Cell type-specific attenuation of brassinosteroid signaling precedes stomatal asymmetric cell division.

In Arabidopsis thaliana, brassinosteroid (BR) signaling and stomatal development are connected through the SHAGGY/GSK3-like kinase BR INSENSITIVE2 (BIN2). BIN2 is a key negative regulator of BR signaling but it plays a dual role in stomatal development. BIN2 promotes or restricts stomatal asymmetric cell division (ACD) depending on its subcellular localization, which is regulated by the stomatal lineage-specific scaffold protein POLAR. BRs inactivate BIN2, but how they govern stomatal development remains unclear. Mapping the single-cell transcriptome of stomatal lineages after triggering BR signaling with either exogenous BRs or the specific BIN2 inhibitor, bikinin, revealed that the two modes of BR signaling activation generate spatiotemporally distinct transcriptional responses. We established that BIN2 is always sensitive to the inhibitor but, when in a complex with POLAR and its closest homolog POLAR-LIKE1, it becomes protected from BR-mediated inactivation. Subsequently, BR signaling in ACD precursors is attenuated, while it remains active in epidermal cells devoid of scaffolds and undergoing differentiation. Our study demonstrates how scaffold proteins contribute to cellular signal specificity of hormonal responses in plants.

Measuring dynamic media bias.

Ideological media bias is increasingly central to the study of politics. Yet, past literature often assumes that the ideological bias of any outlet, at least in the short term, is static and exogenous to the political process. We challenge this assumption. We use longitudinal data from the Stanford Cable News Analyzer (2010 to 2021), which reports the screen time of various political actors on cable news, and quantify the partisan leaning of those actors using their past campaign donation behavior. Using one instantiation of media bias-the mean ideology of political actors on a channel, i.e., visibility bias-we examine weekly, within-day, and program-level estimates of media bias. We find that media bias is highly dynamic even in the short term and that the heightened polarization between TV channels over time was mostly driven by the prime-time shows.

Shaping brassinosteroid signaling through scaffold proteins.

Cellular responses to internal and external stimuli are orchestrated by intricate intracellular signaling pathways. To ensure an efficient and specific information flow, cells employ scaffold proteins as critical signaling organizers. With the ability to bind multiple signaling molecules, scaffold proteins can sequester signaling components within specific subcellular domains or modulate the efficiency of signal transduction. Scaffolds can also tune the output of signaling pathways by serving as regulatory targets. This review focuses on scaffold proteins associated with the plant GLYCOGEN SYNTHASE KINASE3-like kinase, BRASSINOSTEROID-INSENSITIVE2 (BIN2) that serve as a key negative regulator of brassinosteroid (BR) signaling. Here we summarize the current understanding of how scaffold proteins actively shape BR signaling outputs and crosstalk in plant cells via interactions with BIN2.

Dynamic Imaging of Lipid Droplets in Cells and Tissues by Using Dioxaborine Barbiturate-Based Fluorogenic Probes.

Lipids are essential for various cellular functions, including energy storage, membrane flexibility, and signaling molecule production. Maintaining proper lipid levels is important to prevent health problems such as cancer, neurodegenerative disorders, cardiovascular diseases, obesity, and diabetes. Monitoring cellular lipid droplets (LDs) in real-time with high resolution can provide insights into LD-related pathways and diseases owing to the dynamic nature of LDs. Fluorescence-based imaging is widely used for tracking LDs in live cells and animal models. However, the current fluorophores have limitations such as poor photostability and high background staining. Herein, we developed a novel fluorogenic probe based on a push-pull interaction combined with aggregation-induced emission enhancement (AIEE) for dynamic imaging of LDs. Probe 1 exhibits favorable membrane permeability and spectroscopic characteristics, allowing specific imaging of cellular LDs and time-lapse imaging of LD accumulation. This probe can also be used to examine LDs in fruit fly tissues in various metabolic states, serving as a highly versatile and specific tool for dynamic LD imaging in cellular and tissue environments.

Heat wave exposure and increased heat-related hospitalizations in young children in South Korea: A time-series study.

