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We studied the interruption performance of [CF.sub.3]I gas because its environmental effect is smaller than that of [SF.sub.6] gas with a model arc-extinguishing chamber. First, we measured the arc time constant and arc power loss coefficient using Mayr's equation. Comparing [CF.sub.3]I with other gases, the arc time constants are [SF.sub.6] < [CF.sub.3]I < [CO.sub.2] < [H.sub.2] < Air < [N.sub.2]. The arc power loss coefficient is [H.sub.2] > [SF.sub.6] > [CO.sub.2] > Air > [N.sub.2] > [CF.sub.3]I. Next, we evaluated the Short Line Fault (SLF) interruption capability by measuring the di/dtdv/dt characteristic. Consequently, the SLF interruption performance of pure [CF.sub.3]I was about 0.9 times that of [SF.sub.6]. However, [CF.sub.3]I application to gas insulated switchgear (GIS) and gas circuit breakers (GCB) is difficult because the liquefying temperature of the gas is high. Therefore, we adopted a countermeasure to obtain a lower liquefying temperature mixing [CF.sub.3]I with [CO.sub.2]. The result showed that the SLF interruption performance of the mixture approximated that of pure [CF.sub.3]I when the ratio of [CF.sub.3]I exceeds 20%. Index Terms--[CF.sub.3]I, short line fault (SLF), substitute gas for [SF.sub.6].

During a winter thunderstorm on 6 February 2017 in Japan, photonuclear reactions such as 14N(γ, n)13N were triggered by a downward terrestrial gamma‐ray flash (TGF), as reported by Enoto et al. (2017, https://doi.org/10.1038/nature24630). In the present paper, we compare the observation with a simulation model of downward TGFs and subsequent photonuclear reactions constructed by the first paper of the series and Wada, Enoto, Nakazawa, et al. (2019, https://doi.org/10.1103/physrevlett.123.061103). The observation and model consist of three components: annihilation gamma rays from positrons produced by β+‐decay nuclei, deexcitation gamma rays originating from neutron captures, and radiation doses by TGF photons. Each component of the observation is reproduced by the simulation model, and we constrain a relation between the number of avalanche electrons and their production altitude of the downward TGF. The constraints by three components match within an order of magnitude. The downward TGF is estimated to comprise (0.5–2.5) × 1019 avalanche electrons above 1 MeV produced at an altitude of 1.4–2.7 km. Despite differences in altitude, direction, and season, downward TGFs in winter thunderstorms are thought to have the same mechanism of electron acceleration and multiplication in lightning as TGFs observed by in‐orbit satellites. Plain Language Summary: Lightning flashes are sometimes accompanied by strong high‐energy emission called "terrestrial gamma‐ray flashes" (TGFs). The energy of gamma rays in TGFs is high enough to trigger nuclear reactions with atmospheric nuclei such as nitrogen and oxygen. The nuclear reactions produce neutrons and unstable isotopes that emit positrons. In the companion paper of this series, we calculated the nuclear reactions and propagation processes of their products such as positrons and neutrons and modeled their characteristics at ground level by simulations. In the present paper, the simulation model is compared with the actual observation of a TGF and nuclear reactions during winter thunderstorms in Japan. The model successfully reproduces the observation and estimate the production altitude the number of energetic electrons involved in the TGF. Key Points: A simulation model of photonuclear reactions in lightning is compared with an observation during a winter thunderstorm reported by Enoto et al. (2017, https://doi.org/10.1038/nature24630)Three detected signatures originating from positrons, neutrons, and TGF photons are reproduced by the simulation modelA downward TGF triggering photonuclear reactions comprised 1018 to 1019 avalanche electrons produced at 1.4–2.7 km above sea level [ABSTRACT FROM AUTHOR]

We report simulation results of photonuclear reactions in the atmosphere triggered by a downward terrestrial gamma ray flash in lightning. Possible channels of reactions in the atmosphere and their cross‐sections are verified with the ENDF/B‐VII.1 library. Monte Carlo simulations with two stages are then performed with the Geant4 framework. In the first stage, electrons following the relativistic runaway electron avalanche spectrum are produced in a mass model of the atmosphere, and production of photoneutrons and β+‐decay nuclei is calculated based on the nuclear data library. In total 1 × 1013 neutrons and 4 × 1012β+‐decay nuclei are produced by 1018 energetic electrons above 1 MeV. In the second stage, propagation of the photoneutrons and positrons from the β+‐decay nuclei in the previous stage is calculated. As a result, we model on‐ground distributions of fluxes and energy spectra for neutrons, neutron‐related gamma rays, and annihilation ones. The simulation model is to be compared with photonuclear events detected in low‐charge‐center winter thunderstorms. Plain Language Summary: Lightning discharges occasionally emit a powerful flash of gamma rays called terrestrial gamma ray flashes. Gamma rays in terrestrial gamma ray flashes have high energies enough to react with atmospheric nuclei such as nitrogen and oxygen. The nuclear reactions in the atmosphere produce neutrons and unstable isotopes that emit positrons. In this paper, we utilize a Monte Carlo simulation framework, calculate a series of reactions and processes in the atmosphere, and then construct a distribution model of neutrons, neutron‐related gamma rays, and positron‐related ones at ground level. The obtained model can be compared with recent observations of nuclear reactions during winter thunderstorms in Japan. Key Points: Possible channels of atmospheric photonuclear reactions in lightning are surveyed from a nuclear‐reaction data libraryMonte Carlo calculations are performed to simulate photoneutron and β+‐decay‐nuclide productions in the atmosphereOn‐ground distributions of fluxes and spectra for neutrons, neutron‐related gamma rays, and annihilation gamma rays are modeled [ABSTRACT FROM AUTHOR]

