Effect of YC-1102 on the Improvement of Obesity in High-Fat Diet-Induced Obese Mice.

Obesity is one of the major risk factors for metabolic diseases worldwide. This study examined the effects of YC-1102, an extract derived from the roots of Rosa multiflora, on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese mice. In vivo experiments involved the oral administration of YC-1102 (100, 150, and 200 mg/kg body weight) daily to mice for eight weeks. YC-1102 was found to downregulate the expressions of PPARγ and C/EBPα during adipogenesis, inhibiting adipocyte differentiation and upregulating the expression of PGC-1α for energy metabolism to enhance mitochondrial biogenesis and fatty acid oxidation. It has been shown that daily administration of YC-1102 to mice receiving a HFD prevented an increase in body weight and the accumulation of body fat. YC-1102 administration also reduced TG, TC, and LDL cholesterol levels, as well as glucose and leptin levels, and increased adiponectin levels, thus effectively inhibiting the metabolism of lipids. YC-1102-treated mice showed significant reductions in the mRNA expression of PPARγ and C/EBPα. The levels of PGC-1α involved in energy metabolism increased significantly in the YC-1102-treated mice when compared to the HFD-treated mice. According to the findings of this study, YC-1102 has a dual mechanism that reduces transcription factors that promote the differentiation of adipocytes and increases transcription factors that promote energy consumption.

Optimized trans-cranial direct current stimulation for prolonged consciousness disorder in a patient with titanium mesh cranioplasty.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been used for the restoration of awareness in patients with a minimal consciousness state (MCS). Most brains of patients in MCS may structurally and electrophysiologically differ from un-damaged brains. Moreover, tDCS is currently contraindicated for patients with craniotomy or skull with metallic implants. CASE PRESENTATION: We present a case with prolonged MCS over 1 year, who had severe brain damage, ventriculoperitoneal shunt, and cranioplasty with a titanium mesh, which was treated with tDCS which optimized with the simulation of the electric field based on the patient's brain MRI. The patient was resulting in emergence from MCS. Six months later, she ate meals orally and started walking with assistance. DISCUSSION AND PERSPECTIVE: This personalized simulation based on MRI would make the treatment available even to patients with severe brain structural changes and metallic instrumentation.

The Prognostic Utilities of DNA Mismatch Repair Status and KRAS and BRAF Mutation in Korean Colorectal Cancer Patients: The KASID Multicenter Study.

INTRODUCTION: KRAS, BRAF, and DNA mismatch repair (MMR) mutations aid clinical decision-making for colorectal cancer (CRC) patients. To ensure accurate predictions, the prognostic utilities of these biomarkers and their combinations must be individualized for patients with various TNM stages. METHODS: Here, we retrospectively analyzed the clinicopathological features of 904 Korean CRC patients who underwent CRC surgery in three teaching hospitals from 2011 to 2013; we also assessed the prognostic utilities of KRAS, BRAF, and MMR mutations in these patients. RESULTS: The overall frequencies of KRAS and BRAF mutations were 35.8% and 3.2%, respectively. Sixty-nine patients (7.6%) lacking expression of ≥1 MMR protein were considered MMR protein deficient (MMR-D); the remaining patients were considered MMR protein intact. KRAS mutations constituted an independent risk factor for shorter overall survival (OS) in TNM stage I-IV and stage III patients. BRAF mutations were associated with shorter OS in TNM stage I-IV patients. MMR-D status was strongly positive prognostic in TNM stage I-II patients. DISCUSSION/CONCLUSION: To our knowledge, this is the first multicenter study to explore the prognostic utilities of KRAS, BRAF, and MMR statuses in Korean CRC patients. Various combinations of KRAS, BRAF, and DNA MMR mutations serve as genetic signatures that affect tumor behavior; they are prognostic in CRC patients.

Geographical Differences of Risk of Asthma and Allergic Rhinitis according to Urban/Rural Area: a Systematic Review and Meta-analysis of Cohort Studies.

