significant., Conclusions: This study provides one policy for effectively managing ovarian enlargement and timing of second ovarian stimulation during oocyte retrieval via the dual stimulation method for patients with cancer undergoing fertility preservation. If more facilities implement this procedure, more oocytes may be obtained in a short period for fertility preservation purposes., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.)

Low-temperature neutron diffraction experiments at [Formula: see text] GPa have been conducted to investigate the magnetic structures of metallic Holmium at high pressures by employing a long d-spacing high-flux diffractometer and a Paris-Edinburgh press cell inside a cryostat. We find that at [Formula: see text] GPa and [Formula: see text] K, no nuclear symmetry change is observed, keeping therefore the hexagonal closed packed (hcp) symmetry at high pressure. Our neutron diffraction data confirm that the ferromagnetic state does not exist. The magnetic structure corresponding to the helimagnetic order, which survives down to 5 K, is fully described by the magnetic superspace group formalism. These results are consistent with those previously published using magnetization experiments., (© 2023. The Author(s).)

We herein report a fatal case of invasive mucinous adenocarcinoma (IMA) with acute respiratory distress syndrome (ARDS) diagnosed based on autopsy findings. A 76-year-old man presented with severe respiratory discomfort on admission. Computed tomography (CT) revealed a peripheral distribution of consolidation. Although his respiratory status improved after steroid therapy, re-exacerbation occurred, and the patient died on day 131. A bronchoscopic lung biopsy had shown organizing pneumonia, but a post-mortem examination surprisingly revealed IMA with organizing pneumonia. IMA presenting with ARDS as the first symptom is extremely rare.

Introduction: This study aimed to investigate the prevalence of periodontal disease and the factors of the disease among high school students., Method: The participants were all students aged 15-18 years (n = 1202) at a high school in Japan. The data on oral health perceptions and behaviours were collected by a questionnaire survey. The prevalence of periodontal disease among them was investigated with the partial community periodontal index (PCPI). A logistic regression analysis was used to identify the factors associated with the PCPI., Results: A total of 1069 students (88.9%) participated in this study. The prevalence of gingival bleeding, calculus, pocket depth of 4-5 mm, and pocket depth of 6 mm or more were 44.2%, 42.2%, 11.4%, and 1.6%, respectively. Approximately one-third of the students had a fear of dental treatment, and only 28.4% used dental floss. The results of logistic regression analysis, adjusted for sex and school year, showed that not visiting dentists regularly, not using dental floss, brushing teeth for less than 5 min, fear of dental treatment, and drinking sports drinks frequently were positively associated with periodontal conditions., Conclusion: This study identified a high prevalence of periodontal disease among Japanese high school students aged 15-18 years and its risk factors, such as poor oral health behaviours and fear of dental treatment., (© 2023. The Author(s).)

Yeast and lactic acid bacteria (LAB) are known to play an important role in the fermentation process of coffee post-harvest. This study aimed to isolate and screen yeast and LAB to be applied in lab-scale refermentation of commercial green coffee beans and coffee pulp with the aim of modifying the composition of organic acids (OAs) in coffee beans. Yeast and LAB strains were isolated from green coffee beans and dry coffee pulp and identified, and their effect on OA concentration in the coffee beans was quantified. In addition, the effects of different fermentation conditions (additional carbon source, different inoculum dose, and different types of coffee pulp) were evaluated based on OA quantification. Nine yeast isolates of Rhodotorula mucilaginosa and Wickerhamomyces anomalus were identified, and 11 LAB isolates of the species Enterococcus mundtii were identified. Of the 7 OAs quantified, quinic acid was the most abundant. The inoculation of isolated yeasts and LAB led to higher concentrations of OAs, showing the potential to realize modification of the OA composition of green coffee beans by re-fermentation with coffee-originated isolates.

