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Patients with end-stage renal disease have lower fasting plasma glucose and HbA1c levels, with significantly higher insulin levels. For a long time, it has been believed that this higher insulin level in renal failure is due to decreased insulin clearance caused by reduced renal function. However, here we reported that accumulation of the gut microbiota-derived uremic toxin, phenyl sulfate (PS) in the renal failure, increased insulin secretion from the pancreas by enhanced glucose-stimulated insulin secretion. Other endogenous sulfides compounds which accumulated as in the renal failure also increased glucose-stimulated insulin secretion from β-cell. With RNA-seq analyses and gene knock down, we demonstrated that insulin secretion evoked by PS was mediated by Ddah2. In addition, we also found that PS increased insulin resistance through lncRNA expression and Erk phosphorylation in the adipocytes. To confirm the relationship between PS and glucose metabolism in human, we recruited 2 clinical cohort studies (DKD and CKD) including 462 patients, and found that there was a weak negative correlation between PS and HbA1c. Because these trials did not measure fasting insulin level, we alternatively used the urinary C-peptide/creatinine ratio (UCPCR) as an indicator of insulin resistance. We found that PS may induce insulin resistance in patients with eGFR < 60 mL/min/1.73 m 2 . These data suggest that the accumulation of uremic toxins modulates glucose metabolism and induced insulin resistance in CKD and DKD patients. Considering HbA1c as a reflection of chronic hyperglycemia and UCPCR as a reflection of chronic hyperinsulinemia, our findings indicate that PS is negatively associated with hyperglycemia independent of CKD, and positively associated with hyperinsulinemia in DKD patients.

Background/Objectives: Transthoracic echocardiography (TTE) is a non-invasive tool for real-time assessment of cardiac motion and blood flow. It is widely used in emergency and bedside settings as a Focus Cardiac Ultrasound (FoCUS) device. However, standardized training methods and adequate educational environments are limited. Methods: A TTE image assessment artificial intelligence (AI) system was developed in this study, focusing on probe positioning and image quality for non-supervised TTE practice. Results: The view classification model achieved a high F1-score of 0.956. The position evaluation model achieved F1-scores of 0.678, 0.864, and 0.831 for the parasternal long-axis, parasternal short-axis, and apical four-chamber views, respectively. The quality evaluation model achieved F1-scores of 0.674, 0.845, and 0.746. Combining the position and quality models improved the F1-score for the parasternal long-axis view to 0.714, showing the benefit of integrating views with lower baseline performance. Conclusions: This study presents a novel AI-based educational system that assesses probe position and image quality in TTE. The model was developed using a custom dataset of healthy young adults that reflects beginner-level training scenarios, including many suboptimal images similar to those commonly acquired by novices. The proposed framework, which integrates position and quality models, lays the groundwork for future AI-assisted ultrasound training, particularly in unsupervised or resource-limited settings.

Hepatitis E virus (HEV) is one of the leading causes of acute viral hepatitis worldwide. In this work, a pulse-triggered ultrasensitive electrochemical sensor was fabricated using graphene quantum dots and gold-embedded polyaniline nanowires, prepared via an interfacial polymerization and then self-assembly approach. Introducing an external electrical pulse during the virus accumulation step increases the sensitivity towards HEV due to the expanded surface of the virus particle as well as the antibody-conjugated polyaniline chain length, compared to other conventional electrochemical sensors. The sensor was applied to various HEV genotypes, including G1, G3, G7 and ferret HEV obtained from cell culture supernatant and in a series of fecal specimen samples collected from G7 HEV-infected monkey. The sensitivity is similar to that detected by real-time quantitative reverse transcription-polymerase chain (RT-qPCR). These results suggests that the proposed sensor can pave the way for the development of robust, high-performance sensing methodologies for HEV detection. Detection of viral biomarkers is important for disease treatment and prevention. Here, the authors report on a system that uses an electrical pulse-induced electrochemical sensor for the detection of hepatitis E virus, and demonstrate potential application of the device.

