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Abstract: We investigated whether aqueous extract of the root of Platycodon grandiflorum A. de Candolle (APG), platycodinD3 and deapi-platycodin significantly affect the production and secretion of airway mucin using in vivo and in vitro experimental models. Effect of APG was checked on hypersecretion of pulmonary mucin in sulfur dioxide-induced bronchitis in rats. Confluent NCI-H292 cells were pretreated with platycodinD3 or deapi-platycodin for 30min and then stimulated with PMA (phorbol 12-myristate 13-acetate) for 24h. The MUC5AC mucin production and secretion were measured by ELISA. The results were as follows: (1) APG stimulated the secretion of airway mucin in sulfur dioxide-induced bronchitis rat model; (2) platycodinD3 and deapi-platycodin inhibited the production of MUC5AC mucin induced by PMA from NCI-H292 cells, respectively; (3) however, platycodinD3 and deapi-platycodin did not inhibit but stimulated the secretion of MUC5AC mucin induced by PMA from NCI-H292 cells, respectively. This result suggests that aqueous extract of P. grandiflorum A. de Candolle and the two natural products derived from it, platycodinD3 and deapi-platycodin, can regulate the production and secretion of airway mucin and, at least in part, explains the traditional use of aqueous extract of P. grandiflorum A. de Candolle as expectorants in diverse inflammatory pulmonary diseases. [Copyright &y& Elsevier]

Hesperidin, a flavonoid derived from citrus fruits, has been reported to show various biological effects including anticancer activity. This study investigated whether hesperidin affected the proliferation of MCF-7 human breast cancer cells transfected with green fluorescent protein (GFP)/ α-tubulin (MCF-7-GFP-Tubulin cells), androgen-independent PC-3 and DU-145 prostate cancer cells, and androgen-dependent LNCaP prostate cancer cells. The results were as follows. (1) Hesperidin inhibited the proliferation of MCF-7-GFP-Tubulin cells, probably not through an antimitotic mechanism. (2) Hesperidin also inhibited both basal and testosterone-induced proliferation of LNCaP cells. (3) However, hesperidin did not significantly affect the cell proliferation of two hormone-independent prostate cancer cells, PC-3 and DU-145. It is concluded that hesperidin can inhibit the proliferation of breast cancer cells through mechanisms other than antimitosis and it is suggested that hesperidin be further investigated for the possible interaction with androgenic receptors and involvement in signaling pathway after receptor binding in prostate cancer cells through future research. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Recurrence and metastasis remain major obstacles in colorectal cancer (CRC) treatment. Recent studies suggest that a small subpopulation of cells with a self-renewal ability, called cancer stem-like cells (CSCs), promotes recurrence and metastasis in CRC. Unfortunately, no CSC inhibitor has been demonstrated to be more effective than existing chemotherapeutic drugs, resulting in a significant unmet need for effective CRC therapies. In this study, transcriptomic profiling of metastatic tumors from CRC patients revealed significant upregulation in the Wnt pathway and stemness genes. Thus, we examined the therapeutic effect of the small-molecule Wnt inhibitor ICG-001 on cancer stemness and metastasis. The ICG-001 treatment efficiently attenuated self-renewal activity and metastatic potential. Mechanistically, myeloid ecotropic viral insertion site 1 (MEIS1) was identified as a target gene of ICG-001 that is transcriptionally regulated by Wnt signaling. A series of functional analyses revealed that MEIS1 enhanced the CSC behavior and metastatic potential of the CRC cells. Collectively, our findings suggest that ICG-001 efficiently inhibits CRC stemness and metastasis by suppressing MEIS1 expression. These results provide a basis for the further clinical investigation of ICG-001 as a targeted therapy for CSCs, opening a new avenue for the development of novel Wnt inhibitors for the treatment of CRC metastasis. [ABSTRACT FROM AUTHOR]

High heat-endurance bonding between Cu Ni was investigated by hybrid transient liquid phase sintering bonding. By simultaneously adding Cu and Ni to SAC305, the IMC was stably formed, and the bonding strength of hybrid TLPS joint was the highest. It is expected to be used for SiC die attachment of power module packaging. [Display omitted] • Novel hybrid transient liquid phase sintering bonding is developed for Cu Ni bonding. • Fast and stable ternary (Cu,Ni)-Sn IMCs were formed by hybrid transient liquid phase sintering bonding. • Electron probe micro-analyzer was used for investigating the atomic distribution of TLPS joints. A novel approach to copper-nickel bonding was investigated by hybrid transient liquid phase sintering (TLPS) method. Hybrid bonding material containing copper, nickel, and Sn-3.0Ag-0.5Cu (SAC305) and an organic solvent was fabricated to form a fast and stable ternary Cu Ni Sn intermetallic compound (IMC) joint between Cu to Ni joint. The atomic distribution was analyzed by an electron probe micro-analyzer, showing full IMC formation of the hybrid TLPS joint. In addition, by simultaneously adding Cu and Ni to SAC305, the IMC was stably formed, and the bonding strength of hybrid TLPS joint was the highest. [ABSTRACT FROM AUTHOR]

