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Purpose: This study aims to estimate (a) the relationship between disability acceptance and depressive symptoms, and (b) how the quality and quantity of social support might moderate the link between disability acceptance and depressive symptoms. Materials and methods: The data for this study included information from 5165 individuals with disability who participated in 3 waves of the Disability and Life Dynamic Panel spanning years 2018 to 2020. This study employed fixed effects models to estimate the association between disability acceptance and depressive symptoms. Interaction models were used to assess the moderating effects of both the quantity and quality of social support. Results: A lower acceptance of disability was positively associated with depressive symptoms. Moreover, both the quantity and quality of social support were associated with a decrease in depressive symptoms. Only the quality of social support played a significant role in moderating the relationship between disability acceptance and depressive symptoms. Conclusion: A lower acceptance of disability increases depressive symptoms in individuals with disabilities. This study underscores the need for interventions to focus on enhancing the quality of social support to mitigate the link between disability acceptance and depressive symptoms. IMPLICATIONS FOR REHABILITATION: A lower acceptance of disability is positively associated with depressive symptoms among persons with disability. The association between lower disability acceptance and depressive symptoms attenuates as emotional support from family and friends increases. The number of family and friends does not significantly change the relationship between lower disability acceptance and depressive symptoms. The findings highlight the importance of interventions enhancing quality of social support in order to mitigate the association between disability acceptance and psychological health. [ABSTRACT FROM AUTHOR]

Cellulosic biomass hydrolysates are rich in glucose and xylose, but most microorganisms, including Komagataella phaffii, are unable to utilize xylose effectively. To address this limitation, we engineered a K. phaffii strain optimized for xylose metabolism through the xylose oxidoreductase pathway and promoter optimization. A promoter library with varying strengths was used to fine-tune the expression levels of the XYL1, XYL2, and XYL3 genes, resulting in a strain with a strong promoter for XYL2 and weaker promoters for XYL1 and XYL3. This engineered strain exhibited superior growth, achieving 14 g cells/L and a maximal growth rate of 0.4 g cells/L-h in kenaf hydrolysate, outperforming a native strain by 17%. This study is the first to report the introduction of the xylose oxidoreductase pathway into K. phaffii, demonstrating its potential as an industrial platform for producing yeast protein and other products from cellulosic biomass. [ABSTRACT FROM AUTHOR]

Exchange interactions at the interfaces are the root to produce conventional exchange bias in ferromagnet/antiferromagnet (FM/AFM) heterostructures, which are extensively utilized in spintronics. This work proposes an unconventional approach for the growth of the CoMn2O4 interface in Mn2O3@Co3O4 core–shell, which led to an unprecedented exchange bias. Specimens were prepared with a modified two‐step co‐precipitation method followed by the controlled heating episodes, to initiate the Co2+/3+/Mn2+/3+/4+ cation exchange, which facilitates CoMn2O4 interface in the sample (SA‐1). For comparison, Mn2O3@Co3O4 composite was synthesized with inhibited cation exchange (SA‐2 specimen). X‐ray diffraction and high‐resolution transmission electron microscope results confirmed the presence of each phase with core–shell type morphology. SA‐1 sample experiences AFM–FiM (ferrimagnetic) exchange coupling, revealed by the strongly bifurcated zero field‐cooled and field‐cooled magnetization curves below the Néel temperature (TN‐86 K), resulting in large exchange bias field (HEB) strength of 2712 Oe. Training effect data fitted with thermal relaxation and frozen‐rotatable spin relaxation model suggests the dominant character of uncompensated rotating spins in AFM–FiM–AFM interfaces as opposed to the relaxing frozen spins found in conventional AFM–FM interfaces. [ABSTRACT FROM AUTHOR]

Magnetic susceptibility enhancement (kE) is useful for reconstructing terrestrial paleohydroclimate variabilities. However, kE and its driving process(es) in the Korean Peninsula remain uninvestigated. Therefore, this study investigated two kEs of similar magnitudes, dated MIS 1 (Holocene) and late MIS 3 (~ 29–36 ka), from a paleosol sequence in the upland of paleo-fluvial terrace in the central Korean Peninsula. We observed increased ferri- and antiferro-magnetic mineral components,including ultrafine particles, and stronger chlorite weathering for the two kEs, suggesting pedogenic component predominance. The Fe-bearing (phyllo)silicate weathering mechanism proposed for the Chinese Loess Plateau sequences can explain the pedogenesis-induced kEs for the studied site. Superparamagnetic-domain (SPD) to pseudo-single-domain sized particles of pedogenic magnetite are likely major contributors to kEs. Moreover, we recognized the younger kE interval as more SPD contribution but less in total ferrimagnetic contribution, and more antiferromagnetic contribution than the older ones. The magnetic differences between the periods can result from vegetation cover impact and surrounding hydroclimate conditions, consistent with the recent suggestion for part of the southeast Chinese sites with relatively more rainfall. Consequently, our study provides a baseline for improving the relationship between mineral magnetic signals and local/regional hydroclimatic and environmental variabilities. [ABSTRACT FROM AUTHOR]

