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The tumor microenvironment comprises both tumor and non-tumor stromal cells, including tumor-associated macrophages (TAMs), endothelial cells, and carcinoma-associated fibroblasts. TAMs, major components of non-tumor stromal cells, play a crucial role in creating an immunosuppressive environment by releasing cytokines, chemokines, growth factors, and immune checkpoint proteins that inhibit T cell activity. During tumors develop, cancer cells release various mediators, including chemokines and metabolites, that recruit monocytes to infiltrate tumor tissues and subsequently induce an M2-like phenotype and tumor-promoting properties. Metabolites are often overlooked as metabolic waste or detoxification products but may contribute to TAM polarization. Furthermore, macrophages display a high degree of plasticity among immune cells in the tumor microenvironment, enabling them to either inhibit or facilitate cancer progression. Therefore, TAM-targeting has emerged as a promising strategy in tumor immunotherapy. This review provides an overview of multiple representative metabolites involved in TAM phenotypes, focusing on their role in pro-tumoral polarization of M2.

Breast cancer is a frequently occurring malignant tumor that is one of the leading causes of cancer-related deaths in women worldwide. Monoclonal antibodies that block programed cell death 1 (PD-1)/programed cell death ligand 1 (PD-L1) – a typical immune checkpoint – are currently the recommended standard therapies for many advanced and metastatic tumors such as triple-negative breast cancer. However, some patients develop drug resistance, leading to unfavorable treatment outcomes. Therefore, other approaches are required for anticancer treatments, such as downregulation of PD-L1 expression and promotion of degradation of PD-L1. Scoparone (SCO) is a bioactive compound isolated from Artemisia capillaris that exhibits antitumor activity. However, the effect of SCO on PD-L1 expression in cancer has not been confirmed yet. This study aimed to evaluate the role of SCO in PD-L1 expression in breast cancer cells in vitro. Our results show that SCO downregulated PD-L1 expression in a dose-dependent manner, via AKT inhibition. Interestingly, SCO treatment did not alter PTEN expression, but increased the expression of mitogen-activated protein kinase phosphatase-3 (MKP-3). In addition, the SCO-induced decrease in PD-L1 expression was reversed by siRNA-mediated MKP-3 knockdown. Collectively, these findings suggest that SCO inhibited the expression of PD-L1 in breast cancer cells by upregulating MKP-3 expression. Therefore, SCO may serve as an innovative combinatorial agent for cancer immunotherapy.

Lithium niobate on insulator (LNOI) is a promising material platform for applications in integrated quantum photonics. A low optical loss is crucial for preserving fragile quantum states. Therefore, in this study, we have fabri-cated LNOI rib waveguides with a low optical propagation loss of 0.16 dB/cm by optimizing the etching conditions for various parameters. The symmetry and smoothness of the waveguides on x-cut LNOI are improved by employing a shallow etching process. The proposed method is expected to facilitate the development of on-chip quantum photonic devices based on LNOI.

During the laser directed energy deposition (LDED) process, the in-flight thermal dynamics of metal powders lead to the formation of detrimental by-products such as fumes, flames, and metal vapors. In this work, we use a high-speed camera to investigate the nuanced thermal stage changes of the powders, examining how gas flow rates and laser beam powers influence them. We identify distinct stages in the powder's journey: heating up, fusion and vaporization, flaming, tailing, and accelerated falling. Notably, the latter stages adversely affect both the processing environment and surface quality. Control over gas flow rate and laser beam power dictates the trajectory, duration, and intensity of tailing. Additionally, laser irradiation accelerates the falling speed of particles by 6.8–22.8% compared to non-irradiated ones. Higher laser beam powers increase vaporization-induced propulsion, culminating in escalated particle velocities. Optimal gas flow rates enhance the surface quality by significantly minimizing high-temperature spatter. Through this work, the in-flight thermal dynamic behaviors of metal particles and their impact on LDED processing are explained.

