TRIM28 represses renal cell carcinoma cell proliferation by inhibiting TFE3/KDM6A-regulated autophagy.

Autophagy plays a pivotal role in physiology and pathophysiology, including cancer. Mechanisms of autophagy dysregulation in cancer remain elusive. Loss of function of TRIM28, a multifunction protein, is seen in familial kidney malignancy, but the mechanism by which TRIM28 contributes to the etiology of kidney malignancy is unclear. In this study, we show TRIM28 retards kidney cancer cell proliferation through inhibiting autophagy. Mechanistically, we find TRIM28 promotes ubiquitination and proteasome-mediated degradation of transcription factor TFE3, which is critical for autophagic gene expression. Genetic activation of TFE3 due to gene fusion is known to cause human kidney malignancy, but whether and how transcription activation by TFE3 involves chromatin changes is unclear. Here, we find another mode of TFE3 activation in human renal carcinoma. We find that TFE3 is constitutively localized to the cell nucleus in human and mouse kidney cancer, where it increases autophagic gene expression and promotes cell autophagy as well as proliferation. We further uncover that TFE3 interacts with and recruits histone H3K27 demethylase KDM6A for autophagic gene upregulation. We reveal that KDM6A contributes to expression of TFE3 target genes through increasing H3K4me3 rather than demethylating H3K27. Collectively, in this study, we identify a functional TRIM28-TFE3-KDM6A signal axis, which plays a critical role in kidney cancer cell autophagy and proliferation.

Lysine demethylase KDM1A promotes cell growth via FKBP8-BCL2 axis in hepatocellular carcinoma.

Advanced hepatocellular carcinoma (HCC) has a dismal prognosis. KDM1A (lysine demethylase 1A), overexpressed in multiple cancer types, is a lysine demethylase that targets both histone and nonhistone proteins. However, it is unclear how KDM1A expression affects HCC etiology. Here, we show that KDM1A can interact with and demethylate FKBP8 (FKBP prolyl isomerase 8), a cytoplasmic protein that regulates cell survival through the antiapoptotic protein BCL2 (B-cell lymphoma-2). We show that demethylation of FKBP8 enhances its ability to stabilize BCL2. Consistently, we observed positive correlation between KDM1A and BCL2 protein levels in liver cancer patients. Functionally, we reveal that FKBP8 demethylation by KDM1A is critical for liver cancer cell growth in vitro and in vivo. We went on to explore the mechanisms that might regulate KDM1A cytoplasmic localization. We found that the cytoplasmic localization and protein stability of KDM1A were promoted by acetylation at lysine-117 by the acetyl transferase KAT8 (lysine acetyltransferase 8). In agreement with this, we show that KDM1A-K117 (lysine 117) acetylation promotes demethylation of FKBP8 and level of BCL2. Finally, it has been shown that the efficacy of sorafenib, a first-line treatment for advanced HCC, is limited by clinical resistance. We show that KDM1A and BCL2 protein levels are increased during acquired sorafenib resistance, whereas inhibiting KDM1A can antagonize sorafenib resistance. Collectively, these results define a functional KDM1A-FKBP8-BCL2 axis in HCC.

Transboundary health impacts of transported global air pollution and international trade.

Millions of people die every year from diseases caused by exposure to outdoor air pollution. Some studies have estimated premature mortality related to local sources of air pollution, but local air quality can also be affected by atmospheric transport of pollution from distant sources. International trade is contributing to the globalization of emission and pollution as a result of the production of goods (and their associated emissions) in one region for consumption in another region. The effects of international trade on air pollutant emissions, air quality and health have been investigated regionally, but a combined, global assessment of the health impacts related to international trade and the transport of atmospheric air pollution is lacking. Here we combine four global models to estimate premature mortality caused by fine particulate matter (PM2.5) pollution as a result of atmospheric transport and the production and consumption of goods and services in different world regions. We find that, of the 3.45 million premature deaths related to PM2.5 pollution in 2007 worldwide, about 12 per cent (411,100 deaths) were related to air pollutants emitted in a region of the world other than that in which the death occurred, and about 22 per cent (762,400 deaths) were associated with goods and services produced in one region for consumption in another. For example, PM2.5 pollution produced in China in 2007 is linked to more than 64,800 premature deaths in regions other than China, including more than 3,100 premature deaths in western Europe and the USA; on the other hand, consumption in western Europe and the USA is linked to more than 108,600 premature deaths in China. Our results reveal that the transboundary health impacts of PM2.5 pollution associated with international trade are greater than those associated with long-distance atmospheric pollutant transport.

