Background: Reactive oxygen species (ROS) and inflammation are reported to have a fundamental role in the pathogenesis of ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury. The present study investigated the role of pyruvate dehydrogenase kinase 4 (PDK4) in ROS production and inflammation following IR injury. Methods: We used a streptozotocin-induced diabetic C57BL6/J mouse model, which was subjected to IR by clamping both renal pedicles. Cellular apoptosis and inflammatory markers were evaluated in NRK-52E cells and mouse primary tubular cells after hypoxia and reoxygenation using a hypoxia work station. Results: Following IR injury in diabetic mice, the expression of PDK4, rather than the other PDK isoforms, was induced with a marked increase in pyruvate dehydrogenase E1α (PDHE1α) phosphorylation. This was accompanied by a pronounced ROS activation, as well as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) production. Notably, sodium dichloroacetate (DCA) attenuated renal IR injury-induced apoptosis which can be attributed to reducing PDK4 expression and PDHE1α phosphorylation levels. DCA or shPdk4 treatment reduced oxidative stress and decreased TNF-α, IL-6, IL-1β, and MCP-1 production after IR or hypoxia-reoxygenation injury. Conclusion PDK4 inhibition alleviated renal injury with decreased ROS production and inflammation, supporting a critical role for PDK4 in IR mediated damage. This result indicates another potential target for reno-protection during IR injury; accordingly, the role of PDK4 inhibition needs to be comprehensively elucidated in terms of mitochondrial function during renal IR injury.

Our study analyzed 95 solid organ transplant (SOT) and 78 hematopoietic stem cell transplant (HSCT) recipients with prior coronavirus disease 2019 (COVID-19). Patients who underwent transplantation within 30 days of COVID-19 infection comprised the early group, and those who underwent transplantation post-30 days of COVID-19 infection comprised the delayed group. In the early transplantation group, no patient, whether undergoing SOT and HSCT, experienced COVID-19-associated complications. In the delayed transplantation group, one patient each from SOT and HSCT experienced COVID-19-associated complications. Additionally, among early SOT and HSCT recipients, two and six patients underwent transplantation within seven days of COVID-19 diagnosis, respectively. However, no significant differences were observed in the clinical outcomes of these patients compared to those in other patients. Early transplantation following severe acute respiratory syndrome coronavirus 2 infection can be performed without increased risk of COVID-19-associated complications. Therefore, transplantation needs not be delayed by COVID-19 infection.

Background: /Aim: Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOBMRI) further enhances the identification of additional hepatic nodules compared with computed tomography (CT) alone; however, the optimal treatment for such additional nodules remains unclear. We investigated the long-term oncological effect of aggressive treatment strategies for additional lesions identified using EOB-MRI in patients with hepatocellular carcinoma (HCC). Methods: Data from 522 patients diagnosed with solitary HCC using CT between January 2008 and December 2012 were retrospectively reviewed. Propensity score-matched (PSM) analysis was used to compare the oncologic outcomes between patients with solitary HCC and those with additional nodules on EOB-MRI after aggressive treatment (resection or radiofrequency ablation [RFA]). Results: Among the 383 patients included, 59 had additional nodules identified using EOB-MRI. Compared with patients with solitary HCC, those with additional nodules on EOB-MRI had elevated total bilirubin, aspartate transaminase, and alanine transaminase; had a lower platelet count, higher MELD score, and highly associated with liver cirrhosis (P<0.05). Regarding long-term outcomes, 59 patients with solitary HCC and those with additional nodules after PSM were compared. Disease-free survival (DFS) and overall survival (OS) were comparable between the two groups (DFS, 60.4 vs. 44.3 months, P=0.071; OS, 82.8 vs. 84.8 months, P=0.986). Conclusion The aggressive treatment approach, either resection or RFA, for patients with additional nodules identified on EOBMRI was associated with long-term survival comparable with that for solitary HCC. However, further studies are required to confirm these findings.