Abstract A novel auxetic structure applicable to airless tire spokes is designed based on the primitive-type triply periodic minimal surface (P-TPMS) to have higher stiffness through deformation under compressive force. For becoming higher stiffness by deformation, an unit cell of auxetic structure is proposed and its characteristics according to design parameters are studied. Based on the parametric study, a rotated primitive-type auxetic structure (RPAS) is designed, and the deformative behaviors of an airless tire with the RPAS spokes are compared with a generally used honeycomb spoke. Simulation and experiment results show that the designed RPAS tire exhibits more stable behavior through higher rigidity depending on the deformation state when compressed on flat ground and obstacles. This variable stiffness characteristic of RPAS tires can be advantageous for shock absorption and prevention of large local deformations. Also, the manufacturability of the designed auxetic structure is evaluated using real rubber-based additive manufacturing processes for practical application in the tire manufacturing industry.

Abstract Background In metaphyseo-diaphyseal (M-D) mismatched Dorr A femurs, it is difficult to achieve proper fixation with a type 1 stem. Proper interpretation of the geometry of the femur is integral at the preoperative stage in an M-D mismatched femur, but there has been a scarcity of studies on the radiologic indices. Therefore, we analyze the previous radiologic indices and suggest the novel ones for M-D mismatched femurs. Methods Our study was a retrospective review of preoperative radiographs of patients who underwent total hip arthroplasty with the smallest type 1 stem or with type 3 C stem at a single institution from July 2014 to March 2022. A Type 3 C stem was used when the smallest type 1 stem failed to achieve metaphyseal fixation. One hundred twenty-six patients were categorized into two main groups. Canal-flare index, canal-calcar ratio, modified morphological cortical index, and two novel indices (lesser trochanter-to-distal ratio-α and -β [LDR-α and -β]) were assessed on preoperative pelvic radiographs. Results Multivariate and ROC analysis demonstrated that high LDR-β (Exp[B]: 485.51, CI: 36.67-6427.97, p

Laser directed energy deposition (LDED) is a promising way for creating hard surfaces like ceramic-reinforced metal matrix composites (MMC), but it faces a significant challenge in identifying crack formation during the process. As an emerging solution, acoustic signal monitoring is easy to be integrated within the process, and significantly reduces the time needed to detect micro-cracks in as-built MMC surfaces. This study reports on cracking sounds produced while employing LDED with SiC particles on a stainless steel 316 L substrate, examining the sound characteristics across time and frequency domains. Different sound sources in LDED are analyzed in the frequency domain, specifying the suitable frequency range for crack monitoring. Interestingly, the in-process micro-cracking on the hard surfaces produces a distinct audible ‘ping’ sound typically ranging between 12000 and 16000 Hz. By recording this sound, an efficient approach is proposed to identify crack generation during the rapid cooling in the LDED process of hard materials.

Abstract Background Leg length discrepancy (LLD) is one of the troublesome complications of total hip arthroplasty (THA). Previously, several risk factors have been suggested, but they were subjected to their inherent limitations. By controlling confounding variables, we hypothesized that known risk factors be re-evaluated and novel ones be discovered. This study aimed to analyze the independent risk factors for LLD after primary THA in patients with non-traumatic osteonecrosis of the femoral head (ONFH). Methods We retrospectively reviewed patients with non-traumatic ONFH who underwent unilateral THA between 2014 and 2021. All patients were operated by one senior surgeon using a single implant. Demographic data, surgical parameters, and radiological findings (pre-operative LLD, Dorr classification, and femoral neck resection) were analyzed to identify the risk factors of ≥ 5 mm post-operative LLD based on radiological measurement and to calculate odds ratios by logistic regression analysis. Post hoc power analysis demonstrated that the number of analyzed patients was sufficient with 80% power. Results One hundred and eighty-six patients were analyzed, including 96 females, with a mean age of 58.8 years at the time of initial THA. The average post-operative LLD was 1.2 ± 2.9 mm in the control group and 9.7 ± 3.2 mm in the LLD group, respectively. The LLD group tended to have minimal pre-operative LLD than the control group (-3.2 ± 5.1 mm vs. -7.9 ± 5.8 mm p = 2.38 × 10− 8). No significant difference was found between the groups in age, gender, body mass index, femoral cortical index, and implant size. Conclusion Mild pre-operative LLD is associated with an increased risk of post-operative LLD after primary THA in patients with ONFH. Thus, surgeons should recognize pre-operative LLD to achieve an optimal outcome and must inform patients about the risk of developing LLD.

