Search Results (45)

Mitochondrial transplantation (MTx) has emerged as a potential therapeutic approach for diseases associated with mitochondrial dysfunction, yet its scalability and cross-species feasibility remain underexplored. This study aimed to evaluate the dose-dependent uptake and molecular effects of xenogeneic mitochondrial transplantation (xeno-MTx) using rat-derived mitochondria in mouse neuronal systems. HT-22 hippocampal neuronal cells and a murine model of cardiac arrest-induced global cerebral ischemia were used to assess mitochondrial uptake, gene expression, and mitochondrial DNA presence. Donor mitochondria were isolated from rat pectoralis muscle and labeled with MitoTracker dyes. Flow cytometry and confocal microscopy revealed a dose-dependent increase in donor mitochondrial uptake in vitro. Quantitative PCR demonstrated a corresponding increase in rat-specific mitochondrial DNA and upregulation of Mfn2 and Bak1, with no changes in other fusion, fission, or apoptotic genes. Inhibitor studies indicated that mitochondrial internalization may involve actin-dependent macropinocytosis and cholesterol-sensitive endocytic pathways. In vivo, rat mitochondrial DNA was detected in mouse brains post–xeno-MTx, confirming donor mitochondrial delivery to ischemic tissue. These findings support the feasibility of xeno-MTx and its dose-responsive biological effects in neuronal systems while underscoring the need for further research to determine long-term functional outcomes and clinical applicability. Full article

Aquaponics, a biological production system that combines land-based aquaculture and hydroponic cultivation of plants, is a water-sharing and water-saving system that is expected to be a sustainable food production system with water and nutrient resource circulation in agricultural and fisheries fields. The balance among feeding, fish density, and plant absorption capacity was investigated to obtain fundamental data for sustainable aquaponic systems. To clarify the effects of feeding rates on biological production and nitrogen utilization efficiency, fish and plant growth performance and nitrogen flow were evaluated in an aquaponic system that combined loach aquaculture with lettuce hydroponic cultivation. Test groups with different feeding rates and different fish densities were set. As a result, the fertilizer components in loach excreta contributed to plant growth, and the growth rate of lettuce plants tended to be greater than that of control hydroponic cultivation without fish. However, there was no difference in lettuce growth at feeding rates of 0 to 2 g d⁻¹/system, but above 2 g d⁻¹/system, the growth of lettuce plants was suppressed due to an overload of excreta. The yield of loaches increased with increasing daily feeding rate per system, but a minimum feed conversion ratio was detected. The NO₂⁻ concentration increased with increasing daily feeding rate per system and amount of excreta. The nitrogen use efficiency did not change at feeding rates ranging from 0 to 1.5 g d⁻¹/system. In this feeding rate range, 80% of NUE in aquaponics was due to NUE in the plant hydroponic cultivation subsystem. However, above 2 g d⁻¹/system, nitrogen use efficiency decreased with increasing daily feeding rate per system. A feeding rate of approximately 1.5 g d⁻¹/system maximized biological production while maintaining high nitrogen utilization efficiency. In conclusion, a balance among feeding, fish density, and plant absorption capacity is essential to maintain a sustainable aquaponic system for sustainable fish and plant production as a food production system, saving water and chemical fertilizer. Full article

Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Natural killer cells (NK) are major innate effector cells with broad cytotoxicity against tumors. Accordingly, NK cells are ideal candidates for cancer immunotherapy, including glioblastoma (GBM). Hypoxia is a common feature of solid tumors, and tumor cells and normal cells adapt to the tumor microenvironment by upregulating the transcription factor hypoxia-inducible factor (HIF)-1α, which can be detrimental to anti-tumor effector immune cell function, including that of NK cells. We knocked out HIF-1α in human primary NK cells using clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9). Then, cellular characterizations were conducted in normoxic and hypoxic conditions. Electroporating two HIF-1α-targeting guide RNA–Cas9 protein complexes inhibited HIF-1α expression in expanded NK cells. HIF-1α knockout human NK cells, including populations in hypoxic conditions, enhanced the growth inhibition of allogeneic GBM cells and induced apoptosis in GBM-cell-derived spheroids. RNA-sequencing revealed that the cytotoxicity of HIF-1α knockout NK cells could be related to increased perforin and TNF expression. The results demonstrated that HIF-1α knockout human NK cells, including populations, enhanced cytotoxicity in an environment mimicking the hypoxic conditions of GBM. CRISPR–Cas9-mediated HIF-1α knockout NK cells, including populations, could be a promising immunotherapeutic alternative in patients with GBM. Full article