Aims G protein-coupled receptor/free fatty acid receptor 1 ( GPR40/ FFAR1) regulates free fatty acid-induced insulin secretion. This study has been performed to clarify whether or not loss of GPR40/ FFAR1 function exacerbates diabetes, that is, whether GPR40 has an essential physiological role in the development of diabetes or not. Methods We generated GPR40/ FFAR1 knockout ( KO) mice and analysed their phenotypes in vitro and in vivo under the condition of dietary or genetically induced insulin resistance. Results GPR40/ FFAR1 KO mice kept on a high-fat diet became obese, developed glucose intolerance to a similar degree as GPR40/ FFAR1 wild-type ( WT) mice. In addition, the phenotype of KO mice harbouring diabetogenic KK background genes showed glucose intolerance at a level similar to level for control KK mice. In both mouse models with insulin resistance, insulin secretion after oral glucose load and homeostasis model assessment-insulin resistance ( HOMA-IR) did not change between GPR40/ FFAR1 KO and WT mice. Although glucose-induced insulin secretion under high palmitate concentration was significantly lower in KO than in WT islets, pancreatic insulin content and insulin secretion stimulated with glucose alone were not different between KO and WT mice. Conclusions GPR40/ FFAR1 has a major role in regulating fatty-acid-mediated insulin secretion, but the lack of GPR40/ FFAR1 does not exacerbate glucose intolerance and insulin resistance induced by high-fat diet or diabetogenic KK gene. Our findings indicate that loss of GPR40/ FFAR1 function does not play an important role in inducing or exacerbating diabetes. [ABSTRACT FROM AUTHOR]

Centaurus B is a nearby radio galaxy positioned in the southern hemisphere close to the Galactic plane. Here we present a detailed analysis of about 43 months of accumulated Fermi-LAT data of the γ-ray counterpart of the source initially reported in the 2nd Fermi-LAT catalog, and of newly acquired Suzaku X-ray data. We confirm its detection at GeV photon energies and analyze the extension and variability of the γ-ray source in the LAT dataset, in which it appears as a steady γ-ray emitter. The X-ray core of Centaurus B is detected as a bright source of a continuum radiation. We do not detect, however, any diffuse X-ray emission from the known radio lobes, with the provided upper limit only marginally consistent with the previously claimed ASCA flux. Two scenarios that connect the X-ray and γ-ray properties are considered. In the first one, we assume that the diffuse non-thermal X-ray emission component is not significantly below the derived Suzaku upper limit. In this case, modeling the inverse-Compton emission shows that the observed γ-ray flux of the source may in principle be produced within the lobes. This association would imply that efficient in-situ acceleration of the radiating electrons is occurring and that the lobes are dominated by the pressure from the relativistic particles. In the second scenario, with the diffuse X-ray emission well below the Suzaku upper limits, the lobes in the system are instead dominated by the magnetic pressure. In this case, the observed γ-ray flux is not likely to be produced within the lobes, but instead within the nuclear parts of the jet. By means of synchrotron self-Compton modeling, we show that this possibility could be consistent with the broad-band data collected for the unresolved core of Centaurus B, including the newly derived Suzaku spectrum. [ABSTRACT FROM AUTHOR]

