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The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) plays an essential role in glycolysis and in the antioxidant pathway associated with glutathione. Therefore, we investigated the effects of PFKFB3 on oxidative and ischemic damage. We synthesized a fusion protein of transactivator of transcription (Tat)-PFKFB3 to facilitate its passage into the intracellular space and examine its effects against oxidative stress induced by hydrogen peroxide (H 2 O 2 ) treatment and ischemic damage caused by occlusion of the common carotid arteries for 5 min in gerbils. The Tat-PFKFB3 protein was efficiently delivered into HT22 cells in a concentration- and time-dependent manner, with higher levels observed 18 h after treatment. Furthermore, treatment with 6 µM Tat-PFKFB3 demonstrated intracellular delivery into HT22 cells, as analyzed through immunocytochemical staining. Moreover, it significantly ameliorated the reduction of cell viability induced by 200 µM H 2 O 2 treatment. Tat-PFKFB3 treatment also alleviated H 2 O 2 -induced DNA fragmentation and reactive oxygen species formation in HT22 cells. In gerbils, the intraperitoneal administration of 2 mg/kg Tat-PFKFB3 efficiently delivered the substance to all hippocampal areas, including the hippocampal CA1 region. This administration significantly mitigated ischemia-induced hyperlocomotion, long-term memory deficits, and ischemic neuronal death in the hippocampal CA1 region after ischemia. Additionally, treatment with 2 mg/kg Tat-PFKFB3 significantly ameliorated the translocation of Cdk5 from the cytosol to the nucleus in the hippocampal CA1 region 24 h after ischemia, but not in other regions. The treatment also significantly reduced reactive oxygen species formation in the CA1 region. These findings suggest that Tat-PFKFB3 reduces neuronal damage in the hippocampal CA1 region after ischemia through the reduction of Cdk5 signaling and reactive oxygen species formation. Therefore, Tat-PFKFB3 may have potential applications in reducing ischemic damage., (© 2024. The Author(s).)

Background: Individuals with borderline personality traits are known to have disturbed representations of self and others. Specifically, an unstable self-identity and difficulties distinguishing between self and others can impair their mentalizing abilities in interpersonal situations. However, it is unclear whether these traits are linked to differences in neural representation of self and others., Methods: In this study involving 156 young adults, changes in neural function during self-other processing were measured using a Functional Near-Infrared Spectroscopy (fNIRS) task and a self-report survey. During the fNIRS task, participants were asked about their own traits, others' traits, how they believed others perceived them, and the basic meaning of words. The study aimed to determine whether the degree of neural differentiation between the task conditions was related to borderline personality traits., Result: The study found that traits indicative of identity instability could be predicted by similarities in task-dependent connectivity. Specifically, the neural patterns when individuals estimated how others perceived them were more similar to the patterns when they judged their own traits., Conclusions: These findings suggest that borderline personality traits related to identity issues may reflect difficulties in distinguishing between neural patterns when processing self and other information., Competing Interests: Declaration of competing interest The authors report no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The glenoid track concept has enabled the categorization of Hill-Sachs lesions (HSLs) into on-track lesions and off-track lesions. Furthermore, among the on-track lesions, further categorization has been established based on the distance from the medial edge of the Hill-Sachs lesion to the medial edge of the glenoid track, into peripheral-track lesions and central-track lesions. Recent studies on peripheral-track lesions and central-track lesions within the glenoid track have shown inconsistencies in failure rates, which deserves further investigation., Methods: A retrospective cohort comparison of patients who underwent arthroscopic Bankart repair between 2015 and 2020 was performed. 102 patients with peripheral-track HSLs were included. The patients were divided into 2 groups based on the results of the postoperative apprehension test: the apprehension positive group (n = 30), and the apprehension negative group (n = 72). Using preoperative computed tomography (CT) and an image reconstruction program, 3-dimensional (3D) images were segmented to calculate the length, width, depth, and distance of the HSLs. A multivariate logistic regression was used to determine the risk factors of recurrence, for which odds ratio (OR) and 95% confidence interval (CI) were provided., Results: A multivariate logistic regression analysis revealed that the length of the peripheral-track HSLs was a significant independent predictor of failure in this study. (OR 1.380; 95% CI 1.170-1.627; P < .001). The receiver operating characteristics curve (ROC) demonstrated a predictive power (area under the curve = 0.841) and a threshold value of 14.2 mm., Conclusion: Length was the only risk factor for the recurrent instability of peripheral-track HSLs after ABR. In the context of surgical decision-making, utilizing the glenoid track concept, medical practitioners may need to evaluate instability by considering the length as a continuous factor, while differentiating between peripheral-track and central-track classifications., (Copyright © 2024 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Aralia elata (Miq.) Seem. (AES; family Araliaceae) is a medicinal plant and has been reported to have various bioactivities, including anticancer and hepatotoxicity protective activities. However, no studies have investigated the biological activities of AES or its extracts on skin. To address this, we aimed to explore the effect of AES-flower-derived absolute-type essential oil (AESFEO) on skin-related biological activities, especially skin wound healing and whitening-related responses in skin cells (human-derived keratinocytes [HaCaT cells] and melanocytes [B16BL6 cells]) and to identify the components of AESFEO. Cell biological activities were analyzed using WST and BrdU incorporation assays, ELISA, or by immunoblotting. In HaCaT cells, AESFEO promoted proliferation, type IV collagen production, and enhanced the phosphorylations of Erk1/2, p38 MAPK, JNK, and Akt. In B16BL6 cells, AESFEO reduced serum-induced proliferation, α-MSH-stimulated increases in melanin synthesis and tyrosinase activity, and α-MSH-induced increases in MITF, tyrosinase, TRP-1, and TRP-2 expressions. In addition, AESFEO inhibited the phosphorylation of Erk1/2, p38 MAPK, and JNK in α-MSH-stimulated B16BL6 cells. Eighteen compounds were identified in AESFEO by GC/MS. These results suggest that AESFEO has beneficial effects on keratinocyte activities related to skin wound healing and melanocyte activities related to inhibition of skin pigmentation. AESFEO may serve as a useful natural substance for developing agents that facilitate skin wound healing and inhibit melanogenesis.

Background: Total ankle arthroplasty (TAA) enhances patients' subjective outcomes with respect to pain and function. The aim of this study was to analyze the biomechanical changes of the affected limb following TAA using gait analysis with a 3-dimensional multi-segment foot model (3D MFM)., Methods: We reviewed medical records, simple radiographs, and gait analyses using a 3D MFM of patients who underwent TAA for severe varus ankle arthritis. Preoperative and postoperative gait data of 24 patients were compared. Postoperative gait analyses were done at least 1 year after surgery., Results: TAA significantly increased stride length ( p = 0.024). The total range of motion of all planes in the hindfoot and forefoot showed no significant changes between preoperative and postoperative states. Hindfoot was significantly plantarflexed and pronated after TAA, while forefoot was significantly supinated in all phases. After appropriate calculations, the genuine coronal motion of the hindfoot showed no changes after TAA in all phases., Conclusions: TAA did not result in biomechanical improvements of segmental motions in the forefoot and hindfoot, except for changes to the bony structures. Therefore, it is important to point out to patients that TAA will not result in significant improvement of ankle function and range of motion. Clinicians can consider this information during preoperative counseling., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

The anterior inferior tibiofibular ligament (AITFL) avulsion fracture accompanying an ankle fracture can compromise ankle stability, necessitating accurate evaluation and a clear understanding of its pathophysiology.. The aim of this study was to investigate the association between AITFL avulsion fracture and Lauge-Hansen, Wagstaffe classification. A retro-prospective study was conducted at a university-affiliated tertiary care medical center. We selected 128 patients who underwent surgery at our institution between January 2013 and July 2017 and analyzed the association between AITFL avulsion fracture and the foot position. According to the modified Wagstaffe classification system, there were 39 cases of type II, followed by 9 cases of type III and 8 cases of type IV. Of the7 pronation-abduction fractures, 3 were AITFL avulsion fracture (43%), while of the 21 pronation-external rotation fractures, 9 were AITFL avulsion fracture (43%). Of the 95 supination-external rotation fractures, there were 56 cases (59%) of AITFL avulsion fractures. Of the pronation fractures, 0% were fibular avulsion fractures and 43% were tibial avulsion fractures. Of the supination fractures, 44% were fibular avulsion fractures and 16% were tibial avulsion fracture. The difference in the ratio of fibular to tibial avulsion fractures between pronation and supination fractures was significant (p < .001). These results suggest that tibial avulsion fractures of type IV in the modified Wagstaffe classification and pronation fractures occur due to collision with the anterolateral corners of the distal bone when the talus externally rotates. Moreover, in cases of pronation fractures, a new type of AITFL avulsion fracture has been observed., (Copyright © 2023. Published by Elsevier Inc.)