• Low temperature sintering process was performed with intensive pulsed light. • The pulse condition of intensive pulsed light affected on printed Cu circuit. • Electrochemical migration behavior of Cu circuit was investigated. Problems associated with the oxidation of Cu nanopaste have been widely studied in efforts to develop a replacement for Ag nanopaste. The intensive pulsed light (IPL) sintering process has been suggested to solve the oxidation problem because it is a method with a short processing time and is conducted at room temperature. Cu nanopaste was fabricated with Cu nanoparticles and a functional organic matrix. Cu nanopaste screen-printed onto a polyethylene terephthalate substrate was subjected to various IPL sintering conditions, and the effects of pulse power and pulse width on the microstructure, electrical resistivity, and electrochemical migration behavior of the printed Cu patterns were investigated. The electrical properties of the Cu patterns improved with increasing pulse power and pulse width because organic residues were removed by the IPL energy. The electrical properties of the Cu patterns improved with increasing pulse power and pulse width because organic residues were removed by the IPL energy. The electrochemical migration behavior was varied because of leaked ethylene glycol from organic matrix. The dendrites from lower pulse condition has finer microstructure and increased nucleation. [ABSTRACT FROM AUTHOR]

Stretchable electronic devices are desirable for the next application of electronic devices such as stretchable sensors, stretchable energy storage devices, and humanmachine interfaces. Also, stretchable electronic systems require a stretchable metal circuit on the elastomeric substrate for electrical connection to components. The stretchable circuits fabricated by Cu foil lamination on the thermoplastic polyurethane (TPU) film are investigated with various zigzag-patterned circuit designs. The various circuit designs are simulated by finite element analysis (FEA) for fatigue life prediction and the simulation results are compared with experimental results. The 6 types of zigzag-shaped circuit designs with different corner patterns are investigated. The thicknesses of the Cu electrode and TPU substrate are 18 μm and 50 μm, respectively. The stretchability of Cu stretchable circuits is evaluated by the uniaxial tensile test with 10% elongation. Also, the equivalent plastic strain is calculated for fatigue life prediction. The number of stretch cycles to failure increased as decreasing the equivalent plastic strain obtained by FEA. The tendency of crack propagation and fatigue life prediction are well agreed with FEA results. Thus, it is considered that modifying the circuit patterns of the strain concentration area is the most important to enhance the mechanical reliability of stretchable circuits. Unlabelled Image • Cu Stretchable circuits on TPU film were fabricated by Cu foil lamination process. • Various Cu stretchable circuit design by finite element analysis. • 10% elongation uniaxial tensile test was conducted with various designs. [ABSTRACT FROM AUTHOR]

Carbon fiber reinforced plastic (CFRP) is increasingly considered for various industrial applications. CFRP has been applied to the automotive industry to increase fuel efficiency due to its excellent strength and lightweight. Therefore, the demand for dissimilar material joining techniques is gradually increasing. In this study, we investigated the intense pulsed light (IPL) as surface treatment for CFRP. The IPL surface treatment requires a very short processing time and can be easily automated compared with other processes such as chemical and mechanical treatments. The change in morphology and chemical composition of the CFRP-treated surfaces was analyzed using scanning electron microscopy, profiler, and X-ray photoelectron spectroscopy. The bonding strength due to varying IPL exposure time was evaluated by the lap shear test. The apparent shear strength increased by up to 159% in this study. The IPL treatment is very simple and requires short processing time to produce enhanced adhesive joints. [ABSTRACT FROM AUTHOR]

A carbon nanotube (CNT) has remarkable properties, but it has disadvantages in application because of its dispersal- and bonding-related issues. Metal–CNT composite materials are necessary in solving these problems. In this study, nickel (Ni)–multi-walled CNTs (Ni–MWCNTs) are synthesized through sequential processing, functionalizing, and electroless plating processes to deposit Ni nanoparticles on MWCNTs. The synthesized Ni–MWCNTs are used to fabricate composite solders with various contents (0, 0.05, 0.1, and 0.2 wt%). The test kit used for the 3-point bending test in this study is designed with a differential package structure to evaluate the bending reliabilities of the Ni–MWCNT composite materials with various contents. The crack initiation and propagation in the microstructure evolution solder joints are also investigated. The bending reliabilities improve with the BGA structure and indicate that the highest bending cycle fails with 0.1 wt% of Ni–MWCNTs. The chemical composition and distribution of the Ni–MWCNTs in the solder joints are investigated with electron probe microanalysis. • Test-kits for 3-point bending test were designed with differential structure. • Bending test was performed to evaluate the mechanical properties of solder joints. • Ni-MWCNTs composite solder could improve the bending reliability of Sn58Bi solder. [ABSTRACT FROM AUTHOR]

The mechanical properties and microstructure of Sn-58 wt%Bi solder including various levels of Ag-decorated MWCNTs (0, 0.05, 0.1, and 0.2 wt%) were investigated for use in solder joints. The electronic industry relies on Pb-free solders because lead can have harmful effects on the environment and human health. The Sn-58 wt%Bi solder is a representative low temperature Pb-free solder with high tensile strength and good creep resistance. However, the Sn-58 wt%Bi solder has poor ductility for relieving shock impact. To address this drawback, Ag-decorated MWCNTs were used to reinforce the mechanical properties of Sn-58 wt%Bi solder. The Sn-58 wt%Bi-nanocomposite solder paste was fabricated by mechanically mixing Ag-decorated MWCNTs with solder paste. The Sn-58 wt%Bi solder pastes including Ag-decorated MWCNTs were printed on a printed circuit board (PCB), and the joints were aged in an isothermal environment. Inclusion of 0.1 wt% Ag-decorated MWCNTs increased the shear strength of the solder by about 15%. The thickness of the IMC of Sn-58 wt%Bi solder increased with age. • The Ag-decorated MWCNTs were synthesized with functionalizing process. • The Ag-decorated MWCNTs increased shear strength of Sn-58 wt%Bi solder. • Furthermore, Ag-decorated MWCNTs have an effects on microstructure of Sn-58 wt%Bi solder. [ABSTRACT FROM AUTHOR]

