Search

PDF file, 779K, Figure S1. Expressionofp-KIT,p-AKT,andp-ERK increased according to the increased SCF concentrationin two KIT-expressingcelllines. Figure S2. Expression of KIT, p-KIT, p-AKT, and p-ERK after SCF treatment in two tumor cell lines with KIT mutation. FigureS3.Quantification of Westernblotting results for Fig.1E. FigureS4. Membranous KITexpression of DLD-1 was determined by FACS. Figure S5. Mutant KIT is not degraded after SCF treatment. Figure S6. FACS analysis of p-AKT and p-ERK expressing colon cancer cells treated with SCF and PMA. Figure S7. FACS analysis of KIT expression in the DLD-1 cells transfectedwith wild-type (Rab11-WT) or dominant-negative mutant form of Rab11 (Rab11-S25N). Figure S8. Effects of imatinibon CRC cells expressing KIT. FigureS9. DLD-1 cell number and invasion were increased after SCF and PMA treatment. FigureS10. Expression of SCF mRNA expression in CRC cell lines. Figure S11.Colon cancers expressing WT-KIT constantly generated activated KIT-SCF signaling as a result of KIT recycling in a condition of endogenous PKC-delta activation.

PDF file, 160K, Supplementary Table 1. Primer and siRNA sequences Supplementary Table 2. Clinicopathological characteristics of 250 colorectal cancers according to KIT expression.

Purpose: Abnormal signaling through receptor tyrosine kinase (RTK) moieties is important in tumorigenesis and drug targeting of colorectal cancers. Wild-type KIT (WT-KIT), a RTK that is activated upon binding with stem cell factor (SCF), is highly expressed in some colon cancers; however, little is known about the functional role of SCF-dependent KIT activation in colon cancer pathogenesis. We aimed to elucidate the conditions and roles of WT-KIT activation in colon cancer tumorigenesis.Experimental Design: Colorectal cancers with KIT expression were characterized by immunoblotting and immunohistochemistry. The biologic alterations after KIT-SCF binding were analyzed with or without protein kinase C (PKC) activation.Results: We found that WT-KIT was expressed in a subset of colon cancer cell lines and was activated by SCF, leading to activation of downstream AKT and extracellular signal-regulated kinase (ERK) signaling pathways. We also showed that KIT expression gradually decreased, after prolonged SCF stimulation, due to lysosomal degradation. Degradation of WT-KIT after SCF binding was significantly rescued when PKC was activated. We also showed the involvement of activated PKC-δ in the recycling of WT-KIT. We further showed that a subset of colorectal cancers exhibit expressions of both WT-KIT and activated PKC-δ and that expression of KIT is correlated with poor patient survival (P = 0.004).Conclusions: Continuous downstream signal activation after KIT-SCF binding is accomplished through PKC-δ–mediated recycling of KIT. This sustained KIT activation may contribute to tumor progression in a subset of colon cancers with KIT expression and might provide the rationale for a therapeutic approach targeting KIT. Clin Cancer Res; 19(18); 4961–71. ©2013 AACR.

Although the neuroinvasiveness of SARS-CoV-2 has been extensively studied, the correlation between virus infectivity and brain maturation remained unclear. Here, using human-induced pluripotent stem cells-derived three-dimensional cerebral organoids (CBOs), we present the first quantitative data for long-term kinetics of SARS-CoV-2 propagation in brain for 20 days post-infection. We showed that mature brains are more susceptible to SARS-CoV-2 than immature counterparts, evident from increased viral replication rate and higher TUNEL + cells proportion. Transcriptome profiling identified enhancement of corticogenesis and gliogenesis and indicated enrichments in translation machinery- and lipid metabolism-associated genes in mature brain, suggesting the major factors conferring the robust infectivity of SARS-CoV-2. The role of cholesterol in promoting viral replication was confirmed by the reduced number of infected cells in lipid lowering-drugs condition. Together, this study highlights that permissiveness of the brains to SARS-CoV-2 is greatly enhanced with their maturation and suggests cholesterol as a new target for suppressing viral replication.