Phytoestrogens, such as isoflavones, are known for their capacity to simulate various physiological impacts of estrogen in the human body. Our research evaluated the effects of isoflavone-enriched soybean leaves (IESL) on collagen fiber loss prompted by ovariectomy in Sprague Dawley (SD) rats, thereby simulating menopausal changes in women. IESL, bolstered with an increased concentration of isoflavones through a metabolite farming process, contained a significantly higher amount of isoflavones than regular soybean leaves. Our results indicate that the administration of IESL can counteract the decrease in relative optical density and dermal thickness of collagen fibers caused by ovariectomy in SD rats, with more pronounced effects observed at higher isoflavone dosages. These outcomes suggest that soybean leaves rich in isoflavones may hold potential benefits in combating collagen degradation and skin aging symptoms related to menopause. Further research is needed to fully understand the exact molecular pathways at play and the potential clinical relevance of these findings., (© 2024. The Author(s).)

Aim: In this study, we investigated the effects of Dendropanax morbifera extract (DME) on neuroprotection against ischemic damage in gerbils., Methods: DME (100 or 300 mg/kg) was orally administered to gerbils for three weeks, and 2 h after the last DME treatment, transient forebrain ischemia in the common carotid arteries was induced for 5 min. The forebrain ischemia-related cognitive impairments were assessed by spontaneous motor activity and passive avoidance test one and four days after ischemia, respectively. In addition, surviving and degenerating neurons were morphologically confirmed by neuronal nuclei immunohistochemical staining and Fluoro-Jade C staining, respectively, four days after ischemia. Changes of glial morphology were visualized by immunohistochemical staining for each marker such as glial fibrillary acidic protein and ionized calcium-binding protein. Oxidative stress was determined by measurements of dihydroethidium, O 2 · (formation of formazan) and malondialdehyde two days after ischemia. In addition, glutathione redox system such as reduced glutathione, oxidized glutathione levels, glutathione peroxidase, and glutathione reductase activities were measured two days after ischemia., Results: Spontaneous motor activity monitoring and passive avoidance tests showed that treatment with 300 mg/kg DME, but not 100 mg/kg, significantly alleviated ischemia-induced memory impairments. In addition, approximately 67 % of mature neurons survived and 29.3 % neurons were degenerated in hippocampal CA1 region four days after ischemia, and ischemia-induced morphological changes in astrocytes and microglia were decreased in the CA1 region after 300 mg/kg DME treatment. Furthermore, treatment with 300 mg/kg DME significantly ameliorated ischemia-induced oxidative stress, such as superoxide formation and lipid peroxidation, two days after ischemia. In addition, ischemia-induced reduction of the glutathione redox system in the hippocampus, assessed two days after the ischemia, was ameliorated by treatment with 300 mg/kg DME. These suggest that DME can potentially reduce ischemia-induced neuronal damage through its antioxidant properties., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

We investigated the effects of heat shock protein 10 (HSP10) protein on memory function, hippocampal neurogenesis, and other related genes/proteins in adult and aged mice. To translocate the HSP10 protein into the hippocampus, the Tat-HSP10 fusion protein was synthesized, and Tat-HSP10, not HSP10, was successfully delivered into the hippocampus based on immunohistochemistry and western blotting. Tat-HSP10 (0.5 or 2.0 mg/kg) or HSP10 (control protein, 2.0 mg/kg) was administered daily to 3- and 21-month-old mice for 3 months, and observed the senescence maker P16 was significantly increased in aged mice and the treatment with Tat-HSP10 significantly decreased P16 expression in the hippocampus of aged mice. In novel object recognition and Morris water maze tests, aged mice demonstrated decreases in exploratory preferences, exploration time, distance moved, number of object contacts, and escape latency compared to adult mice. Treatment with Tat-HSP10 significantly improved exploratory preferences, the number of object contacts, and the time spent swimming in the target quadrant in aged mice but not adults. Administration of Tat-HSP10 increased the number of proliferating cells and differentiated neuroblasts in the dentate gyrus of adult and aged mice compared to controls, as determined by immunohistochemical staining for Ki67 and doublecortin, respectively. Additionally, Tat-HSP10 treatment significantly mitigated the reduction in sirtuin 1 mRNA level, N -methyl-D-aspartate receptor 1, and postsynaptic density 95 protein levels in the hippocampus of aged mice. In contrast, Tat-HSP10 treatment significantly increased sirtuin 3 protein levels in both adult and aged mouse hippocampus. These suggest that Tat-HSP10 can potentially reduce hippocampus-related aging phenotypes.

Introduction: Osteochondral lesions of the talus (OLT) usually have non-specific clinical symptoms, and radiographs have a low sensitivity for detecting OLT. The purpose of this study is to compare the diagnostic value of CT arthrography (CTa) with that of MRI using arthroscopy as the reference standard for grading OLT., Materials and Methods: We retrospectively reviewed patients who had OLT between 2015 and 2020. Patients with symptomatic OLT as a surgical indication, who were treated arthroscopically, and underwent both CTa and MRI before surgery were included. OLT was evaluated by both CTa and MRI using arthroscopy as the standard. We graded CTa, MRI, arthroscopic findings using Mintz classification., Results: Thirty-five patients were included. Accuracy rates of MRI and CTa for grading OLT, compared to those of arthroscopy, were 57.1% and 88.6%, respectively. Among 15 mismatched cases in MRI, 12 lesions (80%) were matched in CTa and arthroscopy. CTa had significantly higher diagnostic performance than MRI for the detection of grade III lesions (p = 0.041). Using the receiver operating characteristics curves, the area under the curve values for lesion grading were 0.893 for CTa and 0.762 for MRI., Conclusion: CTa was statistically significantly better in detecting chondral flapping or subchondral exposure lesions for OLT than MRI on using arthroscopy as the reference standard. Because the stability of the OLT is essential in determining the treatment method, if an OLT is observed on MRI and is suspected to cause ankle pain, we recommend additional CTa examination to determine the more correct treatment strategies for OLT., Level of Evidence: Diagnostic Level III., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

As individuals age, they may experience a decline in gait automaticity, which requires increased attentional resources for the control of gait. This age-related decline in gait automaticity has been shown to contribute to higher prefrontal cortex (PFC) activation and lower dual-task performance during dual-task walking in older adults. This study is to investigate the effect of treadmill walking on PFC activation and dual-task performance in older adults. A total of 20 older adults (mean age, 64.35 ± 2.74 years) and 20 younger adults (mean age, 30.00 ± 3.15 years) performed single- and dual-task walking in overground and treadmill conditions. A wearable functional near-infrared spectroscopy and gait analyzer were used to analyze PFC activation and dual-task performance, respectively. To determine the dual-task (gait and cognitive) performance, the dual-task cost (DTC) was calculated using the following formula: (single-task - dual-task)/single-task × 100. In both groups, dual-task treadmill walking led to reduced PFC activation and reduced DTC compared to dual-task overground walking. Furthermore, despite a higher DTC in gait variability, correct response, total response, response index and a higher error score in older adults than in younger adults during overground walking, there was no difference in treadmill walking. The difference in PFC activation between single- and dual-tasks was also observed only in overground walking. Performing dual-task walking on a treadmill compared to overground walking results in different levels of dual-task performance and PFC activity. Specifically, older adults are able to maintain similar levels of dual-task performance as younger adults while walking on a treadmill, with reduced PFC activation due to the automaticity induced by the treadmill. Therefore, older adults who exhibit low dual-task performance during overground walking may be able to improve their performance while walking on a treadmill with fewer attentional resources., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Baek 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.)

