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Accurate diagnosis of the localization of prostate cancer (PCa) on magnetic resonance imaging (MRI) remains a challenge. We aimed to assess discrepancy between the location of PCa pathologically diagnosed using surgical specimens and lesions indicated as possible PCa by the Prostate Imaging Reporting and Data System on MRI. The primary endpoint was the concordance rate between the site of probable clinically significant PCa (csPCa) identified using biparametric MRI (bpMRI) and location of PCa in the surgical specimen obtained using robot-assisted total prostatectomy. Among 85 lesions identified in 30 patients; 42 (49.4%) were identified as possible PCa on MRI. The 85 PCa lesions were divided into positive and negative groups based on the bpMRI results. None of the patients had missed csPCa. Although the diagnostic accuracy of bpMRI was relatively high for PCas located in the middle of the prostate (p = 0.029), it was relatively low for PCa located at the base of the prostate, all of which were csPCas. Although current modalities can accurately diagnose PCa, the possibility that PCa is present with multiple lesions in the prostate should be considered, even if MRI does not detect PCa.

This study aimed to determine the predictive value of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) based on biparametric magnetic resonance imaging (bpMRI) with combined target biopsy (TBx) and systematic biopsy (SBx) in patients with suspicion of having clinically significant prostate cancer (csPCa). In this retrospective study, we reviewed the clinical and pathological records of 184 consecutive patients who underwent bpMRI before prostate biopsy. We focused on patients with PI-RADS v2 scores ≥ 3. MRI was performed using a 3-Tesla clinical scanner with a 32-channel phased-array receiver coil. PI-RADS v2 was used to describe bpMRI findings based on T2-weighted imaging and diffusion-weighted imaging scores. The primary endpoint was the diagnostic accuracy rate of PI-RADS v2 based on bpMRI for patients with prostate cancer (PCa) who underwent combined TBx and SBx. A total of 104 patients were enrolled in this study. Combined TBx and SBx was significantly superior to either method alone for PCa detection in patients with suspicious lesions according to PI-RADS v2. TBx and SBx detected concordant csPCa in only 24.1% of the patients. In addition, the rate of increase in the Gleason score was similar between SBx (41.5%) and TBx (34.1%). The diagnostic accuracy of bpMRI is comparable to that of standard multiparametric MRI for the detection of csPCa. Moreover, combined TBx and SBx may be optimal for the accurate determination of csPCa diagnosis, the International Society of Urological Pathology grade, and risk classification.

Alpha-particle radiotherapy has gained considerable attention owing to its potent anti-cancer effect. 211At, with a relatively short half-life of 7.2 h, emits an alpha particle within a few cell diameters with high kinetic energy, which damages cancer cells with high biological effectiveness. In this study, we investigated the intravenous injection of 211At-labeled gold nanoparticles (AuNPs) for targeted alpha-particle therapy (TAT). Different kinds of surface-modified gold nanoparticles can be labeled with 211At in high radiochemical yield in 5 min, and no purification is necessary. The in vivo biodistribution results showed the accumulation of 5 nm 211At-AuNPs@mPEG at 2.25% injection dose per gram (% ID/g) in tumors within 3 h via the enhanced permeability and retention (EPR) effect. Additionally, we observed a long retention time in tumor tissues within 24 h. This is the first study to demonstrate the anti-tumor efficacy of 5 nm 211At-AuNPs@mPEG that can significantly suppress tumor growth in a pancreatic cancer model via intravenous administration. AuNPs are satisfactory carriers for 211At delivery, due to simple and efficient synthesis processes and high stability. The intravenous administration of 5 nm 211At-AuNPs@mPEG has a significant anti-tumor effect. This study provides a new framework for designing nanoparticles suitable for targeted alpha-particle therapy via intravenous injection.

