PARIS (ZNF746) repression of PGC-1α contributes to neurodegeneration in Parkinson's disease.

A hallmark of Parkinson's disease (PD) is the preferential loss of substantia nigra dopamine neurons. Here, we identify a new parkin interacting substrate, PARIS (ZNF746), whose levels are regulated by the ubiquitin proteasome system via binding to and ubiquitination by the E3 ubiquitin ligase, parkin. PARIS is a KRAB and zinc finger protein that accumulates in models of parkin inactivation and in human PD brain. PARIS represses the expression of the transcriptional coactivator, PGC-1α and the PGC-1α target gene, NRF-1 by binding to insulin response sequences in the PGC-1α promoter. Conditional knockout of parkin in adult animals leads to progressive loss of dopamine (DA) neurons in a PARIS-dependent manner. Moreover, overexpression of PARIS leads to the selective loss of DA neurons in the substantia nigra, and this is reversed by either parkin or PGC-1α coexpression. The identification of PARIS provides a molecular mechanism for neurodegeneration due to parkin inactivation.

Silver electroceutical technology to treat sarcopenia.

While the world is rapidly transforming into a superaging society, pharmaceutical approaches to treat sarcopenia have hitherto not been successful due to their insufficient efficacy and failure to specifically target skeletal muscle cells (skMCs). Although electrical stimulation (ES) is emerging as an alternative intervention, its efficacy toward treating sarcopenia remains unexplored. In this study, we demonstrate a silver electroceutical technology with the potential to treat sarcopenia. First, we developed a high-throughput ES screening platform that can simultaneously stimulate 15 independent conditions, while utilizing only a small number of human-derived primary aged/young skMCs (hAskMC/hYskMC). The in vitro screening showed that specific ES conditions induced hypertrophy and rejuvenation in hAskMCs, and the optimal ES frequency in hAskMCs was different from that in hYskMCs. When applied to aged mice in vivo, specific ES conditions improved the prevalence and thickness of Type IIA fibers, along with biomechanical attributes, toward a younger skMC phenotype. This study is expected to pave the way toward an electroceutical treatment for sarcopenia with minimal side effects and help realize personalized bioelectronic medicine.

Anti-intercellular adhesion molecule 1 monomaintenance therapy induced long-term liver allograft survival without chronic rejection.

Calcineurin inhibitors (CNIs) are essential in liver transplantation (LT); however, their long-term use leads to various adverse effects. The anti-intercellular adhesion molecule (ICAM)-1 monoclonal antibody MD3 is a potential alternative to CNI. Despite its promising results with short-term therapy, overcoming the challenge of chronic rejection remains important. Thus, we aimed to investigate the outcomes of long-term MD3 therapy with monthly MD3 monomaintenance in nonhuman primate LT models. Rhesus macaques underwent major histocompatibility complex-mismatched allogeneic LT. The conventional immunosuppression group (Con-IS, n = 4) received steroid, tacrolimus, and sirolimus by 4 months posttransplantation. The induction MD3 group (IN-MD3, n = 5) received short-term MD3 therapy for 3 months with Con-IS. The maintenance MD3 group (MA-MD3, n = 4) received MD3 for 3 months, monthly doses by 2 years, and then quarterly. The MA-MD3 group exhibited stable liver function without overt infection and had significantly better liver allograft survival than the IN-MD3 group. Development of donor-specific antibody and chronic rejection were suppressed in the MA-MD3 group but not in the IN-MD3 group. Donor-specific T cell responses were attenuated in the MA-MD3 group. In conclusion, MD3 monomaintenance therapy without maintenance CNI provides long-term liver allograft survival by suppressing chronic rejection, offering a potential breakthrough for future human trials.

Effect of Chronic Kidney Disease on All-Cause Mortality After Hip Fracture Surgery: A Retrospective Cohort Study.