To evaluate the effectiveness of acupuncture treatment for shoulder impingement syndrome (SIS) a literature review was conducted of randomized controlled trials (RCTs) where acupuncture was used as an intervention for patients diagnosed with SIS. Relevant clinical studies (N = 181) were retrieved from several databases based on the inclusion/exclusion criteria, and the interventions and results were analyzed. Six RCTs were selected to review based on the inclusion and exclusion criteria. In all 6 studies, the acupuncture treatment group showed significant positive changes in indicators evaluating pain, disability, and quality of life. A significant decrease in the evaluation indicators (Shoulder Pain and Disability Index, numeric rating scale, Visual Analogue Scale, Constant Murley Shoulder Assessment Score, patient’s global assessment, and doctor’s global assessment) and a significant increase in the questionnaire scores (UCLA, AL-score, EuroQol 5 Dimension Self-Report Questionnaire, and disabilities of the arm, shoulder, and hand) were observed. In addition, 1 study showed similar improvements in pain and quality of life measures in the acupuncture group and corticosteroid injection group. No major side effects were reported. Acupuncture may be an effective and safe treatment for SIS however, further RCTs are required.

As living liver transplantation has become a standard treatment method with a high success rate, many studies have investigated the experiences of living liver donors; however, their results have not been integrated. This qualitative meta-synthesis aimed to explore the life experiences of living liver donors to provide an in-depth understanding of meaningful common experiences. A comprehensive search on qualitative studies published in English or Korean was conducted in October 2021. The PRISMA statement was used for reporting each phase of the literature search, and MAXQDA2020 software was used for data analysis. Data synthesis was conducted using the three-step thematic synthesis method suggested by Thomas and Harden. Ten articles met the inclusion criteria. The analysis revealed five main themes: "Becoming an earnest donor," "Transitioning from a potential donor to an actual donor," "Difficulties in returning to normal life," "Re-examining the meaning of donation," and "Wishes for prospective donors." The study emphasizes that living liver donors need medical attention and intervention from multilateral perspectives as well as the need for systematic change in the society to enhance support for donors. This review provides comprehensive insights on how individuals became the living liver donor and the important aspects of living donation and other considerations in an integrated manner. Transplant teams, including nurses and coordinators, should have a comprehensive understanding of physical, psychological, and social experiences of donors ranging from decision-making to post donation health management.

PARP inhibitors are the first clinically approved drugs that were developed based on synthetic lethality. PARP inhibitors have shown promising outcomes since their clinical applications and have recently been approved as maintenance treatment for cancer patients with BRCA mutations. PARP inhibitors also exhibit positive results even in patients without homologous recombination (HR) deficiency. Therapeutic effects were successfully achieved; however, the development of resistance was unavoidable. Approximately 40–70% of patients are likely to develop resistance. Here, we describe the mechanisms of action of PARP inhibitors, the causes of resistance, and the various efforts to overcome resistance. Particularly, we determined the survival probability of cancer patients according to the expression patterns of genes associated with HR restoration, which are critical for the development of PARP inhibitor resistance. Furthermore, we discuss the innovative attempts to degrade PARP proteins by chemically modifying PARP inhibitors. These efforts would enhance the efficacy of PARP inhibitors or expand the scope of their usage.