Several studies have demonstrated an association between the risk asthma/allergic rhinitis and the environment. However, to date, no systematic review or meta-analysis has investigated these factors. We conducted a systematic review and meta-analysis to assess the association between urban/rural living and the risk of asthma and allergic rhinitis. We searched the Embase and Medline databases for relevant articles and included only cohort studies to observe the effects of time-lapse geographical differences. Papers containing information on rural/urban residence and respiratory allergic diseases were eligible for inclusion. We calculated the relative risk (RR) and 95% confidence interval (CI) using a 2 × 2 contingency table and used random effects to pool data. Our database search yielded 8388 records, of which 14 studies involving 50,100,913 participants were finally included. The risk of asthma was higher in urban areas compared to rural areas (RR, 1.27; 95% CI, 1.12-1.44, p < 0.001), but not for the risk of allergic rhinitis (RR, 1.17; 95% CI, 0.87-1.59, p = 0.30). The risk of asthma in urban areas compared to rural areas was higher in the 0-6 years and 0-18 years age groups, with RRs of 1.21 (95% CI, 1.01-1.46, p = 0.04) and 1.35 (95% CI, 1.12-1.63, p = 0.002), respectively. However, there was no significant difference in the risk of asthma between urban and rural areas for children aged 0-2 years, with a RR of 3.10 (95% CI, 0.44-21.56, p = 0.25). Our study provides epidemiological evidence for an association between allergic respiratory diseases, especially asthma, and urban/rural living. Future research should focus on identifying the factors associated with asthma in children living in urban areas. The review was registered in PROSPERO (CRD42021249578).

Visual prognosis and surgical timing of Ahmed glaucoma valve implantation for neovascular glaucoma secondary to diabetic vitrectomy.

BACKGROUND: Evaluate the visual outcomes of Ahmed glaucoma valve implantation (AGVI) in patients with neovascular glaucoma (NVG) who underwent diabetic vitrectomy and suggest appropriate AGVI timing. METHODS: Medical records of patients who underwent AGVI due to NVG after diabetic vitrectomy were reviewed. Successful intraocular pressure (IOP) control was defined as an IOP between 6 and 21 mmHg. Visual outcome was compared before NVG diagnosis and after AGVI, and the "favorable" visual outcome was defined as a postoperative deterioration in BCVA of less than 0.3 logMAR units compared to those before the development of NVG. Various factors including surgical timing were evaluated to identify the risk factors associated with unfavorable visual outcome. RESULTS: A total of 35 eyes were enrolled and divided into group 1(medically uncontrolled NVG group, IOP more than 30mmHg, 16 eyes) and group 2(NVG group responded well to the initial non-surgical treatment but eventually required AGVI, 19 eyes). Despite the favorable rate of normalization of post-AGVI IOP (85.7%), 43.8% in Group 1 and 26.3% in Group 2 showed unfavorable visual outcomes. In group 1, delayed surgical timing more than 1 week from the NVG diagnosis showed a significant association with unfavorable visual outcomes (P = 0.041). In group 2, poor patient compliance (follow up loss, refuse surgery) was the main factor of unfavorable visual outcomes. CONCLUSION: When NVG occurs in patients with proliferative diabetic retinopathy after vitrectomy, physicians should be cautious not to delay the surgical intervention, especially in patients with IOP of 30 or more despite non-surgical treatment. Early AGVI within six days might be necessary to preserve useful vision in these patients.

Effect of Total Hip Arthroplasty on Ipsilateral Lower Limb Alignment and Knee Joint Space Width: Minimum 5-Year Follow-up.