The Focusing Optics X-ray Solar Imager (FOXSI) is a NASA sounding rocket mission which will study particle acceleration and coronal heating on the Sun through high sensitivity observations in the hard X-ray energy band (5–15 keV). Combining high-resolution focusing X-ray optics and fine-pitch imaging sensors, FOXSI will achieve superior sensitivity; two orders of magnitude better than that of the RHESSI satellite. As the focal plane detector, a Double-sided Si Strip Detector (DSSD) with a front-end ASIC (Application Specific Integrated Circuit) will fulfill the scientific requirements of spatial and energy resolution, low energy threshold and time resolution. We have designed and fabricated a DSSD with a thickness of 500 \mu\ m and a dimension of 9.6 mm \times 9.6 mm, containing 128 strips with a pitch of 75 \mu\ m, which corresponds to 8 arcsec at the focal length of 2 m. We also developed a low-noise ASIC specified to FOXSI. The detector was successfully operated in the laboratory at a temperature of -20^\circ\ C and with an applied bias voltage of 300 V. Extremely good energy resolutions of 430 eV for the p-side and 1.6 keV for the n-side at a 14 keV line were achieved for the detector. We also demonstrated fine-pitch imaging successfully by obtaining a shadow image. Hence the implementation of scientific requirements was confirmed. [ABSTRACT FROM AUTHOR]

Background and Purpose: Alogliptin, a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, enhances incretin action and pioglitazone enhances hepatic and peripheral insulin actions. Here, we have evaluated the effects of combining these agents in diabetic mice.Experimental Approach: Effects of short-term treatment with alogliptin alone (0.01%-0.1% in diet), and chronic combination treatment with alogliptin (0.03% in diet) and pioglitazone (0.0075% in diet) were evaluated in db/db mice exhibiting early stages of diabetes.Key Results: Alogliptin inhibited plasma DPP-4 activity up to 84% and increased plasma active glucagon-like peptide-1 by 4.4- to 4.9-fold. Unexpectedly, alogliptin alone lacked clear efficacy for improving glucose levels. However, alogliptin in combination with pioglitazone clearly enhanced the effects of pioglitazone alone. After 3-4 weeks of treatment, combination treatment increased plasma insulin by 3.8-fold, decreased plasma glucagon by 41%, both of which were greater than each drug alone, and increased plasma adiponectin by 2.4-fold. In addition, combination treatment decreased glycosylated haemoglobin by 2.2%, plasma glucose by 52%, plasma triglycerides by 77% and non-esterified fatty acids by 48%, all of which were greater than each drug alone. Combination treatment also increased expression of insulin and pancreatic and duodenal homeobox 1 (PDX1), maintained normal beta-cell/alpha-cell distribution in islets and restored pancreatic insulin content to levels comparable to non-diabetic mice.Conclusions and Implications: These results indicate that combination treatment with alogliptin and pioglitazone at an early stage of diabetes improved metabolic profiles and indices that measure beta-cell function, and maintained islet structure in db/db mice, compared with either alogliptin or pioglitazone monotherapy. [ABSTRACT FROM AUTHOR]

Objective: GPR40 is a G protein-coupled receptor regulating free fatty acid-induced insulin secretion. We generated transgenic mice overexpressing the hGPR40 gene under control of the mouse insulin II promoter and used them to examine the role of GPR40 in the regulation of insulin secretion and glucose homeostasis.Research Design and Methods: Normal (C57BL/6J) and diabetic (KK) mice overexpressing the hGPR40 gene under control of the insulin II promoter were generated, and their glucose metabolism and islet function were analyzed.Results: In comparison with nontransgenic littermates, hGPR40 transgenic mice exhibited improved oral glucose tolerance with an increase in insulin secretion. Although islet morphologic analysis showed no obvious differences between hGPR40 transgenic and nontransgenic mice, isolated islets from hGPR40 transgenic mice had enhanced insulin secretion in response to high glucose (16 mmol/l) compared with those from nontransgenic mice, and they both had similar low glucose (3 mmol/l)-stimulated insulin secretion. In addition, hGPR40 transgenic islets significantly increased insulin secretion against a naturally occurring agonist palmitate in the presence of 11 mmol/l glucose. hGPR40 transgenic mice were also found to be resistant to high-fat diet-induced glucose intolerance, and hGPR40 transgenic mice harboring KK background showed augmented insulin secretion and improved oral glucose tolerance compared with nontransgenic littermates.Conclusions: Our results suggest that GPR40 may have a role in regulating glucose-stimulated insulin secretion and plasma glucose levels in vivo and that pharmacological activation of GPR40 may provide a novel insulin secretagogue beneficial for the treatment of type 2 diabetes. [ABSTRACT FROM AUTHOR]

We studied the interruption performance of CF3I gas because its environmental effect is smaller than that of SF6 gas with a model arc-extinguishing chamber. First, we measured the arc time constant and arc power loss coefficient using Mayr's equation. Comparing CF3I with other gases, the arc time constants are SF6 < CF3I < CO2 H2 < Air < N2. The arc power loss coefficient is H2> SF6> CO2 > Air > N2 > CF3I. Next, we evaluated the Short Line Fault (SLF) interruption capability by measuring the di/dt-dv/dt characteristic. Consequently, the SLF interruption performance of pure CF3I was about 0.9 times that of SF6. However, CF3I application to gas insulated switchgear (GIS) and gas circuit breakers (GCB) is difficult because the liquefying temperature of the gas is high. Therefore, we adopted a countermeasure to obtain a lower liquefying temperature mixing CF3I with CO2. The result showed that the SLF interruption performance of the mixture approximated that of pure CF3I when the ratio of CF3I exceeds 20%. [ABSTRACT FROM AUTHOR]