D-π-A-Based Trisubstituted Alkenes as Environmentally Sensitive Fluorescent Probes to Detect Lewy Pathologies.

Lewy pathologies, which mainly consist of insoluble α-synuclein (α-syn) aggregates, are the hallmarks of Parkinson's disease and many other neurodegenerative diseases termed "synucleinopathies". Detection of Lewy pathologies with optical methods is of interest for preclinical studies, while the α-syn fluorescent probe is still in great demand. By rational design, we obtained a series of D-π-A-based trisubstituted alkenes with acceptable optical properties and high binding affinities to α-syn fibrils. Among these probes, FPQXN and TQXN-2 exhibited high binding affinities (6 and 8 nM, respectively), significant fluorescence enhancements (17.2- and 26.6-fold, respectively), and satisfying quantum yields (36.5% and 10.4%, respectively), which met the need for the in vitro neuropathological staining of Lewy pathologies in the PD brain sections. In addition, TQXN-2 showed great potential in fluorescent discrimination of Lewy pathologies and Aß plaques. Our research provides flexible tools for in vitro detection of α-syn aggregates and offers new structural frameworks for the further development of α-syn fluorescent probes.

Considerable Unaccounted Local Sources of NOx Emissions in China Revealed from Satellite.

High-resolution (e.g., 5 km) emission data of nitrogen oxides (NOx = NO + NO2) provide localized knowledge of pollution sources for targeted regulations, yet such data are lacking or inaccurate over most regions at present. Here we improve our PHLET-based inversion method to derive NOx emissions in China at a 5-km resolution in summer 2019, based on the TROPOMI-POMINO satellite product of nitrogen dioxide (NO2) columns. With low computational costs, our inversion explicitly accounts for the effects of horizontal transport and nonlinear chemistry. We find numerous small-to-medium sources related to minor roads and small human settlements at relatively low affluence levels, in addition to clear emission signals along major transportation lines, consistent with road line density and Tencent location data. Many small-to-medium sources and transportation emissions are unclear or missing in the spatial distributions of four widely used emission inventories. Our emissions offer a unique reference for targeted emission control.

Are Proton Pump Inhibitors More Effective Than Histamine-2-Receptor Antagonists for Stress Ulcer Prophylaxis in Critically Ill Patients? A Systematic Review and Meta-Analysis of Cohort Studies.

BACKGROUND: Histamine-2-receptor antagonists (H2RAs) have been largely replaced by proton pump inhibitors (PPIs) for stress ulcer prophylaxis (SUP) despite the inconclusive evidence concerning comparative effectiveness. OBJECTIVE: To compare the effectiveness of PPIs and H2RAs on SUP in real-world setting. METHODS: PubMed, Embase, and the Cochrane Library were searched from inception to September 19, 2021. We included cohort studies comparing PPIs with H2RAs in critically ill adult patients and explicitly reporting the outcome of gastrointestinal (GI) bleeding or mortality. Newcastle-Ottawa Scale was used to assess potential risk of bias. We conducted a random-effects meta-analysis and only the studies with adjusted effect estimates were pooled. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the overall quality of the evidence. RESULTS: Thirteen cohort studies (N = 145 149) were eligible and 11 of them available for full texts were of low to moderate risk of bias. Meta-analysis of adjusted effect estimates indicated that PPIs were associated with a significantly higher risk of GI bleeding, compared with H2RAs (8 studies, odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.30-3.01, low certainty). Post hoc pooling analysis also suggested that PPIs were associated with a slightly higher risk of mortality in comparison with H2RAs (7 studies, OR = 1.27, 95% CI = 1.13-1.42, low certainty). CONCLUSION AND RELEVANCE: The systematic review of cohort studies showed that PPIs were associated with higher risks of GI bleeding and mortality, although the certainty of evidence was low. Overall, we suggest not excluding H2RAs for SUP, while further studies are essential for elucidating the risk stratification, optimal regimen, and specific duration.