Innovative for the scientific community and attracting attention in the extensive biomedical field are novel compact organic chemosensing systems built upon unique core molecular frameworks. These systems may demonstrate customized responses and may be adaptable to analytes, showing promise for potential in vivo applications. Our recent investigation focuses on a precursor of Mycophenolic acid, resulting in the development of LBM (LOD = 13 nM) – a specialized probe selective for H2O2. This paper details the synthesis, characterization, and thorough biological assessments of LBM. Notably, we conducted experiments involving living cells, daphnia, and zebrafish models, utilizing microscopy techniques to determine probe nontoxicity and discern distinct patterns of probe localization. Localization involved the distribution of the probe in the Zebrafish model within the gut, esophagus, and muscles of the antennae. [ABSTRACT FROM AUTHOR]

In several biological processes, H2S is known to function as an endogenous gaseous agent. It is very necessary to monitor H2S and relevant physiological processes in vivo. Herein, a new type of fluorophore with a reliable leaving group allows for excited‐state intramolecular transfer characteristics (ESIPT), inspired by mycophenolic acid. A morpholine ring was connected at the maleimide position of the probe to target the lysosome. Subsequently, the dinitrophenyl group known for a photoinduced electron transfer (PET) effect, was connected to allow for an effective "turn‐on" probe Lyso‐H2S. Lyso‐H2S demonstrated strong selectivity towards H2S, a large Stokes shift (111 nm), and an incredibly low detection limit (41.8 nM). The imaging of endogenous and exogenous H2S in living cells (A549 cell line) was successfully achieved because of the specificity and ultra‐low toxicity (100 % cell viability at 50 μM concentration of Lyso‐H2S.) Additionally, Lyso‐H2S was also employed to visualize the activity of H2S in the gallbladder and intestine in a living zebrafish model. This is the first report of a fluorescent probe to track H2S sensing in specific organ systems to our knowledge. [ABSTRACT FROM AUTHOR]

Inflammation is a natural protective process through which the immune system responds to injury, infection, or irritation. However, hyperinflammation or long-term inflammatory responses can cause various inflammatory diseases. Although idebenone was initially developed for the treatment of cognitive impairment and dementia, it is currently used to treat various diseases. However, its anti-inflammatory effects and regulatory functions in inflammatory diseases are yet to be elucidated. Therefore, this study aimed to investigate the anti-inflammatory effects of idebenone in cecal ligation puncture-induced sepsis and lipopolysaccharide-induced systemic inflammation. Murine models of cecal ligation puncture-induced sepsis and lipopolysaccharide-induced systemic inflammation were generated, followed by treatment with various concentrations of idebenone. Additionally, lipopolysaccharide-stimulated macrophages were treated with idebenone to elucidate its anti-inflammatory effects at the cellular level. Idebenone treatment significantly improved survival rate, protected against tissue damage, and decreased the expression of inflammatory enzymes and cytokines in mice models of sepsis and systemic inflammation. Additionally, idebenone treatment suppressed inflammatory responses in macrophages, inhibited the NF-κB signaling pathway, reduced reactive oxygen species and lipid peroxidation, and normalized the activities of antioxidant enzyme. Idebenone possesses potential therapeutic application as a novel anti-inflammatory agent in systemic inflammatory diseases and sepsis. [ABSTRACT FROM AUTHOR]

This study analyzed the effects of the announcement and publication of the 2019 Public Charge Rule on participation of the special supplemental nutrition program for women, infants, and children (WIC) among pregnant immigrants. A difference-in-differences approach was used to analyze the changes in prenatal WIC participation before and after the 2019 Public Charge Rule announcement and publication among immigrants relative to US natives. We identified 17,623,683 live singletons born in a hospital from 2015 to 2019. Compared to US natives, the odds of prenatal WIC participation among immigrants were 11.4% lower after the 2019 Public Charge Rule announcement, and 19% lower after the final rule was published. The results of this study suggest that pregnant immigrants may decide not to participate in the WIC program due to the fear of jeopardizing their immigration status after the announcement and publication of the 2019 Public Charge Rule. [ABSTRACT FROM AUTHOR]

