This study aimed to identify factors affecting the occurrence of intimate partner violence (IPV) in Korean adults aged 19 years and older. Specifically, we identified the factors in women's ...victimization in and men's perpetration of IPV. This study adopted a cross-sectional and correlational design in conducting secondary data analysis of the 2016 Domestic Violence Survey in Korea. Men (N = 1,272) and women (N = 2,689) with partner were included in the analysis. The ecological model was used as a conceptual framework. Multiple logistic regression analyses were conducted to identify factors affecting women's victimization in and men's perpetration of IPV. The results showed that the prevalence of IPV against female partner was 12.1%. IPV occurrence was higher among women (Odds ratios (OR) = 2.92, Confidence intervals (CI): 1.84-4.63) and men (OR = 2.64, CI: 1.62-4.32) who experienced witnessing inter-parental violence in childhood, and among women (OR = 2.25, CI: 1.40-3.61) and men (OR = 2.68, CI: 1.59-4.52) with a tolerant attitude toward IPV. The occurrence was higher among women who experienced childhood maltreatment by the parents (OR = 1.70, CI: 1.03-2.82) and women whose income was 2 million Korean Won(KRW) to 3 million KRW compared with women whose income was above 4 million KRW (OR = 1.97, CI: 1.10-3.55). The occurrence was lower among women with office jobs compared with other jobs (OR = 0.47, CI: 0.26-0.84). Based on the results of this study, early intervention in abusive families to reduce the negative impact of abuse experiences and witnessing inter-parental violence in childhood, and education and publicity for changing attitudes toward IPV are necessary at the individual and societal levels. The formation of policies for the stable workplace and income of women are required.
Anaplastic lymphoma kinase (ALK) activation has been associated with many types of human cancer. Significant efforts have been devoted to the development of ALK inhibitors to antagonize the kinase ...activity of ALK. Four ALK inhibitors have been approved by the FDA to date for treating patients with ALK-positive non-small cell lung cancers (NSCLC). However, drug resistance has been observed in the majority of patients treated with these inhibitors. New therapeutic strategies (e.g., compounds with novel mechanisms of action) are needed to overcome the drug resistance issue. The emerging PROTAC (Proteolysis Targeting Chimera) technology has been successfully applied to selective degradation of multiple protein targets, but not ALK. Since ALK protein levels are not important for viability in mammals, ALK PROTACs could lead to novel therapeutics with minimal toxicity. Here we report the design, synthesis and biological evaluation of novel PROTACs (degraders) of ALK. MS4077 (5) and MS4078 (6) potently decreased cellular levels of oncogenic active ALK fusion proteins in a concentration- and time-dependent manner in SU-DHL-1 lymphoma and NCI-H2228 lung cancer cells. The ALK protein degradation induced by compounds 5 and 6 was cereblon and proteasome dependent. In addition, compounds 5 and 6 potently inhibited proliferation of SU-DHL-1 cells. Furthermore, compound 6 displayed good plasma exposure in a mouse pharmacokinetic study, thus is suitable for in vivo efficacy studies. We also developed MS4748 (7) and MS4740 (8), very close analogs of 5 and 6 respectively, which are incapable to degrade the ALK fusion proteins, as negative controls. Compounds 5–8 are valuable chemical tools for investigating effects of ALK pharmacological degradation. Our study paved the way for developing the next generation of ALK PROTACs.
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•We discovered novel ALK PROTACs (MS4077 and MS4078) and their close analogs as negative controls.•MS4077 and MS4078 potently reduced cellular ALK protein levels in a cereblon and proteasome dependent manner.•MS4077 and MS4078 potently inhibited cellular ALK signaling.•MS4077 and MS4078 effectively inhibited cancer cell proliferation.•MS4078 displayed good plasma exposure in mice, thus is suitable for in vivo efficacy studies.