Metabolites Identification and Mechanism Prediction of Neobavaisoflavone In Vitro and In Vivo of Rats through UHPLC-Q-Exactive Plus Orbitrap MS Integrated Network Pharmacology.

Neobavaisoflavone is an important isoflavone component isolated from Psoraleae Fructus. It is used extensively worldwide because of its antibacterial, antioxidant, anti-inflammatory, anticancer, and anti-osteoporotic activities. However, there is no systematic and comprehensive research on the metabolism of neobavaisoflavone in vivo and in vitro. The study aimed to analyze the metabolic characteristics and mechanism of neobavaisoflavone for the first time. Firstly, biological samples were pretreated by the solid-phase extraction (SPE) method, methanol precipitation, and acetonitrile precipitation. Secondly, the samples were analyzed on UHPLC-Q-Exactive Plus Orbitrap MS. Thirdly, metabolites were tentatively identified based on retention time, parallel reaction monitoring strategy, diagnostic product ions, and neutral loss fragments. A total of 72 metabolites of neobavaisoflavone were tentatively identified, including 28 in plasma, 43 in urine, 18 in feces, six in the liver, and four in the liver microsome. The results suggested that neobavaisoflavone mainly underwent glucuronidation, sulfation, hydroxylation, methylation, cyclization, hydration, and their composite reactions in vivo and in vitro. In addition, nine active components with high bioavailability and 191 corresponding targets were predicted by the Swiss Drug Design database. The 1806 items of GO and 183 KEGG signaling pathways were enriched. These results showed that metabolites expanded the potential effects of neobavaisoflavone. The present study would provide the scientific basis for the further exploitation and application of neobavaisoflavone.

An empirical study on consumer automobile purchase intentions influenced by the COVID-19 outbreak.

The sudden onset of the coronavirus disease 2019 (COVID-19) may influence individuals' automobile purchase decisions, thus bringing great uncertainty to the automobile industry. To this end, the current study investigates individuals' behaviors regarding the purchase of automobiles, both before and after the outbreak of COVID-19. An ICLV (integrated choice and latent variable) model that integrates the socio-demographics, epidemic-related variables and psychological latent variables is applied. A survey of 960 respondents was conducted in China during the epidemic. The results suggest that there was an increase in the demand for automobiles after the COVID-19 outbreak. Firstly, demand was especially high in the groups of females, citizens, high-income earners, and people who own a driving license or who live in high epidemic risk areas. Secondly, although the severity of the epidemic for residences has a positive effect on automobile demand, travelers' perceived vulnerability is the key factor motivating purchases. Thirdly, the epidemic's negative income effects reduced the purchase propensity. Several dynamic policies are proposed to automobile consumption of the special time of the COVID-19 pandemic.

First High-Resolution Emission Inventory of Levoglucosan for Biomass Burning and Non-Biomass Burning Sources in China.

Levoglucosan (LG) emitted from non-biomass burning (non-BB) sources has given rise to biased or even unreasonable source identification results when adopting LG as a distinct marker of biomass burning (BB). The estimation of LG emission and its spatiotemporal variation for various sources are the keys to reducing uncertainty. This study first developed a LG emission inventory for China from 25 sub-type sources belonging to eight categories, with a 3 km × 3 km spatial resolution and monthly distribution. The total LG emission in 2014 was 145.7 Gg. Domestic BB and open BB contributed 39.2 and 34.3% of the total emission. Non-BB sources, including municipal solid waste burning (9.7%), firework burning (9.6%), meat cooking (5.4%), domestic coal burning (1.5%), ritual item burning (0.2%), and industrial coal burning (0.1%), contributed to 26.5% of the total emission. LG emission varied spatially and temporally. Non-BB sources have a significant spatiotemporal impact on BB source contributions, even in high BB emission regions or in sowing, harvesting, and winter heating seasons. The local BB contributions have been substantially overestimated by 4.28-369% in previous studies, wherein LG was solely referred to as the BB source. By 2018, LG emission from BB might decrease to 63.9% of its total emission. This high-resolution LG emission inventory can be greatly useful for source identification studies in China. It also supports future research on the modeling of smoke aging and pollution control.