To the best of our knowledge, systemic sclerosis with overlapping characteristics of both microscopic polyangiitis and giant cell arteritis (i.e. microscopic polyangiitis involving the superficial temporal artery or giant cell arteritis with myeloperoxidase anti-neutrophil cytoplasmic antibody seropositivity) has not been reported previously. An 82-year-old woman with diffuse cutaneous systemic sclerosis experienced dyspnoea on exertion and fever. No signs of infection were observed on computed tomography. Her fever persisted despite antibiotic treatment for occult bacterial infection and secondary Clostridioides difficile-associated diarrhoea. Microscopic polyangiitis was suspected because of myeloperoxidase anti-neutrophil cytoplasmic antibody seropositivity, and giant cell arteritis was suspected as a differential diagnosis due to swelling of the superficial temporal artery. Arterial biopsy revealed inflammatory cell infiltration with granuloma formation. Based on the presence of granulomatous inflammation in the superficial temporal artery, we concluded that giant cell arteritis with myeloperoxidase anti-neutrophil cytoplasmic antibody seropositivity occurred as a complication. After glucocorticoid therapy, her fever and dyspnoea on exertion improved with a gradual decline in the serum myeloperoxidase anti-neutrophil cytoplasmic antibody levels. It is possible that vasculitis occurs as a complication in patients with systemic sclerosis in cases where the fever persists and cannot be explained by systemic sclerosis itself, infectious disease, or malignancy. Clinicians must be careful not to prematurely diagnose microscopic polyangiitis based on myeloperoxidase anti-neutrophil cytoplasmic antibody seropositivity or giant cell arteritis based on the swelling of the superficial temporal artery. Careful evaluation of the presence of granulomatous inflammation in an arterial biopsy specimen is essential to differentiate between microscopic polyangiitis and giant cell arteritis., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Characterization of spermatogonial stem cells (SSCs) has been hampered by their low frequency and lack of features that distinguish them from committed spermatogonia. Few conserved SSC markers have been discovered. To identify a new SSC marker, we evaluated SIRPA expression in mouse and rat SSCs. SIRPA was expressed in a small population of undifferentiated spermatogonia. SIRPA, and its ligand CD47 were expressed in cultured SSCs. Expression of both SIRPA and CD47 was upregulated by supplementation of GDNF and FGF2, which promoted SSC self-renewal. Sirpa depletion by short hairpin RNA impaired the proliferation of cultured SSCs, and these cells showed decreased MAP2K1 activation and PTPN11 phosphorylation. Immunoprecipitation experiments showed that SIRPA associates with PTPN11. Ptpn11 depletion impaired SSC activity in a manner similar to Sirpa depletion. SIRPA was expressed in undifferentiated spermatogonia in rat and monkey testes. Xenogenic transplantation experiments demonstrated that SIRPA is expressed in rat SSCs. These results suggest that SIRPA is a conserved SSC marker that promotes SSC self-renewal division by activating the MAP2K1 pathway via PTPN11., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The testis is an immune-privileged organ. It is considered that the testis somatic microenvironment is responsible for immune suppression. However, immunological properties of spermatogonial stem cells (SSCs) have remained unknown. Here, we report the birth of allogeneic offspring by enhanced expression of immunosuppressive PD-L1 in SSCs. In vitro supplementation of GDNF and FGF2 increased expression of PD-L1 in SSCs. Cultured SSCs maintained allogeneic spermatogenesis that persisted for >1 year. However, depletion or gene editing of Pd-l1 family genes in SSCs prevented allogeneic spermatogenesis, which suggested that germ cells are responsible for suppression of the allogeneic response. PD-L1 was induced by activation of the MAPK14-BCL6B pathway, which drives self-renewal by reactive oxygen species (ROS) generation. By contrast, reduced ROS or Mapk14 deficiency downregulated PD-L1. Allogeneic offspring were born after SSC transplantation into congenitally infertile and chemically castrated mice. Thus, SSCs have unique immunological properties, which make allogeneic recipients into "surrogate fathers.", Competing Interests: Conflict of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Acute pancreatitis is an uncommon occurrence in acute liver failure. Furthermore, such cases are rarely complicated by parenchymal hemorrhages. Herein, we report the case of a 69-year-old male patient with multiple pancreatic parenchymal hemorrhages concomitant with acute liver failure. The patient underwent conservative treatment for acute liver failure caused by hepatitis B virus infection. Plain computed tomography on the 30th day revealed two high-density mass lesions in the pancreatic body and tail, which were suspected to be multiple pancreatic parenchymal hemorrhages. Despite restarting gabexate mesylate, the patient died of multiple organ failure on the 49th day. The clinical information of the present case and our literature review of 61 similar cases in 43 case reports identified via a systematic keyword search of the PubMed database, which described acute pancreatitis concomitant with acute hepatitis and acute liver failure, will aid physicians in the diagnosis and treatment of this rare condition., (© 2022. Japanese Society of Gastroenterology.)