Background People with disabilities are vulnerable to chronic diseases such as hypertension. In South Korea, over half of the population living with a physical disability suffer from hypertension. Understanding the typology of hypertension self-management patterns will assist with behavioural interventions for people with physical disabilities. Thus, this study aims to identify the typology of hypertension self-management behavioural patterns, the factors associated with the latent classes, and to recognise potential at-risk populations by comparing potential health outcomes among hypertensive adults with physical disabilities. Methods Data of 1551 participants were extracted from the 2017 National Survey of Disabled Persons. Latent classes were analysed using five indicators of self-management: smoking, alcohol consumption, physical activity, diet, and weight control. Determinants of self-management patterns, such as general characteristics, health-related factors, and social relationships, were identified using multinomial logistic regression. Further, health measures, such as health profile, psychological health, and patient experience, were compared. Results The following three latent classes were identified: “high self-management” group (40.8%), “harmful habitual behaviour” group (20.6%), and “inactive behaviour” group (38.6%). Compared with the high self-management group, the predictors of belonging to the harmful habitual behaviour group were being male, young, and single. Being female, employed, severely disabled, dependent, and unsatisfied with friendships were predictors of the inactive behaviour group. Those in the inactive behaviour group had a poor health-related quality of life, poor subjective health, depression, and unmet medical needs. Conclusions This study provides evidence that there are mutually exclusive subgroups of patients with hypertension regarding self-management patterns, identifies an array of predictive factors in each latent class membership, and distinguishes a high-risk group by comparing the health measures among patients with hypertension with physical disabilities. Analysing subgroups may assist in identifying and meeting the diverse needs of self-management support in hypertensive patients with physical disabilities.

Fungal sexual reproduction requires complex cellular differentiation processes of hyphal cells. The plant pathogenic fungus Fusarium graminearum produces fruiting bodies called perithecia via sexual reproduction, and perithecia forcibly discharge ascospores into the air for disease initiation and propagation. Lipid metabolism and accumulation are closely related to perithecium formation, yet the molecular mechanisms that regulate these processes are largely unknown. Here, we report that a novel fungal specific bZIP transcription factor, F. graminearum perithecium overproducing 1 (Fpo1), plays a role as a global transcriptional repressor during perithecium production and maturation in F. graminearum. Deletion of FPO1 resulted in reduced vegetative growth, asexual sporulation and virulence and overproduced perithecium, which reached maturity earlier, compared with the wild type. Intriguingly, the hyphae of the fpo1 mutant accumulated excess lipids during perithecium production. Using a combination of molecular biological, transcriptomic and biochemical approaches, we demonstrate that repression of FPO1 after sexual induction leads to reprogramming of carbon metabolism, particularly fatty acid production, which affects sexual reproduction of this fungus. This is the first report of a perithecium-overproducing F. graminearum mutant, and the findings provide comprehensive insight into the role of modulation of carbon metabolism in the sexual reproduction of fungi.

Molecular glue degraders, such as lenalidomide and pomalidomide, bind to cereblon (CRBN) E3 ligase and subsequently recruit neosubstrate proteins, Ikaros (IKZF1) and Aiolos (IKZF3), for the ubiquitination-proteasomal degradation process. In this study, we explored structure-activity relationship analysis for novel GSPT1 degraders utilizing a benzotriazinone scaffold previously discovered as a novel CRBN binder. In particular, we focused on the position of the ureido group on the benzotriazinone scaffold, substituent effect on the phenylureido group, and methyl substitution on the benzylic position of benzotriazinone. As a result, we identified 34f (TD-522), which exhibits strong anti-proliferative effects in both KG-1 (EC

Summary Objective To compare the skeletal and dentoalveolar changes produced by the Damon system's treatment philosophy to traditional orthodontic treatment techniques. Materials and Methods An electronic search in four major databases was completed: Cochrane, PubMed, EMBASE, and Google Beta Scholar on October 5th, 2018. Randomized controlled trials, prospective and retrospective controlled clinical trials were included in this systematic review. The quality assessment of individual studies was done using two different tools: The Cochrane Risk of Bias Assessment Tool (RTCs) and The Methodological Index for Non-Randomized Studies (MINORS) (non-RCTs). Results Seven studies were included for this qualitative analysis. Six studies compared the Damon system to various types of conventional (non self-ligating bracket) system as a comparison group. One study used a quad helix as a comparison for a few months before a full bonding appointment with conventional brackets. The majority of studies found an increase in maxillary inter-canine, inter-premolar, and intermolar distance after the treatment in both the Damon and comparison groups. Yet, all studies concluded that there is no significant difference in the final transverse dimension between the two groups. One study also found that the transverse expansion was achieved mainly by tipping movement of posterior dentition, and a decrease in the posterior buccal bone area was evident in both groups after treatment. Conclusion There is not enough evidence to support the claim that the Damon system allows additional arch expansion with better tipping control than with traditional techniques.