Abstract
Background
This study aimed to investigate the relationships between the frequency of impairments in daily activities due to the overuse of the Internet, gaming, or smartphones (IGS) and ...sociodemographic characteristics, social relationships (including family) & activities, psychosocial characteristics, health status, and health-related quality of life (HRQoL) of Korean adults.
Methods
Secondary data from the 2017 Community Health Survey, a large-scale sample survey conducted yearly in South Korea, were analyzed for 190,066 adults over 19 years of age. Three categories were created for impairment groups due to IGS overuse: No Impairment, Mild Impairment, and Moderate-to-Severe groups. And between-group differences were examined using a one-way ANOVA for health status measured with the EQ-5D-3 L and chi-square tests for all categorical dependent variables, which included sociodemographic characteristics, social relationships & activities, and psychosocial factors. The association between frequencies of daily activity impairments due to IGS overuse and the dependent variables were examined using a multivariate logistic regression analysis and a linear regression model.
Results
Approximately 21,345 (11.23%) of the 190,066 participants reported experiencing impairments in daily activities due to IGS overuse at least once in the previous year and the impairments were more severe in males than females. Participants experiencing impairments in daily activities contacted their friends a significantly higher number of times (4 times or more per month) and engaged in leisure activities more frequently (more than once per month) than those without impairments. There was also a significant positive relationship between IGS overuse and stress, depression, suicidal ideation, and suicide attempts. Among participants aged 19–64, impairments in daily activities due to IGS overuse were associated with a lower HRQoL. Conversely, for those aged 65 and over, mild and moderate-to-severe impairments due to IGS overuse were associated with a significantly higher HRQoL.
Conclusions
Increased impairments in daily activities due to IGS overuse may negatively affect mental health. However, among older adults, the frequency of such impairments was positively associated with HRQoL. This finding could be considered to apply interventions with Internet usage or ICT devices for older adults to enhance their quality of life.
Phytate (myo-inositol hexakisphosphate salts) can constitute a large fraction of the organic P in soils. As a more recalcitrant form of soil organic P, up to 51 million metric tons of phytate ...accumulate in soils annually, corresponding to ∼65% of the P fertilizer application. However, the availability of phytate is limited due to its strong binding to soils via its highly-phosphorylated inositol structure, with sorption capacity being ∼4 times that of orthophosphate in soils. Phosphorus (P) is one of the most limiting macronutrients for agricultural productivity. Given that phosphate rock is a finite resource, coupled with the increasing difficulty in its extraction and geopolitical fragility in supply, it is anticipated that both economic and environmental costs of P fertilizer will greatly increase. Therefore, optimizing the use of soil phytate-P can potentially enhance the economic and environmental sustainability of agriculture production. To increase phytate-P availability in the rhizosphere, plants and microbes have developed strategies to improve phytate solubility and mineralization by secreting mobilizing agents including organic acids and hydrolyzing enzymes including various phytases. Though we have some understanding of phytate availability and phytase activity in soils, the limiting steps for phytate-P acquisition by plants proposed two decades ago remain elusive. Besides, the relative contribution of plant- and microbe-derived phytases, including those from mycorrhizas, in improving phytate-P utilization is poorly understood. Hence, it is important to understand the processes that influence phytate-P acquisition by plants, thereby developing effective molecular biotechnologies to enhance the dynamics of phytate in soil. However, from a practical view, phytate-P acquisition by plants competes with soil P fixation, so the ability of plants to access stable phytate must be evaluated from both a plant and soil perspective. Here, we summarize information on phytate availability in soils and phytate-P acquisition by plants. In addition, agronomic approaches and biotechnological strategies to improve soil phytate-P utilization by plants are discussed, and questions that need further investigation are raised. The information helps to better improve phytate-P utilization by plants, thereby reducing P resource inputs and pollution risks to the wider environment.