Abstract The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed “mid-old status” cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Remarkably, the microenvironmental change and the functional decline of mid-old cells could be reversed by a young cell-originated protein, SLIT2. Our data identify functional reversion of mid-old cells as a potential method to prevent or ameliorate aspects of aging-related tissue dysfunction.

Objective We previously reported the questionable result of reoperation using metal‐on‐polyethylene (MoP) bearing after the fracture of the ceramic component. After the report, we abandoned the use of MoP; instead, we used ceramic‐on‐ceramic (CoC) bearing. This report aimed to present the outcome of reoperation to CoC bearing after ceramic component failures along with the longer‐term outcome of the previously reported cohort with an MoP bearing. Results The mean follow‐up of the MoP cohort was extended from 4.3 years to 8.8 years. Metallosis had occurred in three of nine patients of the previous cohort, which all required re‐reoperations. Two hips from 11 patients with revision to CoC had re‐reoperations due to ceramic liner fracture and non‐union of the osteotomized fragment, respectively. No metallosis and wear occurred in the cohort revised with CoC articulation. Otherwise, there were no adverse changes in radiographs and no impairment in functions. Methods We conducted an extended prospective evaluation of a previous cohort consisting of six head fractures and three liner fractures. In this cohort, the patients underwent a bearing change to metal‐on‐polyethylene. Additionally, we retrospectively analyzed 11 cases of third‐generation ceramic bearing fractures, comprising nine head fractures and two liner fractures. These cases were subsequently treated with a bearing change to fourth‐generation CoC. We assessed clinical and radiological outcomes, including complication rates, in both groups. Conclusion We recommend the latest CoC as the bearing of choice in reoperation after the fracture of ceramic components. In the case of an MoP bearing after the ceramic component fracture, the risk of metallosis seemed high in the early postoperative period.

This study reports on a single-track laser surface alloying process that utilizes SiO2 powder to disperse both SiO2 particles and oxide inclusions in 316L stainless steel for oxide dispersion strengthening (ODS) purposes. In this process, the SiO2 powders partially dissolve in the melt pool, and the released silicon and oxygen atoms nucleate to form oxide inclusions in-situ within the metal matrix. This dissolution-induced oxide synthesis route demonstrated a high potential for ODS, achieving a high particle number density (6.6 × 104 mm−2) and area fraction (3.3%) comparable to that of bulk 316L samples produced via directed energy deposition. The hardness of the SiO2/316L composites reached a maximum of 232.4 HV compared to that of the 316L substrate (average 170.8 HV). The improvement in hardness was theoretically explained and quantified, significantly originating from the enhanced dislocation density strengthening mechanism resulting from the large difference in the coefficient of thermal expansion between SiO2 and 316L.

Maternal obesity and gestational diabetes are associated with childhood obesity and increased cardiovascular risk. In this review, we will discuss and summarize extensive clinical and experimental studies that metabolically imbalanced environment exposure in early life plays a critical role in influencing later susceptibility to chronic inflammatory diseases and metabolic syndrome. The effect of maternal obesity and metabolic disorders, including gestational diabetes cause Large-for-gestational-age (LGA) children to link future development of adverse health issues such as obesity, atherosclerosis, hypertension, and non-alcoholic fatty liver disease by immune reprogramming to adverse micro-environment. This review also addresses intrauterine environment-driven myeloid reprogramming by epigenetic regulations and the epigenetic markers as an underlying mechanism. This will facilitate future investigations regarding maternal-to-fetal immune regulation and the epigenetic mechanisms of obesity and cardiovascular diseases.