BACKGROUND: This study aimed to 1) assess the effect of total hip arthroplasty (THA) on coronal limb alignment, namely, the hip-knee-ankle angle (HKA), 2) identify factors that determine changes in the HKA, and 3) determine whether alignment changes influence the knee joint space width. METHODS: We retrospectively evaluated 266 limbs of patients who underwent THA. Three types of prostheses with neck shaft angles (NSAs) of 132°, 135°, and 138° were used. Several radiographic parameters were measured in the preoperative and final radiographs (at least 5 years after THA). A paired t-test was used to confirm the effect of THA on HKA change. Multiple regression analysis was performed to identify radiographic parameters related to HKA changes following THA and changes in knee joint space width. Subgroup analyses were performed to reveal the effect of NSA change on the HKA change, and the proportion of total knee arthroplasty usage and changes in radiographic parameters between maintained joint space and narrowed joint space groups were compared. RESULTS: The preoperative mean HKA was 1.4° varus and increased to 2.7° varus after THA. This change was related to changes in the NSA, lateral distal femoral angle, and femoral bowing angle. In particular, in the group with a decrease in NSA of > 5°, the preoperative mean HKA was largely changed from 1.4° varus to 4.6° varus after THA. The prostheses with NSA of 132° and 135° also led to greater varus HKA changes than those with an NSA of 138°. Narrowing of the medial knee joint space was related to changes in the varus direction of the HKA, decrease in NSA, increase in femoral offset. CONCLUSION: A large reduction in NSA can lead to considerable varus limb alignment after THA, which can have adverse effects on the medial compartment of the ipsilateral knee.

Medial Meniscus Posterior Root Repair Restores Contact Pressure and Contact Area to Its Native State Even After Opening-Wedge High Tibial Osteotomy: A Cadaveric Biomechanical Study.

PURPOSE: To elucidate the effect of medial meniscus posterior root (MMPR) repair during opening-wedge high tibial osteotomy (OWHTO) in terms of contact pressure (CP) and contact area (CA). METHODS: Nine fresh-frozen human cadaveric knee specimens were included. Each specimen was tested under 9 conditions comprising 3 different degrees of correction during OWHTO (neutral, 5° of valgus, and 10° of valgus) and 3 different types of MMPR conditions (intact, torn, and repaired). The prepared specimens were attached to a customized tibiofemoral jig in a fully extended state. The CP and CA generated by a tibiofemoral axial load of 650 N was recorded using the Tekscan sensor's pressure mapping software. Statistical analysis was performed using a repeated measures analysis of variance. RESULTS: The increased CP and decreased CA in torn MMPR was decreased and increased, respectively, to the intact MMPR after repairing, irrespective of whether OWHTO was performed. The mean CP at a correction angle of 5° of valgus was 0.4067 ± 0.0768 MPa for intact MMPR, which increased to 0.7340 ± 0.1593 MPa for the torn MMPR and decreased to 0.3614 ± 0.0639 MPa for the repaired MMPR. In addition, the proportion of decrease in CP and increase in CA after MMPR repair was constant, compared with the torn MMPR, irrespective of the degree of correction during OWHTO. CONCLUSIONS: MMPR repair decreases CP and increases CA, irrespective of whether OWHTO is performed. The biomechanical advantage of repairing torn MMPR is maintained, regardless of the degree of correction during OWHTO. CLINICAL RELEVANCE: Both OWHTO and MMPR repair are known to protect the medial compartment of the knee. However, there are concerns in performing 2 procedures simultaneously. Results of our study showed that concurrent repair of the MMPR during OWHTO is useful for protecting the medial compartment of the knee with respect to tibiofemoral contact biomechanics.

Repair of medial meniscus posterior root tear is effective for root healing and cartilage regeneration in opening wedge high tibial osteotomy.