Pathological calcification represents an event that consequently leads to a distinct elevation in the morbidity and mortality of patients with chronic kidney disease (CKD) in addition to ...strengthening its correlation with hyperphosphatemia. Epigenomic regulation by specific microRNAs (miRNAs) is reported to be involved in ectopic calcification. However, the finer molecular mechanisms governing this event remain unclear. Hence, this study aimed to identify the potential miRNAs involved in vascular calcification (VC) development and progression. Initially, mitochondrial membrane potential (MMP), autophagy‐specific markers (LC3II/LC3I and Beclin1) and phenotype‐specific markers of osteoblasts (runt‐related transcription factor 2 and Msx2) were measured to evaluate autophagy and VC in β‐glycerophosphate‐induced vascular smooth muscle cells (VSMCs) with either miR‐30b restoration or miR‐30b knockdown performed in vitro. The VC in vivo was represented by calcified nodule formation in the aorta of the rats undergoing 5/6 nephrectomy followed by a 1.2% phosphorus diet using Alizarin Red staining. SOX9 was verified as the target of miR‐30b according to luciferase activity determination. Restoration of miR‐30b was revealed to markedly diminish the expression of SOX9 while acting to inhibit activation of the mTOR signaling pathway. Knockdown of miR‐30b reduced MMP and autophagy, elevated VC, and suppressed the presence of rapamycin (an inhibitor of the mTOR signaling pathway). In addition, upregulated expression of miR‐30b attenuated VC in vivo. Taken together, the key findings of this study identified the inhibitory role of miR‐30b in VC, presenting an enhanced understanding of miRNA as a therapeutic target to curtail progressive VC in hyperphosphatemia of CKD.
Lithium–sulfur batteries (LSBs) have received much concern as emerging high-power energy storage system. Nevertheless, the low conductivity of sulfur and polysulfide shuttle results in low rate ...capability and rapid capacity decay, which seriously limit its commercial application. Here, facile, sustainable and cost-effective strategy for preparing heteroatom-doped porous activated carbon (PAC) derived from biomass palm kernel shell (PKS) was developed for high-performance LSB applications. The presence of N, P and S heteroatoms with modification of the surface polarity brings about large amounts of active sites and improved adsorption property compared to those of common carbon materials. The PAC sample possesses desirable specific surface area (SSA) (2760 m
2
·g
−1
) as well as pore volume (1.6 cm
3
·g
−1
). Besides, the good electrical conductivity of PAC endows the material with excellent rate performance. The PAC-S electrode with a 60% of sulfur loading has a desirable first discharge capacity (1045 mAh·g
1
, 200 mA·g
−1
) with superb discharge capacity (869.8 mAh·g
−1
, 100th cycle) and cyclability (312.6 mAh·g
−1
, 800 mA·g
−1
, 1000th cycle), which can be mainly ascribed to its unique porous properties and the good conductivity of PAC.
Graphic abstract
In an increasingly multicultural society, cultural competence and transcultural self-efficacy of public health nurses is important for providing culturally congruent care for client from diverse ...cultural background. To improv this, it is needed tailored and effective educational program based on the cultural competence educational needs. This study investigated the moderating effect of cultural competence educational needs on the relationship between transcultural self-efficacy and cultural competence.
This cross-sectional study recruited 217 public health nurses in Korea using convenience sampling from August 2018 to January 2019. A direct questionnaire was used to collect data. Study variables were analyzed using descriptive statistics, correlation, and the Hayes PROCESS macro (Model 1) moderation model.
The mean scores for transcultural self-efficacy, cultural competence educational needs, and cultural competence were 62.33 ± 11.08, 58.19 ± 15.08, and 97.96 ± 17.09, respectively. Transcultural self-efficacy and cultural competence educational needs were positively associated with cultural competence. In the tested model, cultural competence educational needs had a conditional moderating effect on the relationship between transcultural self-efficacy and cultural competence. The positive association between transcultural self-efficacy and cultural competence was significant at low, medium, and high levels of cultural competence educational needs and stronger for those with high needs.
Cultural competence educational needs may be an important determinant of cultural competence among public health nurses. To effectively increase cultural competence, transcultural self-efficacy should be increased by education programs tailored by cultural competence educational needs.