BACKGROUND: Numerous studies have investigated the association between heat wave exposure increased heat-related hospitalizations in the general population. However, little is known about heat-related morbidity in young children who are more vulnerable than the general population. Therefore, we aimed to evaluate the association between hospitalization for heat-related illness in children and heat wave exposure in South Korea. METHODS: We used the National Health Insurance Service (NHIS) database, which provides medical records from 2015 to 2019 in South Korea. We defined daily hospitalizations for heat-related illness of children younger than five years during the summer period (June to August). We considered the definition of heat waves considering the absolute temperature and percentile. A total of 12 different heat waves were used. A time-series analysis was used to investigate the association between heat wave exposure and heat-related hospitalization among children younger than five years. We used a two-stage design involving a meta-analysis after modeling by each region. RESULTS: We included 16,879 daily heat-related hospitalizations among children younger than five years. Overall, heat wave exposure within two days was most related for heat-related hospitalizations in young children. The relative risk (RR) due to heat wave exposure within two days (lag2) (12 definitions: 70th to 90th percentile of maximum temperature) ranged from 1.038 (95% confidence interval (CI): 0.971, 1.110) to 1.083 (95% CI: 1.036, 1.133). We found that boys were more vulnerable to heat exposure than girls. In addition, we found that urban areas were more vulnerable to heat exposure than rural areas. CONCLUSIONS: In our study, heat wave exposure during summer was found to be associated with an increased risk of hospitalization for heat-related illness among children younger than five years. Our findings suggest the need for summer heat wave management and prevention for children.

Perceived familial financial insecurity and obesity among Korean adolescents during the COVID-19 pandemic.

BACKGROUND: In high-income countries, socioeconomically disadvantaged adolescents experience a higher risk of obesity, which may have been further exacerbated during the early phase of the COVID-19 pandemic. This study aimed to investigate the association between obesity and familial financial insecurity, utilizing data on subjective household socioeconomic status (SES) and perceived family-level financial deterioration induced by COVID-19. METHODS: We utilized data from the Korea Youth Risk Behavior Survey, a nationally representative sample of Korean adolescents, in 2020 and 2021. The independent and joint associations of two primary exposures, subjective household SES and perceived family-level financial deterioration, with obesity were assessed using multivariable logistic regression models. RESULTS: Among 106,979 adolescents aged 12-18 years, 16.9% of boys and 9.0% of girls met the criteria for obesity. Notably, 70.5% reported experiencing COVID-19-related financial deterioration. Both subjective household SES and perceived family-level financial deterioration independently and synergistically increased the odds of obesity. A graded association was observed between obesity and lower SES and more severe financial deterioration, particularly among girls. Younger adolescents were more sensitive to household SES, whereas older adolescents were more sensitive to financial deterioration. CONCLUSIONS: While the COVID-19 pandemic presented a unique social context, our findings highlight that financially insecure adolescents were at an increased risk of obesity during the early phase of the pandemic. This underscores the need for obesity-prevention strategies in times of macroeconomic recession to address not only the persistent influence of household SES but also the direct and indirect effects of family-level financial deterioration.

Disparities in the association between ambient temperature and preterm birth according to individual and regional characteristics: a nationwide time-stratified case-crossover study.

BACKGROUND: Several studies have reported that climate change elevates heat exposure in pregnant women and high temperatures during pregnancy are associated with preterm births (PTBs). Although the association might be disproportionate, related evidence remains sparse. We evaluated the disproportionate risk of PTB associated with ambient temperature during pregnancy by individual and regional characteristics in South Korea. METHODS: We collected data on birth certificates and daily mean temperatures during the period from 2011 to 2019. A time-stratified case-crossover design was used to investigate the association between temperature and PTB and stratified analyses were conducted to examine the effect modification of individual and regional characteristics. RESULTS: A total of 160,067 singleton PTBs were recorded in Korea from 2011 to 2019. A 5℃ increase in the mean temperature during the last four weeks before delivery was associated with an increased risk of PTB with an odds ratio (OR) of 1.03 (95% confidence interval [CI]: 1.02, 1.05), and the association was more evident in mothers aged ≥35 years (OR: 1.06 [95% CI: 1.03, 1.10]) and with low education levels (OR: 1.04 [95% CI: 1.02, 1.05]). Additionally, the estimated risk was evident in districts with lower medical resources and more prominent disparities were shown by individual and regional characteristics in rural areas than in urban areas. CONCLUSIONS: This study provides evidence that the risk of PTB related to ambient temperature is disproportionate by individual and regional characteristics and suggests the need for public health policies to alleviate the disparities, especially in rural areas.