Hypoxic signaling occurs under several physiological and pathological conditions, such as in solid tumors. Hypoxia inducible factor 1 (HIF-1) mediates many hypoxic responses, and regulates hundreds of genes involved in many biological processes including tumor angiogenesis, invasion, and metabolism. Although the components of hypoxia that initiate and maintain the hypoxic responses have been well-studied, epigenetic regulation of the hypoxic responses is poorly understood. Thus, it would be useful to summarize current status of the field and discuss future directions. In this review, we will focus on the current understandings of epigenetic regulation in hypoxic response and discuss currently available epigenetic drugs to treat hypoxia-driven or related diseases.

Aberrant epigenetic alteration has been associated with development of various cancers, including breast cancer. Since epigenetic modifications such as DNA methylation and histone modification are reversible, epigenetic enzymes, including histone modifying enzymes and DNA methyltransferases, emerge as attractive targets for cancer therapy. Although epi-drugs targeting histone deacetylation or DNA methylation have received FDA approval for cancer therapy, a very modest anti-tumor activity has been observed with monotherapy in clinical studies of breast cancer. To improve efficacy of epi-drugs in breast cancer, combination of epi-drugs with other therapies currently has been investigated. Additionally, basic researches to elucidate molecular causes of cancer should be extensively and intensively conducted in order to find novel epigenetic druggable targets. In this chapter, we summarize how epigenetic regulation affects the development of breast cancer and how to control cancer phenotype by modulating abnormal epigenetic modifications, and then suggest future research directions in epigenetics for breast cancer treatment.

Hypertension has been identified as the most prevalent chronic disease, accounting for the majority of premature deaths in people with physical disability in South Korea. Self-care is vital in controlling high blood pressure. Health literacy has been implicated in self-care behaviors, however, the mechanisms behind this relationship remain unclear. Therefore, the present study aimed to test a hypothetical path model estimating the association between health literacy and hypertension self-care behaviors and to verify the mediating effects of access to healthcare, provider–patient interactions, hypertension knowledge, and hypertension control self-efficacy in hypertensive people with physical disability. In total, 211 hypertensive adults with physical disability completed an online survey. A path analysis using a multi-mediation model was performed using AMOS 17.0 (IBM SPSS Inc., Chicago, IL, USA), and indirect effects were estimated using phantom variables. As a result, the model fit indices were deemed excellent. Significant indirect pathways were determined from health literacy to hypertension self-care behavior via provider–patient interactions, knowledge, and self-efficacy, although no direct association was found between health literacy and self-care behaviors. The study findings supported the importance of provider–patient interactions, knowledge, and self-efficacy, which play a role in linking health literacy and self-care behavior in hypertensive patients with physical disability.

Aberrant epigenetic alteration has been associated with development of various cancers, including breast cancer. Since epigenetic modifications such as DNA methylation and histone modification are reversible, epigenetic enzymes, including histone modifying enzymes and DNA methyltransferases, emerge as attractive targets for cancer therapy. Although epi-drugs targeting histone deacetylation or DNA methylation have received FDA approval for cancer therapy, a very modest anti-tumor activity has been observed with monotherapy in clinical studies of breast cancer. To improve efficacy of epi-drugs in breast cancer, combination of epi-drugs with other therapies currently has been investigated. Additionally, basic researches to elucidate molecular causes of cancer should be extensively and intensively conducted in order to find novel epigenetic druggable targets. In this chapter, we summarize how epigenetic regulation affects the development of breast cancer and how to control cancer phenotype by modulating abnormal epigenetic modifications, and then suggest future research directions in epigenetics for breast cancer treatment.