Long non-coding RNA MEG3 has been identified as a tumor suppressor which plays important roles in tumorigenesis; however, its potential role in breast cancer has not been fully examined. Here, we ...showed that MEG3 was downregulated in breast cancer tissues and cell lines. Overexpression of MEG3 inhibited breast cancer cell proliferation and invasion, suggesting that MEG3 played an important role in breast cancer progression and metastasis. Moreover, MEG3 upregulation caused marked inhibition of angiogenesis-related factor expression. Conditioned medium derived from MEG3 overexpressed breast cancer cells significantly decreased the capillary tube formation of endothelial cells. Furthermore, elevated expression of MEG3 in breast cancer inhibits in vivo tumorigenesis and angiogenesis in a nude mouse xenograft model. Mechanistically, overexpression of MEG3 results in downregulation of AKT signaling, which is pivotal for breast cancer cell growth, invasion, and tumor angiogenesis. Collectively, these results suggest that MEG3 might suppress the tumor growth and angiogenesis via AKT signaling pathway and MEG3 may serve as a potential novel diagnostic and therapeutic target of breast cancer.
BRAF is among the most frequently mutated oncogenes in human cancers. Multiple small molecule BRAF kinase inhibitors have been approved for treating melanoma carrying BRAF-V600 mutations. However, ...the benefits of BRAF kinase inhibitors are generally short-lived. Small molecule-mediated targeted protein degradation has recently emerged as a novel pharmaceutical strategy to remove disease proteins through hijacking the cellular ubiquitin proteasome system (UPS). In this study, we developed thalidomide-based heterobifunctional compounds that induced selective degradation of BRAF-V600E, but not the wild-type BRAF. Downregulation of BRAF-V600E suppressed the MEK/ERK kinase cascade in melanoma cells and impaired cell growth in culture. Abolishing the interaction between degraders and cereblon or blocking the UPS significantly impaired the activities of these degraders, validating a mechanistic role of UPS in mediating targeted degradation of BRAF-V600E. These findings highlight a new approach to modulate the functions of oncogenic BRAF mutants and provide a framework to treat BRAF-dependent human cancers.
Background
To evaluate the systematic mediastinal lymph node (LN) dissection outcomes and conversion rates of uniportal video‐assisted thoracoscopic surgery (UVATS).
Methods
Patients with ...non‐small‐cell lung cancer who underwent video‐assisted thoracoscopic surgery (VATS) and systematic mediastinal LN dissection between January 2015 and January 2017 were retrospectively reviewed. We categorized the patients into two groups according to the different surgical approaches. Patients' clinical data were collected and compared. The index of estimated benefit from LN dissection was used to evaluate the therapeutic value of LN dissection for each station.
Results
A total of 453 patients underwent VATS, including 197 patients in the UVATS group and 256 patients in the triportal VATS (TVATS) group. There were no significant differences in the 1‐, 2‐ and 3‐year survival rates of these two groups (P > 0.05). There were no statistically significant differences in the operative time, numbers and stations of LNs, numbers and stations of N2 LNs, conversion rate or postoperative complications. The UVATS group had less intraoperative blood loss, a shorter duration of hospital stay, less chest tube drainage and a shorter duration of chest tube drainage than the TVATS group (P < 0.05). The conversion rates in the UVATS and TVATS groups were 5.1% and 4.3%, respectively, and the difference was not significant. The same degree of LN sampling was achieved in both groups.
Conclusion
UVATS permits the same degree of LN sampling as TVATS without a difference in the conversion rate.
>This study was performed to evaluate the systemic mediastinum lymph node dissection and conversive rate in uniportal video‐assisted thoracoscopic lobectomy for the treatment of non‐small‐cell lung cancer compared with three‐port video‐assisted thoracoscopic lobectomy, and the lymph node dissection of uniportal video‐assisted thoracoscopic lobectomy was the same as that of triportal video‐assisted thoracoscopic lobectomy, and there was no difference in the conversive rate.
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