Subjective memory complaints and medication adherence among hypertensive Korean older adults with multimorbidity: mediating effect of depression and social support.

BACKGROUND & AIM(S): Medication adherence (MA) is a key factor in maintaining adequate blood pressure and preventing complications. However, some older adults experience difficulties in taking medicine properly due to declines in cognitive function. Although subjective memory complaints (SMC) are recognized as early markers of cognitive impairment, previous studies concerning the relationship between MA and cognitive function have focused only on objective cognitive function. Furthermore, while depression has a high correlation with SMC, low MA, and social support, there is limited evidence on their relationship. This study aims to understand the effect of SMC on MA and the mediating effect of depression and social support. METHOD(S): This study is a descriptive cross-sectional investigation. A sample of 195 community-dwelling hypertensive older adults with multimorbidity from 3 community senior centers in Gwangju, South Korea were recruited through convenience sampling. Data was collected through face-to-face survey from January to March 2018. The PROCESS macro v4.2 program [Model 6] was used to analyze the mediating effect of depression and social support in the relationship between SMC and MA. Data analysis was performed using SPSS/WIN 26.0 and STATA MP 17.0. RESULTS: The average MA was 6.74. There were significant differences in MA according to awareness of prescribed drugs, awareness of side effects, insomnia, and healthcare accessibility. SMC was positively correlated with depression, while social support and MA were negatively correlated. While depression was a significant mediator of the effect of SMC on MA, the mediating effect of social support was not significant. The multiple mediation effect of depression and social support was not significant. CONCLUSION: The results suggest that medication management of older adults in community settings should be accompanied by a comprehensive health assessment of associated factors. Health professionals should explore strategies to improve memory as well as prevent and alleviate depression to increase MA among hypertensive older adults with multimorbidity.

Targeted and Logical Discovery of Piperazic Acid-Bearing Natural Products Based on Genomic and Spectroscopic Signatures.

A targeted and logical discovery method was devised for natural products containing piperazic acid (Piz), which is biosynthesized from ornithine by l-ornithine N-hydroxylase (KtzI) and N-N bond formation enzyme (KtzT). Genomic signature-based screening of a bacterial DNA library (2020 strains) using polymerase chain reaction (PCR) primers targeting ktzT identified 62 strains (3.1%). The PCR amplicons of KtzT-encoding genes were phylogenetically analyzed to classify the 23 clades into two monophyletic groups, I and II. Cultivating hit strains in media supplemented with 15NH4Cl and applying 1H-15N heteronuclear multiple bond correlation (HMBC) along with 1H-15N heteronuclear single quantum coherence (HSQC) and 1H-15N HSQC-total correlation spectroscopy (HSQC-TOCSY) NMR experiments detected the spectroscopic signatures of Piz and modified Piz. Chemical investigation of the hit strains prioritized by genomic and spectroscopic signatures led to the identification of a new azinothricin congener, polyoxyperuin B seco acid (1), previously reported chloptosin (2) in group I, depsidomycin D (3) incorporating two dehydropiperazic acids (Dpz), and lenziamides A and B (4 and 5), structurally novel 31-membered cyclic decapeptides in group II. By consolidating the phylogenetic and chemical analyses, clade-structure relationships were elucidated for 19 of the 23 clades. Lenziamide A (4) inhibited STAT3 activation and induced G2/M cell cycle arrest, apoptotic cell death, and tumor growth suppression in human colorectal cancer cells. Moreover, lenziamide A (4) resensitized 5-fluorouracil (5-FU) activity in both in vitro cell cultures and the in vivo 5-FU-resistant tumor xenograft mouse model. This work demonstrates that the genomic and spectroscopic signature-based searches provide an efficient and general strategy for new bioactive natural products containing specific structural motifs.

Genomic and Spectroscopic Signature-Based Discovery of Natural Macrolactams.