PURPOSE: This study aimed to determine whether the repair of a medial meniscus posterior root tear (MMPRT) is effective for MMPRT healing, cartilage regeneration, and clinical outcomes in opening wedge high tibial osteotomy (OWHTO). METHODS: This retrospective study included 80 patients who underwent OWHTO and subsequent second-look arthroscopy. The patients were divided into OWHTO-with-MMPRT-repair (n = 40) and OWHTO alone (n = 40) groups, and the healing rates (complete/partial/failure) were compared. Each group was further divided into over- and under-corrected subgroups to compare healing rates. The International Cartilage Repair Society (ICRS) grade, cartilage defect size, Koshino stage, ICRS cartilage repair assessment score of the medial femoral condyle (MFC), and International Knee Documentation Committee (IKDC) scores between the OWHTO-with-MMPRT-repair and OWHTO alone groups were compared according to whether microfracture was performed on the MFC. RESULTS: The overall healing rate of the MMPRT was higher in the OWHTO-with-MMPRT-repair group than that in the OWHTO alone group (P < 0.001). In addition, in the subgroup analysis, no difference in the MMPRT healing rate between the over-correction and under-correction groups when MMPRT repair was performed (n.s). In contrast, without MMPRT repair, the healing rate was lower in the under-correction group than that in the over-correction group (P = 0.03). Cartilage regeneration of the OWHTO-with-MMPRT-repair group was superior to that of the OWHTO alone group (P < 0.05). The IKDC subjective scores of the OWHTO-with-MMPRT-repair and OWHTO alone groups were 34.5 and 33.1 before surgery (n.s) and 50 and 47.2 at one year after surgery, respectively (n.s). These differences between the two groups for cartilage regeneration and IKDC subjective scores showed the same pattern regardless of microfractures. CONCLUSIONS: MMPRT repair during OWHTO might improve MMPRT healing, even with under-correction, and cartilage regeneration of MFC, regardless of microfracture. However, OWHTO with MMPRT repair might not improve short-term clinical outcomes compared to OWHTO alone. Further randomized clinical trials are necessary. LEVEL OF EVIDENCE: III, Retrospective cohort study.

Delayed normalization of C-Reactive protein and erythrocyte sedimentation rate was not associated with inferior clinical outcomes after total knee arthroplasty.

BACKGROUND: The purpose of this study aimed to identify the proportion of patients with delayed normalization of C-reactive protein (CRP) and Erythrocyte sedimentation rate (ESR) after TKA, to determine postoperative thresholds predictive of prolonged elevation. Further, we aimed to determine if the clinical outcomes of patients with prolonged elevation were inferior to those without prolonged elevation. METHODS: The records of 211 unilateral and 320 bilateral TKA were reviewed. Patients were divided into the normal and elevation group based on CRP and ESR levels at 6 weeks and 3 months. The temporal pattern of CRP and ESR change in both groups was compared, and thresholds predictive of elevation at 6 weeks and 3 months were identified. Further, the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and Tegner activity scale of both groups at 6 months, 1 year, and 2 years after TKA were compared. RESULTS: The proportion of patients with elevated CRP and ESR at 6 weeks and 3 months was CRP: 24.2%, 10%, ESR: 51.6%, 29.9% in unilateral and CRP: 31.5%, 10.6%, ESR: 58.1%, 42.7% in bilateral TKA. The thresholds for elevation at 6 weeks and 3 months were 9.5 mg/dL, 11.4 mg/dL (CRP at 6 weeks) and 81.5 mm/h, 74.5 mm/h (ESR at 3 months). There was no difference in the WOMAC score and Tegner activity scale between both groups. CONCLUSIONS: CRP and ESR are often elevated for a prolonged period even in the absence of infection after TKA. Such cases show distinct temporal patterns, which are predictable, and do not appear to have a significant effect on clinical outcome.

Effectiveness of patient education on total knee arthroplasty: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: This study was designed to examine the contents and methods of patient educational interventions about total knee arthroplasty (TKA) and their effectiveness in reducing postoperative pain and enhancing range of motion (ROM) in the literature. BACKGROUND: Patient education has been provided to facilitate recovery after TKA; however, little is known about the contents and methods of the interventions and their effectiveness in reducing postoperative pain and enhancing ROM. DESIGN: This is a systematic review and meta-analysis of randomised controlled trials (RCTs). METHODS: Published studies from June 1998-June 2021 were identified from electronic databases. Two independent investigators assessed the quality of the studies by using the revised Cochrane risk-of-bias tool. Meta-analyses with random-effects models were conducted to assess the effectiveness of the interventions using the Comprehensive Meta-Analysis Software. The study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. RESULTS: Among 12 articles that met the inclusion criteria, three interventions provided education on pain management and mobility/exercises. The most common educational methods were the combinations of oral explanation, written materials, and audiovisual materials, group discussion, while four studies used information technology (IT) devices. The meta-analysis demonstrated that the educational interventions using IT devices were effective in improving pain and ROM, but not the interventions that did not use IT devices. CONCLUSION: Structured education for pain management, communication and/or exercise support programs utilising diverse methods have been provided to patients undergoing TKA. Using IT devices could successfully enhance the effectiveness of educational interventions for patients undergoing TKA. RELEVANCE TO CLINICAL PRACTICE: Integration of postoperative pain management and mobility/exercises with the use of IT devices should be actively considered in providing patient education in clinical nursing practice.