The effect of black residue (BR) formation on the mechanical properties of Sn-58Bi epoxy solder surface finished with an electroless nickel-immersion gold (ENIG) were evaluated with various reflow process conditions. The BR was formed around the solder ball after reflow process, and their area were variated with ramp time and peak temperatures. As peak temperature increased from 160 to 190 °C, the area ratio of the BR decreased from 50.3 to 18.0%. According to XRD, FT-IR, and XPS analyses, we assumed the most probable composition of the BR was epoxy or flux residue with Sn and Bi as well as carboxylate salts such as Bi(RCOO) 3 and Sn(RCOO) 2. These were generated by the carboxyl-based flux to prevent oxidation and reduce the surface tension of the molten solder in the epoxy-based Sn-58Bi soldering. The shear strength increased by 31.3% as the peak temperatures increased from 160 °C to 190 °C, while the fracture energy increased by 18.3%. We also investigated the effects of the addition of epoxy on the mechanical properties of Sn-58Bi solder joints under various reflow conditions. The bonding characteristic of the Sn-58Bi epoxy solder joints were elucidated via chemical analysis and by observing the fractures. The effect of black residue formation on the mechanical properties of Sn—58Bi epoxy solder surface finished with an electroless nickel-immersion gold were evaluated with various reflow process conditions. Unlabelled Image • The effect of black residue on the Sn—58Bi epoxy solder were evaluated. • The reflow profile affected on formation of black residue and mechanical property. • Remaining flux and epoxy were attributed to the formation of black residue. [ABSTRACT FROM AUTHOR]

Abstract Highly reliable bonding materials have attracted tremendous interest due to a growing demand for high-temperature electronics. We developed a fluxless and binder-free paste comprising Cu nanoparticles (NPs), Sn-58Bi (SnBi) particles, and polyvinylpyrrolidone (PVP) dispersing agent, which enables pressureless, low-temperature (190–250 °C) formation of robust joints (over 7 MPa) by means of transient liquid phase sintering (TLPS). Microstructural evolution of the joint was investigated under variations in PVP molecular weight (MW; 10,000, 55,000, 360,000, or 1,300,000) and bonding conditions including temperature and time. In a die-shear test, the joint formed with PVP MW 360,000 was the strongest due to its proper particle dispersion and the formation of intermetallic compounds (IMCs). Conditions of excessive PVP MW, bonding temperature, and time impeded the bonding characteristics of the TLPS joint, with formation of voids and increasing brittleness. TLPS bonding with the optimal dispersing agent enabled pressureless die attach without chip damage, demonstrating applicability as a simple, robust interconnection for high-temperature electronics. Highlights • Pressureless TLPS bonding was conducted with Cu nanoparticles and Sn-58Bi particles. • PVP MW of 360,000 assisted TLPS reactions by dispersing Cu and Sn-58Bi particles. • The process with excessively high energy degenerated strength by formation of voids. • The strength is consistent after aging time of 500 h due to completion of reactions. [ABSTRACT FROM AUTHOR]

Autophagy has bidirectional functions in cancer by facilitating cell survival and death in a context-dependent manner. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a large family of proteins essential for numerous biological processes, including autophagy; nevertheless, their potential function in cancer malignancy remains unclear. Here, we explored the gene expression patterns of SNAREs in tissues of patients with colorectal cancer (CRC) and discovered that SEC22B expression, a vesicle SNARE, was higher in tumor tissues than in normal tissues, with a more significant increase in metastatic tissues. Interestingly, SEC22B knockdown dramatically decreased CRC cell survival and growth, especially under stressful conditions, such as hypoxia and serum starvation, and decreased the number of stress-induced autophagic vacuoles. Moreover, SEC22B knockdown successfully attenuated liver metastasis in a CRC cell xenograft mouse model, with histological signs of decreased autophagic flux and proliferation within cancer cells. Together, this study posits that SEC22B plays a crucial role in enhancing the aggressiveness of CRC cells, suggesting that SEC22B might be an attractive therapeutic target for CRC. • SEC22B is elevated in CRC tumors, with a greater increase in metastatic tissues. • SEC22B inhibition reduces CRC cell survival and growth under stressful conditions. • SEC22B suppression blocks stress-induced autophagic flux. • Targeting SEC22B ameliorates the metastatic ability of CRC cells in vivo. [ABSTRACT FROM AUTHOR]