The logical and effective discovery of macrolactams, structurally unique natural molecules with diverse biological activities, has been limited by a lack of targeted search methods. Herein, a targeted discovery method for natural macrolactams was devised by coupling genomic signature-based PCR screening of a bacterial DNA library with spectroscopic signature-based early identification of macrolactams. DNA library screening facilitated the efficient selection of 43 potential macrolactam-producing strains (3.6% of 1,188 strains screened). The PCR amplicons of the amine-deprotecting enzyme-coding genes were analyzed to predict the macrolactam type (α-methyl, α-alkyl, or ß-methyl) produced by the hit strains. 1H-15N HSQC-TOCSY NMR analysis of 15N-labeled culture extracts enabled macrolactam detection and structural type assignment without any purification steps. This method identified a high-titer Micromonospora strain producing salinilactam (1), a previously reported α-methyl macrolactam, and two Streptomyces strains producing new α-alkyl and ß-methyl macrolactams. Subsequent purification and spectroscopic analysis led to the structural revision of 1 and the discovery of muanlactam (2), an α-alkyl macrolactam with diene amide and tetraene chromophores, and concolactam (3), a ß-methyl macrolactam with a [16,6,6]-tricyclic skeleton. Detailed genomic analysis of the strains producing 1-3 identified putative biosynthetic gene clusters and pathways. Compound 2 displayed significant cytotoxicity against various cancer cell lines (IC50 = 1.58 µM against HCT116), whereas 3 showed inhibitory activity against Staphylococcus aureus sortase A. This genomic and spectroscopic signature-based method provides an efficient search strategy for new natural macrolactams and will be generally applicable for the discovery of nitrogen-bearing natural products.

Antiphotoaging Effect of AGEs Blocker™ in UVB-Irradiated Cells and Skh:HR-1 Hairless Mice.

Chronic exposure to ultraviolet (UV) radiation is a major cause of photoaging. It involves extrinsic aging, wrinkle formation, and skin dehydration, and leads to excessive production of active oxygen that adversely affects the skin. Here, we investigated the antiphotoaging effect of AGEs BlockerTM (AB), which comprises Korean mint aerial part and fig and goji berry fruits. Compared to its individual components, AB was more potent at increasing the expression of collagen and hyaluronic acid and decreasing MMP-1 expression in UVB-irradiated Hs68 fibroblasts and HaCaT keratinocytes. In Skh:HR-1 hairless mice exposed to 60 mJ/cm2 UVB for 12 weeks, oral administration of 20 or 200 mg/kg/day AB restored skin moisture by improving UVB-induced erythema, skin moisture, and transepidermal water loss, and alleviated photoaging by improving UVB-induced elasticity and wrinkles. Moreover, AB upregulated the mRNA levels of hyaluronic acid synthase and collagen-related Col1a1, Col3a1, and Col4a1 genes, increasing hyaluronic acid and collagen expression, respectively. AB inhibited UVB-induced MAPK and AP-1 (c-fos) activation, resulting in significantly downregulated expression of MMP-1 and -9, which are responsible for collagen degradation. AB also stimulated the expression and activity of antioxidative enzymes and reduced lipid peroxidation. Thus, AB is a potential preventive and therapeutic agent for photoaging.

Hierarchically Interpenetrated and Reentrant Microcellular Frameworks for Stretchable Lithium Metal Batteries.

With the rapid development of human-friendly wearable devices, energy storage components are required to have skin-like stretchability or free-form to fit closer and more comfortably to the human body. This study introduces a hierarchically interpenetrated reentrant microcellular structure combined with 2D cellular graphene/MXene/carbon nanotubes (CNTs) and 3D cellular melamine foam. This composite structure works as a stretchable framework of lithium metal composite electrodes to provide stretchability for lithium metal electrodes, which are promising as next-generation energy storage systems. The interpenetrated but independent cellular structures successfully obtain stable structural deformability from the nonconductive and deformable melamine foam, while at the same time, high electrical conductivity, lithiophilicity, and mechanical stability of the graphene/CNT/MXene network serve as a lithium deposition support during the electrodeposition of lithium. The reentrant structure is fabricated by radial compressing the hierarchical cellular structures to take advantage of the structural stretchability of the accordion-like reentrant frameworks. The lithium-deposited composite electrodes exhibit much lower overpotential during Li stripping and plating than lithium metal foil anodes and show stable electrochemical performances under 30% of mechanical strain. The reentrant microcellular electrodes offer great potential for advanced designs of lithium metal electrodes for stretchable batteries with high energy density.