The purpose of this study was to evaluate and compare dental and skeletal changes associated with the Damon and Rapid Maxillary Expander (RME) expansion using Cone-Beam Computed Tomography (CBCT). Eighty-two patients, from The University of Alberta Orthodontic Clinic, were randomly allocated to either Group A or B. Patients in Group A received orthodontic treatment using the Damon brackets. Patients in Group B received treatment using the Hyrax (a type of RME) appliance. CBCT images were taken two times (baseline and after expansion). The AVIZO software was used to locate 18 landmarks (dental and skeletal) on sagittal, axial, and coronal slices of CBCT images. Comparison between two groups showed that transverse movement of maxillary first molars and premolars was much greater in the Hyrax group. The lateral movements of posterior teeth were associated with buccal tipping of crowns. No clinically significant difference in the vertical or anteroposterior direction between the two groups was noted. Alveolar bone next to root apex of maxillary first premolar and molar teeth showed clinically significant lateral movement in the Hyrax group only. The comparison between two groups showed significantly greater transverse expansion of the first molar and first premolars with buccal tipping in the RME group.

연구목적: 본 연구의 목적은 일반초등학교와 인근 특수학교 간의 사물놀이로 구성된 통합교류활동 프로그램이 비장애 초등학생의 정서지능, 장애수용태도에 미치는 영향과 초등 중도․중복 장애학생(청각장애와 지적장애)들에게 미치는 영향을 밝히는 것이다. 연구방법: 연구참여자는 C일반초등학교와 N특수학교의 3학년 학생이며, 실험집단으로 비장애학생 24명과 중도․중복장애학생 8명은 통합동아리 시간에 총 16회기의 ‘통합교류활동 프로그램’에 참여하였다. 비장애학생의 종속변인 양적자료는 독립표본 t검정을 하였고 중도․중복 장애학생의 사전사후 변화는 관찰, N특수학교 담당교사, 특수교육보조원, 공익근무요원과의 면담, 학기 말 성과보고서에서 수합된 질적 자료로 제시하였다. 연구결과: 실험집단 비장애 초등학생들의 정서지능 전체 점수와 하위영역 3가지 점수는 통제집단에 비해 유의하게 높게 나타났다. 비장애 초등학생의 장애수용태도 전체점수와 하위영역에서 실험집단이 통제집단에 비해 유의하게 높게 나타났다. 중도․중복 장애학생들은 통합교류활동 프로그램 참여의 양과 질 향상, 대인관계에서 상호작용의 증진, 개인적 정서적 안정감과 행복감의 표현이 나타났다. 결론: 이 연구는 ‘통합교류활동’을 초등 정규교육과정의 통합동아리 활동으로 실시하고 그 긍정적 효과를 보고하는 첫 연구로서 분리교육 환경의 특수학교 학생들에게 비장애학생들과의 통합경험 제공, 통합동아리 활동 참여 후의 초등학생들의 성장, 사물놀이 활동선정의 적절성, 특수학교의 발전 방향 등에 대한 논의와 연구의 의의 및 제한점이 제공되었다.