High-mobility group box 1 (HMGB1) is a protein that binds to DNA and participates in various cellular processes, including DNA repair, transcription, and inflammation. It is also associated with cancer progression and therapeutic resistance. Despite its known role in promoting tumor growth and immune evasion in the tumor microenvironment, the contribution of HMGB1 to the development of Kaposi’s sarcoma (KS) is not well understood. We investigated the effect of HMGB1 on KS pathogenesis using immortalized human endothelial cells infected with Kaposi’s sarcoma-associated human herpes virus (KSHV). Our results showed that a higher amount of HMGB1 was detected in the supernatant of KSHV-infected cells compared to that of mock-infected cells, indicating that KSHV infection induced the secretion of HMGB1 in human endothelial cells. By generating HMGB1 knockout clones from immortalized human endothelial cells using CRISPR/Cas9, we elucidated the role of HMGB1 in KSHV-infected endothelial cells. Our findings indicate that the absence of HMGB1 did not induce lytic replication in KSHV-infected cells, but the cell viability of KSHV-infected cells was decreased in both 2D and 3D cultures. Through the antibody array for cytokines and growth factors, CXCL5, PDGF-AA, G-CSF, Emmprin, IL-17A, and VEGF were found to be suppressed in HMGB1 KO KSHV-infected cells compared to the KSHV-infected wild-type control. Mechanistically, phosphorylation of p38 would be associated with transcriptional regulation of CXCL5, PDGF-A and VEGF. These observations suggest that HMGB1 may play a critical role in KS pathogenesis by regulating cytokine and growth factor secretion and emphasize its potential as a therapeutic target for KS by modulating the tumor microenvironment.

Tannic acid (TA) is a polyphenolic compound that exerts protective effects under pathological conditions. The diverse mechanisms of TA can exert beneficial anti-oxidative, anti-inflammatory, and anti-cancer effects. Herein, we reported that TA affords robust neuroprotection in an animal model of stroke (transient middle cerebral artery occlusion; tMCAO) and exhibits Zn2+-chelating and anti-oxidative effects in primary cortical neurons. Following tMCAO induction, intravenous administration of TA (5 mg/kg) suppressed infarct formation by 32.9 ± 16.2% when compared with tMCAO control animals, improving neurological deficits and motor function. We compared the chelation activity under several ionic conditions and observed that TA showed better Zn2+ chelation than Cu2+. Furthermore, TA markedly decreased lactate dehydrogenase release following acute Zn2+ treatment and subsequently reduced the expression of p67 (a cytosolic component of NADPH oxidase), indicating the potential mechanism underlying TA-mediated Zn2+ chelation and anti-oxidative effects in primary cortical neurons. These findings suggest that anti-Zn2+ toxicity and anti-oxidative effects participate in the TA-mediated neuroprotective effects in the postischemic brain.

Al nanoparticles are of significant interest due to their enhanced energetic properties and applicability in optics, biology, and the energy industry. We demonstrate the synthesis of core–shell Al nanoparticles via pulsed-laser-ablation-in-liquid, which reduces oxide formation and increases their resistance to reactive environments. When a bulk Al target was ablated in an organic solvent (acetone), high purity nanoparticles with a high Al content in the core part were generated. The size of the nanoparticles (6–7 nm) was not significantly changed according to the experimental conditions. However, low laser energy intensity is preferable due to less aggregation of nanoparticles and low impurity content. Amorphous and graphite carbon species were found in the coating of the core–shell Al nanoparticles. In addition, we show evidence of enolates or carboxylates in the coating material, as evidenced via energy dispersive spectroscopy and Fourier-transform infrared spectroscopy. Aging experiments in deionized water revealed that the passivated Al nanoparticles could maintain high purity in the core part and high stability in reactive environments such as water.