Background: Lipid rafts (LRs), cholesterol‐enriched microdomains on cell membranes, are increasingly viewed as signalling platforms governing critical facets of cancer progression. The phenotype of cancer stem‐like cells (CSCs) presents significant hurdles for successful cancer treatment, and the expression of several CSC markers is associated with LR integrity. However, LR implications in CSCs remain unclear. Methods: This study evaluated the biological and molecular functions of LRs in colorectal cancer (CRC) by using an LR‐disrupting alkylphospholipid (APL) drug, miltefosine. The mechanistic role of miltefosine in CSC inhibition was examined through normal or tumour intestinal mouse organoid, human CRC cell, CRC xenograft and miltefosine treatment gene expression profile analyses. Results: Miltefosine suppresses CSC populations and their self‐renewal activities in CRC cells, a CSC‐targeting effect leading to irreversible disruption of tumour‐initiating potential in vivo. Mechanistically, miltefosine reduced the expression of a set of genes, leading to stem cell death. Among them, miltefosine transcriptionally inhibited checkpoint kinase 1 (CHEK1), indicating that LR integrity is essential for CHEK1 expression regulation. In isolated CD44high CSCs, we found that CSCs exhibited stronger therapy resistance than non‐CSC counterparts by preventing cell death through CHEK1‐mediated cell cycle checkpoints. However, inhibition of the LR/CHEK1 axis by miltefosine released cell cycle checkpoints, forcing CSCs to enter inappropriate mitosis with accumulated DNA damage and resulting in catastrophic cell death. Conclusion: Our findings underscore the therapeutic potential of LR‐targeting APLs for CRC treatment that overcomes the therapy‐resistant phenotype of CSCs, highlighting the importance of the LR/CHEK1 axis as a novel mechanism of APLs. [ABSTRACT FROM AUTHOR]

Cu–Cu bonding was successfully achieved through the transient liquid phase sintering (TLPS) bonding method using Cu and an eutectic Sn–Bi alloy. The bonding process was performed for total bonding process time of 2 h under a pressureless condition in air. The bonding temperature was 220 °C considering that the Cu 6 Sn 5 intermetallic compound (IMC) and Bi react at 195.9 °C to transform into Cu 3 Sn and a liquid. The shear strength of Cu-70(Sn–58Bi) was approximately 22.06 MPa with the formation of the Cu 3 Sn. The residual eutectic Sn–Bi structure remained at Cu-90(Sn–58Bi), and the voids were largely observed at Cu-50(Sn–58Bi). In case of Cu-70(Sn–58Bi) and Cu-50(Sn–58Bi), the remelting temperature increased to 270 °C by the IMC reaction between Cu and Sn. On the other hand, the remelting temperature of Cu-90(Sn–58Bi) joint remained at 139 °C due to residual eutectic Sn–Bi structure. The salt spray test was conducted at 35 °C under the 5% NaCl condition for 24, 48, and 96 h to evaluate the bonding reliability under the salt spray condition. The corrosion behavior was evaluated using the electrochemical impedance spectroscopy measuring method. In addition, the thermal bonding reliability was investigated through a high-temperature storage test at 200 °C for 100, 500, and 1000 h. Analysis results of the experiment showed that the electrochemical and thermal bonding reliabilities were improved with the Cu 3 Sn formation owing to its high resistance properties under the salt spray and high-temperature conditions. • Pressureless transient liquid phase sintering bonding was achieved by composite paste consisted of Cu and Sn–58Bi. • TLPS joint consisted of Cu 3 Sn and Bi, was formed for high heat endurance and high reliable bonding. • Electrochemical and thermal bonding reliability was confirmed by salt spray and high-temperature storage test. [ABSTRACT FROM AUTHOR]

A Cu-cored solder ball (CCSB) is often used as the interconnection material for 3D package. The CCSB has a Cu core surrounded by Sn-Ag-Cu alloy. The effect of the Cu core on mechanical reliability of the CCSB was investigated using thermal shock test. Microstructure and thermal shock reliability of the CCSB with organic solderability preservative (OSP) surface finish was compared with that of Sn-3.0wt.%Ag-0.5wt.%Cu (SAC) solder. The thermal shock test was performed in the temperature range of −40 °C to 125 °C in compliance with JESD22-A104. Failure mechanism was analyzed by finite element method analysis. Average number of thermal shock cycles for the CCSB/OSP joints was 1.15 times higher than that for SAC/OSP joints. Maximum value of simulated plastic strain for the SAC/OSP joints was 1.25 times higher than that for the CCSB/OSP joints because the stand-off height of the CCSB/OSP joints could be maintained by the Cu core. • Thermal shock reliability of Cu cored solder joint was investigated. • Simulated stress and strain were reduced because stand-off height of solder ball was maintained by Cu core. • Crack of solder joint was propagated through the solder matrix that was highest simulated plastic strain regions. • Thermal shock reliability of solder joint was improved due to stand-off height. [ABSTRACT FROM AUTHOR]