Whole-Genome Sequencing Reveals Mutational Signatures Related to Radiation-Induced Sarcomas and DNA-Damage-Repair Pathways.

Radiation-induced sarcoma (RIS) is a rare but serious late complication arising from radiotherapy. Despite unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. We analyzed whole-genome sequencing in 11 RIS genomes matched with normal genomes to identify somatic alterations potentially associated with RIS development. Furthermore, the abundance of mutations, mutation signatures, and structural variants in RIS were compared with those in radiation-naïve spontaneous sarcomas. The mutation abundance in RIS genomes, including one hypermutated genome, was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations. The genomic footprints of nonhomologous end joining are prevalent at indels of RIS genomes compared with those in spontaneous sarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis was identified along with predisposing germline variants in the DNA-damage-repair pathways in RIS genomes. The characterization of RIS genomes on a whole-genome sequencing scale highlighted that the nonhomologous end joining pathway was associated with tumorigenesis, and it might pave the way for the development of advanced diagnostic and therapeutic strategies for RIS.

Downregulation of the RNA-binding protein PUM2 facilitates MSC-driven bone regeneration and prevents OVX-induced bone loss.

BACKGROUND: Although mRNA dysregulation can induce changes in mesenchymal stem cell (MSC) homeostasis, the mechanisms by which post-transcriptional regulation influences MSC differentiation potential remain understudied. PUMILIO2 (PUM2) represses translation by binding target mRNAs in a sequence-specific manner. METHODS: In vitro osteogenic differentiation assays were conducted using human bone marrow-derived MSCs. Alkaline phosphatase and alizarin red S staining were used to evaluate the osteogenic potential of MSCs. A rat xenograft model featuring a calvarial defect to examine effects of MSC-driven bone regeneration. RNA-immunoprecipitation (RNA-IP) assay was used to determine the interaction between PUM2 protein and Distal-Less Homeobox 5 (DLX5) mRNA. Ovariectomized (OVX) mice were employed to evaluate the effect of gene therapy for postmenopausal osteoporosis. RESULTS: Here, we elucidated the molecular mechanism of PUM2 in MSC osteogenesis and evaluated the applicability of PUM2 knockdown (KD) as a potential cell-based or gene therapy. PUM2 level was downregulated during MSC osteogenic differentiation, and PUM2 KD enhanced MSC osteogenic potential. Following PUM2 KD, MSCs were transplanted onto calvarial defects in 12-week-old rats; after 8 weeks, transplanted MSCs promoted bone regeneration. PUM2 KD upregulated the expression of DLX5 mRNA and protein and the reporter activity of its 3'-untranslated region. RNA-IP revealed direct binding of PUM2 to DLX5 mRNA. We then evaluated the potential of adeno-associated virus serotype 9 (AAV9)-siPum2 as a gene therapy for osteoporosis in OVX mice. CONCLUSION: Our findings suggest a novel role for PUM2 in MSC osteogenesis and highlight the potential of PUM2 KD-MSCs in bone regeneration. Additionally, we showed that AAV9-siPum2 is a potential gene therapy for osteoporosis.

Reduced forced expiratory flow between 25% and 75% of vital capacity in children with allergic rhinitis without asthmatic symptoms.