Background: Studies using functional near-infrared spectroscopy (fNIRS) have shown that dual-task walking leads to greater prefrontal cortex (PFC) activation compared to the single-task walking task. However, evidence on age-related changes in PFC activity patterns is inconsistent. Therefore, this study aimed to explore the changes in the activation patterns of PFC subregions in different activation phases (early and late phases) during both single-task and dual-task walking in both older and younger adults., Methods: Overall, 20 older and 15 younger adults performed a walking task with and without a cognitive task. The activity of the PFC subregions in different phases (early and late phases) and task performance (gait and cognitive task) were evaluated using fNIRS and a gait analyzer., Results: The gait (slower speed and lower cadence) and cognitive performance (lower total response, correct response and accuracy rate, and higher error rate) of older adults was poorer during the dual task than that of younger adults. Right dorsolateral PFC activity in the early period in older adults was higher than that in younger adults, which declined precipitously during the late period. Conversely, the activity level of the right orbitofrontal cortex in the dual-task for older adults was lower than for younger adults., Conclusions: These altered PFC subregion-specific activation patterns in older adults would indicate a decline in dual-task performance with aging., (© 2023. The Author(s).)

Background: Osteochondral lesions of the talus are uncommon in children and adolescents. Surgical procedures differ from those used for adults to avoid iatrogenic physeal injuries. This study aimed to evaluate the clinical and radiological outcomes of surgical treatment in pediatric patients with osteochondral lesions, specifically investigating the patient age and the status of distal tibial physis as factors associated with surgical success., Methods: We retrospectively reviewed 28 patients who had symptomatic osteochondral lesions of the talus that were treated surgically between 2003 and 2016. If the lesion was stable and articular cartilage was intact, retrograde drilling was performed under fluoroscopic guidance. Lesions with detached overlying cartilages were treated by debridement of the cartilage combined with microfracture and drilling. Radiographic outcomes, American Orthopaedic Foot & Ankle Society ankle-hindfoot score, and skeletal maturity were evaluated., Results: Radiological improvement was observed in 24 (24/28, 86%) patients and complete and incomplete healing in 8 and 16 patients, respectively. Changes in pain grades, American Orthopaedic Foot & Ankle Society scores, and radiological healing after surgery were significant (pain grade, p < 0.001; American Orthopaedic Foot & Ankle Society, p = 0.018; radiological healing, p < 0.001). In addition, patients in the younger age group (≤13 years) showed greater improvements in pain grades than older patients (p = 0.02). Improvement in pain grade after surgery was better in the skeletally immature group than in the skeletally mature group (p = 0.048)., Conclusion: Clinical and radiological improvements were observed after surgical treatment. The younger age group and open physis group showed more pain improvement., Level of Evidence: Therapeutic level IV., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: T.-J.C. is a member of the Editorial Board of the Journal of Children’s Orthopaedics., (© The Author(s) 2023.)

There are no clinical studies about treatment of distal tibia fractures using far cortical locking (FCL) screws, even though it has been shown to be superior to standard locking screws in biomechanical studies. We compared the efficacy of FCL screws to that of traditional locking screws. Twenty-five distal tibia fractures were treated with minimally invasive plate osteosynthesis using traditional locking screws, whereas 20 were treated using FCL screws. We retrospectively compared time taken for callus formation and radiographic bone union between 2 groups. The effect of age, sex, diabetes, and smoking history on bone healing was analyzed. Complications were also noted. As a result, there was no significant difference in age (p = .292), sex (p = 1.0), diabetes (p = 1.0), or smoking history (p = .704) between 2 groups. Time to callus formation was 77.5 days in the FCL group, and 96 days in the traditional group (p = .023). Average time to bone union was 134.8 days, and 163.1 days in the FCL group and the traditional group, respectively (p = .017). There was one case of screw loosening in the FCL group, and one case of screw breakage in the traditional group. This study suggests that FCL screws promote quicker healing of distal tibia fractures than traditional locking screws., (Copyright © 2022. Published by Elsevier Inc.)

Bis(2-ethylhexyl) phthalate (DEHP) is the most used member of the phthalate class of compounds. Extensive use of this plasticizer allows daily exposure to humans via various routes. A positive relationship between DEHP exposure and neurobehavioral disorders is suspected. But, there are insufficient data on the harmfulness of neurobehavioral disorders caused by DEHP exposure, particularly at daily exposure levels. In this study, we assessed the consequences of daily DEHP ingestion (2 and 20 mg/kg diets) in male mice for at least 100 days and examined its effects on neuronal functions associated with neurobehavioral disorders, such as depression and cognitive decline. We found the marked depressive behaviors and reduced learning and memory function in the DEHP-ingestion groups, and that biomarkers related to chronic stress were increased in plasma and brain tissues. Long-term DEHP ingestion induced collapse of glutamate (Glu) and glutamine (Gln) homeostasis as a result of disruption of the Glu-Gln cycle in the medial prefrontal cortex and hippocampus. The reduced glutamatergic neurotransmission activity caused by DEHP ingestion was demonstrated using an electrophysiological method. This study revealed that long-term exposure to DEHP is hazardous and can cause neurobehavioral disorders, even at daily exposure levels., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Capsular contracture is a well-known etiology in the primary stiff shoulder; thus capsular contracture and resultant decreased joint volume could lead to postoperative stiffness, which is a commonly reported morbidity after arthroscopic rotator cuff repair (ARCR). The purpose of this study was (1) to quantify the joint volume (total joint volume and each quadrant compartmental volume) using computed tomography arthrography (CTA) and (2) to demonstrate the relationship between joint volume and postoperative range of motion (ROM) after ARCR., Materials and Methods: Eighty-three patients (60 ± 5.11 years, men = 26, women = 57) who had undergone ARCR between January 2015 to December 2020 due to small to medium full-thickness tear and followed by CTA 6 months postoperatively were retrospectively reviewed. An image reconstruction program (3D Slicer, version 4.11.2 software) was used to calculate the joint volume (total joint volume and quadrant compartment joint volumes; anteroinferior, anterosuperior, posterosuperior and posteroinferior). For shoulder ROM, data including scaption (Sc), external rotation on side (ERs), external rotation at 90° (ER90), and internal rotation on back (IRb) were collected 6 months postoperatively. An evaluation of the correlation between joint volume and each shoulder motion was performed., Results: There were moderate correlations between the total joint volume and each motion (Sc: Pearson coefficient, 0.32, p = 0.0047; ERs: Pearson coefficient, 0.24, p = 0.0296; ER90: Pearson coefficient, 0.33, p = 0.0023; IRb: Pearson coefficient, 0.23, p = 0.0336). Among the quadrant compartments, the anteroinferior (Sc: Pearson coefficient, 0.26, p = 0.0199; ERs: Pearson coefficient, 0.23, p = 0.0336; ER90: Pearson coefficient, 0.25, p = 0.0246; IRb: Pearson coefficient, 0.26, p = 0.0168) and posterosuperior (Sc: Pearson coefficient, 0.24, p = 0.029; ER90: Pearson coefficient, 0.29, p = 0.008; IRb: Pearson coefficient, 0.22, p = 0.0491) and posteroinferior (Sc: Pearson coefficient, 0.30, p = 0.0064; ER90: Pearson coefficient, 0.29, p = 0.0072) showed moderate correlations with each shoulder motion., Conclusion: Total joint volume, anteroinferior compartment joint volume, posterosuperior compartment joint volume and posteroinferior compartment joint volume were related to postoperative ROM after ARCR. Perioperative methods to increase the joint volume, especially the anteroinferior, posterosuperior and posteroinferior parts of the capsule may prevent postoperative stiffness after ARCR., Level of Evidence: Level III; Retrospective Case-Control Study., (© 2023. The Author(s).)