In this retrospective cohort study, we investigated: (1) The impact of comorbid chronic kidney disease (CKD) on postoperative mortality in patients with a hip fracture; (2) mortality variations by dialysis type, potentially indicating CKD stage; (3) the efficacy of different hip fracture surgical methods in reducing mortality for patients with CKD. This study included 25,760 patients from the Korean National Health Insurance Service-Senior cohort (2002-2019) who underwent hip fracture surgery. Participants were categorized as CKD and Non-CKD. Mortality rate was determined using a generalized linear model with a Poisson distribution. The effect size was presented as a hazard ratio (HR) through a Cox proportional-hazard model. During follow-up, we ascertained that 978 patients (3.8%) had CKD preoperatively. Compared to the Non-CKD group, the mortality risk (HR) in the CKD group was 2.17 times higher (95% confidence interval [CI], 1.99-2.37). In sensitivity analysis, the mortality risk of in patients who received peritoneal dialysis and hemodialysis was 6.21 (95% CI, 3.90-9.87) and 3.62 times (95% CI, 3.11-4.20) higher than that of patients who received conservative care. Mortality risk varied by surgical method: hip hemiarthroplasty (HR, 2.11; 95% CI, 1.86-2.40), open reduction and internal fixation (HR, 2.21; 95% CI, 1.94-2.51), total hip replacement (HR, 2.27; 95% CI, 1.60-3.24), and closed reduction and percutaneous fixation (HR, 3.08; 95% CI, 1.88-5.06). Older patients with CKD undergoing hip fracture surgery had elevated mortality risk, necessitating comprehensive pre- and postoperative assessments and management.

Association between nurse staffing level in intensive care settings and hospital-acquired pneumonia among surgery patients: result from the Korea National Health Insurance cohort.

This study examined the association between the number of nursing staff in intensive care units (ICUs) and hospital-acquired pneumonia (HAP) among surgical patients in South Korea. Data were obtained between 2008 and 2019 from the Korean National Health Insurance Service Cohort Database; 37,706 surgical patients who received critical care services were included in the analysis. Patients with a history of pneumonia 1 year prior to surgery or those who had undergone lung-related surgery were excluded. The ICU nursing management fee is an admission fee that varies based on the grading determined by nurse-to-bed ratio. Using this grading system, we classified four groups from the highest to the lowest level based on the proportion of beds to nurses (high, high-mid, mid-low, and low group). HAP was defined by the International Classification of Disease, 10th revision (ICD-10) code. Multilevel logistic regression was used to investigate the relationship between the level of ICU nurse staffing and pneumonia, controlling for variables at the individual and hospital levels. Lower levels of nurse staffing were associated with a greater incidence of HAP than higher levels of nurse staffing (mid-high, OR: 1.33, 95% CI: 1.12-1.57; mid-low, OR: 1.61, 95% CI: 1.27-2.04; low, OR: 2.13, 95% CI: 1.67-2.71). The intraclass correlation coefficient value was 0.177, and 17.7% of the variability in HAP was accounted for by the hospital. Higher ICU nursing management fee grades (grade 5 and above) in general and hospital settings were significantly associated with an increased risk of HAP compared to grade 1 admissions. Similarly, in tertiary hospitals, grade 2 and higher ICU nursing management fees were significantly associated with an increased risk of HAP compared to grade 1 admissions. Especially, a lower level of nurse staffing was associated with bacterial pneumonia but not pneumonia due to aspiration. In conclusion, this study found an association between the level of ICU nurse staffing and HAP among surgical patients. A lower level of nurse staffing in the ICU was associated with increased rates of HAP among surgical patients. This indicates that having fewer beds assigned to nurses in the ICU setting is a significant factor in preventing HAP, regardless of the size of the hospital.

Differences in end-of-life care patterns between types of hospice used for cancer patients: a retrospective cohort study.