Background: Lymphocyte antigen 6 complex locus K (LY6K), a glycosylphosphatidylinositol‐anchored protein, plays a dynamic role in cancer metastasis. In the current study, we deciphered the effects of LY6K on transforming growth factor‐β (TGF‐β) and epidermal growth factor (EGF) signaling through clathrin‐ and caveolin‐1 (CAV‐1)‐mediated endocytosis. Methods: Analysis of the TCGA and GTEx dataset were performed to explore the expression and survival of LY6K in cancer patients. Short interfering RNA (siRNA) was used to knockdown the expression of LY6K in human cervical cancer patients. The effect of lack of LY6K on cell proliferation, migration, and invasion was performed, and RT‐qPCR and immunoblotting were performed to identify LY6K‐affected TGF‐β and EGF signaling pathways. Additionally, Immunofluorescence (IF) and transmission electron microscope (TEM) were performed to identify the role of LY6K in CAV‐1‐ and Clathrin‐mediated endocytosis. Results: Lymphocyte antigen 6 complex locus K expression level is elevated in higher grade cervical cancer patients correlating with poor overall survival, progression‐free survival, and disease‐free survival. LY6K‐depletion in HeLa and SiHa cancer cells suppressed EGF‐induced proliferation and TGF‐β‐enhanced migration and invasion. Both TGF‐β receptor‐I (TβRI) and EGF receptor (EGFR) localized at the plasma membrane regardless of LY6K expression, and LY6K bound TβRI irrespective of the presence of TGF‐β; however, LY6K did not bind EGFR. LY6K‐depleted cells showed impaired Smad2 phosphorylation upon TGF‐β treatment and lower proliferation rates following long‐term treatment with EGF. We revealed the atypical movement of TβRI and EGFR from plasma membrane upon ligand stimulation in LY6K‐depleted cells and an impaired movement of the endocytic proteins clathrin and CAV‐1. Conclusions: Our study demonstrates the key role of LY6K in both clathrin‐ and CAV‐1‐mediated endocytic pathways regulated by TGF‐β and EGF, and it suggests a correlation between LY6K overexpression in cervical cancer cells and poor overall survival. [ABSTRACT FROM AUTHOR]

Routine physical activity is important for everyone, and most urban areas have an infrastructure of neighborhood parks that are intended to serve as a setting for recreation and leisure. However, parks are not used proportionally by all age groups, genders, and socioeconomic groups. This paper explores factors associated with park use by different age and gender groups in low-income neighborhoods in Los Angeles, CA. We found that women's visits to parks generally centered around children, whereas men's visits were more likely to be associated with their own physical activity. Barriers for seniors are associated with limited facilities and programming that meet their needs. Park managers should consider park renovations that include social meeting places, comfortable sitting areas, and walking paths to better serve women and seniors. [ABSTRACT FROM AUTHOR]

This study estimates the effects of the COVID-19 pandemic on life satisfaction and stress and examines whether these effects vary across different sociodemographic groups using a nationally representative sample in South Korea. We estimate the causal effects of COVID-19 on psychological well-being by exploiting regional variation in the spread of the pandemic in South Korea. While the number of confirmed cases was very small in other provinces in the first half of 2020, the coronavirus spread rapidly in Daegu after an outbreak in one church. We employ a difference-in-differences approach that compares changes in people's life satisfaction and stress before-and-after the initial surge of COVID-19 cases in Daegu and other provinces. Our results show that the proportion of people who are dissatisfied with life increased by 2.8–6.5 percentage points more in Daegu than in other provinces after the COVID-19 outbreak. During the same period, the proportion of people who reported feeling stressed increased more in Daegu than in other provinces by 5.8–8.9 percentage points. Our results also suggest that the negative impact of the COVID-19 outbreak on psychological well-being is significantly greater for men, young adults, middle-aged adults, self-employed workers, and middle-income individuals. On the other hand, the proportion of people who report feeling stressed among the highest-educated (a master's degree or higher) and high-income individuals decreased after the onset of the COVID-19 outbreak. [ABSTRACT FROM AUTHOR]