This study determined that the adsorption of azo dyes, Methyl Orange (MO) and Sunset Yellow FCF (SYF), using the pristine pine sawdust biochar (PSB) and post-modified PSB with Mg/Al layered double hydroxides (PSB-LDH MgAl ) was examined to offer valuable information into the differences in their adsorption mechanisms. Although a lower specific surface area of PSB-LDH MgAl (147.2 m 2  g -1 ) than PSB (495.7 m 2  g -1 ), LDH MgAl were successfully functionalized on the PSB surface through co-precipitation, which was highly related to the improvements of adsorption capacity of PSB-LDH MgAl toward MO and SYF. The MO and SYF adsorption kinetics by PSB and PSB-LDH MgAl were confirmed to the pseudo-second-order and considered chemisorption. The adsorption capacity of MO and SYF adsorbed onto PSB-LDH MgAl (MO = 21.8 mg g -1 , SYF = 23.6 mg g -1 ) were significantly higher than that of PSB (MO = 2.2 mg g -1 , SYF = 1.6 mg g -1 ). The adsorption isotherms of MO and SYF by PSB were well fitted by Freundlich isotherm, whereas the MO and SYF via PSB-LDH MgAl were by Langmuir isotherm. Even after 3 adsorption-desorption cycles using desorbents, the PSB-LDH MgAl remained excellent reusability (reuse efficiency: >81.2%). These findings suggest that post-modification with LDH MgAl might accelerate the adsorption performance (i.e., electrostatic interaction) of azo dyes to PSB in water., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

(1) Background: Somatostatin (SST) exhibits expressional changes in the brain during development, but its role is not still clear in brain development. (2) Methods: We investigated postnatal SST expression and its effects on hippocampal neurogenesis via administering SST subcutaneously to P7 mice for 7 days. (3) Results: In the hippocampal CA1 region, SST immunoreactivity reaches peak at P14. However, SST immunoreactivity significantly decreased at P21. In the CA2/3 region, the SST expression pattern was similar to the CA1, and SST-immunoreactive cells were most abundant at P14. In the dentate gyrus, SST-immunoreactive cells were most abundant at P7 and P14 in the polymorphic layer; as in CA1-3 regions, the immunoreactivity decreased at P21. To elucidate the role of SST in postnatal development, we administered SST subcutaneously to P7 mice for 7 days. In the subgranular zone of the hippocampal dentate gyrus, a significant increase was observed in immunoreactivity of doublecortin (DCX)-positive neuroblast after administration of SST.; (4) Conclusions: SST expression in the hippocampal sub-regions is transiently increased during the postnatal formation of the hippocampus and decreases after P21. In addition, SST is involved in neuroblast differentiation in the dentate gyrus of the hippocampus.

The etiology of hyperglycemic-induced depressive behaviors is unclear. We hypothesized that long-term hyperglycemia may induce long-lasting disturbances in glutamatergic signaling and neural damages, causing depressive behaviors. To prove our hypothesis, a C57BL/6N mouse model of hyperglycemia was maintained for 4 weeks (equivalent to approximately 3 years in humans), after which insulin treatment was administered for an additional 4 weeks to normalize hyperglycemia-induced changes. Hyperglycemic mice showed depressive-like behaviors. Glutamatergic neurons and glial cells in the medial prefrontal cortex (mPFC) were affected by hyperglycemia. Insulin treatment improved blood glucose, water intake, and food intake to normoglycemic levels, but did not improve depressive-like behaviors. Glutamatergic signaling decreased with long-term hyperglycemia and did not normalize with insulin-induced normoglycemia. Importantly, hyperglycemia-induced changes in the mPFC were almost not reversed by the 4-week insulin treatment. In particular, levels of insulin receptor beta subunit (IRβ), IRS-1, vesicular glutamate transporter 1, glutamine transporter SNAT2, phosphate-activated glutaminase, and GLUT-3 were not changed by insulin. Nitration and the dephosphorylation of IRβ in the PFC also did not improve with insulin treatment. Therefore, our results suggest that hypoactive glutamatergic activity in the mPFC is involved in diabetic-associated depressive behaviors, and it is difficult to cure with glycemic regulation alone.

Background: In clinical fields, many types of insoles are used to not only realign movement patterns, but also treat pressure-related foot diseases. However, the characteristics of and plantar pressure in each type of insole are still unclear. Therefore, the aim of this study was to validate the plantar pressure-relieving effect of three representative types of insoles (metatarsal padding insole [MPI], lateral heel wedge insole [LHI], and arch support insole [ASI]) in asymptomatic men., Methods: A total of 35 feet of 35 asymptomatic men with a mean age of 23.4 ± 2.0 years were included. Pedobarographic data were evaluated by dividing the foot into eight designated regions to compare the three types of insoles. Peak plantar pressure (PPP) and pressure time integral (PTI) were assessed using the Pedar-X system. A repeated measures analysis of variance was used for statistical analyses., Results: In the hallux region, there was no statistically significant difference. MPI showed highest pressure in the 2nd-5th toe and midfoot region, but lowest in the central and lateral forefoot regions. Meanwhile, ASI showed highest pressure in the medial forefoot region but lowest in the lateral heel region. Lastly, pressure in the lateral heel region was highest in LHI. Overall, results of PTI were similar to those of PPP., Conclusions: This study demonstrated that the three types of insole each could reduce and redistribute pressure of specific part of the foot to help select an appropriate insole for each purpose., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2022 by The Korean Orthopaedic Association.)

Background: Rotator cuff tendon retears after rotator cuff repair cause glenohumeral joint instability, which results in changes in the glenoid and humerus head. However, limited data are available on the bone change after repair of small- to medium-sized rotator cuff tears. The aim of this study was to evaluate the difference of glenoid and humerus bone changes between healing and retear groups after repair of small- to medium-sized rotator cuff tears., Methods: Among patients who had arthroscopic repair due to small- to medium-sized rotator cuff tears from January 2009 to January 2017, 49 patients who underwent both preoperative and postoperative (at least 3 years after surgery) shoulder computed tomography were enrolled. Using three-dimensional reconstruction program (3D Slicer) and shape analysis program (SlicerSALT), we compared the occurrence and degree of glenoid bone change, glenoid inclination change, retroversion change, and glenoid center, as well as the degree of humerus head change, between the healing and retear groups., Results: The occurrence of glenoid bone change was significantly more common in the retear group than in the healing group ( p = 0.026). The degree of bone change in the 11-1 o'clock axial plane and 10-8 o'clock, 11-7 o'clock, and 12-6 o'clock coronal plane and the degree of glenoid inclination change were significantly larger in the retear group than the healing group ( p = 0.026, p = 0.026, p = 0.026, p = 0.026, and p = 0.014, respectively), but the average value of glenoid bone change in the retear group was within the range of 0.14 to 1.01 mm for each plane. The mean humeral head change was 5.69 ± 3.67 mm increase in the retear group and 1.27 ± 2.02 mm increase in the healing group. Compared with the healing group, the retear group showed statistically significantly increased humeral head change ( p < 0.001)., Conclusions: There was difference in glenoid and humerus bone change between the healing and retear groups at midterm follow-up after repair of small- to medium-sized tears. However, considering the measurement bias, the difference between the two groups was within the measurement error range., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2022 by The Korean Orthopaedic Association.)

This study investigates the electrical heating (also known as Joule heating) characteristics of cementitious composites containing multi-walled carbon nanotubes (CNT) and carbon fibers (CF) as electrically conductive media in an attempt to develop an eco-friendly and sustainable solution to snow and ice removal on roadway pavements during the winter season. Various dosages of CNT and CF between 0 and 1.0% (by weight of cement) were tested to find the optimum mixture proportions that yield high-energy and efficient electrical-heating performance with superior mechanical properties. The electrical properties were characterized by measuring the electrical resistivity and temperature rise when attached to a power source. Furthermore, this study examined how the crack width affects the electrical resistivity of cementitious composites containing CNT and/or CF. Compressive and flexural strengths were also measured at different ages of 1, 3, 7, and 28 days to identify how the additions of CNT and CF affect the mechanical properties. Results have shown that adding CF in combination with CNT substantially reduces the electrical resistivity and, in turn, improves the heating performance, as CFs further densify the electrically conductive network in the hydrated matrix; adding either CNT or CF alone was not an effective option to enhance the electrical characteristics. The findings of this study are expected to provide essential information for the design and construction of an electrically heated concrete pavement system with promoted energy efficiency, which will offer a promising solution to enhance winter road maintenance, improve public safety, and provide substantial social cost savings.

(1) Background: The estrogen decline during perimenopause can induce various disorders, including cognitive impairment. Phytoestrogens, such as isoflavones, lignans, and coumestans, have been tried as a popular alternative to avoid the side effects of conventional hormone replacement therapy, but their exact mechanisms and risk are not fully elucidated. In this study, we investigated the effects of isoflavone-enriched soybean leaves (IESLs) on the cognitive impairment induced by ovariectomy in female mice. (2) Methods: Ovariectomy was performed at 9 weeks of age to mimic menopausal women, and the behavior tests for cognition were conducted 15 weeks after the first administration. IESLs were administered for 18 weeks. (3) Results: The present study showed the effects of IESLs on the cognitive function in the OVX (ovariectomized) mice. Ovariectomy markedly increased the body weight and fat accumulation in the liver and perirenal fat, but IESL treatment significantly inhibited them. In the behavioral tests, ovariectomy impaired cognitive functions, but administration of IESLs restored it. In addition, in the OVX mice, administration of IESLs restored decreased estrogen receptor (ER) β and PI3K/Akt expression in the hippocampus. (4) Conclusions: The positive effects of IESLs on cognitive functions may be closely related to the ER-mediated PI3/Akt signaling pathway in the hippocampus.