Fisetin, an Anti-Inflammatory Agent, Overcomes Radioresistance by Activating the PERK-ATF4-CHOP Axis in Liver Cancer.

Fisetin, a well-known plant flavonol from the natural flavonoid group, is found in traditional medicines, plants, vegetables, and fruits. Fisetin also has anti-oxidant, anti-inflammatory, and anti-tumor effects. This study investigated the anti-inflammatory effects of fisetin in LPS-induced Raw264.7 cells and found that fisetin reduced the LPS-induced production of pro-inflammation markers, such as TNF-α, IL-1ß, and IL-6, demonstrating the anti-inflammatory effects of fisetin. Furthermore, this study investigated the anti-cancer effects of fisetin and found that fisetin induced apoptotic cell death and ER stress through intracellular calcium (Ca2+) release, the PERK-ATF4-CHOP signaling pathway, and induction of GRP78 exosomes. However, the suppression of PERK and CHOP inhibited the fisetin-induced cell death and ER stress. Interestingly, fisetin induced apoptotic cell death and ER stress and inhibited the epithelial-mesenchymal transition phenomenon under radiation in radiation-resistant liver cancer cells. These findings indicate that the fisetin-induced ER stress can overcome radioresistance and induce cell death in liver cancer cells following radiation. Therefore, the anti-inflammatory agent fisetin, in combination with radiation, may be a powerful immunotherapy strategy to overcome resistance in an inflammatory tumor microenvironment.

Targeting ER Stress with Saikosaponin A to Overcome Resistance under Radiation in Gastric Cancer Cells.

Saikosaponin A is a triterpene saponin and a potentially bioactive compound derived from Bupleurum falcatum L. However, the molecular mechanisms and effects of saikosaponin A in gastric cancer remain unknown. In the present study, I evaluated the effects of saikosaponin A on cell death and endoplasmic reticulum stress via calcium and reactive oxygen species release. Targeting reactive oxygen species with diphenyleneiodonium and N-acetylcysteine inhibited cell death and protein kinase RNA-like ER kinase signaling pathway by down-regulating Nox4 and inducing glucose-regulated protein 78 exosomes. Furthermore, saikosaponin A caused a synergistic inhibitory effect of the epithelial mesenchymal transition phenomenon, indicating the reversible phenotype modulation by epithelial cells under radiation exposure in radiation-resistant gastric cancer cells. These results suggest that saikosaponin A-mediated calcium and reactive oxygen species-induced endoplasmic reticulum stress overcome radio-resistance and induce cell death under radiation in gastric cancer cells. Therefore, saikosaponin A in combination with radiation may be a potential strategy for gastric cancer therapy.

6-Shogaol Overcomes Gefitinib Resistance via ER Stress in Ovarian Cancer Cells.