Numerous technological advances have been made in the depolymerization and fermentation of lignocellulosic biomass. Nevertheless, economic feasibility is still a major concern for the bioconversion of lignocellulose into value-added products. Acetate—the most abundant carbon source after the sugars in cellulosic hydrolysates—has been considered a fermentation inhibitor, but it can also be a good substrate in industrial biotechnological processes. Co-consumption of acetate and cellulosic sugars by yeasts will improve the economic feasibility of any bioconversion processes using cellulosic hydrolysates. This study investigates state-of-the-art technologies for the utilization of the hemicellulose fractions of lignocellulosic biomass, rich in acetate and xylose. Furthermore, the potentials of acetate- and xylose-rich hydrolysates will be highlighted in diversifying the product profiles for lignocellulosic bioprocesses from bioethanol to drop-in fuels and other value-added chemicals. [ABSTRACT FROM AUTHOR]

Objectives This study investigates longitudinal within-person associations between urinary incontinence (UI) and depressive symptoms among older women. Drawing on activity theory, this study also adds to limited knowledge about the mediating role of physical activity and social engagement in the association between UI and depressive symptoms. Methods Using 6 waves of a nationally representative longitudinal study of older adults in Korea between 2008 and 2018, this study examined the relationship between UI and depressive symptoms among women aged 70 and older. Fixed effects models were estimated to account for unobserved time-invariant confounding factors. Sobel mediation tests were conducted to formally test for mediation. Results Fixed effects estimates showed that, after adjusting for a wide array of time-varying covariates, having UI is positively associated with depressive symptoms among older women (b = 0.238, p <.05). Results revealed that individuals who begin to experience UI tend to have less frequent social interactions and participate in fewer social activities. UI, however, is only marginally associated with a decrease in physical activity. Reductions in physical activity, social connections, and social activities jointly explain about 22% of the association between UI and depressive symptoms, rendering it statistically insignificant. Discussion UI poses a threat to psychological well-being among older women. This is partly explained by a decrease in physical activity and disruption in social engagement. This study reaffirms the significance of the programs that promote physical and social activity among older adults. [ABSTRACT FROM AUTHOR]

Introduction: Multistakeholder engagement is crucial for conducting health services research. Delphi‐based methodologies combining iterative rounds of questions with feedback on and discussion of group results are a well‐documented approach to multistakeholder engagement. This study develops hypotheses about the impact of panel composition and topic on the propensity and meaningfulness of response changes in multistakeholder modified‐Delphi panels. Methods: We conducted three online modified‐Delphi (OMD) multistakeholder panels using the same protocol. We assigned 60 maternal and child health professionals to a homogeneous (professionals only) panel, 60 pregnant or postpartum women (patients) to a homogeneous panel, and 30 professionals and 30 patients to a mixed panel. In Round 1, participants rated the seriousness of 11 maternal and child health outcomes using a 0–100 scale and explained their ratings. In Round 2, participants saw their own and their panel's Round 1 results and discussed them using asynchronous, anonymous discussion boards moderated by the study investigators. In Round 3, participants revised their original ratings. Our outcome measures included binary indicators of response changes to ratings of the low, medium and high severity maternal and child health outcomes and their meaningfulness, measured by a change of 10 or more points. Results: Participants changed 818 of 1491 (55%) of responses; the majority of response changes were meaningful. Patterns of response changes were different for patients and professionals and for different levels of outcome seriousness. Using study results and the literature, we developed three hypotheses. First, OMD participants, regardless of their stakeholder group, are more likely to change their responses on preference‐sensitive topics where there is a range of viable alternatives or perspectives. Second, patients are more likely to change their responses and to do so meaningfully in mixed panels, whereas professionals are more likely to do so in homogeneous panels. Third, the association between panel composition and response change varies according to the topic (e.g., the level of outcome seriousness). Conclusions: Results of our work not only helped generate empirically derived hypotheses to be tested in future research but also offer practical recommendations for designing multistakeholder OMD panels. Patient or Public Contribution: Pregnant or postpartum women were involved in this study. [ABSTRACT FROM AUTHOR]