Abstract We investigated the effect of Ag-coated multi-walled carbon nanotubes (Ag-MWCNT) on the microstructures and electromigration behaviors of a Sn58%Bi solder and organic solderability preservative (OSP) surface finished on the FR-4 printed circuit board (PCB) joint under a current stress of 3000 A/cm2 at 100 °C. Electromigration of Ag-MWCNT Sn58%Bi composite solder was investigated by daisy-chain test-kit. Reaction layers formed at the anode side and cathode side of the Sn58%Bi solder joints consisted of three microstructures; Bi-rich layer, Sn-rich layer, and intermetallic compounds (IMCs, Cu 6 Sn 5 and Cu 3 Sn). The Bi-rich layer was mainly formed at the anode side in the couple of the Sn58%Bi solder joint with various times of applying current stress. The Bi-rich layer of the Ag-MWCNT Sn58%Bi composite solder joint was approximately 2 times thinner than that of the Sn58%Bi solder joint because the Ag-MWCNT acts as a diffusion barrier. Also, the Cu 6 Sn 5 and Cu 3 Sn IMCs that formed at the interface between the Ag-MWCNT Sn58%Bi composite solder joints were thinner than those of the Sn58%Bi solder joints. The time to failure (TTF) was longest at the 0.05% Ag-MWCNT Sn58%Bi composite solder joint. Therefore, Ag MWCNT is expected to improve the reliability of electromigration in the Sn58%Bi composite solder joint. Highlights • The electromigration of the Ag-MWCNT Sn58%Bi composite solders were investigated. • Ag-coated MWCNTs were widely distributed in the Sn58%Bi solder joint. • MWCNT suppressed growths of Cu-Sn IMCs and Bi-rich layer under current stress. • TTF value of the 0.05 wt% Ag-MWCNT Sn58%Bi composite solder joint was the longest. [ABSTRACT FROM AUTHOR]

Ag circuit embedded in polydimethylsiloxane (PDMS) substrate were fabricated through photonic sintering and transfer of Ag nanoparticles (NPs) for reducing processing time, cost, damage to the substrate, and delamination caused by the low surface energy of PDMS. The photonic energy led to the microstructural evolution of a printed Ag circuit by rapid cluster formation and by removing the organics within several microseconds. Variations of surface roughness showed increasing trends at higher photonic energy conditions and drastic decrease after the embedding process. Hardness and electrical resistivity were measured before and after PDMS embedding, and after the second photonic sintering at various photonic energy conditions. The Ag circuit embedded in the PDMS substrate showed improved hardness by 207% due to the denser microstructure of the flipped surface and increased electrical resistivity increasing by 54% on average. Moreover, the effects of second sintering on the microstructure, electrical, and mechanical properties and the electrochemical reliability of the embedded Ag circuit are also studied. [ABSTRACT FROM AUTHOR]

Luteolin, a flavonoidal compound derived from Lonicera japonica Thunb. and Chrysanthemum indicum L., has been reported to show anti-inflammatory, anti-oxidative and anti-carcinogenic effects. In this study, we investigated whether luteolin significantly affects the secretion, production and gene expression of airway mucin. Confluent NCI-H292 cells were pretreated with luteolin for 30 min and then stimulated with EGF (epidermal growth factor) or PMA (phorbol 12-myristate 13-acetate) for 24 h or the indicated periods. The MUC5AC mucin gene expression was measured by RT-PCR. Production and secretion of MUC5AC mucin protein were measured by ELISA. To elucidate the action mechanism of luteolin, effect of luteolin on PMA-induced NF-κB signaling pathway was investigated by western blot analysis. The results were as follows: (1) Luteolin inhibited the secretion of MUC5AC mucin protein induced by EGF or PMA; (2) Luteolin inhibited the production of MUC5AC mucin protein and the expression of MUC5AC mucin gene induced by EGF or PMA; (3) Luteolin inhibited PMA-induced phosphorylation and degradation of inhibitory kappa Bα (IκBα); (4) Luteolin inhibited PMA-induced phosphorylation and nuclear translocation of nuclear factor kappa B (NF-κB) p65. This result suggests that luteolin can regulate the secretion, production and gene expression of mucin by acting on airway epithelial cells via regulation of NF-kB signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we investigated whether daidzein significantly affects secretion, production and gene expression of mucin from cultured airway epithelial cells. Confluent primary rat tracheal surface epithelial (RTSE) cells were pretreated with adenosine triphosphate (ATP) for 5 min and then chased for 30 min in the presence of daidzein to assess the effect on mucin secretion using ELISA. At the same time, confluent NCI-H292 cells were pretreated with daidzein for 30 min and then stimulated with EGF and PMA for 24 h, respectively. The MUC5AC mucin gene expression and mucin protein production were measured by RT-PCR and ELISA. The results were as follows: (1) daidzein significantly decreased ATP-induced mucin secretion from cultured RTSE cells; (2) daidzein inhibited the production of MUC5AC mucin protein induced by EGF or PMA from NCI-H292 cells; (3) daidzein also inhibited the expression of MUC5AC mucin gene induced by EGF or PMA from NCI-H292 cells. This result suggests that daidzein can regulate secretion, production and gene expression of mucin, by directly acting on airway epithelial cells. [Copyright &y& Elsevier]

(Meth)acrylate polymers are commonly used as photoresist materials in photolithography. However, these polymers encounter the problem of swelling during the development process. To address this, we explored the use of a hydrophobic group to control the solubility in the hydrophilic developer. In this study, we synthesized two types of polymers to evaluate the impact of the developer on (meth)acrylate polymers for photoresist applications. Adamantyl methacrylate (AdMA) was selected as the hydrophobic group, while 2-ethoxyethyl acrylate (2-EEA) served as the hydrophilic group, enabling the synthesis of both hydrophilic and hydrophobic polymers. Our goal was to assess how the presence of adamantyl monomers influenced the solubility of the polymer. This study demonstrated that solubility was primarily influenced by functional groups, particularly hydrophobic groups, rather than other factors. Polymers with more than 50% hydrophobic groups can be effectively controlled for their solubility in TMAH. These findings show that the solubility of photoresist polymers in TMAH can be tuned by incorporating a high proportion of hydrophobic groups. The study further confirms the role of adamantyl monomers as effective hydrophobic (aliphatic) groups in modulating the solubility of (meth)acrylate polymers in developer solutions.

