Benzophenone-3 (BP-3) has been widely used in sunscreens and many other consumer products, including cosmetics. The widespread use of BP-3 has resulted in its release into the water environment, and ...hence its potential impact on aquatic ecosystem is of concern. To better understand the risk associated with BP-3 in aquatic ecosystems, we conducted a thorough review of available articles regarding the physicochemical properties, toxicokinetics, environmental occurrence, and toxic effects of BP-3 and its suspected metabolites. BP-3 is lipophilic, photostable, and bioaccumulative, and can be rapidly absorbed via oral and dermal routes. BP-3 is reported to be transformed into three major metabolites in vivo, i.e., benzophenone-1 (BP-1), benzophenone-8 (BP-8), and 2,3,4-trihydroxybenzophenone (THB). BP-1 has a longer biological half-life than its parent compound and exhibits greater estrogenic potency in vitro. BP-3 has been detected in water, soil, sediments, sludge, and biota. The maximum detected level in ambient freshwater and seawater is 125ng/L and 577.5ng/L, respectively, and in wastewater influent is 10,400ng/L. The major sources of BP-3 are reported to be human recreational activities and wastewater treatment plant (WWTP) effluents. BP-3 and its derivatives have been also detected in fish lipid. In humans, BP-3 has been detected in urine, serum, and breast milk samples worldwide. BP-1 has also been detected in placental tissues of delivering women. While sunscreens and cosmetics are known to be major sources of exposure, the fact that BP-3 has been detected frequently among young children and men suggests other sources. An increasing number of in vitro studies have indicated the endocrine disrupting capacity of BP-3. Based on a receptor binding assay, BP-3 has shown strong anti-androgenic and weak estrogenic activities but at the same time BP-3 displays anti-estrogenic activity as well. Predicted no effect concentration (PNEC) for BP-3 was derived at 1.32μg/L. The levels observed in ambient water are generally an order of magnitude lower than the PNEC, but in wastewater influents, hazard quotients (HQs) greater than 1 were noted. Considering limited ecotoxicological information and significant seasonal and spatial variations of BP-3 in water, further studies on environmental monitoring and potential consequences of long-term exposure in aquatic ecosystem are warranted.
•BP-3 has been widely used in sunscreens and detected in both environment and biota.•Major sources of BP-3 include human recreational activities and municipal wastewater.•BP-3 is often metabolized into more bioactive products such as BP-1.•Spatial & temporal variations of environmental occurrences warrant further studies.•Ecological risks are generally low but may be expected in hotspot areas.
The association between body mass index (BMI) and cognitive function is a public health issue. This study investigated the relationship between obesity and cognitive impairment which was assessed by ...the Korean version of the Mini-mental state examination (K-MMSE) among mid- and old-aged people in South Korea.
A cohort of 5,125 adults, age 45 or older with normal cognitive function (K-MMSE≥24) at baseline (2006), was derived from the Korean Longitudinal Study of Aging (KLoSA) 2006~2012. The association between baseline BMI and risk of cognitive impairment was assessed using multiple logistic regression models. We also assessed baseline BMI and change of cognitive function over the 6-year follow-up using multiple linear regressions.
During the follow-up, 358 cases of severe cognitive impairment were identified. Those with baseline BMI≥25 kg/m2 than normal-weight (18.5≤BMI<23 kg/m2) were marginally less likely to experience the development of severe cognitive impairment (adjusted odds ratio aOR = 0.73, 95% CI = 0.52 to 1.03; Ptrend = 0.03). This relationship was stronger among female (aOR = 0.63, 95% CI = 0.40 to 1.00; Ptrend = 0.01) and participants with low-normal K-MMSE score (MMSE: 24-26) at baseline (aOR = 0.59, 95% CI = 0.35 to 0.98; Ptrend<0.01). In addition, a slower decline of cognitive function was observed in obese individuals than those with normal weight, especially among women and those with low-normal K-MMSE score at baseline.