Here, in Ppara−/− mice, we found that an increased DNL stimulated the cartilage degradation and identified ACOT12 as a key regulatory factor. Suppressed level of ACOT12 was observed in cartilages of OA patient and OA-induced animal. To determine the role and association of ACOT12 in the OA pathogenesis, we generated Acot12 knockout (KO) (Acot12−/−) mice using RNA-guided endonuclease. Acot12−/− mice displayed the severe cartilage degradation with the stimulation of matrix MMPs and chondrocyte apoptosis through the accumulation of acetyl CoA. Delivery of acetyl CoA-conjugated chitosan complex into cartilage stimulated DNL and cartilage degradation. Moreover, restoration of ACOT12 into human OA chondrocytes and OA-induced mouse cartilage effectively rescued the pathophysiological features of OA by regulating DNL. Taken together, our study suggested ACOT12 as a novel regulatory factor in maintaining cartilage homeostasis and targeting ACOT12 could contribute to developing a new therapeutic strategy for OA. Increasing evidence suggested that dysregulation in lipid metabolism is linked to OA pathogenesis, but the underlying regulatory mechanism is not well understood. Here, the authors show that PPARα-ACOT12 signalling regulates cartilage homeostasis by regulating de novo lipogenesis in mice. [ABSTRACT FROM AUTHOR]

We comprehensively analyzed sediments obtained from an archeological excavation. A trench sediment profile of Maedun Cave (MC), South Korea, was analyzed geoarchaeologically. Multi‐proxy analyses (palynomorphs, grain size, magnetic susceptibility, animal bones and artifacts) reflected the vegetation, hydroclimate and lives of prehistoric people at Marine Isotope Stage (MIS) 3 (ca. 40–30k cal a bp) in the early Late Paleolithic. The palynoflora consisted of pollen and non‐pollen palynomorphs. Under the air‐circulation system in the cave, anemophilous pollen flowed in during the day, whereas waterborne pollen and spores, and freshwater algae, were transported by flooding during the summer monsoon rainy season. Mixed conifer and deciduous broad‐leaved forest with an understory of pteridophytes flourished around the north‐east central Korean Peninsula during MIS 3. Freshwater algae and grass pollen records may reflect precipitation intensity. It is assumed that they had flowed in during flooding caused by high precipitation during the enhanced East Asian summer monsoon, corresponding to Dansgaard–Oeschger (D/O) events 5 and 8 of δ18O GISP2 and Hulu Cave. The prehistoric people hunted herbivorous animals in the area around MC and sheltered inside it seasonally. They also used the grains of oats growing near the dwelling as a source of food. Highlights: Multi‐proxy records from cave sediments of the Korean Peninsula shed light on vegetation cover and climate conditions during MIS 3 (40–30k cal a BP).Herbaceous pollen and non‐pollen palynomorphs flowed into the cave due to flooding caused by high precipitation under the enhanced East Asia summer monsoon.Fossilized mammal bones and artifacts shed light on the lifestyle of prehistoric people in the early Late Paleolithic.Geoarchaeological evidence provides insight into the responses of ancient societies to climate conditions in northeast central Korea. [ABSTRACT FROM AUTHOR]

Background: IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo. Results: The ik KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in ik KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The ik KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of ik reduces myod1 expression and upregulates pax7a, preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells. Conclusion: This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro. [ABSTRACT FROM AUTHOR]

Background: IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo. Results: The ik KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in ik KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The ik KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of ik reduces myod1 expression and upregulates pax7a, preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells. Conclusion: This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro. [ABSTRACT FROM AUTHOR]

Background: IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo. Results: The ik KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in ik KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The ik KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of ik reduces myod1 expression and upregulates pax7a, preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells. Conclusion: This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro. [ABSTRACT FROM AUTHOR]

Background: IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo. Results: The ik KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in ik KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The ik KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of ik reduces myod1 expression and upregulates pax7a, preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells. Conclusion: This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro. [ABSTRACT FROM AUTHOR]

Radiocarbon (14C) dating has been widely used to determine the age of deposits, but there have been frequent reports of inconsistencies in age among different dating materials. In this study, we performed radiocarbon dating on a total of 33 samples from 8-m-long sediment cores recovered from the wetland of the Muljangori volcanic cone on Jeju Island, South Korea. Ten pairs of humic acid (HA) and plant fragments (PF) samples, and three pairs of HA and humin samples, from the same depths were compared in terms of age. The PF were consistently younger than the HA. Interestingly, the age difference between HA and PF samples showed a long-term change during the past 8000 years. To test whether there was an association between this long-term age difference and climate change, we compared with the carbon/nitrogen (C/N) ratios and total organic carbon isotope (δ13CTOC) values of the sediments, as indicators of the relative abundance of terrestrial and aquatic plants; these parameters showed similar long-term trends. This suggests that the increasing (decreasing) trend in age difference was influenced by long-term dry (wet) climate change. [ABSTRACT FROM AUTHOR]