Current approaches to regulating osteoarthritis primarily focus on symptom management; however, these methods often have significant side effects and may not be suitable for long-term care. As an alternative to conventional treatments, injecting stem cells into knee joint cartilage is a promising option for repairing damaged cartilage. In this review, we outline the general procedure for stem cell treatment of knee joint cartilage regeneration, emphasizing the potential of intra-articular stem cell injections as a therapeutic option for osteoarthritis. We examined and summarized patient evaluation and preparation for knee joint stem cell therapy, stem cell harvesting, stem cell preparation, injection procedures for stem cell therapy, post-injection care and monitoring, potential outcomes of stem cell therapy, and considerations and risks associated with stem cell therapy. Overall, stem cell injections for knee joint cartilage damage represent a promising frontier in orthopedic care. They offer potential benefits such as pain and inflammation reduction, promotion of cartilage repair and regeneration, and the possibility of avoiding more invasive treatments such as knee surgery. Ongoing collaboration among researchers, clinicians, and regulatory organizations is crucial for advancing this field and translating scientific discoveries into effective clinical applications.

The dynamic alteration of the tumor microenvironment (TME) serves as a driving force behind the progression and metastasis of colorectal cancer (CRC). Within the intricate TME, a pivotal player is the extracellular matrix (ECM), where modifications in components, degradation, and stiffness are considered critical factors in tumor development. In this study, we find that the membrane glycoprotein dysadherin directly targets matrix metalloprotease 9 (MMP9), initiating ECM remodeling within the TME and amplifying cancer progression. Mechanistically, the dysadherin/MMP9 axis not only enhances CRC cell invasiveness and ECM proteolytic activity but also activates cancer-associated fibroblasts, orchestrating the restructuring of the ECM through the synthesis of its components in human CRC cells, patient samples, and mouse models. Notably, disruption of ECM reorganization by dysadherin knockout results in a discernible reduction in the immunosuppressive and proangiogenic milieu in a humanized mouse model. Intriguingly, these effects are reversed upon the overexpression of MMP9, highlighting the intricate and pivotal role of the dysadherin/MMP9 axis in shaping the development of a malignant TME. Therefore, our findings not only highlight that dysadherin contributes to CRC progression by influencing the TME through ECM remodeling but also suggest that dysadherin may be a potential therapeutic target for CRC., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Photoresist polymers containing cycloaliphatic acrylic monomers have been synthesized for use in the microcircuits of semiconductors. Although cycloaliphatic acrylic monomers exhibit a high etch resistance and excellent thermal properties, their large size increases the distance between the main chains of the resulting polymers. This increased distance facilitates the penetration of a developer between the main chains, which leads to swelling and thus pattern collapse, distortion, and delamination, thereby complicating the fabrication of microcircuits. To solve this problem, various large developers were used in previous studies to reduce the swelling effect. However, these developers could not easily dissolve the unexposed regions of the resist. To overcome this issue, we designed photoresist polymers with smaller functional groups to decrease the degree of swelling. Specifically, ArF photoresist polymers were synthesized from monomers with various sizes of functional groups. We confirmed that the polymer synthesized using cyclohexyl methacrylate (CHMA), which had the smallest functional group, exhibited the shortest distance between the main chains. Consequently, this polymer showed the least swelling, with a swelling ratio of 109%. In contrast, the polymers synthesized using isobornyl acrylate (IBOA) and dicyclopentanyl methacrylate (TCDMA), which have large functional groups, exhibited greater distances between the main chains, resulting in swelling ratios of 114% and 112%, respectively. The polymer with a swelling ratio of 109% showed excellent patterning properties, while those with swelling ratios of 114% and 112% were delaminated by the developer. Our work introduces a novel approach to help reduce the swelling effect and achieve high-quality patterns in negative photoresists.

The aim of this study was to evaluate emodin, a natural trihydroxyanthraquinone compound found in the roots and barks of several plants including rhubarb and buckthorn, might attenuate epidermal growth factor (EGF)-induced airway MUC5AC mucin gene expression. The human pulmonary mucoepidermoid NCI-H292 cells were pretreated with for 30 min and then stimulated with EGF for the following 24 h. The effect of emodin on EGF-induced mitogen-activated protein kinase (MAPK) signaling pathway was examined. As a result, emodin blocked the expression of MUC5AC mucin mRNA and production of mucous glycoprotein via suppressing the phosphorylation of EGF receptor (EGFR), phosphorylation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) 1 and 2 (MEK1/2), phosphorylation of p38 MAPK, phosphorylation of ERK 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These findings imply that emodin has a potential to mitigate EGF-stimulated mucin gene expression by inhibiting the EGFR-MAPK-Sp1 signaling pathway, in NCI-H292 cells.