Plasma ApoA-1 and endothelin-1 levels changes in early Parkinson disease and its relationship with cognitive function and cerebral white matter structure change.

The study aimed to investigate the plasma apolipoprotein A-1 (ApoA-1) and endothelin -1 (ET-1) changes in early Parkinson disease (PD), and analyze their relationship with cognitive function and cerebral white matter structure (WMS) change. 76 early PD patients were selected as group PD, and 30 cases of healthy persons were selected as control group. They all scanned with magnetic resonance imaging (MRI) diffusion tensor. The ApoA-1, ET-1, WMS changes, and Montreal Cognitive Assessment (MoCA) scores were recorded in the two groups of subjects. The results revealed that ApoA-1 level and Mo CA score in PD group decreased, FA value in bilateral temporal lobe, left anterior cingulate tract, corpus callosum, and other cerebral WMS area in PD group were also decreased, and ET-1 level in PD group increased (P<0.05). Compared with those of PD group patients with Mo CA≥26, plasma ApoA-1 levels and cerebral WMS FA values of the patients with Mo CA<26 were decreased, (P<0.05); the MoCA score of PD group was positively correlated with the cerebral WMS FA values (P<0.05). In short, the ApoA-1 level in patients with early PD decreased, while the ET-1 level increased, and both were related to cognitive function and WMS.

The Benefit of Individualized Vancomycin Dosing Via Pharmacokinetic Tools: A Systematic Review and Meta-analysis.

Background: Various pharmacokinetic (PK) equations and software have been developed to individualize vancomycin dosing. However, the benefit of using any PK information to guide vancomycin dosing has not been fully elucidated. Objective: To appraise available evidence on the effectiveness and safety of individualized vancomycin dosing via PK tools. Methods: PubMed, EMBASE, the Cochrane Library, and 2 Chinese literature databases were searched through August 1, 2019. Randomized controlled trials (RCTs) and cohort studies that reported the PK and clinical outcomes of individualized vancomycin dosing versus empirical dosing were included. Pooled risk ratios (RRs) and mean differences were calculated for dichotomous and continuous outcomes, respectively. Results: A total of 21 studies involving 4346 patients were finally included, of which 3 were RCTs and 18 were cohort studies. Meta-analysis revealed that PK-guided vancomycin dosing significantly increased the attainment of target trough concentration (RR = 1.59; 95% CI = 1.49-1.70) and decreased the incidence of nephrotoxicity (RR = 0.57; 95% CI = 0.46-0.71). Additionally, the available evidence showed that target area under the curve/minimum inhibitory concentration attainment rate and time to target concentration could improve. However, the evidence on clinical outcomes was scarce, and no significant differences were detected in clinical response rate, microbiological eradication rate, mortality, and length of hospital stay between PK-guided vancomycin dosing and empirical dosing strategies. Conclusion and Relevance: Individualized vancomycin dosing via PK tools significantly increases the attainment of target trough concentration and decreases the incidence of nephrotoxicity. Evidence on clinical effectiveness was limited and showed no significant benefit. Further well-designed studies are warranted to assess its clinical effectiveness and inform routine care.

Exosomal and extracellular HMGB1 have opposite effects on SASH1 expression in rat astrocytes and glioma C6 cells.