Summary Because glioblastoma (GBM) exhibits high heterogeneity, it is desirable to use patient-derived cells from the first stage of screening for GBM drug discovery. Here, we describe a protocol to culture patient-derived GBM cells on the extracellular matrix-coated plates to allow high-throughput screening. Further, we detail approaches to identify the mechanism of action (MOA) of the selected effective drug through proteomics. This protocol will be useful for researchers interested in drug screening and the MOA of drugs. For complete details on the use and execution of this protocol, please refer to Nam et al. (2021)., Graphical abstract, Highlights • Methods for patient-derived GBM cell culture • Automated high-throughput screening methods using chemical libraries • Quantitative mass spectrometry to elucidate mechanism of action of drugs • Methods to perform data analysis from mass spectrometry, Because glioblastoma (GBM) exhibits high heterogeneity, it is desirable to use patient-derived cells from the first stage of screening for GBM drug discovery. Here, we describe a protocol to culture patient-derived GBM cells on the extracellular matrix-coated plates to allow high-throughput screening. Further, we detail approaches to identify the mechanism of action (MOA) of the selected effective drug through proteomics. This protocol will be useful for researchers interested in drug screening and the MOA of drugs.

Retinoic acid-related orphan receptor α (RORα) regulates diverse physiological processes, including inflammatory responses, lipid metabolism, circadian rhythm, and cancer biology. RORα has four different isoforms which have distinct N-terminal domains but share identical DNA binding domain and ligand binding domain in human. However, lack of specific antibody against each RORα isoform makes biochemical studies on each RORα isoform remain unclear. Here, we generate RORα2-specific antibody and characterize the role of RORα2 in promoting tumor progression in breast cancer. RORα2 requires lysine specific demethylase 1 (LSD1/KDM1A) as a coactivator for transcriptional activation of RORα2 target genes, exemplified by CTNND1. Intriguingly, RORα2 and LSD1 protein levels are dramatically elevated in human breast cancer specimens compared to normal counterparts. Taken together, our studies indicate that LSD1-mediated RORα2 transcriptional activity is important to promote tumor cell migration in human breast cancer as well as breast cancer cell lines. Therefore, our data establish that suppression of LSD1-mediated RORα2 transcriptional activity may be potent therapeutic strategy to attenuate tumor cell migration in human breast cancer.

Summary Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor with poor survival rate. Temozolomide (TMZ) is used as standard chemotherapy to treat GBM, but a large number of patients either respond poorly and/or develop resistance after long-term use, emphasizing the need to develop potent drugs with novel mechanisms of action. Here, using high-throughput compound screening (HTS), we found that azathioprine, an immunosuppressant, is a promising therapeutic agent to treat TMZ-resistant GBM. Through integrative genome-wide analysis and global proteomic analysis, we found that elevated lipid metabolism likely due to hyperactive EGFR/AKT/SREBP-1 signaling was inhibited by azathioprine. Azathioprine also promoted ER stress-induced apoptosis. Analysis of orthotopic xenograft models injected with patient-derived GBM cells revealed reduced tumor volume and increased apoptosis after azathioprine and TMZ co-treatment. These data indicate that azathioprine could be a powerful therapeutic option for TMZ-resistant GBM patients., Graphical abstract, Highlights • Azathioprine as a promising drug for temozolomide-resistant GBM treatment • Azathioprine inhibits aberrantly elevated lipid metabolism in GBM • Azathioprine promotes ER stress-induced apoptosis in GBM • Through orthotropic xenograft models, anti-GBM effect of azathioprine is confirmed, Biological Sciences; Cell Biology; Proteomics; Cancer Systems Biology; Cancer

Hypoxia-inducible factor-1α (HIF-1α) mediates hypoxic responses and regulates gene expression involved in angiogenesis, invasion and metabolism. Among the various HIF-1α posttranslational modifications, HIF-1α methylation and its physiological role have not yet been elucidated. Here we show that HIF-1α is methylated by SET7/9 methyltransferase, and that lysine-specific demethylase 1 reverses its methylation. The functional consequence of HIF-1α methylation is the modulation of HIF-1α stability primarily in the nucleus, independent of its proline hydroxylation, during long-term hypoxic and normoxic conditions. Knock-in mice bearing a methylation-defective Hif1aKA/KA allele exhibit enhanced retinal angiogenesis and tumour vascularization via HIF-1α stabilization. Importantly, S28Y and R30Q mutations of HIF-1α, found in human cancers, are involved in the altered HIF-1α stability. Together, these results demonstrate a role for HIF-1α methylation in regulating protein stability, thereby modulating biological output including retinal and tumour angiogenesis, with therapeutic implications in human cancer., HIF-1α is a pivotal protein involved in angiogenesis and is known to be regulated posttranslationally. Here, the authors show that HIF-1α is methylated by Set7/9 methyltransferase, which reduces protein stability and contributes to reduced angiogenesis.