Reactive oxygen species are involved in a diversity of biological phenomena such as inflammation, carcinogenesis, aging, and atherosclerosis. We and other investigators have shown that the level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker for oxidative stress, is increased in either the urine or the mononuclear cells of the blood of type 2 diabetic patients. However, the association between type 2 diabetes and oxidative stress in the pancreatic beta-cells has not been previously described. We measured the levels of 8-OHdG and 4-hydroxy-2-nonenal (HNE)-modified proteins in the pancreatic beta-cells of GK rats, a model of nonobese type 2 diabetes. Quantitative immunohistochemical analyses with specific antibodies revealed higher levels of 8-OHdG and HNE-modified proteins in the pancreatic beta-cells of GK rats than in the control Wistar rats, with the levels increasing proportionally with age and fibrosis of the pancreatic islets. We further investigated whether the levels of 8-OHdG and HNE-modified proteins would be modified in the pancreatic beta-cells of GK rats fed with 30% sucrose solution or 50 ppm of voglibose (alpha-glucosidase inhibitor). In the GK rats, the levels of 8-OHdG and HNE-modified proteins, as well as islet fibrosis, were increased by sucrose treatment but reduced by voglibose treatment. These results indicate that the pancreatic beta-cells of GK rats are oxidatively stressed, and that chronic hyperglycemia might be responsible for the oxidative stress observed in the pancreatic beta-cells. [ABSTRACT FROM AUTHOR]

The effect of long-term (6 months) administration of voglibose in a dietary mixture (10 ppm) on intestinal disaccharidase activity was examined in non obese type 2 diabetes model Goto-Kakizaki (GK) rats. The postprandial blood glucose level in voglibose-treated GK rats was significantly lower than in untreated GK rats (190±19 vs. 250±25 mg/dl, P<0.01; 1 h, 212±23 vs. 256±20, P<0.05; 2 h), and the activities of maltase, sucrase, and isomaltase remained significantly lower throughout the 6 months of voglibose treatment. The expressions of protein and mRNA of sucrase–isomaltase (SI) complex were significantly higher in voglibose-treated GK rats. Voglibose administration then was stopped after 6 months of treatment. The mRNA level and protein level of the SI complex became normalized during the interruption of drug administration, and disaccharidase activities increased almost to the level of the untreated group 1 month after treatment was stopped. After 1 day of re-administration of the drug, however, disaccharidase activities again became significantly inhibited. These results indicate that voglibose may improve glucose tolerance since it inhibits activities of disaccharidases in spite of increasing the expression of them on intestine, furthermore voglibose may be reversible and reproducible through interruption and re-administration. [Copyright &y& Elsevier]

Granulocyte colony-stimulating factor (G-CSF)-producing lung tumours are rare, with their imaging features and effective treatments remaining elusive. Similarly, mesenchymal-epithelial transition (MET) exon 14 skipping mutations are also uncommon. Herein, we report a case of G-CSF-producing lung adenocarcinoma positive for a MET exon 14 skipping mutation, mimicking lung abscess. A 61-year-old man presented with cough and high fever. Contrast-enhanced chest computed tomography revealed a mass with a cavity and internal fluid accumulation. The patient initially underwent diagnostic treatment for a lung abscess but was ultimately diagnosed with lung adenocarcinoma positive for a MET exon 14 skipping mutation. Following tepotinib therapy, the primary lesion shrank, and serum G-CSF levels decreased, leading to a diagnosis of G-CSF-producing lung cancer. G-CSF-producing lung tumours can present imaging findings that mimic lung abscesses. Tepotinib therapy may be effective for patients with MET exon 14 skipping mutation, including those with G-CSF-producing lung cancer., (© 2024 The Author(s). Respirology Case Reports published by John Wiley & Sons Australia, Ltd on behalf of The Asian Pacific Society of Respirology.)