An increasing number of patients are receiving rehabilitation after stroke. But the impact of intensive rehabilitation on the long-term prognosis of patients with stroke remains to be elucidated. The purpose of this study was to identify the impact of intensive rehabilitation on the long-term prognosis of patients with stroke using data from the National Health Insurance Service database. This is a register-based, retrospective cohort study. Using data from the National Health Insurance Service database, we included the patients who received rehabilitation for stroke from 2006 to 2013. Of the 14,984 patients diagnosed with stroke, 2483 died within 1 year, and 2866 did not receive rehabilitation; hence, they were also excluded. The final sample included 9635 (49.2% men, 50.8% women) patients. After correcting for covariates, the Cox model was used to evaluate the effects of physical therapy (PT) and occupational therapy (OT) on survival. We estimated the independent contribution of each factor to the risk of death from the initiation of rehabilitation. Significant differences in mortality were observed according to age, Charlson comorbidity index (CCI), income level, and stroke type. Patients with stroke who received both PT and OT had a better long-term prognosis than those who received either treatment alone. Therapy performed by a physical therapist with more than 120 hours of training effectively improved the patients' long-term prognosis. Intensive PT and OT will help improve the long-term prognosis of patients with stroke. This study emphasizes the importance of intensive rehabilitation in these patients., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke., Methods: We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations., Results: Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke., Conclusion: PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.

Background: Lipocalin-2 (LCN2) is an acute-phase protein that has been linked to insulin resistance, diabetes, and neuroinflammatory diseases. Triggering receptor expressed on myeloid cells-2 (TREM2) has been also implicated in microglia-mediated neuroinflammation. However, the potential role of LCN2 on TREM2 in diabetic mouse models is not fully understood., Methods: We investigated hepatic and hippocampal TREM2 expressions in high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic LCN2 knockout (KO) mice., Results: In addition to increased serum LCN2 level, diabetic wild-type (WT) mice had insulin resistance and hepatic steatosis. However, LCN2 deletion attenuated these metabolic parameters in diabetic mice. We also found that LCN2 deletion reduced hepatic inflammation and microglial activation in diabetic mice. In particular, diabetic LCN2 KO mice had a reduction in hepatic and hippocampal TREM2 expressions compared with diabetic WT mice. Furthermore, we found that many TREM2-positive Kupffer cells and microglia in diabetic WT mice were reduced through LCN2 deletion., Conclusions: These findings indicate that LCN2 may promote hepatic inflammation and microglial activation via upregulation of TREM2 in diabetic mice.

Background: We do not yet fully understand how the subtalar joint position is related to the varus osteoarthritic ankle joint. The purposes of this study were (1) to investigate the coronal orientation of the calcaneus relative to the talus according to the ankle osteoarthritis stage, talar tilt (TT), and (2) to determine if there is TT threshold at which apparent subtalar compensation begins to fade., Methods: We retrospectively reviewed 132 ankles that underwent weightbearing computed tomography (WBCT) for varus ankle osteoarthritis. The TT, subtalar inclination angle (SIA), and calcaneal inclination angle (CIA) were measured using WBCT. Ankles were divided into 5 groups according to Takakura stage and 2 groups according to the apparent compensation status of the subtalar joint and compared the index of the inclination of the subtalar joint relative to the ankle (SIA) or the index of the inclination of the calcaneus relative to the ankle (CIA). Additionally, we explored the relationship between SIA or CIA and the TT., Results: Apparent subtalar compensation (SIA and CIA) was significantly lower in Takakura stages 3b and 4. The SIA and CIA significantly differed according to the apparent compensation status ( P < .001 and P = .030, respectively). The CIA of the noncompensated group varied widely, whereas the SIA was relatively constant. Furthermore, TT was greater than 9.5, which indicated a high probability of a noncompensated heel (sensitivity, 92.6%; specificity, 89.7%)., Conclusion: The position of the calcaneus appears compensatory with coronal plane orientation in varus ankle osteoarthritis when the TT is ≤9.5 degrees., Level of Evidence: Level IV, case series.

Background: The type of footwear is one of several factors that affect foot pressure. Despite its usefulness in identifying pathology and preventing and treating foot-related diseases, the type of shoes has been investigated and compared in only a few studies. This study aimed to investigate differences in plantar pressure, induced by flat, running, and high-heeled shoes in healthy, young women., Methods: A total of 27 healthy women (27 feet) with a mean age of 21.5 ± 2.03 years were included in this study. Based on demographic data, radiologic measurements, clinical scores, temporal gait parameters, and kinematic parameters of gait, we confirmed the participants had normal feet. Then, pedobarographic data were measured by dividing each foot into seven regions to compare the three types of shoes. Peak plantar pressure and pressure-time integral were calculated using the Pedar-X system. The one-way analysis of variance and the Kruskal-Wallis test with Mann Whitney U -test were used for statistical analyses., Results: Regarding the 7 regions of the foot, flat shoes resulted in a significantly higher pressure than running shoes in the hallux and lesser toes and the highest pressure in the metatarsal head (MTH) 3-5 and the hindfoot. In contrast, in the MTH 1 and MTH 2 regions, the high-heeled shoes had the highest measured pressure, followed by the flat shoes. Lastly, there was no high pressure in running shoes in any region except for the midfoot compared to the other shoes., Conclusions: It can be inferred from our findings that flat and high-heeled shoes can generate a considerable burden on specific parts of the foot, which will aid in choosing appropriate shoes. Also, wearing running shoes places less burden on the overall foot., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2022 by The Korean Orthopaedic Association.)

In this study, the influence of graphene oxide nanoparticles on the bond-slip behavior of fiber and fly-ash-based geopolymer paste was examined. Geopolymer paste incorporating a graphene oxide nanoparticle solution was cast in half briquetted specimens and embedded with a fiber. Three types of fiber were used: steel, polypropylene, and basalt. The pullout test was performed at two distinct speeds: 1 mm/s and 3 mm/s. The results showed that the addition of graphene oxide increased the compressive strength of the geopolymer by about 7%. The bond-slip responses of fibers embedded in the geopolymer mixed with graphene oxide exhibited higher peak stress and toughness compared to those embedded in a normal geopolymer. Each fiber type also showed a different mode of failure. Both steel and polypropylene fibers showed full bond-slip responses due to their high ductility. Basalt fiber, on the other hand, because of its brittleness, failed by fiber fracture mode and showed no slip in pullout responses. Both bond strength and toughness were found to be rate-sensitive. The sensitivity was higher in the graphene oxide/geopolymer than in the conventional geopolymer.