BACKGROUND: In response to the rapid aging population and increasing number of cancer patients, discussions on dignified end-of-life (EoL) decisions are active around the world. Therefore, this study aimed to identify the differences in EoL care patterns between types of hospice used for cancer patients. METHODS: In this population-based cohort study, the Korean National Health Insurance Service cohort data containing all registered cancer patients who died between 2017 and 2021 were used. A total of 408,964 individuals were eligible for analysis. The variable of interest, the type of hospice used in the 6 months before death, was classified as follows: (1) Non-hospice users; (2) Hospital-based hospice single users; (3) Home-based hospice single users; (4) Combined hospice users. The outcomes were set as patterns of care, including intense care and supportive care. To identify differences in care patterns between hospice types, a generalized linear model with zero-inflated negative binomial distribution was applied. RESULTS: Hospice enrollment was associated with less intense care and more supportive care near death. Notably, those who used combined hospice care had the lowest probability and frequency of receiving intense care (aOR: 0.18, 95% CI: 0.17-0.19, aRR: 0.47, 95% CI: 0.44-0.49), while home-based hospice single users had the highest probability and frequency of receiving supportive care (Prescription for narcotic analgesics, aOR: 2.95, 95% CI: 2.69-3.23, aRR: 1.45, 95% CI: 1.41-1.49; Mental health care, aOR: 3.40, 95% CI: 3.13-3.69, aRR: 1.35, 95% CI: 1.31-1.39). CONCLUSION: Our findings suggest that although intense care for life-sustaining decreases with hospice enrollment, QoL at the EoL actually improves with appropriate supportive care. This study is meaningful in that it not only offers valuable insight into hospice care for terminally ill patients, but also provides policy implications for the introduction of patient-centered community-based hospice services.

Association Between Economic Activity and Depressive Symptoms Among Women With Parenting Children.

BACKGROUND: Balancing parenting and work life poses challenges for women with children, potentially making them vulnerable to depression owing to their dual responsibilities. Investigating working mothers' mental health status is important on both the individual and societal levels. This study aimed to explore the relationship between economic activity participation and depressive symptoms among working mothers. METHODS: This study was a cross-sectional study and used data from the Korea National Health and Nutrition Examination Survey collected in 2014, 2016, 2018, and 2020. The participants in the study were women aged 19 to 50 who were residing with their children. In the total, 3,151 participants were used in the analysis. The independent variable was economic activity, categorized into two groups: 1) economically active and 2) economically inactive. The dependent variable was the depressive symptoms, categorized as present for a Patient Health Questionnaire-9 score of ≥ 10 and absent for a score < 10. Multiple logistic regression analysis was performed to assess the association between economic activity and depressive symptoms, and sensitivity analyses were performed based on the severity of depressive symptoms. RESULTS: Among women with children, economically active women had reduced odds ratio of depressive symptoms compared with economically inactive women (odds ratio [OR], 0.54; 95% confidence interval [CI], 0.36-0.80). In additional analysis, women working as wage earners had the lowest odds of depressive symptoms (OR, 0.43; 95% CI, 0.28-0.66). Women working an average of 40 hours or less per week were least likely to have depressive symptoms (OR, 0.42; 95% CI, 0.25-0.69). CONCLUSION: Economic activity is significantly associated with depressive symptoms among women with children. Environmental support and policy approaches are needed to ensure that women remain economically active after childbirth.

Associations of social interactions during the COVID-19 pandemic with cognitive function among the South Korean older adults.

BACKGROUND: We aimed to demonstrate the associations between social interactions within social distancing norms during the coronavirus disease 2019 (COVID-19) pandemic and cognitive function among South Korean older adults. METHODS: Data from the 2017 and 2020 Survey of Living Conditions and Welfare Needs of Korean Older Persons were used. There were 18,813 participants (7,539 males; 11,274 females). T-test and multiple logistic regression analyses verified whether the mean difference in older adults' cognitive function before and during the COVID-19 pandemic was statistically significant. We also examined the associations between social interactions and cognitive function. The key results were presented as odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: All participants were more likely to experience cognitive impairment during the COVID-19 pandemic than before (males: OR 1.56, 95% CI 1.3-1.78; females: OR 1.26, 95% CI: 1.14-1.40). Cognitive impairment increased linearly with the decreased frequency of face-to-face contact with non-cohabiting children. Possible cognitive impairment was greater for females who had not visited senior welfare centers for the past year (OR 1.43, 95% CI 1.21-1.69). CONCLUSION: Korean older adults' cognitive function declined during the COVID-19 pandemic and was associated with reduced social interactions because of social distancing measures. Alternative interventions should be promoted for safely restoring social networks, considering the adverse effects of long-term social distancing on older adults' mental health and cognitive function.