In this nationally representative study, we found that obesity was associated with lower risk of cognitive decline among mid- and old-age population.
•Exposure to BP-3 led to adverse reproduction effects on Japanese medaka at 26μg/L.•Changes in sex hormones and steroidogenic gene transcription were observed.•Parental exposure to BP-3 influenced on ...the growth of second generation fish.
Benzophenone-3 (BP-3) has been widely used in sunscreens and cosmetics to protect human skin from the harmful effects of UV irradiation. While BP-3 has been frequently detected in surface waters, sediments and biota, only limited information is available on its in vivo toxicity, particularly in fish. In the present study the endocrine disrupting capacity of BP-3 and its underlying mechanisms were investigated using Japanese medaka (Oryzias latipes). Adult Japanese medaka pairs (F0) were exposed to 0, 4.7, 8.4, 26, or 90μg/L (or 0, 15, 50, 150, or 500μg/L of BP-3 based on nominal concentration) for 14 d and its effects on sex steroid hormones, and transcription of various associated genes were determined. Following additional 14 d of exposure, the F1 eggs reproduced were counted and were further exposed to 0, 5.4, 12, or 30μg/L of BP-3 (or 0, 15, 50, or 150μg/L based on nominal concentrations) until 30 d after hatching. Chemical analysis of the exposed media confirmed transformation of BP-3 to benzophenone-1 (BP-1), a more potent estrogen agonist. After 14 d of the adult fish exposure, plasma concentrations of testosterone (T) significantly increased in male fish. The 17β-estradiol (E2) to T (E2/T) ratio showed significant decreases in both male and female fish. Overall down-regulation of gonadal steroidogenic genes such as star, cyp11a, cyp17, hsd3b, hsd17b3, and cyp19a was also observed. After 28 d of exposure, the daily average egg reproduction per female was significantly reduced at 26μg/L of BP-3. However, hatchability of F1 eggs was not affected by continuous exposure. After continued exposure until 30 dph, juvenile fish showed concentration-dependent decrease of condition factor, but mortality was not affected. Our observation clearly indicates that endocrine balance and reproduction performance in fish could be affected by μg/L level exposure to BP-3. Consequences of longer term exposure over multi-generations warrant further investigation.
This study examines the inequality between people with and without disabilities regarding unmet healthcare needs and preventable hospitalization.
We used the Korea Health Panel of 2016-2018; the ...final analytical observations were 43,512, including 6.95% of persons with disabilities. We examined the differences in contributors to the two dependent variables and decomposed the observed differences into explained and unexplained components using the Oaxaca-Blinder approach.
Unmet healthcare needs and preventable hospitalizations were 5.6% p (15.36% vs. 9.76%) and 0.68% p (1.82% vs. 0.61%), respectively, higher in people with disabilities than in those without, of which 48% and 35% were due to characteristics that the individual variables cannot explain. Decomposition of the distributional effect showed that sex, age, and chronic disease significantly increased disparities for unmet healthcare needs and preventable hospitalization. Socioeconomic factors such as income level and Medical aid significantly increased the disabled-non-disabled disparities for unmet healthcare needs.
Socioeconomic conditions increased the disparities, but around 35%-48% of the disparities in unmet healthcare needs and preventable hospitalization were due to unexplained factors, such as environmental barriers.
Mitochondria participate in a wide range of cellular processes. One essential function of mitochondria is to be a platform for antiviral signaling proteins during the innate immune response to viral ...infection. Recently, studies have revealed that mitochondrion-derived DNAs and RNAs are recognized as non-self molecules and act as immunogenic ligands. More importantly, the cytosolic release of these mitochondrial nucleic acids (mt-NAs) is closely associated with the pathogenesis of human diseases accompanying aberrant immune activation. The release of mitochondrial DNAs (mtDNAs) via BAX/BAK activation and/or VDAC1 oligomerization activates the innate immune response and inflammasome assembly. In addition, mitochondrial double-stranded RNAs (mt-dsRNAs) are sensed by pattern recognition receptors in the cytosol to induce type I interferon expression and initiate apoptotic programs. Notably, these cytosolic mt-NAs also mediate adipocyte differentiation and contribute to mitogenesis and mitochondrial thermogenesis. In this review, we summarize recent studies of innate immune signaling pathways regulated by mt-NAs, human diseases associated with mt-NAs, and the emerging physiological roles of mt-NAs.