Exosomes are a type of extracellular vesicles derived from cells and mediators of intercellular communication. Different cell types have their own unique exosomes for exchanging information. We previously found that SASH1, a tumor suppressor, was lowly expressed or absent in glioma tissues and glioma C6 cells, but the structure and function of the corresponding exosomes had been unclear. Hence, we aimed to investigate whether exosomes generated from normal glial cells and glioma cells form different protein patterns and whether those derived from normal glial cells affect SASH1 expression in glioma cells. We collected exosomes from astrocytes and C6 cells and identified their exosomal proteins through mass spectrometry. We also performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses, whose results showed that both the total and unique exosomal proteins from each cell type were similar. Moreover, the KEGG analysis revealed different clusters of unique exosomal proteins in glial cells and glioma cells. In the normal glial cells, the top clusters were mainly involved in processes with RNA transcripts and proteins, whereas in glioma cells the clusters were attributed to PI3K-Akt signaling, cell adhesion, and cancer-related pathways. Western blot analysis showed that HMGB1 exists in exosomes derived from cultured astrocytes, although its expression was higher in glioma C6 cells. Furthermore, we found that exosomes extracted from astrocytes could increase SASH1 expression in C6 cells (P = 0.040), whereas those derived from HMGB1-depleted astrocytes could not (P = 0.6133). The expression levels of SASH1 decreased after the addition of extracellular recombinant HMGB1 protein, whereas that of TLR4 increased. Our study is the first to demonstrate that HMGB1 plays different roles depending on its form: as an extracellular protein, HMGB1 decreases SASH1 expression, but as an exosomal protein, HMGB1 increases SASH1 expression. Nevertheless, the mechanism, which partly depends on the TLR4 pathway, behind these opposing effects requires further study. Our novel findings on the structure-dependent roles of the cytokine HMGB1 in promoting or inhibiting cancer provide a fresh insight into the interactions of cancer cells with the microenvironment.

Effect of follicle-stimulating hormone receptor Asn680Ser polymorphism on the outcomes of controlled ovarian hyperstimulation: an updated meta-analysis of 16 cohort studies.

PURPOSE: The purpose of this study is to evaluate the influence of follicle-stimulating hormone receptor (FSHR) Asn680Ser polymorphism on the ovarian response to exogenous follicle-stimulating hormone (FSH) and clinical outcomes in women undergoing controlled ovarian hyperstimulation (COH). METHODS: A database search was conducted to identify the eligible studies that investigated the effect of FSHR Asn680Ser polymorphism on ovarian response and clinical outcomes. A pooled analysis was performed with the odds ratio (OR) or weighted mean difference (WMD) and their respective 95 % confidence interval (CI) by the STATA software with random effects model. RESULTS: Sixteen cohort studies comprising a total of 4287 subjects were included. The number of retrieved oocytes was significantly fewer in subjects with the SS genotype at position 680, compared to subjects with the NN or NS genotype (WMD = -1.36, 95 % CI = -1.85 to -0.87). Lack of association was detected between the genotypes (SS genotype vs. NN or NS genotype) and clinical outcomes such as exogenous FSH dose (WMD = 98.96 IU, 95 % CI = -22.33 to 220.24), poor response (OR = 1.08, 95 % CI = 0.71-1.64), ovarian hyperstimulation syndrome (OHSS) (OR = 1.58, 95 % CI = 0.41-6.07), and clinical pregnancy rate (OR = 1.10, 95 % CI = 0.86-1.40). However, poor ovarian response and number of retrieved oocytes were significantly influenced by the Asn680Ser polymorphism in the Asian subjects. In addition, no publication bias was detected. CONCLUSION: FSHR Asn680Ser polymorphism might be a significant biomarker for predicting the number of retrieved oocytes and poor response, especially in Asian subjects. Other outcomes such as exogenous FSH dose, OHSS, and pregnancy rate were not influenced by FSHR Asn680Ser polymorphism.

Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats.