The impact of assisted reproductive technology treatment coverage on marriage, pregnancy, and childbirth in women of childbearing age: an interrupted time-series analysis.

BACKGROUND: Korea is encountering major challenges related to its declining birth rate and aging population. Various policies have been introduced to prevent further population decrease and boost the birth rate, but their effectiveness has not been verified. Therefore, this study examined the effects of assisted reproductive technology (ART) insurance coverage on marriage, pregnancy, and childbirth in women of childbearing age. METHODS: All information on marriage, pregnancy, childbirth of women of childbearing age was obtained from Statistics Korea and Korean National Health Insurance Service database. During a total follow-up period of 54 months (July 2015 to December 2019), an average of 12,524,214 women of childbearing age per month, and 29,701 live births per month were included in the analysis. An interrupted time series with segmented regression was performed to analyze the time trend and changes in outcomes. RESULTS: The implementation of ART coverage policies had no significant impact on marriage or pregnancy rates. However, it did affect multiple pregnancy and multiple birth rates, which increased by 1.0% (Exp(ß3) = 1.010, P-value = 0.0001) and 1.4% (Exp(ß3) = 1.014, P-value = < 0.0001), respectively, compared to the pre-intervention period. Although the effect of covering ART treatment on total birth rates were not confirmed, a slightly slower decline was observed after the intervention (Exp(ß1) = 0.993, P-value = < 0.0001, Exp(ß1 + ß3) = 0.996 P-value = 0.012). CONCLUSION: This study identified the effects of ART health insurance coverage policy on the rates of multiple pregnancies and births. After the policy implementation, the downward trend in the total birth rate reduced slightly. Our findings suggest that interventions to support infertile couples should be expanded to solve the problem of low fertility rates. To address the intricate problems related to low birth rates, the Korean government introduced a policy that provides financial support and health insurance coverage for assisted reproductive technology (ART) treatment for infertile couples. As a result of evaluating the effectiveness of the ART coverage policy, it led to higher rates of pregnancies and births. In addition, although the total birth rate has been continuously decreasing over time, the decline may have been slowed down slightly by this policy.

Association between caregiver type and catastrophic health expenditure among households using inpatient medical services: using Korean health panel.

BACKGROUND: Caregiving services often place a financial burden on individuals and households that use inpatient medical services. Consequently, this study aimed to examine the association between the type of caregiver and catastrophic health expenditure among households utilizing inpatient medical services. METHODS: Data were extracted from the Korea Health Panel Survey conducted in 2019. This study included 1126 households that used inpatient medical and caregiver services. These households were classified into three groups: formal caregivers, comprehensive nursing services, and informal caregivers. Multiple logistic regression was used to analyze the association between caregiver type and catastrophic health expenditure (CHE). RESULTS: Households receiving formal caregiving had an increased likelihood of CHE at threshold levels of 40% compared to those who received care from family (formal caregiver: OR 3.11; CI 1.63-5.92). Compared to those who received formal caregiving, households using comprehensive nursing services (CNS) had a decreased likelihood of CHE (CNS: OR, 0.35; CI 0.15-0.82). In addition, considering the economic value associated with informal care, there was no significant relationship between households received formal caregiving and informal caregiving. CONCLUSION: This study found that the association with CHE differed based on the type of caregiving used by each household. Households using formal care had a risk of developing CHE. Households using CNSs were likely to have a decreased association with CHE, compared to households using informal and formal caregivers. These findings highlight the need to expand policies to mitigate the burden on caregivers for households forced to use formal caregivers.

Associations between the type of help after sexual harm and adolescents' suicidal ideation.

INTRODUCTION: This cross-sectional study aimed to determine the association between receiving external help after sexual harm and suicidal ideation among Korean adolescents. The help received was classified into professional and nonprofessional to test the strength of the association according to the type of help. METHODS: Using data from the 2017-2019 Korean children and youth rights study, we analyzed a total of 18,740 middle and high school students. The dependent variable was suicidal ideation; the primary and secondary independent variable was experience of sexual harm and receiving help after sexual harm, respectively. Data were analyzed using χ2  tests and multivariable logistic regression analyses. RESULTS: Experience of sexual harm was significantly associated with higher suicidal ideation, and receiving help after sexual harm was significantly associated with lower suicidal ideation compared with not receiving help, regardless of gender. Furthermore, lower suicidal ideation was more strongly associated with receiving professional help in female adolescents, and receiving nonprofessional help in male adolescents. CONCLUSIONS: Receiving help after sexual harm was negatively associated with suicidal ideation, and the strength of this association varied with gender and the type of help received. These results can aid the development of evidence-based crisis intervention for victims of sexual harm.