In this study, the potential effects of pyronaridine, an antimalarial agent, on airway MUC5AC mucin gene expression were investigated. The human pulmonary epithelial NCI-H292 cells were pretreated with pyronaridine for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. The effect of pyronaridine on the PMA-induced nuclear factor kappa B (NF-κB) signaling pathway was also examined. Pyronaridine inhibited glycoprotein production and mRNA expression of MUC5AC mucins induced by PMA through the inhibition of degradation of inhibitory kappa Bα and NF-κB p65 nuclear translocation. These results suggest that pyronaridine suppresses gene expression of mucin through regulation of the NF-κB signaling pathway in human pulmonary epithelial cells.

Dysregulation of cancer cell motility is a key driver of invasion and metastasis. High dysadherin expression in cancer cells is correlated with invasion and metastasis. Here, we found the molecular mechanism by which dysadherin regulates the migration and invasion of colon cancer (CC). Comprehensive analysis using single-cell RNA sequencing data from CC patients revealed that high dysadherin expression in cells is linked to cell migration-related gene signatures. We confirmed that the deletion of dysadherin in tumor cells hindered local invasion and distant migration using in vivo tumor models. In this context, by performing cell morphological analysis, we found that aberrant cell migration resulted from impaired actin dynamics, focal adhesion turnover and protrusive structure formation upon dysadherin expression. Mechanistically, the activation of focal adhesion kinase (FAK) was observed in dysadherin-enriched cells. The dysadherin/FAK axis enhanced cell migration and invasion by activating the FAK downstream cascade, which includes the Rho family of small GTPases. Overall, this study illuminates the role of dysadherin in modulating cancer cell migration by forcing actin dynamics and protrusive structure formation via FAK signaling, indicating that targeting dysadherin may be a potential therapeutic strategy for CC patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)-β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

In this study, artesunate, an antimalarial agent, was investigated for its potential effect on the gene expression of airway MUC5AC mucin. The human pulmonary epithelial NCI-H292 cells were pretreated with artesunate for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of artesunate on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also examined. Artesunate inhibited the glycoprotein production and mRNA expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest artesunate suppresses the gene expression of mucin through regulation of NF-kB signaling pathway, in human pulmonary epithelial cells.

The current study aimed to reveal the potential effect of meclofenamate, a nonsteroidal anti-inflammatory drug, on the gene expression of airway MUC5AC mucin. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with meclofenamate for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. Thereafter, the effect of meclofenamate on the PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was assessed. Meclofenamate inhibited glycoprotein production and mRNA expression of MUC5AC mucins induced by PMA by inhibiting the degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest meclofenamate suppresses mucin gene expression by regulating NF-kB signaling pathway in human pulmonary epithelial cells.

Background: Predicting the survival of cancer patients provides prognostic information and therapeutic guidance. However, improved prediction models are needed for use in diagnosis and treatment., Objective: This study aimed to identify genomic prognostic biomarkers related to colon cancer (CC) based on computational data and to develop survival prediction models., Methods: We performed machine-learning (ML) analysis to screen pathogenic survival-related driver genes related to patient prognosis by integrating copy number variation and gene expression data. Moreover, in silico system analysis was performed to clinically assess data from ML analysis, and we identified RABGAP1L, MYH9, and DRD4 as candidate genes. These three genes and tumor stages were used to generate survival prediction models. Moreover, the genes were validated by experimental and clinical analyses, and the theranostic application of the survival prediction models was assessed., Results: RABGAP1L, MYH9, and DRD4 were identified as survival-related candidate genes by ML and in silico system analysis. The survival prediction model using the expression of the three genes showed higher predictive performance when applied to predict the prognosis of CC patients. A series of functional analyses revealed that each knockdown of three genes reduced the protumor activity of CC cells. In particular, validation with an independent cohort of CC patients confirmed that the coexpression of MYH9 and DRD4 gene expression reflected poorer clinical outcomes in terms of overall survival and disease-free survival., Conclusions: Our survival prediction approach will contribute to providing information on patients and developing a therapeutic strategy for CC patients., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Betulin is a triterpenoid natural product contained in several medicinal plants including Betulae Cortex. These medicinal plants have been used for controlling diverse inflammatory diseases in folk medicine and betulin showed anti-inflammatory, antioxidative, and anticancer activities. In this study, we tried to examine whether betulin exerts a regulative effect on the gene expression of MUC5AC mucin under the status simulating a pulmonary inflammation, in human airway epithelial cells. Confluent NCI-H292 cells were pretreated with betulin for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h or the indicated periods. The MUC5AC mucin mRNA expression and mucin glycoprotein production were measured by reverse transcription - polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. To elucidate the action mechanism of betulin, effect of betulin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated by western blot analysis. The results were as follows: 1) Betulin significantly suppressed the production of MUC5AC mucin glycoprotein and down-regulated MUC5AC mRNA expression induced by PMA in NCI-H292 cells. 2) Betulin inhibited NF-κB activation stimulated by PMA. Suppression of inhibitory kappa B kinase (IKK) by betulin led to the inhibition of the phosphorylation and degradation of inhibitory kappa B alpha (IκBα), and the nuclear translocation of NF-κB p65. This, in turn, led to the down-regulation of MUC5AC glycoprotein production in NCI-H292 cells. These results suggest betulin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

In this study, we examined whether engeletin exerts an effect on the gene expression of MUC5AC mucin, in human pulmonary epithelial NCI-H292 cells. The cells were pretreated with engeletin for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of engeletin on PMA-induced nuclear factor kappa B (NF-kB) signaling pathway was also investigated. Engeletin suppressed the mRNA expression and production of MUC5AC mucin, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest engeletin inhibits the gene expression of mucin through regulation of NF-kB signaling pathway, in human airway epithelial cells.