Among the members of flaviviruses, the Zika virus (ZIKV) remains a potent infectious disease agent, with its associated pandemic prompting the World Health Organization (WHO) to declare it a global public health concern. Thus, rapid and accurate diagnosis of the ZIKV is needed. In this study, we report a new immunofluorescence biosensor for the detection of nonstructural protein 1 (NS1) of the ZIKV, which operates using the localized surface plasmon resonance (LSPR) signal from plasmonic gold nanoparticles (AuNPs) to amplify the fluorescence intensity signal of quantum dots (QDs) within an antigen-antibody detection process. The LSPR signal from the AuNPs was used to amplify the fluorescence intensity of the QDs. For ultrasensitive, rapid, and quantitative detection of NS1 of the ZIKV, four different thiol-capped AuNPs were investigated. Our biosensor could detect the ZIKV in a wide concentration range from 10-107 RNA copies/mL, and we found that the limit of detection (LOD) for the ZIKV followed the order Ab-L-cysteine-AuNPs (LOD = 8.2 copies/mL) > Ab-3-mercaptopropionic acid-AuNPs (LOD = 35.0 copies/mL). Immunofluorescence biosensor for NS1 exhibited excellent specificity against other negative control targets and could also detect the ZIKV in human serum.

In 2011, the International Commission on Radiological Protection (ICRP) recommended a significant reduction in the lens-equivalent radiation dose limit, thus from an average of 150 to 20 mSv/year over 5 years. In recent years, the occupational dose has been rising with the increased sophistication of interventional radiology (IVR); management of IVR staff radiation doses has become more important, making real-time radiation monitoring of such staff desirable. Recently, the i3 real-time occupational exposure monitoring system (based on RaySafeTM) has replaced the conventional i2 system. Here, we compared the i2 and i3 systems in terms of sensitivity (batch uniformity), tube-voltage dependency, dose linearity, dose-rate dependency, and angle dependency. The sensitivity difference (batch uniformity) was approximately 5%, and the tube-voltage dependency was <±20% between 50 and 110 kV. Dose linearity was good (R2 = 1.00); a slight dose-rate dependency (~20%) was evident at very high dose rates (250 mGy/h). The i3 dosimeter showed better performance for the lower radiation detection limit compared with the i2 system. The horizontal and vertical angle dependencies of i3 were superior to those of i2. Thus, i3 sensitivity was higher over a wider angle range compared with i2, aiding the measurement of scattered radiation. Unlike the i2 sensor, the influence of backscattered radiation (i.e., radiation from an angle of 180°) was negligible. Therefore, the i3 system may be more appropriate in areas affected by backscatter. In the future, i3 will facilitate real-time dosimetry and dose management during IVR and other applications.

A key challenge in treating solid tumors is that the tumor microenvironment often inhibits the penetration of therapeutic antibodies into the tumor, leading to reduced therapeutic efficiency. It has been reported that the combination of ultrasound-responsive micro/nanobubble and therapeutic ultrasound (TUS) enhances the tissue permeability and increases the efficiency of delivery of macromolecular drugs to target tissues. In this study, to facilitate efficient therapeutic antibody delivery to tumors using this combination system, we developed therapeutic antibody-modified nanobubble (NBs) using an Fc-binding polypeptide that can quickly load antibodies to nanocarriers; since the polypeptide was derived from Protein G. TUS exposure to this Herceptin®-modified NBs (Her-NBs) was followed by evaluation of the antibody’s own ADCC activity, resulting the retained activity. Moreover, the utility of combining therapeutic antibody-modified NBs and TUS exposure as an antibody delivery system for cancer therapy was assessed in vivo. The Her-NBs + TUS group had a higher inhibitory effect than the Herceptin and Her-NBs groups. Overall, these results suggest that the combination of therapeutic antibody-modified NBs and TUS exposure can enable efficient antibody drug delivery to tumors, while retaining the original antibody activity. Hence, this system has the potential to maximize the therapeutic effects in antibody therapy for solid cancers.