Healthcare vulnerability disparities in pancreatic cancer treatment and mortality using the Korean National Sample Cohort: a retrospective cohort study.

BACKGROUND: The gap in treatment and health outcomes after diagnosis of pancreatic cancer is a major public health concern. We aimed to investigate the differences in the health outcomes and treatment of pancreatic cancer patients in healthcare vulnerable and non-vulnerable areas. METHODS: This retrospective cohort study evaluated data from the Korea National Health Insurance Corporation-National Sample Cohort from 2002 to 2019. The position value for relative comparison index was used to define healthcare vulnerable areas. Cox proportional hazard regression was used to estimate the risk of mortality in pancreatic cancer patients according to healthcare vulnerable areas, and multiple logistic regression was used to estimate the difference in treatment. RESULTS: Among 1,975 patients, 279 (14.1%) and 1,696 (85.9%) lived in the healthcare vulnerable and non-vulnerable areas, respectively. Compared with the non-vulnerable area, pancreatic cancer patients in the vulnerable area had a higher risk of death at 3 months (hazard ratio [HR]: 1.33, 95% confidence interval [CI] = 1.06-1.67) and 6 months (HR: 1.23, 95% CI = 1.03-1.48). In addition, patients with pancreatic cancer in the vulnerable area were less likely to receive treatment than patients in the non-vulnerable area (odds ratio [OR]: 0.70, 95% CI = 0.52-0.94). This trend was further emphasized for chemotherapy (OR: 0.68, 95% CI = 0.48-0.95). CONCLUSION: Patients with pancreatic cancer belonging to medically disadvantaged areas receive less treatment and have a higher risk of death. This may be a result of the late diagnosis of pancreatic cancer among these patients.

Association of perceived life satisfaction with attitudes toward life-sustaining treatment among the elderly in South Korea: a cross-sectional study.

BACKGROUND: Amidst rapid population aging, South Korea enacted the Well-dying Act, late among advanced countries, but public opinion on the act is not still clear. Against this background, this study aims to: 1) investigate factors affecting elderly individuals' attitude toward life-sustaining treatment, and 2) examine whether attitude toward life-sustaining treatment is related to their perceived life satisfaction. METHODS: Data from the 2020 Survey of Living Conditions and Welfare Needs of Korean Older Persons were used. There were 9,916 participants (3,971 males; 5,945 females). We used multivariable-adjusted Poisson regression models with robust variance to examine the association between perceived life satisfaction and attitude toward life-sustaining treatment and calculate prevalence ratios (PR) and 95% confidence intervals (CI). RESULTS: After adjusting potential confounders, the probabilities that the elderly who were dissatisfied with their current life would favor life-sustaining treatment were 1.52 times (95% CI: 1.15-1.64) and 1.28 times (95% CI: 1.09-1.51) higher for men and women, respectively, than the elderly who were satisfied. In addition, attitudes in favor of life-sustaining treatment were observed prominently among the elderly with long schooling years or high household income, when they were dissatisfied with their life. CONCLUSIONS: Our results suggested that for the elderly, life satisfaction is an important factor influencing how they exercise their autonomy and rights regarding dying well and receiving life-sustaining treatment. It is necessary to introduce interventions that would enhance the life satisfaction of the elderly and terminally ill patients and enable them to make their own decisions according to the values of life.

Associations between environmental tobacco smoke exposure and oral health symptoms in adolescents.