Abstract
Background
Unmet healthcare need is a critical indicator, showing a plausible picture of how the healthcare system works in the unprecedented pandemic situation. It is important to ...understand what factors affect healthcare services of older adults in the midst of the outbreak, as this could help identify service- and performance-related challenges and barriers to the healthcare system. This study aimed to identify factors associated with unmet healthcare needs among the older Korean population amid the COVID-19 pandemic.
Methods
Cross-sectional data were used from the Experience Survey on Healthcare Use of Older Adults during the COVID-19 (COVID-19 Survey) in Korea (n = 1,917). Our main outcome, unmet healthcare need, was measured based on self-reported experience of overall, regular, and irregular outpatient care services-related unmet healthcare needs. Independent variables were selected based on previous studies on determinants of unmet healthcare need during the COVID-19 pandemic and Andersen’s expanded behavioural model, which theorizes that healthcare-seeking behaviours are driven by psychosocial, enabling, and need factors.
Results
Using multiple logistic regression models, we identified a good understanding of the nation’s health system was associated with lower likelihood of all types of unmet healthcare needs among older Korean adults (OR: 0.39, 95%CI: 0.25–0.61; OR: 0.36, 95%CI: 0.20–0.63; OR: 0.41, 95%CI: 0.23–0.75). Decreased social activities (i.e., shopping and visiting family members) and worsened psychological health issues (i.e., increased anxiety & nervousness and greater difficulty sleeping) were also factors affecting overall and irregular outpatient services-related unmet needs.
Conclusions
To ensure timely access to necessary healthcare services for older adults in the era of the COVID-19 outbreak, improving older adult’s understanding on how the healthcare system works is necessary. Moreover, changes in psychological condition and daily activities due to COVID-19 should be considered as possible barriers to healthcare services among older adults during the global pandemic.
2,3-Butanediol is a promising valuable chemical that can be used in various areas as a liquid fuel and a platform chemical. Here, 2,3-butanediol production in Saccharomyces cerevisiae was improved ...stepwise by eliminating byproduct formation and redox rebalancing. By introducing heterologous 2,3-butanediol biosynthetic pathway and deleting competing pathways producing ethanol and glycerol, metabolic flux was successfully redirected to 2,3-butanediol. In addition, the resulting redox cofactor imbalance was restored by overexpressing water-forming NADH oxidase (NoxE) from Lactococcus lactis. In a flask fed-batch fermentation with optimized conditions, the engineered adh1Δadh2Δadh3Δadh4Δadh5Δgpd1Δgpd2Δ strain overexpressing Bacillus subtilis α-acetolactate synthase (AlsS) and α-acetolactate decarboxylase (AlsD), S. cerevisiae 2,3-butanediol dehydrogenase (Bdh1), and L. lactis NoxE from a single multigene-expression vector produced 72.9g/L 2,3-butanediol with the highest yield (0.41g/g glucose) and productivity (1.43g/(L·h)) ever reported in S. cerevisiae.
•We developed Saccharomyces cerevisiae strain for efficient 2,3-butanediol production.•Both ethanol and glycerol production was abolished for high-yield production.•Redox imbalance was successfully restored by expressing NADH oxidase, NoxE.•72.9 g/L of 2,3-butanediol was produced in a flask fed-batch fermentation.•The strain achieved the highest yield and productivity ever reported in S. cerevisiae.
Objectives:
Mental health is the cornerstone of public health, particularly for older adults. There is a clear need to examine the impact of COVID-19 on mental health among older adults in South ...Korea, where the incidence of COVID-19 was relatively low and widespread transmission was controlled without a national lockdown.