γδ T cells are a rare and unique prototype of T cells that share properties with natural killer cells in secondary lymphoid organs. Although many studies have revealed the function and importance of adult-derived γδ T cells in cancer biology and regenerative medicine, the low numbers of these cells hamper their application as therapeutic cell sources in the clinic. To solve this problem, pluripotent stem cell-derived γδ T cells are considered alternative cell sources; however, few studies have reported the generation of human pluripotent stem cell-derived γδ T cells. In the present study, we investigated whether lymphoid lineage γδ T cells were successfully generated from human pluripotent stem cells via hemogenic endothelium under defined culture conditions. Our results revealed that pluripotent stem cells successfully generated γδ T cells with an overall increase in transcriptional activity of lymphoid lineage genes and cytolytic factors, indicating the importance of the optimization of culture conditions in generating lymphoid lineage γδ T cells. We uncovered an initial step in differentiating γδ T cells that could be applied to basic and translational investigations in the field of cancer biology. Based on our result, we will develop an appropriate method to purify γδ T cells with functionality and it helpful for the study of basic mechanism of γδ T cells in pathophysiologic condition as well as clinic application.

Dental primary afferent (DPA) neurons and proprioceptive mesencephalic trigeminal nucleus (MTN) neurons, located in the trigeminal ganglion and the brainstem, respectively, are essential for controlling masticatory functions. Despite extensive transcriptomic studies on various somatosensory neurons, there is still a lack of knowledge about the molecular identities of these populations due to technical challenges in their circuit-validated isolation. Here, we employed high-depth single-cell RNA sequencing (scRNA-seq) in combination with retrograde tracing in mice to identify intrinsic transcriptional features of DPA and MTN neurons. Our transcriptome analysis revealed five major types of DPA neurons with cell type-specific gene enrichment, some of which exhibit unique mechano-nociceptive properties capable of transmitting nociception in response to innocuous mechanical stimuli in the teeth. Furthermore, we discovered cellular heterogeneity within MTN neurons that potentially contribute to their responsiveness to mechanical stretch in the masseter muscle spindles. Additionally, DPA and MTN neurons represented sensory compartments with distinct molecular profiles characterized by various ion channels, receptors, neuropeptides, and mechanoreceptors. Together, our study provides new biological insights regarding the highly specialized mechanosensory functions of DPA and MTN neurons in pain and proprioception.
Animals ; Mice ; Neurons ; Proprioception ; Gene Expression Profiling ; Pain ; Sequence Analysis, RNA

Background and Objectives: Human CD34＋hematopoietic stem cells can reconstitute the human hematopoietic system when transplanted into immunocompromised mice after irradiation. Human leukapheresis peripheral blood (LPB)-and cord blood (CB)-derived CD34＋ cells have a similar capacity to reconstitute myeloid lineage cells in a humanized mice (hu-mice) model. However, potent stem cells, such as CB-CD34＋ cells, efficiently reconstitute the lymphoid system in vivo compared to LPB-CD34 ＋ cells. Modeling the human hematolymphoid system is vital for studying immune cell crosstalk in human xenografted mice, with CB-CD34＋ cells used as an optimized cell source because they are essential in reconstituting lymphoid lineage cells. Methods: and Results: In this study, we established hu-mice that combined human characteristics with long-term survival and investigated the efficiency of the engraftment of lymphoid lineage cells derived from LPB- and CB-CD34＋cells in the bone marrow, spleen, and LPB. We found an overall increase in the transcriptional activity of lymphoid lineage genes in CB-CD34＋ cells. Our results revealed that potent CB-CD34＋ cells displaying a general upregulation of the expression of genes involved in lymphopoiesis could contribute to the hematolymphoid system in the humanized mice model with longevity. Conclusions Our data suggest that humanized mouse model by usage of CB-CD34 ＋ cells displaying high expression of TFs for lymphoid lineage cells can contribute to study the immune response against lymphocytes.

Purpose: This study analyzed the current status of face mask usage. It also identified factors related to the knowledge and behavior regarding the same among older adults living alone during the COVID-19 pandemic. Methods: This descriptive study was conducted via a telephone survey involving 283 older adults living alone in S City from March to April 2020. Knowledge and behavior pertaining to face mask usage were measured using Hilda Ho’s Face Mask Use Scale; reliability of the measurement was Kuder-Richardson formula-20 = .62, Cronbach’s α = .92. Data were analyzed using descriptive analysis, independent t-test, Pearson’s correlation coefficient, and multiple linear regression. Results: Older adults used one mask for 3.55 days on an average. The knowledge level was 9.97 (± 1.84) out of 12 and behavior level was 15.49 (± 1.55) out of 16. Level of education (β = - .31, p < .001), living region (β = .13, p = .017), personal income (β = .12, p = .041) significantly affected the face mask usage-related knowledge, and living region (β = .15, p = .010) significantly affected the face mask usage-related behavior. Conclusion Older adults living alone are aware of the effects of using face masks. However, their mask usage is inappropriate, for example, the prolonged use of the same mask. Considering the low level of face mask usage-related knowledge, it is necessary to develop customized education programs and infectious disease prevention strategies for older adults possessing low educational levels living alone in urban-rural complex areas.