Purpose: To identify the risk factors for perioperative complications to prevent perioperative complications after complete ipsilateral upper urinary stone removal using flexible ureterorenoscopy., Materials and Methods: We retrospectively examined 111 patients who underwent flexible ureterorenoscopy for ipsilateral renal stones with a diameter ≥ 5 mm at the same time as ureterorenoscopy for ureteric stones. The flexible ureterorenoscopy procedures were performed following the fragmentation technique. Patients who experienced (complication group) and did not experience (non-complication group) perioperative complications were compared. The complication group included 33 patients with Clavien-Dindo classification scores of I, II, III, or IV and/or those with a body temperature of > 37.5 ℃ during hospitalization., Results: The overall stone volume, stone-free rate and procedure duration were 1.71 mL, 96.4% and 77 min, respectively. The rate of perioperative complications was 29.7% (grade 1, 2 and 3 was 23.4%, 5.4% and 0.9%, respectively). Severe complications (Clavien-Dindo grade 4) were not observed. Multivariable analysis revealed that ureteral stone volume and female patients were independent predictors of perioperative complications after flexible ureterorenoscopy (p = 0.015 and 0.017, respectively)., Conclusions: This study showed that ureteral stone volume and female gender have the possibility to increase perioperative complications. These preliminary data help to select for patients who are at low risk of complications. Therefore, in these selected patients, complete ipsilateral upper urinary tract stone removal using flexible ureterorenoscopy may reduce the recurrence of urolithiasis without increasing perioperative complications., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Variations in color and texture of histopathology images are caused by differences in staining conditions and imaging devices between hospitals. These biases decrease the robustness of machine learning models exposed to out-of-domain data. To address this issue, we introduce a comprehensive histopathology image dataset named PathoLogy Images of Scanners and Mobile phones (PLISM). The dataset consisted of 46 human tissue types stained using 13 hematoxylin and eosin conditions and captured using 13 imaging devices. Precisely aligned image patches from different domains allowed for an accurate evaluation of color and texture properties in each domain. Variation in PLISM was assessed and found to be significantly diverse across various domains, particularly between whole-slide images and smartphones. Furthermore, we assessed the improvement in domain shift using a convolutional neural network pre-trained on PLISM. PLISM is a valuable resource that facilitates the precise evaluation of domain shifts in digital pathology and makes significant contributions towards the development of robust machine learning models that can effectively address challenges of domain shift in histological image analysis., (© 2024. The Author(s).)

The classical organ culture method, in which tissue is placed at the gas‒liquid interphase, is effective at inducing mouse spermatogenesis. However, due to reginal variations in the supply of oxygen and nutrients within a tissue, the progress of spermatogenesis was observed only in limited areas of a tissue. In addition, haploid cell formation and its differentiation to spermatozoon, i.e. spermiogenesis, were infrequent and inefficient. Here, we show that the polydimethylsiloxane (PDMS)-chip ceiling (PC) method, which ensures a uniform supply of nutrients and oxygen throughout the tissue by pressing it into a thin, flat shape, can provide control over the culture space. We used this method to culture testis tissue from neonatal mice, aged 1 to 4 days, and found that modulating the culture space during the experiment by replacing one chip with another that had a higher ceiling effectively increased tissue growth. This adjustment also induced more efficient spermatogenesis, with the process of spermiogenesis being particularly promoted. Meiotic cells were observed from culture day 14 onward, and haploid cells were confirmed at the end of each experiment. This technique was also shown to be a sensitive assay for testicular toxicity. Culture-space control will be a critical regulation parameter for sophisticated tissue culture experiments., (© 2023. The Author(s).)

Introduction: Vasculitis does not usually induce glandular tissue lesions. Herein, we present a case of vasculitis with a distribution similar to that of immunoglobulin-G4-related disease (IgG4-RD), including that of the submandibular and lacrimal glands, and periaortitis., Case Report: A 70-year-old man presented with shortness of breath. Laboratory findings revealed an IgG4 level of 191 mg/dL, negative antineutrophil cytoplasmic antibody test, and C-reactive protein level of 8.33 mg/dL. Magnetic resonance imaging of the head and computed tomography of the neck revealed bilaterally enlarged submandibular and lacrimal glands. Neck-to-pelvis computed tomography revealed bilateral infiltrative shadows in the lower lobes of both lungs, mass shadows in both lungs, and periaortitis of the abdominal aorta extending to the common iliac artery. Thus, the patient was diagnosed with IgG4-related respiratory disease and periaortitis/periarteritis. Prednisolone was administered at a dose of 35 mg (0.6 mg/kg daily). The dose was gradually tapered while observing the effects of the treatment. Imaging findings indicated an improvement and the C-reactive protein and IgG4 levels decreased, indicating a successful treatment course. However, after reexamination of the pathological findings, the diagnosis changed from IgG4-RD to vasculitis. One year after treatment initiation, the patient symptoms have stabilized., Conclusion: Vasculitis can present with lesions and pathological findings similar to those of IgG4-RD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Single-cell multi-omics analysis has emerged as a crucial tool in modern biology due to its capacity to uncover the intricate molecular heterogeneity within individual cells. Glycan structural diversity on the cell surface creates a "cell signature" that varies by cell type and state. However, single-cell glycan analysis remains a challenge. This protocol presents a series of techniques and procedures that enable the simultaneous measurements of glycan and RNA at the single-cell level via DNA-barcoded lectin-based sequencing (scGR-seq). The techniques include (1) the preparation of DNA-barcoded lectins, (2) a step-by-step protocol for single-cell glycan/RNA sequencing, and (3) a data analysis approach for the integration of glycan and RNA data. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Preparation of DNA-barcoded lectins Basic Protocol 2: Single-cell glycan/RNA sequencing., (© 2023 Wiley Periodicals LLC.)