We report the first air-passivated ambipolar BP transistor formed by applying benzyl viologen, which serves as a surface charge transfer donor for BP flakes. The passivated BP devices exhibit excellent stability under both an ambient atmosphere and vacuum; their transistor performance is maintained semi-permanently. Unlike their intrinsic p-type properties, passivated BP devices present advantageous ambipolar properties with much higher electron mobility up to ∼83 cm(2) V(-1) s(-1) from 2-terminal measurement at 300 K, compared to other reported studies on n-type BP transistors. On the basis of the n-type doping effect that originated from benzyl viologen, we also systematically investigated the BP thickness dependence of our devices on electrical properties, in which we found the best electron transport performance to be attained when an ∼10 nm thick BP flake was used.

A biomimetic multifunctional nanocomposite was synthesized, in which a polydopamine (PDA) thin film was deposited on a layered double hydroxide (LDH) through an interlayer polymerization. Kinetic controlled polymerization of dopamine (DA) in a basic buffer solution under a nitrogen atmosphere provided a synthetic pathway for the nanostructured PDA/LDH composites without polymer agglomerates, allowing the crystallinity of the pristine LDH nanoparticles to be maintained. The contraction of the interlayer spacing for the (00l) reflection of PDA/LDH nanocomposites demonstrated intercalation of PDA into the LDH interlayer space. The catalytic activity of the PDA/LDH nanocomposites was evaluated by observing the reduction of p-nitrophenol in the presence of NaBH4, in which the PDA layer acts as a protection layer against surface contamination of the nanocomposites. Electrochemical capacitive performance was also observed due to the strong adhesion of PDA to the Ni foam electrode. The nanostructure of the PDA/LDH nanocomposites induced by interlayer polymerization drove the incorporative organic–inorganic functional materials with blocked surfaces and improved the electrochemical properties, providing a reliable synthetic pathway to prepare multifunctional nanohybrid materials.

Triple-negative breast cancer (TNBC) has an aggressive phenotype and poor prognosis due to the lack of specific targeted treatments. The development of an effective therapeutic strategy with a novel mechanism is essential for TNBC management. Olaparib, a PARP inhibitor, has been approved for the treatment of breast or ovarian cancer patients with breast cancer gene 1/2 (BRCA1/2) mutations. Here, we report the development of a small molecule targeting PARP1 based on the hydrophobic tagging (HyT) method. Targeted protein misfolding and consequent degradation are caused by HyT. Hydrophobic-tagged olaparib induces the proteasome-dependent degradation of PARP1 and shows enhanced antitumor effects compared to olaparib in TNBC cells. In addition, hydrophobic-tagged olaparib causes ER stress-related unfolded protein response (UPR), autophagy, and apoptosis. These results point towards encouraging prospects for chemically modifying approved drugs that not only exhibit superior effects compared to those of the original drugs by triggering novel mechanisms but also provide great feasibility in the translational scenario.

Safety and security system have been internationally enhanced in a field of shipping logistics. Accordingly, techniques for safety and security have been studied steadily. The need of portable radiation detection device is increasing by the search of the container is enhanced. In this paper, we propose a study to improve the life of the system and the realization of portable radiation detection device based on Cortex-A9. Configuration of a portable radiation detection device is configured largely to an analog board and the digital platform and the sensor module. The power used in each stage of the analog board is varied. Uses a switching regulator to use various power supply thereby to generate an error result and cause the switching noise. It is proposed to reduce the power consumption reducing technique for the study.