Mitochondrial fission factor (MFF) is an adapter that targets dynamin-related protein 1 from the cytosol to the mitochondria for fission. Loss-of-function MFF mutations cause encephalopathy due to defective mitochondrial and peroxisomal fission 2 (EMPF2). To elucidate the molecular mechanisms that were involved, we analyzed the functional effects of MFF depletion in deciduous teeth-derived dental pulp stem cells differentiating into dopaminergic neurons (DNs). When treated with MFF-targeting small interfering RNA, DNs showed impaired neurite outgrowth and reduced mitochondrial signals in neurites harboring elongated mitochondria. MFF silencing also caused mitochondrial Ca2+ accumulation through accelerated Ca2+ influx from the endoplasmic reticulum (ER) via the inositol 1,4,5-trisphosphate receptor. Mitochondrial Ca2+ overload led DNs to produce excessive reactive oxygen species (ROS), and downregulated peroxisome proliferator-activated receptor-gamma co-activator-1 alpha (PGC-1α). MFF was co-immunoprecipitated with voltage-dependent anion channel 1, an essential component of the ER-mitochondrial Ca2+ transport system. Folic acid supplementation normalized ROS levels, PGC-1α mediated mitochondrial biogenesis, and neurite outgrowth in MFF depleted DNs, without affecting their mitochondrial morphology or Ca2+ levels. We propose that MFF negatively regulates the mitochondrial Ca2+ influx from the ER. MFF-insufficiency recapitulated the EMPF2 neuropathology with increased oxidative stress and suppressed mitochondrial biogenesis. ROS and mitochondrial biogenesis might be potential therapeutic targets for EMPF2.

The flow control capability (especially for separation control) of a dielectric-barrier-discharge plasma actuator (DBD-PA) has been investigated extensively. However, these studies have been conducted under ideal conditions, such as wind tunnels and computational environments, and limited studies have investigated the effects of plasma actuators in an actual environment. In this study, the flow control capability of a DBD-PA under natural and in-flight conditions was investigated via field flight tests using an unmanned aerial vehicle (UAV). The DBD-PA driving system was constructed with a small high-voltage power supply on a 2-m-span UAV. With the support of an autonomous flight system, the pitch angle gradually increased as the airspeed decreased, and the stall occurred from the cruise state. This flight procedure was conducted with the DBD-PA on or off, and 246 pairs of flights were operated. The results revealed that a flight state with a higher pitch angle and lower airspeed occurred when DBD-PA was switched on. In addition, the moment of stall was quantitatively determined from the flight log, and it was confirmed that the maximum pitch angle when DBD-PA was switched on tended to be larger than that when DBD-PA was switched off. These results indicate that flow control with a DBD-PA on a 2-m-span UAV was effective in natural and in-flight situations.

Tumor blood flow (TBF) is related to drug delivery and hypoxia, both of which can impact the efficacy of anti-cancer therapies. Although integrin αvβ3 expression is related to tumor angiogenesis, it remains unclear whether the degree of angiogenesis affects TBF. This study aimed to evaluate the expression of integrin αvβ3 in mouse tumor models using [68Ga]Ga-DOTA-c(RGDfK) peptide positron emission tomography (PET) and immunohistochemical staining. PET studies were conducted using mouse C6 glioma models and MIA PaCa-2 (n = 6 each). The [68Ga]Ga-DOTA-c(RGDfK) peptide was injected via the tail vein (2.17 ± 0.28 MBq), and 10 min static PET scans were performed. Immunohistochemical analysis was conducted using an integrin αVβ3 antibody. [68Ga]Ga-DOTA-c(RGDfK) peptide PET revealed higher uptake of the radiotracer in C6 gliomas than in MIA PaCa-2 tumors. The mean standardized uptake value was significantly higher in C6 gliomas (0.35 ± 0.058) than in MIA PaCa-2 tumors (0.17 ± 0.045). Histological analysis revealed intense integrin αVβ3 expression in the C6 gliomas, whereas the MIA PaCa-2 tumors had low expression levels. This study showed that the expression of integrin αvβ3 can be differentiated by the [68Ga]Ga-DOTA-c(RGDfK) peptide, suggesting the potential applicability of this peptide in the evaluation of the relationship between angiogenesis and TBF.