Clinical observations have revealed that non-resolving low-grade inflammation is linked to the pathogenesis of chronic inflammatory diseases, for example arthritis, atherosclerosis, Alzheimer’s disease, diabetes, and chronic kidney disease. Interestingly, low levels of circulating lipopolysaccharides (LPS) derived from the outer membrane of gram-negative bacteria appear to be one of the primary causes of persistent low-grade inflammation. The inner surface of the blood vessels is lined with endothelial cells; therefore, even low levels of circulating LPS can directly activate these cells and elicit specific cellular responses, such as an increase in the expression levels of cell adhesion molecules and proinflammatory mediators. In endothelial cells, LPS exposure results in an inflammatory response through activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases. Cynarin, a phytochemical found in artichokes, has several pharmacological properties against endothelial inflammation. In the present study, we discovered that cynarin suppressed the LPS-induced increase in the expression levels of vascular cell adhesion molecule-1 and proinflammatory mediators such as monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and interleukin-1β in EA.hy926 cells. Further, cynarin inhibited the activation of p38 and NF-κB pathways by inducing the negative regulator mitogen-activated protein kinase phosphatase 3 (MKP-3) in LPS-stimulated EA.hy926 cells. In conclusion, cynarin alleviates inflammation by upregulating MKP-3, a negative regulator of p38 and NF-κB, and it may be a therapeutic option for treating endothelial inflammation-related diseases.

Abstract Objective To evaluate the current incidence and economic cost and to estimate the future burden of periprosthetic fracture (PF) after joint arthroplasties in South Korea. Methods This study was a retrospective registry‐based study of patients who were diagnosed as periprosthetic fractures (PFs) in South Korea. Cases of PF from 2010 to 2017 in South Korea using Health Insurance and Review and Assessment (HIRA) database, which contains all medical claims for all South Korean patients, were identified. The operational definitions of PFs were identified from the Electronic Data Interchange (EDI) code of the Korean National Health Insurance Program (KHNIP). The annual incidence and medical costs during the period were calculated and the future increase of PF and its cost were projected through 2030 using generalized linear model with quasi‐poisson link. Results During the 8‐year period, 14,456 patients were treated due to PFs. The annual number of patients with PF remarkably increased from 1,322 in 2010 to 2,636 in 2017. The increment was prominent in age groups of 70–79 and ≧80. Total number of patients with PF were 9752 in women and 4704 in men during the study period. Mean personal costs were 1,155.4 USD in women and 1,185.5 USD in men. The total cost of PFs increased from 779,533 USD in 2010 to 3,888,402 USD in 2017. The personal cost of PFs also increased from 589.7 USD in 2010 to 1,475.1 USD in 2017. In 2017, the number of PF patients exponentially increased after 50 years of age especially in women. Estimated with our projection model, the number of PFs will increase by 2.5 times and the cost will increase by 10 times in the next 10 years. Conclusion The incidence and cost of PFs are rising and will represent a serious socioeconomic burden in South Korea.

Despite the well-known effects of loading rate and specimen size on glass strength, the fracture criterion of products containing tempered glass panels (TGPs) has been established based on the static fracture strength (SFS) of a standard-sized TGP due to procedural difficulties in determining large scale dynamic fracture strength (DFS). This impractical fracture criterion that has universally been adopted in industrial fields results in a use of excessive safety factor in product design and development process. In this work, large scale DFS of full-edge mounted TGPs is numerically predicted using ball drop impact (BDI) simulation, which realize in-service dynamic loading conditions and constraints. The numerical prediction results were verified by a remarkable correlation with a deformation deviation of 1.0–5.0% and stress deviation within about 6.9% comparing to BDI fracture test results. It was found that the average DFS derived in the practical BDI condition was 2.0 times higher than the average SFS derived in standard flexural test condition. We believe this study contributes to setting more efficient fracture criterion when designing or developing products in which TGPs are mounted, with emphasizing difference in glass strength derived from the in-service conditions and the standard test conditions.