Lead poisoning remains a persistent health issue for both humans and wildlife, despite strides to reduce lead contamination in the environment. Using Geographic Information Systems (GIS), this study explores the associations between blood lead levels (BLLs) in wildlife sentinels and possible built environment lead exposure risk factors in the Minneapolis-Saint Paul, Minnesota urban area. Results show a high-level of heterogeneity in animal BLLs (n = 472) across our urban environment and suggest that each kilometer increase in road density is associated with a 17.07% (95% CI: 1.48%, 35.05%) increase in BLL in our study species of Virginia opossums and Eastern gray squirrels, and a 14.28% (95% CI: 1.16%, 29.09%) increase in BLL of rock pigeons. For squirrels and opossums, we see an additional 5.72% (95% CI: 0.59%, 10.85%) increased risk of BLL for every 1000 people per square-mile. The relationship between animal sentinels and environmental hazards can give us an insight into the potential lead exposure risks for humans. The use of wildlife sentinel data to explore environmental risk factors supports a One Health approach to better address public health questions and aid in wildlife rehabilitation related to residual lead poisoning from ambient environmental exposures., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Plants often generate secondary metabolites as defense mechanisms against parasites. Although some fungi may potentially overcome the barrier presented by antimicrobial compounds, only a limited number of examples and molecular mechanisms of resistance have been reported. Here, we found an Aglaia plant-parasitizing fungus that overcomes the toxicity of rocaglates, which are translation inhibitors synthesized by the plant, through an amino acid substitution in a eukaryotic translation initiation factor (eIF). De novo transcriptome assembly revealed that the fungus belongs to the Ophiocordyceps genus and that its eIF4A, a molecular target of rocaglates, harbors an amino acid substitution critical for rocaglate binding. Ribosome profiling harnessing a cucumber-infecting fungus, Colletotrichum orbiculare , demonstrated that the translational inhibitory effects of rocaglates were largely attenuated by the mutation found in the Aglaia parasite. The engineered C. orbiculare showed a survival advantage on cucumber plants with rocaglates. Our study exemplifies a plant-fungus tug-of-war centered on secondary metabolites produced by host plants., Competing Interests: MC, NK, HS, RM, MN, MM, PG, NI, KS, TI, YS, SI No competing interests declared, (© 2023, Chen, Kumakura et al.)