Despite standard multimodality treatment, containing maximum safety resection, temozolomide, radiotherapy, and a tumor-treating field, patients with glioblastoma (GBM) present with a dismal prognosis. Natural killer cell (NKC)-based immunotherapy would play a critical role in GBM treatment. We have previously reported highly activated and ex vivo expanded NK cells derived from human peripheral blood, which exhibited anti-tumor effect against GBM cells. Here, we performed preclinical evaluation of the NK cells using an in vivo orthotopic xenograft model, the U87MG cell-derived brain tumor in NOD/Shi-scid, IL-2RɤKO (NOG) mouse. In the orthotopic xenograft model, the retro-orbital venous injection of NK cells prolonged overall survival of the NOG mouse, indirectly indicating the growth-inhibition effect of NK cells. In addition, we comprehensively summarized the differentially expressed genes, especially focusing on the expression of the NKC-activating receptors’ ligands, inhibitory receptors’ ligands, chemokines, and chemokine receptors, between murine brain tumor treated with NKCs and with no agents, by using microarray. Furthermore, we also performed differentially expressed gene analysis between an internal and external brain tumor in the orthotopic xenograft model. Our findings could provide pivotal information for the NK-cell-based immunotherapy for patients with GBM. Full article

Glioblastoma (GBM) is the leading malignant intracranial tumor, where prognosis for which has remained extremely poor for two decades. Immunotherapy has recently drawn attention as a cancer treatment, including for GBM. Natural killer (NK) cells are immune cells that attack cancer cells directly and produce antitumor immunity-related cytokines. The adoptive transfer of expanded and activated NK cells is expected to be a promising GBM immunotherapy. We previously established an efficient expansion method that produced highly purified, activated primary human NK cells, which we designated genuine induced NK cells (GiNKs). The GiNKs demonstrated antitumor effects in vitro and in vivo, which were less affected by blockade of the inhibitory checkpoint receptor programmed death 1 (PD-1). In the present study, we assessed the antitumor effects of GiNKs, both alone and combined with an antibody targeting killer Ig-like receptor 2DLs (KIR2DL1 and DL2/3, both inhibitory checkpoint receptors of NK cells) in vitro and in vivo with U87MG GBM-like cells and the T98G GBM cell line. Impedance-based real-time cell growth assays and apoptosis detection assays revealed that the GiNKs exhibited growth inhibitory effects on U87MG and T98G cells by inducing apoptosis. KIR2DL1 blockade attenuated the growth inhibition of the cell lines in vitro. The intracranial administration of GiNKs prolonged the overall survival of the U87MG-derived orthotopic xenograft brain tumor model. The KIR2DL1 blockade did not enhance the antitumor effects; rather, it attenuated it in the same manner as in the in vitro experiment. GiNK immunotherapy directly administered to the brain could be a promising immunotherapeutic alternative for patients with GBM. Furthermore, KIR2DL1 blockade appeared to require caution when used concomitantly with GiNKs. Full article

Shoulder disorders occasionally cause intractable pain. Central sensitization (CS) may be involved in such pain. Identifying risk factors associated with CS is crucial for effective pain control. This study aimed to determine the effects of shoulder osteoarthritis and rotator cuff tears (RCT) on CS and associated factors. This study included patients evaluated for CS using the Central Sensitization Inventory (CSI) before surgery for shoulder osteoarthritis, RCT, or cuff tear arthropathy. Patients with a CSI score of 40 or higher were defined as having CS. The relationships between glenohumeral osteoarthritis (GHOA), RCT size, and CS were statistically analyzed. Multiple regression analysis was performed to examine the factors affecting CSI scores. Subjects included 167 patients: 131 patients had RCT without GHOA, 23 had GHOA with RCT, and 13 had GHOA without RCT. The GHOA group had a significantly higher CSI score (27.5 [10.8–40.5] vs. 18.0 [10.0–27.5]) and CS prevalence (27.8% vs. 8.4%) than the RCT without GHOA group. There was no significant correlation between RCT size and CSI scores. Multiple regression analysis showed that female sex, severe pain, and long pain duration were associated with higher CSI scores. Considering the risk factors for CS might be helpful in shoulder treatment. Full article