In women, ovary cancer is already the fifth leading cause of mortality worldwide. The use of cancer therapies, such as surgery, radiotherapy, and chemotherapy, may be a powerful anti-cancer therapeutic strategy; however, these therapies still have many problems, including resistance, toxicity, and side effects. Therefore, natural herbal medicine has the potential to be used for cancer therapy because of its low toxicity, fewer side effects, and high success. This study aimed to investigate the anti-cancer effect of 6-shogaol in ovarian cancer cells. 6-shogaol induces ER stress and cell death via the reduction in cell viability, the increase in LDH cytotoxicity, caspase-3 activity, and Ca2+ release, and the upregulation of GRP78, p-PERK, p-eIF2α, ATF-4, CHOP, and DR5. Moreover, 6-shogaol treatment medicates endoplasmic reticulum (ER) stress and cell death by upregulating Nox4 and releasing ROS. The knockdown of Nox4 in ovarian cancer cells inhibits ER stress and cell death by blocking the reduction in cell viability and the enhancement of LDH cytotoxicity, caspase-3 activity, Ca2+, and ROS release. In gefitinib-resistant ovarian cancer cells, A2780R and OVCAR-3R, 6-shogaol/gefitinib overcomes gefitinib resistance by inhibiting EMT phenomena such as the reduction in E-cadherin, and the increase in N-cadherin, vimentin, Slug, and Snail. Therefore, our results suggest that 6-shogaol exerts a potential anti-cancer effect in ovarian cancer and combination treatment with 6-shogaol and gefitinib may provide a novel anti-tumor therapeutic strategy in gefitinib-resistant ovarian cancer.

Anatomical Study of the Lateral Tibial Spine as a Landmark for Weight Bearing Line Assessment during High Tibial Osteotomy.

Background: Accurate pre-operative planning is essential for successful high tibial osteotomy (HTO). The lateral tibial spine is a commonly used anatomical landmark for weight-bearing line assessment. However, studies on the mediolateral (M-L) position of the lateral tibial spine on the tibial plateau and its variability are limited. Purpose: This study aimed to (1) analyze the M-L position of the lateral tibial spine on the tibial plateau and its variability, (2) investigate radiologic parameters that affect the position of the lateral tibial spine, and (3) determine whether the lateral tibial spine can be a useful anatomical landmark for weight-bearing line assessment during HTO. Materials and Methods: Radiological evaluation was performed on 200 participants (64% female, mean age 42.3 ± 13.2 years) who had standing anterior-posterior plain knee radiographs with a patellar facing forward orientation. The distances from the medial border of the tibial plateau to the lateral spine peak (dLSP) and lateral spine inflection point (dLSI) were measured using a picture archiving and communication system. The medial-lateral inter-spine distance (dISP) was also measured. All parameters were presented as percentages of the entire tibial plateau width. The relationships between the parameters were also investigated. Results: The mean value of dLSP was 56.9 ± 2.5 (52.4-64.5)%, which was 5% lower than the Fujisawa point (62%). The mean value of dLSI was 67.9 ± 2.2 (63.4-75.8)%, which was approximately 5% higher than the Fujisawa point. The values of the dLSP and dLSI were variable among patients, and the upper and lower 10% groups showed significantly higher and lower dLSP and dLSI, respectively, than the middle 10% group. The mean value of dISP was 16.5 ± 2.4%, and it was positively correlated with dLSP and dLSI. Conclusions: On average, the dLSP and dLSI were located -5% and +5% laterally from the conventional Fujisawa point, and they may be useful landmarks for correction amount adjustment during HTO. However, it should be noted that correction based on the lateral tibial spine can be affected by anatomical variations, especially in patients with small or large inter-spine distances.

Single Nucleotide Polymorphisms May Increase the Risk of Aspiration Pneumonia in Post-Stroke Patients with Dysphagia.

This study aimed to evaluate whether genetic polymorphism is associated with an increased risk of infection, specifically post-stroke aspiration pneumonia. Blood samples were obtained from a total of 206 post-stroke participants (males, n = 136; mean age, 63.8 years). Genotyping was performed for catechol-O-methyltransferase (rs4680, rs165599), dopamine receptors (DRD1; rs4532, DRD2; rs1800497, DRD3; rs6280), brain-derived neurotrophic factor (rs6265), apolipoprotein E (rs429358, rs7412), and the interleukin-1 receptor antagonist gene (rs4251961). The subjects were stratified into two groups, aged < 65 (young) and ≥ 65 (elderly). Functional parameters and swallowing outcomes were measured at enrollment and at 3 months post-onset. The primary outcome was the incidence of aspiration pneumonia. Analysis of the association between genetic polymorphisms and aspiration pneumonia history showed that a minor C rs429358 allele was associated with the occurrence of aspiration pneumonia in the young group, both in the additive and the dominant models (odds ratio: 4.53; 95% CI: 1.60−12.84, p = 0.004). In the multivariable analysis, the minor C rs429358 allele increased the risk of post-stroke aspiration pneumonia in young stroke patients by 5.35 (95% CI: 1.64−20.88). In contrast, no such association was observed in the elderly group. Apolipoprotein E polymorphism may affect the risk of post-stroke aspiration pneumonia.