Endothelial cell dysfunction and inflammatory responses play critical roles in the development of atherosclerosis. Recent data on the processes underlying atherogenesis indicate the substantial role of endotoxins (lipopolysaccharides; LPS) of the intestinal microflora in the initiation and progression of atherosclerosis. Mitogen-activated protein (MAP) kinase phosphatase-3 (MKP-3) is a cytoplasmic dual-specificity protein phosphatase that specifically binds to and inactivates MAP kinases in mammalian cells, but its biological function in endothelial cell dysfunction and inflammatory responses remains largely unknown. The aim of the present study was to investigate the role of MKP-3 in endotoxin-induced endothelial inflammation by western blotting, quantitative polymerase chain reaction, and immunofluorescence. The results of our study demonstrated that MKP-3 overexpression markedly inhibited the adhesion of human monocytic THP-1 cells to human umbilical vein endothelial cells (HUVECs) by downregulating the expression of vascular cell adhesion protein 1 (VCAM-1) and pro-inflammatory cytokines. In contrast, MKP-3-encoding gene knockdown by small interfering RNA (siRNA) exacerbated LPS-induced endothelial dysfunction. Additionally, we found that MKP-3 overexpression inhibited LPS-induced p38 MAPK phosphorylation and decreased the nuclear translocation of nuclear factor kappa B (NF-κB) after LPS treatment, suggesting its implication in the LPS/Toll-like receptor 4 (TLR4)/p38/NF-κB pathway. Overall, these observations suggest that MKP-3 plays a protective role in endothelial dysfunction and may be a therapeutic target.

Free-piston Stirling coolers (FPSCs), where the spring is connected to a piston instead of a crankshaft to eliminate the complicated mechanism, have a simple structure, and exhibit high thermal efficiency and reliability. The present study conducted a numerical analysis of the cooling performance of the FPSC system for various design factors such as the wire mesh number and porosity of the regenerator and displacer clearance. The system analysis model using the commercial SAGE software was established for heat exchangers with wire meshes. Also, this study investigated the effect of the cooling temperature at the acceptor wall on the cooling performance under the optimal condition. It was found that as the wire mesh number and porosity of the regenerator increased, the cooling capacity of the FPSC decreased. The friction loss decreased, but the leakage loss increased with the increase in displacer clearance thickness.

This study numerically investigated the cooling characteristics of a free-piston Stirling cooler (FPSC), which is considered as an alternative cooling system. In particular, the effect of the heat transfer area of the regenerator on the cooling performance and pressure loss of the FPSC was estimated. Commercial code ANSYS Fluent (v.17.2) was used for numerical analysis. A thermal non-equilibrium model was adopted to consider the effect of the heat transfer area of the wire mesh type regenerator. Furthermore, the dynamic mesh method was used to simulate the behavior of the dynamic components. As the heat transfer area of the regenerator increased, the cold end temperature that reached the quasi-steady state decreased. However, simultaneously, the pressure drop of the regenerator increased, which increased the input PV power required to drive the FPSC and decreased efficiency.