Viral non-structural proteins, such as NSs of the newly emerging severe fever with thrombocytopenia syndrome virus, are well established virulence factors, mediating viral pathogenesis and disease progression through various mechanisms. NSs has been described as a potent interferon antagonist and NF-κB agonist, two divergent signaling pathways in many immune responses upon a viral encounter. In this review, we highlight the many mechanisms used by NSs on the host that promote viral replication and hyper-inflammation. Understanding these host-pathogen interactions is crucial for antiviral therapy development.

This study aimed to develop and validate an automated segmentation method for surface muscles using a three-dimensional (3D) U-Net based on selective voxel patches from whole-body computed tomography (CT) images. Our method defined a voxel patch (VP) as the input images, which consisted of 56 slices selected at equal intervals from the whole slices. In training, one VP was used for each case. In the test, multiple VPs were created according to the number of slices in the test case. Segmentation was then performed for each VP and the results of each VP merged. The proposed method achieved a segmentation accuracy mean dice coefficient of 0.900 for 8 cases. Although challenges remain in muscles adjacent to visceral organs and in small muscle areas, VP is useful for surface muscle segmentation using whole-body CT images with limited annotation data. The limitation of our study is that it is limited to cases of muscular disease with atrophy. Future studies should address whether the proposed method is effective for other modalities or using data with different imaging ranges.

Mineral dust aerosols, which comprise multiple mineral species, are transported far from their source desert areas to the open ocean. After an Asian dust outflow event was observed over a marine boundary layer in the western North Pacific on February 29, 2012 on research vessel (R/V) Hakuho Maru, two dust particles of about 6 μm diameter were analyzed. First, they were sliced by using a focused ion beam (FIB). Their mineralogical structures and the elemental distribution of their cross-sections were subsequently analyzed with the use of transmission electron microscopy (TEM) and energy-dispersive X ray spectrometry (EDS). These analyses revealed that the dust particles consisted mainly of calcite and silica. Furthermore, Fe-containing domains were found in the submicrometer area surrounded by calcite and silica. A sulfur-containing domain that co-exists with calcium was found in a small domain near the particle surface, but no clear sign of atmospheric aging was found in most of the calcite domain. The inhomogeneous particle structure implies that the dissolution of iron and calcite in dust particles after ocean deposition depends on the physical structures of particles and their degree of aging according to atmospheric conditions during transport. Those factors must be adequately treated when estimating Asian dust effects on marine primary production.

Fluorocitrate (FC) is a specific metabolic inhibitor of the tricarboxylic acid (TCA) cycle in astrocytes. The purpose of this study was to evaluate whether inhibition of the astrocyte TCA cycle by FC would affect the oxygen metabolism in the rat brain. At 4 h after the intracranial FC injection, the rats (n = 9) were investigated by 15O-labeled gas PET to measure the cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO2), oxygen extraction fraction (OEF), and cerebral blood volume (CBV). After the 15O-gas PET, the rats were given an intravenous injection of 14C-acetate for autoradiography. 15O-gas PET showed no significant differences in any of the measured parameters between the ipsilateral and contralateral striatum (high dose group: CBF (54.4 ± 8.8 and 55.3 ± 11.6 mL/100 mL/min), CMRO2 (7.0 ± 0.9 and 7.1 ± 1.2 mL/100 mL/min), OEF (72.0 ± 8.9 and 70.8 ± 8.2%), and CBV (4.1 ± 0.8 and 4.2 ± 0.9 mL/100 mL), respectively). In contrast, the 14C-acetate autoradiography revealed a significant inhibition of the astrocyte metabolism in the ipsilateral striatum. The regional cerebral oxygen consumption as well as the hemodynamic parameters were maintained even in the face of inhibition of the astrocyte TCA cycle metabolism in the rat brain.