Nanocrack-regulated self-humidifying membranes.

The regulation of water content in polymeric membranes is important in a number of applications, such as reverse electrodialysis and proton-exchange fuel-cell membranes. External thermal and water management systems add both mass and size to systems, and so intrinsic mechanisms of retaining water and maintaining ionic transport in such membranes are particularly important for applications where small system size is important. For example, in proton-exchange membrane fuel cells, where water retention in the membrane is crucial for efficient transport of hydrated ions, by operating the cells at higher temperatures without external humidification, the membrane is self-humidified with water generated by electrochemical reactions. Here we report an alternative solution that does not rely on external regulation of water supply or high temperatures. Water content in hydrocarbon polymer membranes is regulated through nanometre-scale cracks ('nanocracks') in a hydrophobic surface coating. These cracks work as nanoscale valves to retard water desorption and to maintain ion conductivity in the membrane on dehumidification. Hydrocarbon fuel-cell membranes with surface nanocrack coatings operated at intermediate temperatures show improved electrochemical performance, and coated reverse-electrodialysis membranes show enhanced ionic selectivity with low bulk resistance.

Cinnamaldehyde induces autophagy-mediated cell death through ER stress and epigenetic modification in gastric cancer cells.

Previous reports suggested that cinnamaldehyde (CA), the bioactive ingredient in Cinnamomum cassia, can suppress tumor growth, migratory, and invasive abilities. However, the role and molecular mechanisms of CA in GC are not completely understood. In the present study, we found that CA-induced ER stress and cell death via the PERK-CHOP axis and Ca2+ release in GC cells. Inhibition of ER stress using specific-siRNA blocked CA-induced cell death. Interestingly, CA treatment resulted in autophagic cell death by inducing Beclin-1, ATG5, and LC3B expression and by inhibiting p62 expression whereas autophagy inhibition suppressed CA-induced cell death. We showed that CA induces the inhibition of G9a and the activation of LC3B. Moreover, CA inhibited G9a binding on Beclin-1 and LC3B promoter. Overall, these results suggested that CA regulates the PERK-CHOP signaling, and G9a inhibition activates autophagic cell death via ER stress in GC cells.

Regulation of mRNA export through API5 and nuclear FGF2 interaction.

API5 (APoptosis Inhibitor 5) and nuclear FGF2 (Fibroblast Growth Factor 2) are upregulated in various human cancers and are correlated with poor prognosis. Although their physical interaction has been identified, the function related to the resulting complex is unknown. Here, we determined the crystal structure of the API5-FGF2 complex and identified critical residues driving the protein interaction. These findings provided a structural basis for the nuclear localization of the FGF2 isoform lacking a canonical nuclear localization signal and identified a cryptic nuclear localization sequence in FGF2. The interaction between API5 and FGF2 was important for mRNA nuclear export through both the TREX and eIF4E/LRPPRC mRNA export complexes, thus regulating the export of bulk mRNA and specific mRNAs containing eIF4E sensitivity elements, such as c-MYC and cyclin D1. These data show the newly identified molecular function of API5 and nuclear FGF2, and provide a clue to understanding the dynamic regulation of mRNA export.

Effect of distance between the feet on knee joint line orientation after total knee arthroplasty in standing full-limb radiographs.