Polyunsaturated fatty acids (PUFAs) have important functions in biological systems. The beneficial effects of dietary PUFAs against inflammatory diseases, cardiovascular diseases, and metabolic disorders have been shown. Studies using cancer cells have presented the anti-tumorigenic effects of docosahexaenoic acid (DHA), an n-3 PUFA, while arachidonic acid (AA), an n-6 PUFA, has been shown to elicit both pro- and anti-tumorigenic effects. In the current study, the anti-tumorigenic effects of AA were evaluated in HT-29 human colon cancer cells. Upon adding AA in the media, more than 90% of HT-29 cells died, while the MCF7 cells showed good proliferation. AA inhibited the expression of SREBP-1 and its target genes that encode enzymes involved in fatty acid synthesis. As HT-29 cells contained lower basal levels of fatty acid synthase, a target gene of SREBP-1, than that in MCF7 cells, the inhibitory effects of AA on the fatty acid synthase levels in HT-29 cells were much stronger than those in MCF-7 cells. When oleic acid (OA), a monounsaturated fatty acid that can be synthesized endogenously, was added along with AA, the HT-29 cells were able to proliferate. These results suggested that HT-29 cells could not synthesize enough fatty acids for cell division in the presence of AA because of the suppression of lipogenesis. HT-29 cells may incorporate more AA into their membrane phospholipids to proliferate, which resulted in ER stress, thereby inducing apoptosis. AA could be used as an anti-tumorigenic agent against cancer cells in which the basal fatty acid synthase levels are low.

Purpose: This study examined the methods for treatment of femoral neck fracture (FNF) preferred by members of the Korean Hip Society (KHS) and identified factors that influence decisions regarding the surgical intervention of choice. Materials and Methods: A total of 97 members of the KHS responded to the 16-question survey which included questions about the mean number of surgeries performed each month for treatment of femoral neck fractures, the cut-off age for deciding between internal fixation and arthroplasty, the implant used most often, usage of cement, and factors influencing each decision. Results: The mean cut-off age used when deciding between internal fixation and arthroplasty was 64 years old. Hemiarthroplasty (HA) (70%) was the most preferred option for treatment of displaced FNFs in cases where arthroplasty was indicated (total hip arthroplasty [THA] 19% and dual mobility THA 11%). The main reasons for selection of arthroplasty over reduction with internal fixation were age and pre-fracture ambulatory status. Pre-trauma ambulatory status and/or sports activity were the main factors in selection of HA over THA. Cement was used by 33% of responders. Poor bone quality and a broad femoral canal were factors that influenced the usage of cement. Conclusion: Management of FNFs in the elderly is a major health problem worldwide; thus, remaining alert to current trends in treatment is essential for surgeons. The mean cut-off age used in deciding between internal fixation and arthroplasty was 64 years old. HA is the preferred method for treatment of displaced FNFs for members of the KHS. [ABSTRACT FROM AUTHOR]

Platycodin D (PD) is a major active component of the roots of Platycodon grandiflorum (Jacq.) A.DC. and possesses multiple biological and pharmacological properties, including anti-cancer activity. The aim of this study was to characterize PD-induced cytoplasmic vacuolation in human cancer cells and investigate the underlying mechanisms. PD-induced cancer cell death was associated with cytoplasmic pinocytic and autophagic vacuolation. Cellular energy levels were decreased by this compound, leading to the activation of AMP-activated protein kinase (AMPK). Additionally, compound C, an inhibitor of AMPK, completely prevented PD-induced vacuolation. These results suggest that PD induces cancer cell death, associated with excessive vacuolation through AMPK activation when cellular energy levels are low. Therefore, our findings provide a mechanistic rationale for a novel combinatorial approach using PD to treat cancer.

Abstract Cellular senescence can either support or inhibit cancer progression. Here, it is shown that intratumoral infiltration of CD8+ T cells is negatively associated with the proportion of senescent tumor cells in colorectal cancer (CRC). Gene expression analysis reveals increased expression of C‐X‐C motif chemokine ligand 12 (CXCL12) and colony stimulating factor 1 (CSF1) in senescent tumor cells. Senescent tumor cells inhibit CD8+ T cell infiltration by secreting a high concentration of CXCL12, which induces a loss of CXCR4 in T cells that result in impaired directional migration. CSF1 from senescent tumor cells enhance monocyte differentiation into M2 macrophages, which inhibit CD8+ T cell activation. Neutralization of CXCL12/CSF1 increases the effect of anti‐PD1 antibody in allograft tumors. Furthermore, inhibition of CXCL12 from senescent tumor cells enhances T cell infiltration and results in reducing the number and size of tumors in azoxymethane (AOM)/dextran sulfate sodium (DSS)‐induced CRC. These findings suggest senescent tumor cells generate a cytokine barrier protecting nonsenescent tumor cells from immune attack and provide a new target for overcoming the immunotherapy resistance of CRC.