The number of elderly patients with cervical trauma is increasing. Such patients are considered to be at high risk for delirium, which is an acute neuropsychological disorder that reduces the patient’s capacity to interact with their environment due to impairments in cognition. This study aimed to establish a risk score that predicts delirium in elderly patients with cervical SCI and/or cervical fracture regardless of treatment type. This retrospective cohort study included 1512 patients aged ≥65 years with cervical SCI and/or cervical fracture. The risk factors for delirium according to treatment type (surgical or conservative) were calculated using multivariate logistic regression. A delirium risk score was established as the simple arithmetic sum of points assigned to variables that were significant in the multivariate analyses. Based on the statistical results, the delirium risk score was defined using six factors: old age (≥80 years), hypoalbuminemia, cervical fracture, major organ injury, dependence on pre-injury mobility, and comorbid diabetes. The score’s area under the curve for the prediction of delirium was 0.66 (p < 0.001). Although the current scoring system must be validated with an independent dataset, the system remains beneficial because it can be used after screening examinations upon hospitalization and before deciding the treatment strategy. Full article

Pi-SAR2 is an airborne polarimetric synthetic aperture radar operated by the National Institute of Information and Communications Technology. The polarimetric observation data of Pi-SAR2 are very valuable because of its high resolution, but it cannot be used effectively because the data are not well calibrated with respect to elevation. Therefore, we have calibrated the data according to the observation conditions. The Pi-SAR2 observation data are very large due to its high resolution and require sufficient computational resources to be calibrated. We utilized the AI Bridging Cloud Infrastructure (ABCI), constructed and operated by the National Institute of Advanced Industrial Science and Technology, to calculate them. This paper reports on the calibration, scattering power decomposition, and orthorectification of the Pi-SAR2 observation data using the ABCI. Full article

A new scattering power decomposition method is developed for accurate tropical forest monitoring that utilizes data in dual-polarization mode instead of quad-polarization (POLSAR) data. This improves the forest classification accuracy and helps to realize rapid deforestation detection because dual-polarization data are more frequently acquired than POLSAR data. The proposed method involves constructing scattering power models for dual-polarization data considering the radar scattering scenario of tropical forests (i.e., ground scattering, volume scattering, and helix scattering). Then, a covariance matrix is created for dual-polarization data and is decomposed to obtain three scattering powers. We evaluated the proposed method by using simulated dual-polarization data for the Amazon, Southeast Asia, and Africa. The proposed method showed an excellent forest classification performance with both user’s accuracy and producer’s accuracy at >98% for window sizes greater than 7 × 14 pixels, regardless of the transmission polarization. It also showed a comparable deforestation detection performance to that obtained by POLSAR data analysis. Moreover, the proposed method showed better classification performance than vegetation indices and was found to be robust regardless of the transmission polarization. When applied to actual dual-polarization data from the Amazon, it provided accurate forest map and deforestation detection. The proposed method will serve tropical forest monitoring very effectively not only for future dual-polarization data but also for accumulated data that have not been fully utilized. Full article

Irradiated murine induced-pluripotent stem cells (iPSCs) elicit the antitumor response in vivo. However, it is unclear whether human iPSCs would elicit antitumor effects. In the present study, we investigated the capability of human iPSC lysate (iPSL)-pulsed dendritic cells (DCs) (iPSL/DCs) to induce cancer-responsive cytotoxic T lymphocytes (CTLs) in vitro. iPSCs and DCs were induced from peripheral blood mononuclear cells isolated from a human leukocyte antigen (HLA)-A33 homozygous donor. The iPSL was pulsed with immature DCs, which were then stimulated to allow full maturation. The activated DCs were co-cultured with autologous CTLs and their responses to SW48 colorectal carcinoma cells (HLA-A32/A33), T47D breast cancer cells (HLA-A33/A33), and T98G glioblastoma cells (HLA-A02/A02) were tested with enzyme-linked immunospot (ELISPOT) assays. Comprehensive gene expression analysis revealed that the established iPSCs shared numerous tumor-associated antigens with the SW48 and T47D cells. Immunofluorescent analysis demonstrated that the fluorescent-labeled iPSL was captured by the immature DCs within 2 h. iPSL/DCs induced sufficient CTL numbers in 3 weeks for ELISPOT assays, which revealed that the induced CTLs responded to SW48 and T47D cells. Human iPSL/DCs induced cancer-responsive CTLs on HLA-A33-matched cancer cells in vitro and could be a promising universal cancer vaccine for treating and preventing cancer. Full article