The chemical investigation of the 90% EtOH extract from Cicadidae Periostracum led to the isolation and identification of seven known N-acetyldopamine dimers (1-7). These compounds were identified by comparing mass spectrometry data and NMR spectroscopic data with those previously reported. In this study, complete interpretation of 1D and 2D NMR data of 1 and 2 were reported for the first time. In addition, compounds 3 and 4 were isolated from this material for the first time. All isolates were obtained as racemic mixtures, as confirmed by chiral HPLC. Furthermore, we evaluated the neuroprotective activities of compounds 1–7 and found that compounds 1, 5, and 6 significantly attenuated rotenone-induced death of SH-SY5Yneuroblastoma cells at a concentration of 100 μM. Parallel to this result, compounds 3 and 6 displayed antioxidant effects in the cytoplasm, as determined by CM-H2DCFDA fluorescence intensity, while compounds 1 and 5 showed antioxidant effects in the mitochondria, as assessed by MitoSox fluorescence intensity. Overall, these results suggest that some of these compounds protect neuroblastoma cells by ameliorating the release of reactive oxygen species. Further studies are warranted to elucidate the underlying mechanisms by which these compounds exhibit antioxidant and neuroprotective actions.

Objective: The aim of this study was to evaluate the correlation between the vertical position of maxillary first molar and vertical skeletal measurements in lateral cephalograms by using new linear measurements on the vertical axis of coordinates with calibration. Methods: The vertical position of maxillary first molar (U6-SN), and the conventionally used variables (ConV) and the newly derived linear variables (NwLin) for vertical skeletal patterns were measured in the lateral cephalograms of 103 Korean adults with normal occlusions. Pearson correlation analyses and multiple linear regression analyses were performed with and without calibration using the anterior and posterior cranial base (ACB and PCB, respectively) lengths to identify variables related to U6-SN. Results: The PCB-calibrated statistics showed the best power of explanation. ConV indicating skeletal hyperdivergency was significantly correlated with U6-SN.Six NwLin regarding the position of palatal plane were positively correlated with U6-SN. Each multiple linear regression analysis generated a two-variable model: sella and nasion to palatal plane. Among the three models, the PCBcalibrated model yielded highest adjusted R2 value, 0.880. Conclusions U6-SN could be determined by the vertical position of the maxilla, which could then be used to plan the amount of molar intrusion and estimate its clinical stability. Cephalometric calibration on the vertical axis of coordinates by using PCB for vertical linear measurements could strengthen the analysis itself.

The chemical investigation of the 90% EtOH extract from Cicadidae Periostracum led to the isolation and identification of seven known N-acetyldopamine dimers (1-7). These compounds were identified by comparing mass spectrometry data and NMR spectroscopic data with those previously reported. In this study, complete interpretation of 1D and 2D NMR data of 1 and 2 were reported for the first time. In addition, compounds 3 and 4 were isolated from this material for the first time. All isolates were obtained as racemic mixtures, as confirmed by chiral HPLC. Furthermore, we evaluated the neuroprotective activities of compounds 1–7 and found that compounds 1, 5, and 6 significantly attenuated rotenone-induced death of SH-SY5Yneuroblastoma cells at a concentration of 100 μM. Parallel to this result, compounds 3 and 6 displayed antioxidant effects in the cytoplasm, as determined by CM-H2DCFDA fluorescence intensity, while compounds 1 and 5 showed antioxidant effects in the mitochondria, as assessed by MitoSox fluorescence intensity. Overall, these results suggest that some of these compounds protect neuroblastoma cells by ameliorating the release of reactive oxygen species. Further studies are warranted to elucidate the underlying mechanisms by which these compounds exhibit antioxidant and neuroprotective actions.