Objectives: Emerging oncotherapeutic strategies require the induction of an immunostimulatory tumor microenvironment (TME) containing numerous tumor‐reactive CD8+ T cells. Interleukin‐7 (IL‐7), a T‐cell homeostatic cytokine, induces an antitumor response; however, the detailed mechanisms underlying the contributions of the IL‐7 to TME remain unclear. Here, we aimed to investigate the mechanism underlying the induction of antitumor response by hybrid Fc‐fused long‐acting recombinant human IL‐7 (rhIL‐7‐hyFc) through regulation of both adaptive and innate immune cells in the TME. Methods: We evaluated rhIL‐7‐hyFc‐mediated antitumor responses in murine syngeneic tumor models. We analysed the cellular and molecular features of tumor‐infiltrating lymphocytes (TILs) and changes in the TME after rhIL‐7‐hyFc treatment. Furthermore, we evaluated the antitumor efficacy of rhIL‐7‐hyFc combined with chemotherapy and checkpoint inhibitors (CPIs). Results: Systemic delivery of rhIL‐7‐hyFc induced significant therapeutic benefits by expanding CD8+ T cells with enhanced tumor tropism. In tumors, rhIL‐7‐hyFc increased both tumor‐reactive and bystander CD8+ TILs, all of which displayed enhanced effector functions but less exhausted phenotypes. Moreover, rhIL‐7‐hyFc suppressed the generation of immunosuppressive myeloid cells in the bone marrow of tumor‐bearing mice, resulting in the immunostimulatory TME. Combination therapy with chemotherapy and CPIs, rhIL‐7‐hyFc elicited a strong antitumor response and even under a T lymphopenic condition by restoring CD8+ T cells. When combined with chemotherapy and CPIs, rhIL‐7‐hyFc administration enhanced antitumor response under intact andlymphopenic conditions by restoring CD8+ T cells. Conclusion: Taken together, these data demonstrate that rhIL‐7‐hyFc induces antitumor responses by generating T‐cell‐inflamed TME and provide a preclinical proof of concept of immunotherapy with rhIL‐7‐hyFc to enhance therapeutic responses in the clinic. [ABSTRACT FROM AUTHOR]

Neighborhood parks are important venues for the urban population to do moderate-to-vigorous physical activity in leisure time. Parks can be particularly important for low-income neighborhoods, whose residents suffer from high rates of chronic diseases and may have less access to fee-based fitness exercise facilities. This study assessed the contribution of parks to local populations' physical activity in 48 high-poverty neighborhoods in the city of Los Angeles, using systematic observation of park use and surveys of park users and residents conducted between 2013 and 2015. We found that parks accounted for approximately 2.1% (between-park SD = 1.4%) of moderate physical activity time and 3.1% (between-park SD = 2.1%) of vigorous physical activity time of the local population, both of which were notably lower than the city-level average previously reported. Parks' contribution to physical activity was positively associated with park size (β = 0.13, p < 0.0001) and negatively associated with poverty (β = - 0.10, p < 0.0001) and local population density (β = - 0.25, p = 0.005). Parks in high-poverty neighborhoods in Los Angeles are underutilized, and more efforts are needed to fully realize their potential for population health. [ABSTRACT FROM AUTHOR]

Here, we investigated the possible anti-cancer properties of bromelain in Kras mutant human colorectal carcinoma cell lines and a mouse model harboring a Kras mutation. Cell growth and proliferation were significantly reduced in the Kras mutant colorectal carcinoma cell lines following treatment with 50 μg/mL bromelain as assessed by crystal violet staining and a proliferation assay. To identify the molecules responsible for this action, the expression levels of genes involved in signaling pathways and miRNAs were analyzed by real-time PCR. Among the genes tested, down-regulation of ACSL-4 and up-regulation of miRNAs targeting ASCL-4 were observed in Caco2 cells. Compared to the Kras wild-type colorectal carcinoma cell lines, Kras mutant colorectal carcinoma cell lines exhibited a remarkably up-regulated expression of ACSL-4, which is responsible for ferroptosis sensitivity. Moreover, the knockdown of ACSL-4 by a specific shRNA inhibited erastin-induced ferroptosis in Kras mutant DLD-1 cells as assessed by propidium iodide staining and lipid reactive oxygen species measurement. Our findings indicate that bromelain effectively exerts cytotoxic effects in Kras mutant colorectal cancer cells compared to in Kras wild-type colorectal cancer cells. Differential expression of ACSL-4 is responsible for the differential action of bromelain in regulating ferroptotic cell death. [ABSTRACT FROM AUTHOR]