Mouse spermatogenesis, from spermatogonial stem cell proliferation to sperm formation, can be reproduced in vitro by culturing testis tissue masses of neonatal mice. However, it remains to be determined whether this method is also applicable when testis tissues are further divided into tiny fragments, such as segments of the seminiferous tubule (ST), a minimal anatomical unit for spermatogenesis. In this study, we investigated this issue using the testis of an Acrosin-GFP/Histone H3.3-mCherry (Acr/H3) double-transgenic mouse and monitored the expression of GFP and mCherry as indicators of spermatogenic progression. Initially, we noticed that the cut and isolated stretches of ST shrunk rapidly and conglomerated. We therefore maintained the isolation of STs in two ways: segmental isolation without truncation or embedding in soft agarose. In both cases, GFP expression was observed by fluorescence microscopy. By whole-mount immunochemical staining, meiotic spermatocytes and round and elongating spermatids were identified as Sycp3-, crescent-form GFP-, and mCherry-positive cells, respectively. Although the efficiency was significantly lower than that with tissue mass culture, we clearly showed that spermatogenesis can be induced up to the elongating spermatid stage even when the STs were cut into short segments and cultured in isolation. In addition, we demonstrated that lowered oxygen tension was favorable for spermatogenesis both for meiotic progression and for producing elongating spermatids in isolated STs. Culturing isolated STs rather than tissue masses is advantageous for explicitly assessing the various environmental parameters that influence the progression of spermatogenesis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Feng 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.)

We experimentally show that the 1s^{2}2s^{2}2p&#95;{1/2}-1s2s^{2}2p&#95;{1/2}^{2} transition in Pb^{77+} emitted in dielectronic recombination of Pb^{78+} is strongly polarized, although it is an intrinsically unpolarized J=1/2 to 1/2 transition. This unanticipated polarization is shown to be due to quantum interference with radiative recombination. The interference effect has been studied on an asymmetric resonance profile but has never been studied on polarization. In this Letter, we show that the effect on polarization can arise from a different cross term than that responsible for asymmetry, resulting in unexpectedly large polarization even for a nearly symmetric resonance suggesting a small interference.

Numerous cancer histopathology specimens have been collected and digitized over the past few decades. A comprehensive evaluation of the distribution of various cells in tumor tissue sections can provide valuable information for understanding cancer. Deep learning is suitable for achieving these goals; however, the collection of extensive, unbiased training data is hindered, thus limiting the production of accurate segmentation models. This study presents SegPath-the largest annotation dataset (>10 times larger than publicly available annotations)-for the segmentation of hematoxylin and eosin (H&E)-stained sections for eight major cell types in cancer tissue. The SegPath generating pipeline used H&E-stained sections that were destained and subsequently immunofluorescence-stained with carefully selected antibodies. We found that SegPath is comparable with, or outperforms, pathologist annotations. Moreover, annotations by pathologists are biased toward typical morphologies. However, the model trained on SegPath can overcome this limitation. Our results provide foundational datasets for machine-learning research in histopathology., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Neurotrophins are a family of secreted proteins expressed in the peripheral nervous system and the central nervous system that support neuronal survival, synaptic plasticity, and neurogenesis. Brain-derived neurotrophic factor (BDNF) and its high affinity receptor TrkB are highly expressed in the cortical and hippocampal areas and play an essential role in learning and memory. The decline of cognitive function with aging is a major risk factor for cognitive diseases such as Alzheimer's disease. Therefore, an alteration of BDNF/TrkB signaling with aging and/or pathological conditions has been indicated as a potential mechanism of cognitive decline. In this review, we summarize the cellular function of neurotrophin signaling and review the current evidence indicating a pathological role of neurotrophin signaling, especially of BDNF/TrkB signaling, in the cognitive decline in aging and age-related cognitive diseases. We also review the therapeutic approach for cognitive decline by the upregulation of the endogenous BDNF/TrkB-system.