Background: Whether calf muscles and peroneal muscles have a role in the occurrence of an ankle fractures remains unclear. This study aimed to quantify the calf muscle mass and peroneal muscle mass in patients with an ankle fracture and in controls, then to analyze them together with demographic factors to identify the effects of the regional muscles on the risk of developing ankle fracture., Methods: A total of 101 ankles with computed tomography (CT) images were retrospectively reviewed. Of them, 51 ankles showed fractures (all unilateral) and 50 ankles, in controls who underwent CT for screening the other diseases, were clinically diagnosed with simple contusion. The cross-sectional areas (CSA) of the calf muscles and the peroneal muscles were measured at approximately 6 cm above the Achilles myotendinous junction in the axial plane of ankle CT. These parameters were compared between the two groups and analyzed with respect to age, sex, body mass index (BMI), laterality, and bone attenuations of the ankle., Results: The demographic factors, including bone attenuation of the ankle showed no significant association with ankle fracture. The ratio of the CSA of the peroneal muscle group to the CSA of the entire calf muscle group was smaller in patients with an fracture (0.12 ± 0.03) than in controls (0.14 ± 0.02) (p = 0.027). The odds ratio for the effect of the calf muscle CSA on the risk of developing ankle fractures was 1.38 (95% confidence interval 1.12-1.69, p = 0.003), whereas that for the effect of peroneal muscle CSA on the risk of developing ankle fractures was 0.18 (95% confidence interval 0.05 to 0.66, p = 0.010)., Conclusion: The ratio of the peroneal muscle CSA to the entire calf muscle CSA was negatively related to the occurrence of ankle fractures in this study. Further prospective studies on whether peroneal muscle-strengthening exercise are effective in preventing ankle fractures may be needed., Level of Evidence: III, case-control study., (Copyright © 2020 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Objectives: Vacuolar H + -ATPase is a highly conserved enzyme that plays an important role in maintaining an acidic environment for lysosomal function and accumulating neurotransmitters in synaptic vesicles. In the present study, we investigated the time-dependent changes in the expression of vacuolar H + -ATPase V 1 B 2 (ATP6V1B2), a major neuronal subtype of vacuolar H + -ATPase located in the hippocampus, after 5 min of transient forebrain ischemia in gerbils. We also examined the pH and lactate levels in the hippocampus after ischemia to elucidate the correlation between ATP6V1B2 expression and acidosis., Materials and Methods: Transient forebrain ischemia was induced by occlusion of both common carotid arteries for 5 min and animals were sacrificed at various time points after ischemia for immunohistochemical staining of ATP6V1B2 and measurements of pH and lactate levels in the hippocampus., Results: ATP6V1B2 immunoreactivity was found to be transiently increased in the hippocampal CA1 region and dentate gyrus 12-24 hr after ischemia when the pH and lactate levels were decreased. In addition, ATP6V1B2 immunoreactivity significantly increased in the hippocampal CA3 and dentate gyrus, regions relatively resistant to ischemic damage, 4 days after ischemia, when the NeuN-positive, mature neuron numbers were significantly decreased in the hippocampal CA1 region., Conclusion: These results suggest that ATP6V1B2 expression is transiently increased in the hippocampus following ischemia, which may be intended to compensate for ischemia-related dysfunction of ATP6V1B2 in the hippocampus., Competing Interests: None declared

PurposeThis study aimed to evaluate the relationship between talofibular impingement and increased talar tilt in incongruent varus ankle osteoarthritis. Methods: Incongruent varus ankle osteoarthritis was defined as a talar tilt of more than 4° on standard ankle anteroposterior radiographs. We retrospectively reviewed 30 patients with unilateral incongruent varus ankle osteoarthritis with normal alignment of the contralateral ankle. All patients underwent bilateral weightbearing computed tomography and standing plain radiographs. The talar tilt and the distance between the talar lateral process and lateral malleolar tip were measured from a standing ankle anteroposterior radiograph of both sides. Talar and fibular spurs were assessed on the coronal and axial views of weightbearing computed tomography. After simulating the correction of the talar tilt in varus ankle osteoarthritis, talofibular bony impingement was reassessed. Results: On the varus side, the distance between the talar lateral process and the lateral malleolar tip was significantly shorter than that on the contralateral side ( p < .001). Talar spur was present in the varus side of all 30 patients on the axial view of weightbearing computed tomography and in the control side of 10 patients. After the simulation of talar tilt correction, talofibular impingement (overlap) occurred in all 30 patients with a larger extent in the severe talar tilt subgroup ( p < .001). Conclusion: Talofibular impingement by lateral gutter osteophytes is closely related to increased talar tilt in patients with incongruent varus ankle osteoarthritis. Therefore, lateral gutter osteophytes should be resected to stabilize mortise and improve clinical outcomes.

Entacapone, a catechol-O-methyltransferase inhibitor, can strengthen the therapeutic effects of levodopa on the treatment of Parkinson's disease. However, few studies are reported on whether entacapone can affect hippocampal neurogenesis in mice. To investigate the effects of entacapone, a modulator of dopamine, on proliferating cells and immature neurons in the mouse hippocampal dentate gyrus, 60 mice (7 weeks old) were randomly divided into a vehicle-treated group and the groups treated with 10, 50, or 200 mg/kg entacapone. The results showed that 50 and 200 mg/kg entacapone increased the exploration time for novel object recognition. Immunohistochemical staining results revealed that after entacapone treatment, the numbers of Ki67-positive proliferating cells, doublecortin-positive immature neurons, and phosphorylated cAMP response element-binding protein (pCREB)-positive cells were significantly increased. Western blot analysis results revealed that treatment with tyrosine kinase receptor B (TrkB) receptor antagonist significantly decreased the exploration time for novel object recognition and inhibited the expression of phosphorylated TrkB and brain-derived neurotrophic factor (BDNF). Entacapone treatment antagonized the effects of TrkB receptor antagonist. These results suggest that entacapone treatment promoted hippocampal neurogenesis and improved memory function through activating the BDNF-TrkB-pCREB pathway. This study was approved by the Institutional Animal Care and Use Committee of Seoul National University (approval No. SNU-130730-1) on February 24, 2014., Competing Interests: None

Aberrant Ras signaling is linked to a wide spectrum of hyperproliferative diseases, and components of the signaling pathway, including Ras, have been the subject of intense and ongoing drug discovery efforts. The cellular activity of Ras is modulated by its association with the guanine nucleotide exchange factor Son of sevenless (Sos), and the high-resolution crystal structure of the Ras-Sos complex provides a basis for the rational design of orthosteric Ras ligands. We constructed a synthetic Sos protein mimic that engages the wild-type and oncogenic forms of nucleotide-bound Ras and modulates downstream kinase signaling. The Sos mimic was designed to capture the conformation of the Sos helix-loop-helix motif that makes critical contacts with Ras in its switch region. Chemoproteomic studies illustrate that the proteomimetic engages Ras and other cellular GTPases. The synthetic proteomimetic resists proteolytic degradation and enters cells through macropinocytosis. As such, it is selectively toxic to cancer cells with up-regulated macropinocytosis, including those that feature oncogenic Ras mutations., Competing Interests: The authors declare no competing interest.

Geopolymer concrete (GPC) offers a potential solution for sustainable construction by utilizing waste materials. However, the production and testing procedures for GPC are quite cumbersome and expensive, which can slow down the development of mix design and the implementation of GPC. The basic characteristics of GPC depend on numerous factors such as type of precursor material, type of alkali activators and their concentration, and liquid to solid (precursor material) ratio. To optimize time and cost, Artificial Neural Network (ANN) can be a lucrative technique for exploring and predicting GPC characteristics. In this study, the compressive strength of fly-ash based GPC with bottom ash as a replacement of fine aggregates, as well as fly ash, is predicted using a machine learning-based ANN model. The data inputs are taken from the literature as well as in-house lab scale testing of GPC. The specifications of GPC specimens act as input features of the ANN model to predict compressive strength as the output, while minimizing error. Fourteen ANN models are designed which differ in backpropagation training algorithm, number of hidden layers, and neurons in each layer. The performance analysis and comparison of these models in terms of mean squared error (MSE) and coefficient of correlation (R) resulted in a Bayesian regularized ANN (BRANN) model for effective prediction of compressive strength of fly-ash and bottom-ash based geopolymer concrete.

The role of vascular smooth muscle cells (VSMCs) in vascular calcification, which is related to chronic kidney disease (CKD), has been studied in greater detail in the major arteries relative to the peripheral arteries. We compared the calcifying characteristics of peripheral VSMCs relative to non-pathologic major VSMCs in patients with severe peripheral artery disease (PAD). We isolated peripheral VSMCs from the posterior tibial artery of 10 patients with CKD who underwent below-knee amputation for critical limb ischemia (CLI). Using normal human aortic VSMCs as a control group, we cultured the cells in normal and high phosphate media for 10 days, and subsequently tested by immunofluorescence staining. We compared the calcification levels between the two groups using various assays, tests for cell viability, and scanning electron microscopy. As a result, calcification of pathologic peripheral VSMCs increased significantly with time ( p = 0.028) and was significantly higher than that in human aortic VSMCs in calcium assays ( p = 0.043). Dead cells in the pathologic VSMC group were more distinct in high phosphate media than in human aortic VSMCs. In conclusion, VSMCs from the peripheral artery of patients with severe CKD and CLI who underwent amputation surgery showed marked calcifying characteristics compared to normal human aortic VSMCs.