A functional cure of hepatitis B virus (HBV) infection or HB antigen loss is rarely achieved by nucleos(t)ide analogs which target viral polymerase. HBx protein is a regulatory protein associated with HBV replication. We thought to identify antiviral compounds targeting HBx protein by analyzing HBx binding activity. Recombinant GST-tagged HBx protein was applied on an FDA-approved drug library chip including 1018 compounds to determine binding affinity by surface plasmon resonance imaging (SPRi) using a PlexArray HT system. GST protein alone was used for control experiments. Candidate compounds were tested for anti-HBV activity as well as cell viability using HepG2.2.15.7 cells and HBV-infected human hepatocytes. Of the 1018 compounds screened, 24 compounds showed binding to HBx protein. Of the top 6 compounds with high affinity to HBx protein, tranilast was found to inhibit HBV replication without affecting cell viability using HepG2.2.15.7 cells. Tranilast also inhibited HBV infection using cultured human hepatocytes. Tranilast reduced HB antigen level dose-dependently. Overall, theSPRi screening assay identified novel drug candidates targeting HBx protein. Tranilast and its related compounds warrant further investigation for the treatment of HBV infection. Full article

This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan. Full article

Why is there disparity in the miss rates of pedestrian detection between different age attributes? In this study, we propose to (i) improve the accuracy of pedestrian detection using our pre-trained model; and (ii) explore the causes of this disparity. In order to improve detection accuracy, we extend a pedestrian detection pre-training dataset, the Weakly Supervised Pedestrian Dataset (WSPD), by means of self-training, to construct our Self-Trained Person Dataset (STPD). Moreover, we hypothesize that the cause of the miss rate is due to three biases: (1) the apparent bias towards “adults” versus “children”; (2) the quantity of training data bias against “children”; and (3) the scale bias of the bounding box. In addition, we constructed an evaluation dataset by manually annotating “adult” and “child” bounding boxes to the INRIA Person Dataset. As a result, we confirm that the miss rate was reduced by up to 0.4% for adults and up to 3.9% for children. In addition, we discuss the impact of the size and appearance of the bounding boxes on the disparity in miss rates and provide an outlook for future research. Full article

This study aimed to investigate the acute effect of capacitive and resistive electric transfer (CRet) intervention on eccentrically damaged muscle. A total of 28 healthy and sedentary male volunteers were randomly allocated to either CRet intervention or control groups. The participants performed a bout of eccentric exercise of the knee extensors with the dominant leg and received 30 min of CRet intervention of the quadriceps 48 h after the exercise. The dependent variables for the analysis were knee flexion range of motion (ROM), muscle soreness and maximum voluntary isometric (MVC-ISO), and concentric contraction (MVC-CON) torque of the knee extensors. These were measured prior to exercise (baseline) and before and after CRet intervention (48 h after the exercise). The results showed that knee flexion ROM, muscle strength (MVC-ISO and MVC-CON), and muscle soreness significantly improved after CRet intervention. CRet intervention may improve muscle soreness and loss of muscle function in an eccentrically damaged muscle. Full article

KAGRA is a gravitational-wave (GW) detector constructed in Japan with two unique key features: It was constructed underground, and the test-mass mirrors are cooled to cryogenic temperatures. These features are not included in other kilometer-scale detectors but will be adopted in future detectors such as the Einstein Telescope. KAGRA performed its first joint observation run with GEO600 in 2020. In this observation, the sensitivity of KAGRA to GWs was inferior to that of other kilometer-scale detectors such as LIGO and Virgo. However, further upgrades to the detector are ongoing to reach the sensitivity for detecting GWs in the next observation run, which is scheduled for 2022. In this article, the current situation, sensitivity, and future perspectives are reviewed. Full article