Our understanding of how each hereditary kidney cancer adapts to its tissue microenvironment is incomplete. Here, we present single-cell transcriptomes of 108,342 cells from patient specimens including from six hereditary kidney cancers. The transcriptomes displayed distinct characteristics of the cell of origin and unique tissue microenvironment for each hereditary kidney cancer. Of note, hereditary leiomyomatosis and renal cell carcinoma (HLRCC)-associated kidney cancer retained some characteristics of proximal tubules, which were completely lost in lymph node metastases and present as an avascular tumor with suppressed T cells and TREM2-high macrophages, leading to immune tolerance. Birt-Hogg-Dubé (BHD)-associated kidney cancer exhibited transcriptomic intratumor heterogeneity (tITH) with increased characteristics of intercalated cells of the collecting duct and upregulation of FOXI1-driven genes, a critical transcription factor for collecting duct differentiation. These findings facilitate our understanding of how hereditary kidney cancers adapt to their tissue microenvironment., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

In order to support bone marrow regeneration after myeloablation, hematopoietic stem cells (HSCs) actively divide to provide both stem and progenitor cells. However, the mechanisms regulating HSC function and cell fate choice during hematopoietic recovery remain unclear. We herein provide novel insights into HSC regulation during regeneration by focusing on mitochondrial metabolism and ATP citrate lyase (ACLY). After 5-fluorouracil-induced myeloablation, HSCs highly expressing endothelial protein C receptor (EPCR high ) were enriched within the stem cell fraction at the expense of more proliferative EPCR Low HSCs. These EPCR High HSCs were initially more primitive than EPCR Low HSCs and enabled stem cell expansion by enhancing histone acetylation, due to increased activity of ACLY in the early phase of hematopoietic regeneration. In the late phase of recovery, HSCs enhanced differentiation potential by increasing the accessibility of cis-regulatory elements in progenitor cell-related genes, such as CD48. In conditions of reduced mitochondrial metabolism and ACLY activity, these HSCs maintained stem cell phenotypes, while ACLY-dependent histone acetylation promoted differentiation into CD48 + progenitor cells. Collectively, these results indicate that the dynamic control of ACLY-dependent metabolism and epigenetic alterations is essential for HSC regulation during hematopoietic regeneration., (© 2022 The Authors.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest gastrointestinal cancers with a 5-year survival rate of less than 10%. Biomarkers for early PDAC detection are useful in treating patients with PDAC. Extracellular vesicles (EVs) are lipid-bound vesicles that are potential biomarkers of various diseases such as PDAC. In this study, we quantitatively measured the serum levels of EVs (CD63 + -EVs) or platelet-derived EVs (CD41 + - and CD61 + -EVs) and evaluated their potential use as biomarkers of PDAC., Methods: We measured the serum levels of CD63 + -, CD41 + -, CD61 + -EVs using sandwich enzyme-linked immunosorbent assay based on Tim4 with specificity for phosphatidylserine on EVs in age- and sex-matched healthy controls (HCs, n = 39) and patients with PDAC (n = 39). We also examined the effect of tumor burden on the serum EV levels after surgical resection (n = 28). CA19-9, a clinical PDAC biomarker, was also measured for comparison., Results: Serum levels of CD63 + -EVs, CD41 + -EVs, and CD61 + -EVs were significantly increased in patients with PDAC compared to HCs. Receiver operating characteristic analysis revealed that CD63 + -EVs exhibited the highest diagnostic performance to discriminate patients with PDAC from HCs (area under the curve (AUC): 0.846), which was comparable to CA19-9 (AUC: 0.842). CA19-9 showed lower AUC values in early stages (I-II, AUC: 0.814) than in late stages (III-IV, AUC: 0.883) PDAC. Conversely, CD63 + -EVs, CD41 + -EVs, and CD61 + -EVs showed comparable AUCs between early- and late-stage PDAC. The combined use of CA19-9 and CD63 + -EVs showed a higher diagnostic performance for early-stage PDAC (AUC: 0.903) than CA19-9. The serum levels of CD63 + -EVs, CD41 + -EVs, CD61 + -EVs, and CA19-9 decreased significantly after surgical resection, demonstrating that EVs are increased in sera of patients depending on the tumor burden., Conclusions: The serum levels of CD63 + -EVs and platelet-derived EVs (CD41 + -EVs, CD61 + -EVs) are increased in patients with PDAC than HCs. Since CD63 + -EVs showed a high AUC to discriminate patients with PDAC from HCs; they might be useful as potential biomarkers for PDAC., (© 2022. The Author(s).)