BACKGROUND: Oral health condition in adolescence impacts the oral well-being throughout life. This study aimed to determine the association between environmental tobacco smoke (ETS) exposure and oral health in adolescents, using nationally representative data. METHODS: Using data from the 2020 Korea Youth Risk Behavior Web-based Survey, we assessed self-reported data on ETS exposure and oral health symptoms in 37,591 non-smoking adolescents. The dependent variables were self-reported oral health symptoms of adolescents (tooth fracture, dental pain, and gum bleeding). ETS exposure was the primary independent variable. Chi-square tests and multivariable logistic regression analyses were performed to examine these relationships. RESULTS: ETS exposure was positively associated with oral symptoms compared to no-ETS exposure in adolescents [boys, odds ratio (OR) 1.56, 95% confidence interval (CI) 1.46-1.66; girls, OR 1.50, 95% CI 1.41-1.60]; individuals with good oral health habits such as frequent tooth brushing [boys, three times or more a day, OR 1.38, 95% CI 1.24-1.53] and less soda consumption [girls, less than once a day, OR 1.73, 95% CI 1.29-2.33] had a weaker association. ETS exposure was positively associated with dental pain [boys, OR 1.55, 95% CI 1.45-1.66; girls, OR 1.50, 95% CI 1.41-1.60] and gum bleeding [boys, OR 1.43, 95% CI 1.29-1.58; girls, OR 1.32, 95% CI 1.21-1.44]; however, tooth fracture was significantly associated only in girls [OR 1.28, 95% CI 1.13-1.45]. CONCLUSIONS: ETS in various environments is negatively associated with oral health in adolescents. This association could vary depending on health habits. Sophisticated policies to protect South Korean adolescents from ETS can be developed from these findings.

Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A.

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous disease affecting the peripheral nervous system that is caused by either the demyelination of Schwann cells or degeneration of the peripheral axon. Currently, there are no treatment options to improve the degeneration of peripheral nerves in CMT patients. In this research, we assessed the potency of farnesol for improving the demyelinating phenotype using an animal model of CMT type 1A. In vitro treatment with farnesol facilitated myelin gene expression and ameliorated the myelination defect caused by PMP22 overexpression, the major causative gene in CMT. In vivo administration of farnesol enhanced the peripheral neuropathic phenotype, as shown by rotarod performance in a mouse model of CMT1A. Electrophysiologically, farnesol-administered CMT1A mice exhibited increased motor nerve conduction velocity and compound muscle action potential compared with control mice. The number and diameter of myelinated axons were also increased by farnesol treatment. The expression level of myelin protein zero (MPZ) was increased, while that of the demyelination marker, neural cell adhesion molecule (NCAM), was reduced by farnesol administration. These data imply that farnesol is efficacious in ameliorating the demyelinating phenotype of CMT, and further elucidation of the underlying mechanisms of farnesol's effect on myelination might provide a potent therapeutic strategy for the demyelinating type of CMT.

Cell Seeding Technology for Microarray-Based Quantitative Human Primary Skeletal Muscle Cell Analysis.

Pipetting techniques play a crucial role in obtaining reproducible and reliable results, especially when seeding cells on small target areas, such as on microarrays, biochips or microfabricated cell culture systems. For very rare cells, such as human primary skeletal muscle cells (skMCs), manual (freehand) cell seeding techniques invariably result in nonuniform cell spreading and heterogeneous cell densities, giving rise to undesirable variations in myogenesis and differentiation. To prevent such technique-dependent variation, we have designed and fabricated a simple, low-cost pipet guidance device (PGD), and holder that works with hand-held pipettes. This work validates the accuracy and reproducibility of the PGD platform and compares its effectiveness with manual and robotic seeding techniques. The PGD system ensures reproducibility of cell seeding, comparable to that of more expensive robotic dispensing systems, resulting in a high degree of cell uniformity and homogeneous cell densities, while also enabling cell community studies. As compared to freehand pipetting, PGD-assisted seeding of C2C12 mouse myoblasts showed 5.3 times more myotube formation and likewise myotubes derived from PGD-seeded human primary skMCs were 3.6 times thicker and 2.2 times longer. These results show that this novel, yet simple PGD-assisted pipetting technique provides precise cell seeding on small targets, ensuring reproducible and reliable high-throughput cell assays.

Cellular Stress-Modulating Drugs Can Potentially Be Identified by in Silico Screening with Connectivity Map (CMap).