Gynura procumbens has been used in Southeast Asia for the treatment of hypertension, hyperglycemia, and skin problems induced by ultraviolet irradiation. Although considerable studies have reported the biological properties of Gynura procumbens root extract (GPE-R), there are no studies on the effects of GPE-R in brain damages, for example following brain ischemia. In the present study, we screened the neuroprotective effects of GPE-R against ischemic damage and neuroinflammation in the hippocampus based on behavioral, morphological, and biological approaches. Gerbils received oral administration of GPE-R (30 and 300 mg/kg) every day for three weeks and 2 h after the last administration, ischemic surgery was done by occlusion of both common carotid arteries for 5 min. Administration of 300 mg/kg GPE-R significantly reduced ischemia-induced locomotor hyperactivity 1 day after ischemia. Significantly more NeuN-positive neurons were observed in the hippocampal CA1 regions of 300 mg/kg GPE-R-treated animals compared to those in the vehicle-treated group 4 days after ischemia. Administration of GPE-R significantly reduced levels of pro-inflammatory cytokines such as interleukin-1β, -6, and tumor necrosis factor-α 6 h after ischemia/reperfusion. In addition, activated microglia were significantly decreased in the 300 mg/kg GPE-R-treated group four days after ischemia/reperfusion compared to the vehicle-treated group. These results suggest that GPE-R may be one of the possible agents to protect neurons from ischemic damage by reducing inflammatory responses.

Entacapone, a reversible inhibitor of catechol-O-methyl transferase, is used for patients in Parkinson's disease because it increases the bioavailability and effectiveness of levodopa. In the present study, we observed that entacapone increases novel object recognition and neuroblasts in the hippocampus. In the present study, two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were performed to compare the abundance profiles of proteins expressed in the hippocampus after entacapone treatment in mice. Results of 2-DE, MALDI-TOF mass spectrometry, and subsequent proteomic analysis revealed an altered protein expression profile in the hippocampus after entacapone treatment. Based on proteomic analysis, 556 spots were paired during the image analysis of 2-DE gels and 76 proteins were significantly changed more than two-fold among identified proteins. Proteomic analysis indicated that treatment with entacapone induced expressional changes in proteins involved in synaptic transmission, cellular processes, cellular signaling, the regulation of cytoskeletal structure, energy metabolism, and various subcellular enzymatic reactions. In particular, entacapone significantly increased proteins related to synaptic trafficking and plasticity, such as dynamin 1, synapsin I, and Munc18-1. Immunohistochemical staining showed the localization of the proteins, and western blot confirmed the significant increases in dynamin I (203.5% of control) in the hippocampus as well as synapsin I (254.0% of control) and Munc18-1 (167.1% of control) in the synaptic vesicle fraction of hippocampus after entacapone treatment. These results suggest that entacapone can enhance hippocampal synaptic trafficking and plasticity against various neurological diseases related to hippocampal dysfunction.

This study evaluates the tensile properties, including the tensile strength and elongation at break, and dynamic behavior, including shock absorption and vertical deformation, of an elastic rubber layer in synthetic sports surfaces produced using waste tire chips containing styrene-butadiene rubber (SBR). The primary variables of the investigation were the number of compactions, resin-rubber granule ratio, and curing conditions, such as aging, the temperature, and the relative humidity. The test results showed an increase in the tensile strength of the elastic rubber layer with recycled SBR as the number of compactions, resin-rubber granule ratio, curing period, and temperature increased, while the elongation at break was affected by the curing temperature and period. Shock absorption and vertical deformation decreased with an increasing resin-rubber granule ratio and number of compactions due to the increased hardness. However, these properties were not significantly affected by the curing conditions. Furthermore, the test results indicated that the curing temperature has a pronounced effect on the tensile properties of the elastic rubber layer, and maintaining the appropriate curing temperature-approximately 50 °C-is a possible solution for improving the relatively low tensile properties of the elastic rubber layer.

Laminaria japonica is widely cultivated in East Asia, including South Korea. Fucoidan, a main component of L. japonica , protects neurons from neurological disorders such as ischemia and traumatic brain injury. In the present study, we examined the effects of extract from fermented L. japonica on the reduction of proliferating cells and neuroblasts in mice that were physically (with electric food shock) or psychologically (with visual, auditory and olfactory sensation) stressed with the help of a communication box. Vehicle (distilled water) or fermented L. japonica extract (50 mg/kg) were orally administered to the mice once a day for 21 days. On the 19th day of the treatment, physical and psychological stress was induced by foot shock using a communication box and thereafter for three days. Plasma corticosterone levels were significantly increased after exposure to physical stress and decreased Ki67 positive proliferating cells and doublecortin immunoreactive neuroblasts. In addition, western blot analysis demonstrated that physical stress as well as psychological stress decreased the expression levels of brain-derived neurotrophic factor (BDNF) and the number of phosphorylated cAMP response element binding protein (pCREB) positive nuclei in the dentate gyrus. Fermentation of L. japonica extract significantly increased the contents of reduced sugar and phenolic compounds. Supplementation with fermented L. japonica extract significantly ameliorated the increases of plasma corticosterone revels and decline in the proliferating cells, neuroblasts, and expression of BDNF and pCREB in the physically stressed mice. These results indicate that fermented L. japonica extract has positive effects in ameliorating the physical stress induced reduction in neurogenesis by modulating BDNF and pCREB expression in the dentate gyrus.

In this study, the thermal storage properties of lightweight concrete incorporating two types of phase change materials (PCM) with two different fusion points were investigated. Two types of PCM, polyethylene glycol (PEG) and paraffin (PRF), were impregnated into porous aggregates using high temperatures. The PCM aggregates were mixed with concrete at different proportions of PEG/PRF aggregates from 0/100 to 100/0 with 25% intervals. The experimental series consisted of thermal property tests (such as thermal conductivity, specific heat, and latent heat), and some basic properties (such as compressive strength, density, water absorption, and abrasion resistance). The results showed that incorporating PCM aggregates into lightweight concrete helped increase the workability, lower the moisture absorption, and increase the mechanical properties. For thermal properties, both thermal conductivity (k) and specific heat were found to depend strongly on the state of PCM. The latent heat of lightweight concrete with PCM aggregates in hybrid form were found to be higher than that of single type PCM aggregates., (© 2020 The Author(s).)

Peptides and peptidomimetics represent the middle space between small molecules and large proteins-they retain the relatively small size and synthetic accessibility of small molecules while providing high binding specificity for biomolecular partners typically observed with proteins. During the course of our efforts to target intracellular protein-protein interactions in cancer, we observed that the cellular uptake of peptides is critically determined by the cell line-specifically, we noted that peptides show better uptake in cancer cells with enhanced macropinocytic indices. Here, we describe the results of our analysis of cellular penetration by different classes of conformationally stabilized peptides. We tested the uptake of linear peptides, peptide macrocycles, stabilized helices, β-hairpin peptides, and cross-linked helix dimers in 11 different cell lines. Efficient uptake of these conformationally defined constructs directly correlated with the macropinocytic activity of each cell line: high uptake of compounds was observed in cells with mutations in certain signaling pathways. Significantly, the study shows that constrained peptides follow the same uptake mechanism as proteins in macropinocytic cells, but unlike proteins, peptide mimics can be readily designed to resist denaturation and proteolytic degradation. Our findings expand the current understanding of cellular uptake in cancer cells by designed peptidomimetics and suggest that cancer cells with certain mutations are suitable mediums for the study of biological pathways with peptide leads.

We investigated the effects of pyridoxine deficiency on ischemic neuronal death in the hippocampus of gerbil ( n = 5 per group). Serum pyridoxal 5'-phosphate levels were significantly decreased in Pyridoxine-deficient diet (PDD)-fed gerbils, while homocysteine levels were significantly increased in sham- and ischemia-operated gerbils. PDD-fed gerbil showed a reduction in neuronal nuclei (NeuN)-immunoreactive neurons in the medial part of the hippocampal CA1 region three days after. Reactive astrocytosis and microgliosis were found in PDD-fed gerbils, and transient ischemia caused the aggregation of activated microglia in the stratum pyramidale three days after ischemia. Lipid peroxidation was prominently increased in the hippocampus and was significantly higher in PDD-fed gerbils than in Control diet (CD)-fed gerbils after ischemia. In contrast, pyridoxine deficiency decreased the proliferating cells and neuroblasts in the dentate gyrus in sham- and ischemia-operated gerbils. Nuclear factor erythroid-2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF) levels also significantly decreased in PDD-fed gerbils sham 24 h after ischemia. These results suggest that pyridoxine deficiency accelerates neuronal death by increasing serum homocysteine levels and lipid peroxidation, and by decreasing Nrf2 levels in the hippocampus. Additionally, it reduces the regenerated potentials in hippocampus by decreasing BDNF levels. Collectively, pyridoxine is an essential element in modulating cell death and hippocampal neurogenesis after ischemia.