Glycans are structurally diverse molecules found on the surface of living cells. The protocol details a system developed for combined analysis of glycan and RNA in single cells (scGR-seq) using human induced pluripotent stem cells (hiPSCs) and hiPSC-derived neural progenitor cells (NPCs). scGR-seq consists of DNA-barcoded lectin-based glycan profiling by sequencing (scGlycan-seq) and single-cell transcriptome profiling (scRNA-seq). scGR-seq will be an essential technique to delineate the cellular heterogeneity of glycans across multicellular systems. For complete details on the use and execution of this profile, please refer to Minoshima et al. (2021)., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

A lung cancer coexists with non-caseous epithelioid granulomas (NEG) in the same lesion is uncommon. A 62-year-old female was referred to our hospital for examination of a right lung S3 nodule which was recently increasing in its size. Positron emission tomography-computed tomography (PET-CT) examination revealed positive signals at the S3 nodule as well as mediastinal lymph nodes, apex of heart and right pleura. Pathological examination revealed the S3 nodule coexisting with both adenocarcinoma and NEG. The differential diagnosis between the systemic sarcoidosis and sarcoid reaction is usually important in such a case. Since the pleura and mediastinal lymph nodes contained many NEGs, the adenocarcinoma arising based on the systemic sarcoidosis was possibly suggested in the present case.

Single-cell sequencing has emerged as an indispensable technology to dissect cellular heterogeneity but never been applied to the simultaneous analysis of glycan and RNA. Using oligonucleotide-labeled lectins, we first established lectin-based glycan profiling of single cells by sequencing (scGlycan-seq). We then combined the scGlycan-seq with single-cell transcriptome profiling for joint analysis of glycan and RNA in single cells (scGR-seq). Using scGR-seq, we analyzed the two modalities in human induced pluripotent stem cells (hiPSCs) before and after differentiation into neural progenitor cells at the single-cell resolution. The combination of RNA and glycan separated the two cell types clearer than either one of them. Furthermore, integrative analysis of glycan and RNA modalities in single cells found known and unknown lectins that were specific to hiPSCs and coordinated with neural differentiation. Taken together, we demonstrate that scGR-seq can reveal the cellular heterogeneity and biological roles of glycans across multicellular systems., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Purpose: To assess the effect of our new classification on surgical outcomes after flexible ureteroscopy (fURS) for kidney stones., Methods: We retrospectively examined 128 patients after single renal fURS procedures performed using ureteral access sheaths (UASs) with the fragmentation technique. Based on the gap (calculated by subtracting the ureteroscope diameter from the UAS diameter), enrolled patients were divided into three groups: small (< 0.6 mm), medium (0.6 to < 1.2 mm), and large space groups (≥ 1.2 mm). Stone-free (SF) status was defined as either complete absence of stones (SF) or the presence of stones < 4 mm in diameter on non-contrast computed tomography (NCCT)., Results: The SF rate was significantly lower in the small space group (50% in small, 97.9% in medium, 89.2% in large; p = 0.001). Perioperative complications over Clavien-Dindo Grade I were observed in 16.7%, 4.2%, and 8.1% of patients, respectively (p = 0.452). The ratio of stone volume and operative time (efficiency of stone removal) was significantly higher in the large space group compared to the small and medium space groups (0.009 ± 0.003 ml/min, 0.013 ± 0.005 ml/min, 0.027 ± 0.012 ml/min, respectively; p < 0.001)., Conclusion: Our findings that gaps > 0.6 mm (1.8 Fr), including the combination of a 9.5-Fr UAS and a small caliber ureteroscope, improve SF rates, and larger gaps facilitate stone removal efficiency providing the basis for future development of clinical protocols aimed at improving outcomes., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

The reactivity of titanium cluster ions and their oxides with molecular dinitrogen was examined using a tandem-type mass spectrometer at a low collision energy of 0.5 eV. The clusters can adsorb dinitrogen and release a titanium atom to consume the obtained excess energy. This indicates that N 2 adsorption energy is large enough to break the titanium cluster. While the smaller clusters have relatively low reactivity, the measured reaction cross section increases with the cluster size and reaches nearly one-third of the Langevin cross section at the larger clusters. Density functional theory calculations indicate that the reaction proceeds exothermically and that molecular dinitrogen adsorbs on the clusters dissociatively. It is suggested that the energy levels of the highest occupied molecular orbitals of the titanium clusters are decisively important for N 2 activation.

Gamma-ray bursts (GRBs), which are bright flashes of gamma rays from extragalactic sources followed by fading afterglow emission, are associated with stellar core collapse events. We report the detection of very-high-energy (VHE) gamma rays from the afterglow of GRB 190829A, between 4 and 56 hours after the trigger, using the High Energy Stereoscopic System (H.E.S.S.). The low luminosity and redshift of GRB 190829A reduce both internal and external absorption, allowing determination of its intrinsic energy spectrum. Between energies of 0.18 and 3.3 tera-electron volts, this spectrum is described by a power law with photon index of 2.07 ± 0.09, similar to the x-ray spectrum. The x-ray and VHE gamma-ray light curves also show similar decay profiles. These similar characteristics in the x-ray and gamma-ray bands challenge GRB afterglow emission scenarios., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)