The Aira caldera, located in southern Kyushu, Japan, originally formed 100 ka, and its current shape reflects the more recent 30 ka caldera-forming eruptions (hereafter, called the AT eruptions). This study aimed to delineate the detailed two-dimensional (2D) seismic velocity structure of the Aira caldera down to approximately 15 km, by means of the travel-time tomography analysis of the seismic profile across the caldera acquired in 2017 and 2018. A substantial structural difference in thickness in the subsurface low-velocity areas in the Aira caldera between the eastern and western sides, suggest that the Aira caldera comprises at least two calderas, identified as the AT and Wakamiko calderas. The most interesting feature of the caldera structure is the existence of a substantial high-velocity zone (HVZ) with a velocity of more than 6.8 km/s at depths of about 6–11 km beneath the central area of the AT caldera. Because no high ratio of P- to S-wave velocity zones in the depth range were detected from the previous three-dimensional velocity model beneath the AT caldera region, we infer that the HVZ is not an active magma reservoir but comprises a solidified and cool remnant. In addition, a poorly resolved low-velocity zone around 15 km in depth suggests the existence of a deep active magma reservoir. By superimposing the distribution of the known pressure sources derived from the observed ground inflation and the volcanic earthquake distribution onto the 2D velocity model, the magma transportation path in the crust was imaged. This image suggested that the HVZ plays an important role in magma transportation in the upper crust. Moreover, we estimated that the AT magma reservoir in the 30 ka Aira caldera-forming eruptions has the total volume of 490 km3 DRE and is distributed in a depth range of 4–11 km.

We investigate the bound orbits of massive/massless, neutral particles and photons moving around regular black holes of Fan and Wang. For massive particles, we show the existence of stable/unstable circular orbits and the charge dependence of the radius of the innermost stable circular orbit. Remarkably, we find an unstable circular orbit of photons inside the event horizon. For massless particles and photons, we show that both stable and unstable circular orbits can exist in a regular and horizonless spacetime with a slight overcharge. Then, we also discuss the periapsis shift of massive neutral particles orbiting around the black hole, and show that the charge gives a negative correction to the shift for black holes with small nonlinearity of electrodynamics.

We have performed magnetic susceptibility, magnetization, and specific heat measurements on a chiral magnet GdNi\\(_3\\)Ga\\(_9\\), belonging to the trigonal space group \\(R32\\) (\\#155). A magnetic phase transition takes place at \\(T_ N\\) = 19.5 K. By applying a magnetic field along the \\(a\\) axis at 2 K, the magnetization curve exhibits two jumps at \\(\\) 3 kOe and = 45 kOe. To determine the magnetic structure, we performed a resonant X-ray diffraction experiment by utilizing a circularly polarized beam. It is shown that a long-period antiferromagnetic (AFM) helical order is realized at zero field. The Gd spins in the honeycomb layer are coupled in an antiferromagnetic manner in the \\(c\\) plane and rotate with a propagation vector \\(q\\) = (0, 0, 1.485). The period of the helix is 66.7 unit cells (\\( 180\\)~nm). In magnetic fields above 3~kOe applied perpendicular to the helical \\(c\\) axis, the AFM helical order changes to an AFM order with \\(q\\) = (0, 0, 1.5).

We introduce PLaMo-100B, a large-scale language model designed for Japanese proficiency. The model was trained from scratch using 2 trillion tokens, with architecture such as QK Normalization and Z-Loss to ensure training stability during the training process. Post-training techniques, including Supervised Fine-Tuning and Direct Preference Optimization, were applied to refine the model's performance. Benchmark evaluations suggest that PLaMo-100B performs well, particularly in Japanese-specific tasks, achieving results that are competitive with frontier models like GPT-4. The base model is available at https://huggingface.co/pfnet/plamo-100b.