Rationale: Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that selectively marks cancer stem-like cells (CSCs) and promotes malignant progression in colorectal cancer (CRC). However, the exact molecular mechanism by which DCLK1 drives the aggressive phenotype of cancer cells is incompletely determined. Methods: Here, we performed comprehensive genomics and proteomics analyses to identify binding proteins of DCLK1 and discovered X-ray repair cross-complementing 5 (XRCC5). Thus, we explored the biological role and downstream events of the DCLK1/XRCC5 axis in human CRC cells and CRC mouse models. Results: The results of comprehensive bioinformatics analyses suggested that DCLK1-driven CRC aggressiveness is linked to inflammation. Mechanistically, DCLK1 bound and phosphorylated XRCC5, which in turn transcriptionally activated cyclooxygenase-2 expression and enhanced prostaglandin E 2 production; these events collectively generated the inflammatory tumor microenvironment and enhanced the aggressive behavior of CRC cells. Consistent with the discovered mechanism, inhibition of DCLK1 kinase activity strongly impaired the tumor seeding and growth capabilities in CRC mouse models. Conclusion: Our study illuminates a novel mechanism that mediates the pro-inflammatory function of CSCs in driving the aggressive phenotype of CRC, broadening the biological function of DCLK1 in CRC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Rationale : Dysadherin is a tumor-associated, membrane-embedded antigen found in multiple types of cancer cells, and associated with malignant behavior of cancer cells; however, the fundamental molecular mechanism by which dysadherin drives aggressive phenotypes of cancer is not yet fully determined. Methods : To get a mechanistic insight, we explored the physiological relevance of dysadherin on intestinal tumorigenesis using dysadherin knockout mice and investigated its impact on clinicopathological features in patients with advanced colorectal cancer (CRC). Next, to discover the downstream signaling pathways of dysadherin, we applied bioinformatic analysis using gene expression data of CRC patient tumors and dysadherin knockout cancer cells. Additionally, comprehensive proteomic and molecular analyses were performed to identify dysadherin-interacting proteins and their functions. Results : Dysadherin deficiency suppressed intestinal tumorigenesis in both genetic and chemical mouse models. Moreover, increased dysadherin expression in cancer cells accounted for shorter survival in CRC patients. Comprehensive bioinformatics analyses suggested that the effect of dysadherin deletion is linked to a reduction in the extracellular matrix receptor signaling pathway. Mechanistically, the extracellular domain of dysadherin bound fibronectin and enhanced cancer cell adhesion to fibronectin, facilitating the activation of integrin-mediated mechanotransduction and leading to yes-associated protein 1 activation. Dysadherin-fibronectin interaction promoted cancer cell growth, survival, migration, and invasion, effects collectively mediated the protumor activity of dysadherin. Conclusion : Our results highlight a novel function of dysadherin as a driver of mechanotransduction that stimulates CRC progression, providing a potential therapy strategy for CRC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Towards the end of 2019, an atypical acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China and subsequently named Coronavirus disease 2019 (COVID-19). The rapid dissemination of COVID-19 has provoked a global crisis in public health. COVID-19 has been reported to cause sepsis, severe infections in the respiratory tract, multiple organ failure, and pulmonary fibrosis, all of which might induce mortality. Although several vaccines for COVID-19 are currently being administered worldwide, the COVID-19 pandemic is not yet effectively under control. Therefore, novel therapeutic agents to eradicate the cause of the disease and/or manage the clinical symptoms of COVID-19 should be developed to effectively regulate the current pandemic. In this review, we discuss the possibility of managing the clinical symptoms of COVID-19 using natural products derived from medicinal plants used for controlling pulmonary inflammatory diseases in folk medicine. Diverse natural products have been reported to exert potential antiviral effects in vitro by affecting viral replication, entry into host cells, assembly in host cells, and release. However, the in vivo antiviral effects and clinical antiviral efficacies of these natural products against SARS-CoV-2 have not been successfully proven to date. Thus, these properties need to be elucidated through further investigations, including randomized clinical trials, in order to develop optimal and ideal therapeutic candidates for COVID-19.

In this study, we investigated whether eriodictyol exerts an effect on the production and gene expression of MUC5AC mucin in human pulmonary epithelial NCI-H292 cells. The cells were pretreated with eriodictyol for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. The effect of eriodictyol on PMA-induced nuclear factor kappa B (NF-κB) signaling pathway was also investigated. Eriodictyol suppressed the MUC5AC mucin production and gene expression induced by PMA via suppression of inhibitory kappa Bα degradation and NF-κB p65 nuclear translocation. These results suggest that eriodictyol inhibits mucin gene expression and production in human airway epithelial cells via regulation of the NF-κB signaling pathway.