Methods:
This analysis included a total of 1917 participants from the Experience Survey on Healthcare Use of Older Adults, which was conducted for adults aged 65 years or older by face-to-face interview.
Results:
The results showed that older adults with a good understanding of COVID-19 public health measures were less likely to experience mental health problems. In contrast, those with a greater risk perception of contracting COVID-19 had higher odds of experiencing tension and anxiety in addition to sadness and depression. Older adults who had a greater fear of COVID-19 and perceived higher-risk of contracting COVID-19 experienced more sleep problems.
Conclusion:
The findings provide new evidence on the factors that influence the mental health of older adults in South Korea during the pandemic and suggest the development of policy interventions.
Many innate immune response proteins recognize foreign nucleic acids from invading pathogens to initiate antiviral signaling. These proteins mostly rely on structural characteristics of the nucleic ...acids rather than their specific sequences to distinguish self and nonself. One feature utilized by RNA sensors is the extended stretch of double‐stranded RNA (dsRNA) base pairs. However, the criteria for recognizing nonself dsRNAs are rather lenient, and hairpin structure of self‐RNAs can also trigger an immune response. Consequently, aberrant activation of RNA sensors has been reported in numerous human diseases. Yet, in most cases, the activating antigens remain unknown. Recent studies have developed sequencing techniques tailored to specifically capture dsRNAs and identified that various noncoding elements in the nuclear and the mitochondrial genome can generate dsRNAs. Here, the identity of endogenous dsRNAs, their recognition by dsRNA sensors, and their implications in the pathogenesis of human diseases ranging from inflammatory to degenerative are presented.
Human cells naturally express double‐stranded RNAs (dsRNAs). Repeat elements of the nuclear genome are transcribed into long hairpin dsRNAs while bidirectional transcription of the mitochondrial genome generates intermolecular mitochondrial dsRNAs (mt‐dsRNAs). In the cytosol, these dsRNAs can lead to aberrant activation of the innate immune response proteins including protein kinase RNA‐activated (PKR) and melanoma differentiation‐associated protein 5 (MDA5).
2-Ethylhexyl 4-methoxycinnamate (EHMC) is one of the most widely used UV-filters, and hence has been frequently detected in water environment. EHMC has been reported to induce short-term reproductive ...toxicity in fish, and thyroid disrupting effects in other animal studies. However, limited information is available for its long-term effects on fecundity, and thyroid disrupting effects in fish. In the present study, effects of EHMC on fecundity, measured as number of eggs, were evaluated in Japanese medaka (Oryzias latipes), and its underlying mechanisms on sex and thyroid hormone disruption were explored. For this purpose, a five-month long (154 d) exposure to F0 generation was conducted on fertilized eggs (<24 h post-fertilization (hpf)), with nominal concentration of 0, 0.05, 0.158, 0.5, 1.58, or 5 mg/L EHMC, followed by a 3-8-d exposure of F1 generation. After >3 months exposure, significant decreases in reproductive performances were observed at all test concentrations as low as 0.05 mg/L. Reproduction effects were not accompanied with sex hormone changes, but up-regulation of vitellogenin gene was observed. Thyroid hormones were decreased by EHMC exposure in F1 fish at -38 day post-fertilization (dpf). In addition, down-regulation of type II iodothyronine deiodinase (dio2) and up-regulation of thyrotropin releasing hormone (trh) were observed in both F0 and F1 juvenile fish, suggesting thyroid disruption potential of EHMC. Our observation suggests that EHMC at the levels one to two orders of magnitude higher than those detected in ambient water may affect reproduction and thyroid hormonal balance of fish.
•Long-term exposure to EHMC resulted in reduced fecundity in medaka fish.•EHMC induced thyroid disrupting effects in both F0 and F1 generations.•Thyroid hormone levels were decreased at juvenile stages of F1 generation.