Accompanied by increased life span, aging-associated diseases, such as metabolic diseases and cancers, have become serious health threats. Recent studies have documented that aging-associated diseases are caused by prolonged cellular stresses such as endoplasmic reticulum (ER) stress, mitochondrial stress, and oxidative stress. Thus, ameliorating cellular stresses could be an effective approach to treat aging-associated diseases and, more importantly, to prevent such diseases from happening. However, cellular stresses and their molecular responses within the cell are typically mediated by a variety of factors encompassing different signaling pathways. Therefore, a target-based drug discovery method currently being used widely (reverse pharmacology) may not be adequate to uncover novel drugs targeting cellular stresses and related diseases. The connectivity map (CMap) is an online pharmacogenomic database cataloging gene expression data from cultured cells treated individually with various chemicals, including a variety of phytochemicals. Moreover, by querying through CMap, researchers may screen registered chemicals in silico and obtain the likelihood of drugs showing a similar gene expression profile with desired and chemopreventive conditions. Thus, CMap is an effective genome-based tool to discover novel chemopreventive drugs.

Amelioration of Mitochondrial Quality Control and Proteostasis by Natural Compounds in Parkinson's Disease Models.

Parkinson's disease (PD) is a well-known age-related neurodegenerative disorder associated with longer lifespans and rapidly aging populations. The pathophysiological mechanism is a complex progress involving cellular damage such as mitochondrial dysfunction and protein homeostasis. Age-mediated degenerative neurological disorders can reduce the quality of life and also impose economic burdens. Currently, the common treatment is replacement with levodopa to address low dopamine levels; however, this does not halt the progression of PD and is associated with adverse effects, including dyskinesis. In addition, elderly patients can react negatively to treatment with synthetic neuroprotection agents. Recently, natural compounds such as phytochemicals with fewer side effects have been reported as candidate treatments of age-related neurodegenerative diseases. This review focuses on mitochondrial dysfunction, oxidative stress, hormesis, proteostasis, the ubiquitin‒proteasome system, and autophagy (mitophagy) to explain the neuroprotective effects of using natural products as a therapeutic strategy. We also summarize the efforts to use natural extracts to develop novel pharmacological candidates for treatment of age-related PD.

Parkin loss leads to PARIS-dependent declines in mitochondrial mass and respiration.

Mutations in parkin lead to early-onset autosomal recessive Parkinson's disease (PD) and inactivation of parkin is thought to contribute to sporadic PD. Adult knockout of parkin in the ventral midbrain of mice leads to an age-dependent loss of dopamine neurons that is dependent on the accumulation of parkin interacting substrate (PARIS), zinc finger protein 746 (ZNF746), and its transcriptional repression of PGC-1α. Here we show that adult knockout of parkin in mouse ventral midbrain leads to decreases in mitochondrial size, number, and protein markers consistent with a defect in mitochondrial biogenesis. This decrease in mitochondrial mass is prevented by short hairpin RNA knockdown of PARIS. PARIS overexpression in mouse ventral midbrain leads to decreases in mitochondrial number and protein markers and PGC-1α-dependent deficits in mitochondrial respiration. Taken together, these results suggest that parkin loss impairs mitochondrial biogenesis, leading to declining function of the mitochondrial pool and cell death.

Fast Adaptive RNN Encoder⁻Decoder for Anomaly Detection in SMD Assembly Machine.

Surface Mounted Device (SMD) assembly machine manufactures various products on a flexible manufacturing line. An anomaly detection model that can adapt to the various manufacturing environments very fast is required. In this paper, we proposed a fast adaptive anomaly detection model based on a Recurrent Neural Network (RNN) Encoder⁻Decoder with operating machine sounds. RNN Encoder⁻Decoder has a structure very similar to Auto-Encoder (AE), but the former has significantly reduced parameters compared to the latter because of its rolled structure. Thus, the RNN Encoder⁻Decoder only requires a short training process for fast adaptation. The anomaly detection model decides abnormality based on Euclidean distance between generated sequences and observed sequence from machine sounds. Experimental evaluation was conducted on a set of dataset from the SMD assembly machine. Results showed cutting-edge performance with fast adaptation.