PURPOSE: Although knee joint line orientation (KJLO) after total knee arthroplasty (TKA) has been emphasized as an important factor that can affect postoperative knee kinematics, the effect of foot position on KJLO has not been fully understood. This study aimed to (1) identify the anatomical and positional factors that determine KJLO after TKA, and (2) determine the effect of foot position on KJLO after TKA. The hypothesis of this study was that the post-TKA KJLO would change depending on the distance between the feet, as well as the coronal implant positions. METHODS: A total of 92 radiographs from 46 patients who underwent TKA were retrospectively reviewed. Two postoperative standing full-limb anteroposterior radiographs taken with the feet in different positions (with both feet in contact with each other or shoulder width apart) from each patient were evaluated. The correlation between KJLO after TKA and possible anatomical and positional factors, including leg length, lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), ankle joint line orientation (AJLO), mechanical tibiofemoral angle (mTFA), and distance between the feet, were analyzed, and the KJLO equation was computed using multiple linear regression. KJLO was also compared among different combinations of valgus or varus alignment of the femoral and tibial components. RESULTS: LDFA, MPTA, AJLO, and distance between the feet were identified as determinants of KJLO after TKA, and the distance between the feet was strongly correlated with KJLO. Based on the KJLO equation (KJLO [°] = 107.548 - 0.441 × LDFA [°] - 0.832 × MPTA [°] + 0.093 × AJLO [°] + 0.037 × ITD [mm]), KJLO changes by 3.7° per 100 mm of distance between the feet. The KJLO of patients with valgus femoral and varus tibial components was more parallel to the ground than those with other combinations. CONCLUSION: KJLO after TKA was strongly affected by the distance between the feet when taking full-limb radiography, and the KJLO changed by 3.7° per 100 mm of distance between the feet. To assess the KJLO after TKA reproducibly, standardization of the distance between the feet is necessary. LEVEL OF EVIDENCE: IV.

Asymmetric transepicondylar axis between varus and valgus osteoarthritic knees in windswept deformity can be predicted by hip-knee-ankle angle difference.

PURPOSE: Studies regarding the best strategy to determine appropriate femoral component rotation during bilateral total knee arthroplasty (TKA) in wind swept deformities (WSD) are very limited. The purpose of this study was (1) to evaluate whether femoral rotational profiles differ between varus and valgus osteoarthritic knees in WSD and (2) to analyze the correlation between femoral rotational profiles and coronal radiologic parameters. METHODS: A total of 40 patients who were diagnosed with bilateral knee osteoarthritis with WSD between January 2010 and December 2020 at a single institution were retrospectively reviewed. On axial computed tomography scans, femoral rotational profile parameters such as the clinical transepicondylar axis (cTEA) and anterior-posterior (AP) axis were compared between valgus and varus osteoarthritic knees. In standing full-limb AP radiographs, coronal radiographic parameters including hip-knee-ankle angle (HKA), valgus correction angle (VCA), lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA) were measured in both knees. The correlation between the varus-valgus cTEA difference, and differences in coronal radiologic parameters was analyzed. RESULTS: In valgus osteoarthritic knees, cTEA was significantly increased compared to varus osteoarthritic knees by 1.5° (valgus: 7.65° ± 1.82°, varus: 6.15° ± 1.58°, p < 0.001). All coronal radiologic parameters, including HKA, LDFA, MPTA, JLCA, and VCA, were significantly different between valgus and varus knees. In correlation analysis, the varus-valgus cTEA difference was significantly correlated with LDFA (r = 0.365, p = 0.021), MPTA (r = 0.442, p = 0.004), and HKA differences (r = 0.693, p < 0.001), with the HKA difference showing the strongest correlation with the cTEA difference. CONCLUSION: In bilateral knee osteoarthritis with WSD, valgus knees showed significantly increased cTEA compared to varus knees, and the cTEA difference positively correlated with the HKA difference between valgus and varus knees. To determine the optimal femoral component rotation during TKA in WSD, assessment of cTEA with pre-operative CT scans or careful intra-operative measurement is recommended, especially in patients with large HKA difference. LEVEL OF EVIDENCE: III, Retrospective cohort study.