The prion-like domain (PrLD) is a class of intrinsically disordered regions. Although its propensity to form condensates has been studied in the context of neurodegenerative diseases, the physiological role of PrLD remains unclear. Here, we investigated the role of PrLD in the RNA-binding protein NFAR2, generated by a splicing variant of the Ilf3 gene. Removal of the PrLD in mice did not impair the function of NFAR2 required for survival, but did affect the responses to chronic water immersion and restraint stress (WIRS). The PrLD was required for WIRS-sensitive nuclear localization of NFAR2 and WIRS-induced changes in mRNA expression and translation in the amygdala, a fear-related brain region. Consistently, the PrLD conferred resistance to WIRS in fear-associated memory formation. Our study provides insights into the PrLD-dependent role of NFAR2 for chronic stress adaptation in the brain., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Introduction: This study aimed to evaluate the association between the preoperative Controlling Nutritional Status (CONUT) score, survival outcomes, and recurrence pattern in patients with resectable biliary tract cancer (BTC)., Methods: A total of 224 BTC patients (gallbladder, n = 69; intrahepatic bile ducts, n = 26; perihilar bile ducts, n = 72; distal bile duct, n = 57) who underwent surgery with curative intent were enrolled. The best cutoff point of the preoperative CONUT score in discriminating survival was determined using χ 2 scores. The sites of recurrence were subclassified as locoregional or distant., Results: Patients were subdivided into the CONUT-low (score ≤ 3, n = 156) and the CONUT-high (score > 3; n = 68) groups. In-hospital mortality occurred more frequently in the CONUT-high group than in the CONUT-low group (7.4% vs. 1.3%; p = 0.028). A high preoperative CONUT score was independently associated with worse overall survival (hazard ratio [HR] 1.906, p = 0.001), worse disease-specific survival (HR 1.840, p = 0.006), and worse recurrence-free survival (HR 1.680, p = 0.005). Recurrence developed in 110 (49.1%) patients. A high preoperative CONUT score was independently associated with a higher risk of distant recurrence (HR 2.245, p = 0.001), but not locoregional recurrence. The incidences of distant recurrence at 5 years were 55.4% and 34.2% in the CONUT-high and CONUT-low groups, respectively (p = 0.001)., Conclusions: The preoperative CONUT score independently predicts survival outcomes and may serve as a surrogate marker of aggressive systemic disease recurrence in patients with resectable BTC., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Although numerous ecotoxicological assessments of European honeybee ( Apis mellifera L.) have been performed, Japanese wild bees are less well studied in this regard. To address this knowledge gap, we assessed the mortality and acute toxicity (LD 50 ) of 3 common agricultural insecticides (clothianidin, fipronil, and diazinon) on as many as 6 species of Japanese wild bees ( Andrena prostomias Perez , Apis cerana japonica Radoszkowski , Bombus deuteronymus Perez , Bombus honshuensis Tkalcu , Bombus hypocrita Perez , and Eucera spp.; all or any of them). The datasets were obtained via standard acute toxicity testing, with assessment of mortality at 24 and 48 h after exposure to the insecticides. These data provide important information regarding the effects of insecticides on Japanese wild bees and their conservation., Competing Interests: 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., (© 2023 The Authors. Published by Elsevier Inc.)

Oogenesis depends on close interactions between oocytes and granulosa cells. Abnormal signaling between these cell types can result in infertility. However, attempts to manipulate oocyte-granulosa cell interactions have had limited success, likely due to the blood-follicle barrier (BFB), which prevents the penetration of exogenous materials into ovarian follicles. Here, we used adenoviruses (AVs) to manipulate the oocyte-granulosa cell interactions. AVs penetrated the BFB and transduced granulosa cells through ovarian microinjection. Although AVs caused transient inflammation, they did not impair fertility in wild-type mice. Introduction of Kitl-expressing AVs into congenitally infertile Kitl Sl-t /Kitl Sl-t mutant mouse ovaries, which contained only primordial follicles because of a lack of Kitl expression, restored fertility through natural mating. The offspring showed no evidence of AV integration and exhibited normal genomic imprinting patterns for imprinted genes. These results demonstrate the usefulness of AVs for manipulating oogenesis and suggest the possibility of gene therapies for human female infertility.

Evaluating the patterns and generality of ontogenetic dietary shifts (ODSs) contributes to understanding prey-predator interactions and food web dynamics. Numerous studies have focused on predators that target distinctively lower trophic-level organisms. However, the ODS of predators that routinely prey on organisms at similar trophic levels (i.e., predator-eating predators) have been neglected in ODS research. The ODS patterns of predator eaters may not fit into conventional frameworks owing to constraints of potential capture risk (e.g., deadly counterattack from prey) and body size. We aimed to reveal the ODS patterns of predator eaters and determine whether the patterns were affected by body size and capture risk. Assuming that capture risk is a significant factor in ODS patterns, we expected: (1) juvenile araneophagic spiders to forage on non-dangerous prey (insects) and capture larger non-dangerous prey more frequently than dangerous prey (spiders); and (2) as they grow, their prey types will shift from non-dangerous to dangerous prey because larger predators will be able to capture dangerous prey as the optimal food. As a result of field observations, we revealed that the major ODS pattern in these spiders changed from a mixed (both insect and spider) to a spider-dominant diet. The model selection approach showed that this diet shift was partly due to predator size, and the relative importance of predator size was higher than the life stage per se and almost equal to species identity. In these spiders, the body size of spider prey tended to be smaller than that of insects when the predators were small, suggesting that capture risk may be a critical factor in determining the ODS patterns of these predators. Therefore, our study adds to the evidence that the capture risk is crucial in comprehensively understanding the mechanisms determining ODS patterns in natural systems., Competing Interests: None of the authors have any conflict of interest., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)