Cannabinoid receptor-interacting protein 1a (CRIP1a) binds to the C -terminal domain of cannabinoid 1 receptor (CB1R) and regulates CB1R activities. In this study, we made Tat-CRIP1a fusion proteins to enhance CRIP1a penetration into neurons and brain and to evaluate the function of CRIP1a in neuroprotection following oxidative stress in HT22 hippocampal cells and transient forebrain ischemia in gerbils. Purified exogenous Tat-CRIP1a was penetrated into HT22 cells in a time and concentration-dependent manner and prevented H 2 O 2 -induced reactive oxygen species formation, DNA fragmentation, and cell damage. Tat-CRIP1a fusion protein also ameliorated the reduction of 14-3-3η expression by H 2 O 2 treatment in HT22 cells. Ischemia-reperfusion damage caused motor hyperactivity in the open field test of gerbils; however, the treatment of Tat-CRIP1a significantly reduced hyperactivity 1 day after ischemia. Four days after ischemia, the administration of Tat-CRIP1a restored the loss of pyramidal neurons and decreased reactive astrocytosis and microgliosis induced by ischemic damage in the hippocampal cornu Ammonis (CA)1 region. Ischemic damage decreased 14-3-3η expression in all hippocampal sub-regions 4 days after ischemia; however, the treatment of Tat-CRIP1 ameliorated the reduction of 14-3-3η expression. These results suggest that Tat-CRIP1a attenuates neuronal damage and hyperactivity induced by ischemic damage, and it restores normal expression levels of 14-3-3η protein in the hippocampus.

Protein-protein interactions (PPIs) play a critical role in fundamental biological processes. Competitive inhibition of these interfaces requires compounds that can access discontinuous binding epitopes along a large, shallow binding surface area. Conformationally defined protein surface mimics present a viable route to target these interactions. However, the development of minimal protein mimics that engage intracellular targets with high affinity remains a major challenge because mimicry of a portion of the binding interface is often associated with the loss of critical binding interactions. Covalent targeting provides an attractive approach to overcome the loss of noncovalent contacts but have the inherent risk of dominating noncovalent contacts and increasing the likelihood of nonselective binding. Here, we report the iterative design of a proteolytically stable α 3 β chimeric helix mimic that covalently targets oncogenic Ras G12C as a model system. We explored several electrophiles to optimize preferential alkylation with the desired C12 on Ras. The designed lead peptide modulates nucleotide exchange, inhibits activation of the Ras-mediated signaling cascade, and is selectively toxic toward mutant Ras G12C cancer cells. The relatively high frequency of acquired cysteines as missense mutations in cancer and other diseases suggests that covalent peptides may offer an untapped therapeutic approach for targeting aberrant protein interactions.

In the present study, we investigated the effects of cuprizone on cell death, glial activation, and neuronal plasticity induced by hypothermia after ischemia in gerbils. Food was supplemented with cuprizone at 0.2% ad libitum for eight weeks. At six weeks after diet feeing, gerbils received transient forebrain ischemia with or without hypothermic preconditioning. Cuprizone treatment for 8 weeks increased the number of astrocytes, microglia, and pro-inflammatory cytokine levels in the hippocampus. In addition, cuprizone treatment significantly decreased the number of proliferating cells and neuroblasts in the dentate gyrus. Brain ischemia caused cell death, disruption of myelin basic proteins, and reactive gliosis in CA1. In addition, ischemia significantly increased pro-inflammatory cytokines and the number of proliferating cells and differentiating neuroblasts in the dentate gyrus. In contrast, hypothermic conditioning attenuated these changes in CA1 and the dentate gyrus. However, cuprizone treatment decreased cell survival induced by hypothermic preconditioning after ischemia and increased the number of reactive microglia and astrocytes in CA1 as well as that of macrophages in the subcallosal zone. These changes occurred because the protective effect of hypothermia in ischemic damage was disrupted by cuprizone administration. Furthermore, cuprizone decreased ischemia-induced proliferating cells and neuroblasts in the dentate gyrus.

Pyridoxine, one of the vitamin B 6 vitamers, plays a crucial role in amino acid metabolism and synthesis of monoamines as a cofactor. In the present study, we observed the effects of pyridoxine deficiency on novel object recognition memory. In addition, we examined the levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenethylamine (DA), 3,4-dihydroxyphenylacetic acid, and homovanillic acid and the number of proliferating cells and neuroblasts in the hippocampus. We also examined the effects of pyridoxine deficiency on protein profiles applying a proteomic study. Five-week-old mice fed pyridoxine-deficient diets for 8 weeks and showed a significant decrease in the serum and brain (cerebral cortex, hippocampus, and thalamus) levels of pyridoxal 5'-phosphate, a catalytically active form of vitamin-B 6 , and decline in 5-HT and DA levels in the hippocampus compared to controls fed a normal chow. In addition, pyridoxine deficiency significantly decreased Ki67-positive proliferating cells and differentiated neuroblasts in the dentate gyrus compared to controls. A proteomic study demonstrated that a total of 41 spots were increased or decreased more than two-fold. Among the detected proteins, V-type proton ATPase subunit B2 (ATP6V1B2) and heat shock cognate protein 70 (HSC70) showed coverage and matching peptide scores. Validation by Western blot analysis showed that ATP6V1B2 and HSC70 levels were significantly decreased and increased, respectively, in pyridoxine-deficient mice compared to controls. These results suggest that pyridoxine is an important element of novel object recognition memory, monoamine levels, and hippocampal neurogenesis. Pyridoxine deficiency causes cognitive impairments and reduction in 5-HT and DA levels, which may be associated with a reduction of ATP6V1B2 and elevation of HSC70 levels in the hippocampus.

This study aims to examine the mechanical, shrinkage and chemical properties of photocatalytic cementitious materials containing synthetic fibers and a shrinkage-reducing admixture (SRA). Two types of titanium dioxide (TiO 2 ) powders and white Portland cement were considered along with ordinary Portland cement (OPC) as a control. Two types of synthetic fibers, i.e., glass and polyethylene (PE), and an SRA with contents varying from 0% to 3% were also considered. Using the TiO 2 powders and the white Portland cement was effective in reducing the nitrogen oxides (NO x ) concentration in cement composites. The use of PE fibers was more effective than glass fibers in terms of the mechanical properties, i.e., the compressive strength and tensile performance. With the addition of TiO 2 powders and SRA or the replacement of OPC with white cement, the mechanical properties of the cement mortar generally deteriorated. The total shrinkage of the mortar could be reduced by incorporating the fibers at volume fractions greater than 1%, and the glass fiber was more effective than the PE fiber in this regard. The TiO 2 powders had no significant impact on the shrinkage reduction of the cement mortar, whereas the SRA and the white Portland cement effectively reduced shrinkage. The addition of 3% SRA decreased the total shrinkage by 43%, while the replacement of the OPC with white cement resulted in a 20% reduction in the shrinkage.

Epilepsy is a chronic neurological disease characterized by spontaneous recurrent seizures and caused by various factors and mechanisms. Malfunction of the olfactory bulb is frequently observed in patients with epilepsy. However, the morphological changes in the olfactory bulb during epilepsy-induced neuropathology have not been elucidated. Therefore, in the present study, we investigated the expression of parvalbumin (PV), one of the calcium-binding proteins, and morphological changes in the rat main olfactory bulb (MOB) following pilocarpine- induced status epilepticus (SE). Pilocarpine-induced SE resulted in neuronal degeneration in the external plexiform layer (EPL) and glomerular layer (GL) of the MOB. PV immunoreactivity was observed in the neuronal somas and processes in the EPL and GL of the control group. However, six hours after pilocarpine administration, PV expression was remarkably decreased in the neuronal processes compared to the somas and the average number of PV-positive interneurons was significantly decreased. Three months after pilocarpine treatment, the number of PV-positive interneurons was also significantly decreased compared to the 6 hour group in both layers. In addition, the number of NeuN-positive neurons was also significantly decreased in the EPL and GL following pilocarpine treatment. In double immunofluorescence staining for PV and MAP2, the immunoreactivity for MAP2 around the PV-positive neurons was significantly decreased three months after pilocarpine treatment. Therefore, the present findings suggest that decreases in PV-positive GABAergic interneurons and dendritic density in the MOB induced impaired calcium buffering and reciprocal synaptic transmission. Thus, these alterations may be considered key factors aggravating olfactory function in patients with epilepsy. [BMB Reports 2020; 53(4): 234-239].