INTRODUCTION: Allergic rhinitis (AR) and asthma are closely associated in children. Reduced FEF25%-75% which reflects small airway airflow limitation is frequently observed in asthma. This study aimed to examine the proportion of small airway dysfunction in children with AR and to determine its associated factors.Methods: The medical records of 144 aged 6-18-year children with AR without overt asthmatic symptoms were retrospectively reviewed. Subjects were divided into 2 groups according to the FEF25%-75% values; normal FEF25%-75% group (n = 129) and reduced FEF25%-75% group (n = 15). Clinical data, allergen sensitization profile, exhaled nitric oxide, spirometry, and methacholine provocation test results were compared between the two groups.Results: The mean FEV1 and FEF25%-75% values in the reduced FEF25%-75% group (73.5 ± 9.4%pred and 56.0 ± 7.7%pred, respectively) were significantly lower than in the normal FEF25%-75% group (87.0 ± 12.5%pred and 99.1 ± 21.4%pred, respectively). The mean disease duration was significantly longer in the reduced FEF25%-75% group than in the normal FEF25%-75% group (5.39 ± 1.85 y vs 3.14 ± 1.80 y, p < 0.001). Subjects with positive bronchial hyperresponsiveness (MChPC20<16 mg/mL) were more frequently detected in the reduced FEF25%-75% group than in the normal FEF25%-75% group (26.7% vs 8.52%, p = 0.013). Long disease duration and severity of AR were significantly associated with impaired FEF25%-75% values.Conclusions: Subjects with AR alone may have impaired FEF25%-75% values which is considered as a marker of early bronchial involvement. Longer disease duration and severity of AR are important risk factors for progressive declines in small airway function. Physicians should be aware of need for the measurement of FEF25%-75% values for early detection of small airway dysfunction, particularly in children with severe long-lasting allergic rhinitis.

Use of gastrointestinal prokinetics and the risk of parkinsonism: A population-based case-crossover study.

BACKGROUND: The disease burden of parkinsonism is extremely costly in the United States. Unlike Parkinson's disease, drug-induced parkinsonism (DIP) is acute and reversible; exploring the causative drug is important to prevent DIP in patients at high-risk of parkinsonism. OBJECTIVE: To examine whether the use of gastrointestinal (GI) prokinetics is associated with an increased risk of parkinsonism. METHODS: We conducted a case-crossover study using nationally representative data. We included patients who were newly diagnosed with parkinsonism (ICD-10 G20, G21.1, G25.1) between January 1, 2007 and December 1, 2015. The first prescription date of G20, G21.1, or G25.1 diagnoses was defined as the index date (0 day). Patients with prior extrapyramidal and movement disorders or brain tumors were excluded. We assessed the exposure within the risk (0-29 days) and control periods (60-89 days), before or on the index date. Conditional logistic regression estimated the adjusted odds ratio (aOR) for parkinsonism. RESULTS: Overall, 2268 and 1674 patients were exposed to GI prokinetics during the risk and control periods, respectively. The use of GI prokinetics significantly increased the occurrence of parkinsonism (aOR = 2.31; 95% Confidence Interval [CI], 2.06-2.59). The use of GI prokinetics was associated with a higher occurrence of parkinsonism in elderly patients (≥65 years old; aOR = 2.69; 95% CI, 2.30-3.14) than in younger patients (aOR = 1.90; 95% CI, 1.59-2.27). CONCLUSIONS: The use of GI prokinetics was significantly associated with higher occurrences of parkinsonism, necessitating close consideration when using GI prokinetics.

Can individual protective measures safeguard cardiopulmonary health from air pollution? A systematic review and meta-analysis.

Evidence supporting the effect of individual protective measures (IPMs) on air pollution is relatively scarce. In this study, we performed a systematic review and meta-analysis to investigate the effects of air purifiers, air-purifying respirators, and cookstove changes on cardiopulmonary health outcomes. We searched PubMed, Scopus, and Web of Science until December 31, 2022, 90 articles and 39,760 participants were included. Two authors independently searched and selected the studies, extracted information, and assessed each study's quality and risk of bias. We performed meta-analyses when three or more studies were available for each IPMs, with comparable intervention and health outcome. Systematic review showed that IPMs were beneficial in children and elderly with asthma along with healthy individuals. Meta-analysis results showed a reduction in cardiopulmonary inflammation using air purifiers than in control groups (with sham/no filter) with a decrease in interleukin 6 by -0.247 µg/mL (95% confidence intervals [CI] = -0.413, -0.082). A sub-group analysis for air purifier as an IPMs in developing counties reduced fractional exhaled nitric oxide by -0.208 ppb (95% confidence intervals [CI] = -0.394, -0.022). However, evidence describing the effects of air purifying respirator and cook stove changes on cardiopulmonary outcomes remained insufficient. Therefore, air purifiers can serve as efficient IPMs against air pollution. The beneficial effect of air purifiers is likely to have a greater effect in developing countries than in developed countries.