Even though increasing evidence indicates the importance of peroxisomal lipid metabolism in regulating biological and pathological events, its involvement in cartilage development has not been well studied. Here, we identified the importance of peroxisomal function, particularly the functional integrity of ABCD2, in the pathogenesis of osteoarthritis (OA). Knockdown of ABCD2 in OA chondrocytes induced the accumulation of very long chain fatty acids (VLCFAs) and apoptotic cell death. Moreover, knockdown of ABCD2 altered profiles of miRNAs that affect the expression level of ACSL4, a known direct regulator of lipid metabolism. Suppression of ACSL4 in human chondrocytes‐induced VLCFA accumulation, MMP‐13 expression, and apoptotic cell death. In vivo morph‐down of the ACSL4 homologue in zebrafish resulted in significant defects in cartilage development and in vivo knockdown of ACSL4 in cartilage tissue of an OA model mice promoted severe cartilage degradation. In summary, to the best of our knowledge, this is the first report suggesting that the regulatory network among peroxisomal ABCD2:ACSL4:VLCFA serves as a novel regulator of cartilage homeostasis, and these data may provide novel insights into the role of peroxisomal fatty acid metabolism in pathogenesis of human OA. Significance of the study: Our study indicates that peroxisomal dysfunction is closely related to OA pathogenesis. Particularly, the functional integrity of ABCD2 may play an important role in OA pathogenesis via the accumulation of VLCFAs and stimulation of apoptotic death through altering profiles of miRNAs that target ACSL4. Our findings suggest that targeting the regulatory network among the peroxisomal ABCD2:ACSL4:VLCFA axis may provide a new potential therapeutic strategy for OA pathogenesis. [ABSTRACT FROM AUTHOR]

Human astroviruses are recognized as an important cause of infantile gastroenteritis around the world. In South Korea, sporadic cases of HAstV infection have been reported since 2002. However, hitherto, there have been no studies reporting the whole genome sequence of an HAstV isolate from South Korea. Hence, we sequenced and analyzed the entire genome of an HAstV-1 strain (lhar) that was isolated in Seoul, South Korea. The whole-genome sequence analysis revealed 3 open reading frames comprising the whole genome: ORF1a (2,763 bp), ORF1b (1,548 bp), and ORF2 (2,364 bp). The lhar strain showed amino acid identities with 8 other reference strains of 87.6-98.7%, 94.2-98.8%, and 62.6-99.0% in the ORF1a, ORF1b, and ORF2 regions, respectively. The amino acid sequence of the capsid region encoded by ORF2 was compared with a total of 19 HAstV-1 strains and 8 HAstVs reference strains isolated in various countries. This revealed 1 amino acid substitution, at aa412 (Pro → Arg) in ORF2. This study, the first to report the full-length sequence of an HAstV isolated in South Korea, is meaningful in that it can be used as a full-length HAstV sequence standard for future comparison studies. It may also prove useful to the field of public health field by facilitating the diagnosis and the prediction of new emerging variants. [ABSTRACT FROM AUTHOR]

RT-PCR, nucleotide sequencing, and phylogenetic analysis were performed for genotyping and molecular characterization of noroviruses isolated from Korean groundwater. Among 160 samples collected from 80 sites between 2008 and 2010, 14 samples (8.7 %) from 12 sites were positive for noroviruses (NoVs). The percentages of NoV-positive samples in 2008, 2009, and 2010 were 22.2, 3.2, and 0 %, respectively, representing a yearly decrease. GII-positive samples ( n = 9, 5.6 %) outnumbered GI-positive samples ( n = 5, 3.1 %). The genotypes of the GI NoVs were GI.2, GI.5, and GI.6, and the genotypes of the GII NoVs were all GII.4. One sample, HM623465, was very similar to CUK-3 and CBNU2 and two GII.4 sequences isolated from the stool of Korean gastroenteritis patients. A BLASTN search revealed several nucleotide sequences highly similar to those of NoVs isolated in this study. The original isolation sources for these similar NoVs were mostly stool ( n = 731, 80.0 %) and groundwater ( n = 135, 14.8 %), and all the countries from which they were isolated were almost in Asia (96.0 %); specifically, China ( n = 192, 21.0 %), Japan ( n = 383, 41.9 %), Korea ( n = 296, 32.4 %), and other Asian countries ( n = 6, 0.7 %). These results suggest that Korean groundwater might be contaminated with NoVs from the stool of infected patients and that these NoVs in turn cause new cases of gastroenteritis through a typical fecal-oral route with region-specific circulation. Therefore, it is important to properly treat sewage, which may include waterborne viruses and manage point sources in groundwater for national health and sanitation. In addition, continuous molecular surveillance remains important for understanding circulating NoVs. [ABSTRACT FROM AUTHOR]