Abstract Background Atherosclerosis is a chronic vascular inflammatory disease. Since even low-level endotoxemia constitutes a powerful and independent risk factor for the development of atherosclerosis, it is important to find therapies directed against the vascular effects of endotoxin to prevent atherosclerosis. Taraxacum officinale (TO) is used for medicinal purposes because of its choleretic, diuretic, antioxidative, anti-inflammatory, and anti-carcinogenic properties, but its anti-inflammatory effect on endothelial cells has not been established. Methods We evaluated the anti-inflammatory activity of TO filtered methanol extracts in LPS-stimulated human umbilical vein endothelial cells (HUVECs) by monocyte adhesion and western blot assays. HUVECs were pretreated with 100 μg/ml TO for 1 h and then incubated with 1 μg/ml LPS for 24 h. The mRNA and protein expression levels of the targets (pro-inflammatory cytokines and adhesion molecules) were analyzed by real-time PCR and western blot assays. We also preformed HPLC analysis to identify the components of the TO methanol extract. Results The TO filtered methanol extracts dramatically inhibited LPS-induced endothelial cell–monocyte interactions by reducing vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1, and pro-inflammatory cytokine expression. TO suppressed the LPS-induced nuclear translocation of NF-κB, whereas it did not affect MAPK activation. Conclusions Our findings demonstrated that methanol extracts of TO could attenuate LPS-induced endothelial cell activation by inhibiting the NF-κB pathway. These results indicate the potential clinical benefits and applications of TO for the prevention of vascular inflammation and atherosclerosis.

Background: The main purposes of this study were to assess the levels of parenting stress in the mothers of children with congenital hand or foot differences and to evaluate the effects of this stress on the preferred roles of mothers in surgical decision-making for their children. Methods: This study included 89 mothers of children with polydactyly of the hand, polydactyly of the foot, a hypoplastic thumb, or macrodactyly. The parenting stress level was assessed using the Parenting Stress Index–Short Form (PSI-SF). Additionally, the mothers were requested to indicate their preferred and retrospectively perceived levels of involvement in surgical decision-making for their children using the Control Preferences Scale, which is comprised of five levels ranging from fully active to fully passive. Results: The average PSI-SF scores were 73.9, and 15 mothers (17%) had a clinically significant level of stress (PSI-SF ≥ 90). In the mothers of children with polydactyly of the foot, the PSI score was associated with the preferred role in surgical decision-making. Conclusion: The assessment of parenting stress levels in the mothers of children with congenital hand or foot differences can play an important role in the screening of candidates who require psychiatric treatment or support. An evaluation of the PSI in mothers of children with congenital hand or foot differences may aid physicians to modify their style of decision-making based on the preferred role of the mother. Level of evidence: Level IV Therapeutic study.

This study investigates the transient behavior of an electro-thermal drilling probe (ETDP) during a close-contact melting process within a glacier. In particular, the present work analyzes the effect of the tip temperature on the formation of molten thin liquid films and the subsequent rate of penetration (ROP) through numerical simulation. We used the commercial code of ANSYS Fluent (v.17.2) to solve the Reynolds-averaged Navier–Stokes equation, together with an energy equation considering the solidification and melting model. The ROP of the drilling probe is determined based on the energy balance between the heating power and melting rate of ice. As the results, the ETDP penetrates the ice through a close-contact melting process. The molten liquid layer with less than 1 mm of thickness forms near the heated probe tip. In addition, the ROP increases with the heated temperature of the probe tip.