Human Argonaute 2 Has Diverse Reaction Pathways on Target RNAs.

Argonaute is a key enzyme of various RNA silencing pathways. We use single-molecule fluorescence measurements to characterize the reaction mechanisms of the core-RISC (RNA-induced silencing complex) composed of human Argonaute 2 and a small RNA. We found that target binding of core-RISC starts at the seed region, resulting in four distinct reaction pathways: target cleavage, transient binding, stable binding, and Argonaute unloading. The target cleavage requires extensive sequence complementarity and dramatically accelerates core-RISC recycling. The stable binding of core-RISC is efficiently established with the seed match only, providing a potential explanation for the seed-match rule of miRNA (microRNA) target selection. Target cleavage on perfect-match targets sensitively depends on RNA sequences, providing an insight into designing more efficient siRNAs (small interfering RNAs).

Interaction between blood cadmium and lead concentration and physical activity on hypertension from the Korean national health and nutrition examination survey in 2008-2013.

BACKGROUND: Previous studies have suggested that blood Cd, Pb exposure, and physical activity levels may influence the development of hypertension. This study aimed to investigate the relationship between blood Cd, Pb levels, and hypertension by the level of physical activity in Korean adults using The Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: We used data from the KNHANES (2008-2013), a nationally representative, cross-sectional, population-based study. We included 8,510 participants who had records of blood Cd, Pb and, blood pressure measurements. Multiple logistic regression was used to examine the association between blood Cd and Pb exposure and the development of hypertension, as well as the modifying effects of physical activity levels. Additive interaction was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). RESULTS: Following covariates adjustments, we found significant associations of blood Cd and Pb with higher hypertension prevalence. This association was more apparent in low physical activity while blood Cd and Pb concentrations were not significantly associated with hypertension in participants with more activity. Additionally, there was a significant interaction between blood Cd and physical activity on hypertension risk (RERI = 0.17, 95% CI: -0.36-0.7; AP = 0.12, 95% CI: -0.28-0.52; S = 1.75, 95% CI:1.36-2.14). CONCLUSIONS: Our results suggest that low physical activity may substantially amplify the adverse effects of blood Pb and Cd exposure on hypertension risk. However, interactions were only found for Cd. Further studies are needed to confirm these findings.

Evaluation of a technology-enhanced, integrated community health and wellness program for seniors (HWePS): protocol of a non-randomized comparison trial.

BACKGROUND: Healthy aging for all in the community is a shared public health agenda for countries with aging populations, but there is a lack of empirical evidence on community-wide preventive models that promote the health of older people residing in socially-disadvantaged communities. The Health and Wellness Program for Seniors (HWePS) is a technology-enhanced, multi-level, integrated health equity intervention model. This study evaluates the effect of the HWePS on the health and well-being of older adults residing in urban, low-income communities.  METHODS/DESIGN: HWePS is a prospective, non-randomized comparison trial conducted in an intervention and a control neighborhood (dong) in Seoul, South Korea, over 12 months. Older people who reside in the small areas and meet the inclusion/exclusion criteria are eligible to participate. The multi-level, multi-faceted HWePS intervention is a preventive community care model for older residents guided by the expanded chronic care model, the comprehensive health literacy intervention model, and the Systems for Person-centered Elder Care model along with health equity frameworks. HWePS consists of four components: a health literacy intervention based on individual and community needs assessments, personalized (self-)care management featuring nurse coaching and peer support, a healthy-living and healthy-aging community initiative, and information and communication technology (ICT) systems. The primary outcomes are self-reported health and health-related quality of life. Outcome assessors and data analysts are blinded to group assignment. Process evaluation will be also conducted. DISCUSSION: As a multi-level health equity project, HWePS has adopted a novel study design that simultaneously targets individual- and community-level factors known to contribute to health inequality in later life in the community. The study will provide insights into the effectiveness and implementation process of an integrated, multi-level, preventive community care model, which in turn can help improve the health outcomes of older residents and reduce disparities in underserved urban communities. TRIAL REGISTRATION: ISRCTN29103760. Registered 2 September 2021, https://www.isrctn.com/ISRCTN29103760.