Simple Summary: Non-small cell lung cancer (NSCLC) is the most severe cancer showing a low 5-year survival rate of metastatic NSCLC, but there are few previous reports for prediction of metastatic potential and identification of therapeutic targets of lung squamous cell carcinoma (SQCC), a major type of NSCLC, with different metastatic potential based on metabolic and lipidomic profiling. We identified metabolites and intact lipid species relevant to lung SQCC metastatic potential, which could be applied to develop potential biomarkers and therapeutic targets. SQCC is a major type of NSCLC, which is a major cause of cancer-related deaths, and there were no reports regarding the prediction of metastatic potential of lung SQCC by metabolomic and lipidomic profiling. In this study, metabolomic and lipidomic profiling of lung SQCC were performed to predict its metastatic potential and to suggest potential therapeutic targets for the inhibition of lung SQCC metastasis. Human bronchial epithelial cells and four lung SQCC cell lines with different metastatic potentials were analyzed using gas chromatography–mass spectrometry and direct infusion-mass spectrometry. Based on the obtained metabolic and lipidomic profiles, we constructed models to predict the metastatic potential of lung SQCC; glycerol, putrescine, β-alanine, hypoxanthine, inosine, myo-inositol, phosphatidylinositol (PI) 18:1/18:1, and PI 18:1/20:4 were suggested as characteristic metabolites and intact lipid species associated with lung SQCC metastatic potential. In this study, we established predictive models for the metastatic potential of lung SQCC; furthermore, we identified metabolites and intact lipid species relevant to lung SQCC metastatic potential that may serve as potential therapeutic targets for the inhibition of lung SQCC metastasis. [ABSTRACT FROM AUTHOR]

Hye In Ka and Hyemin Seo contributed equally to this work. B Publisher Correction to: BMC Biol 9, 44 (2021) b B https://doi.org/10.1186/s12915-021-00980-y b Following publication of the original article [[1]], the authors identified an error in the distinction between the given name and family name in the article metadata for author "Hye In Ka", which caused an error in the citation information on PubMed. [Extracted from the article]

Studies have suggested that dysregulation of peroxisomal lipid metabolism might play an important role in colorectal cancer (CRC) development. Here, we found that KrasG12D-driven CRC tumors demonstrate dysfunctional peroxisomal β-oxidation and identified Nudt7 (peroxisomal coenzyme A diphosphatase NUDT7) as one of responsible peroxisomal genes. In KrasG12D-driven CRC tumors, the expression level of Nudt7 was significantly decreased. Treatment of azoxymethane/dextran sulfate sodium (AOM/DSS) into Nudt7 knockout (Nudt7−/−) mice significantly induced lipid accumulation and the expression levels of CRC-related genes whereas xenografting of Nudt7-overexpressed LS-174T cells into mice significantly reduced lipid accumulation and the expression levels of CRC-related genes. Ingenuity pathway analysis of microarray using the colon of Nudt7−/− and Nudt7+/+ mice treated with AOM/DSS suggested Wnt signaling as one of activated signaling pathways in Nudt7−/− colons. Upregulated levels of β-catenin were observed in the colons of KrasG12D and AOM/DSS-treated Nudt7−/− mice and downstream targets of β-catenin such as Myc, Ccdn1, and Nos2, were also significantly increased in the colon of Nudt7−/− mice. We observed an increased level of palmitic acid in the colon of Nudt7−/− mice and attachment of palmitic acid-conjugated chitosan patch into the colon of mice induced the expression levels of β-catenin and CRC-related genes. Overall, our data reveal a novel role for peroxisomal NUDT7 in KrasG12D-driven CRC development. [ABSTRACT FROM AUTHOR]