Calpain 3 (CAPN3), also known as p94, is a skeletal muscle-specific member of the calpain family that is involved in muscular dystrophy; however, the roles of CAPN3 in muscular atrophy and regeneration are yet to be understood. In the present study, we attempted to explain the effect of CAPN3 in muscle atrophy by evaluating CAPN3 expression in rat gastrocnemius muscle following reversible sciatic nerve injury. After nerve injury, the wet weight ratio and cross sectional area (CSA) of gastrocnemius muscle were decreased gradually from 1-14 days and then recovery from 14-28 days. The active form of CAPN3 (~62 kDa) protein decreased slightly on day 3 and then increased from day 7 to 14 before a decrease from day 14 to 28. The result of linear correlation analysis showed that expression of the active CAPN3 protein level was negatively correlated with muscle wet weight ratio. CAPN3 knockdown by short interfering RNA (siRNA) injection improved muscle recovery on days 7 and 14 after injury as compared to that observed with control siRNA treatment. Depletion of CAPN3 gene expression could promote myoblast differentiation in L6 cells. Based on these findings, we conclude that the expression pattern of the active CAPN3 protein is linked to muscle atrophy and regeneration following denervation: its upregulation during early stages may promote satellite cell renewal by inhibiting differentiation, whereas in later stages, CAPN3 expression may be downregulated to stimulate myogenic differentiation and enhance recovery. These results provide a novel mechanistic insight into the role of CAPN3 protein in muscle regeneration after peripheral nerve injury.

Machine-learning-based corrections of CMIP6 historical surface ozone in China during 1950-2014.

Due to a lack of long-term observations in China, reports on historical ozone concentration are severely limited. In this study, by combining observation, reanalysis and model simulation data, XGBoost machine learning algorithm is used to correct the surface ozone concentration from CMIP6 climate model, and the long-term and large-scale surface ozone concentration of China during 1950-2014 is obtained. The long-term evolutions and trends of ozone and meteorological effects on interannual ozone variations are further analyzed. The results reveal that CMIP6 historical simulations have a large underestimation in ozone concentrations and their trends. The XGB-derived ozone are closer to observations, with R2 value of 0.66 and 0.74 for daily and monthly retrievals, respectively. Both the concentrations and exceedances of ozone in most parts of China have shown increasing trends from 1950 to 2014. The daily mean ozone concentration without climate change effects is estimated to be 117 ppb in the year 1950 averaged over China. It indicates that the increase in anthropogenic emissions of China has a significant contribution to ozone enhancement between 1950 and 2014. The higher ozone growth rates of XGB retrievals than those from the model indicate a regional surface ozone penalty due to the warming climate. The relatively significant increment in ozone are estimated in the Central and Western China. Seasonally, the ozone enhancement is largest in spring, indicating a shift in seasonal variation of ozone. Given the uncertainty in simulating historical ozone by climate model, we show that machine learning approaches can provide improved assessment of evolution in surface ozone, along with valuable information to guide future model development and formulate future ozone pollution prevention and control policies.

Achievements and challenges in improving air quality in China: Analysis of the long-term trends from 2014 to 2022.

Due to the implementation of air pollution control measures in China, air quality has significantly improved, although there are still additional issues to be addressed. This study used the long-term trends of air pollutants to discuss the achievements and challenges in further improving air quality in China. The Kolmogorov-Zurbenko (KZ) filter and multiple-linear regression (MLR) were used to quantify the meteorology-related and emission-related trends of air pollutants from 2014 to 2022 in China. The KZ filter analysis showed that PM2.5 decreased by 7.36 ± 2.92% yr-1, while daily maximum 8-h ozone (MDA8 O3) showed an increasing trend with 3.71 ± 2.89% yr-1 in China. The decrease in PM2.5 and increase in MDA8 O3 were primarily attributed to changes in emission, with the relative contribution of 85.8% and 86.0%, respectively. Meteorology variations, including increased ambient temperature, boundary layer height, and reduced relative humidity, also contributed to the reduction of PM2.5 and the enhancement of MDA8 O3. The emission-related trends of PM2.5 and MDA8 O3 exhibited continuous decrease and increase, respectively, from 2014 to 2022, while the variation rates slowed during 2018-2020 compared to that during 2014-2017, highlighting the challenges in further improving air quality, particularly in simultaneously reducing PM2.5 and O3. This study recommends reducing NH3 emissions from the agriculture sector in rural areas and transport emissions in urban areas to further decrease PM2.5 levels. Addressing O3 pollution requires the reduction of O3 precursor gases based on site-specific atmospheric chemistry considerations.

Potentially Inappropriate Medication Use Among Older Patients with Diabetes in a Chinese Community.

BACKGROUND: Potentially inappropriate medications (PIMs) are frequently prescribed to older people with diabetes. This study aimed to assess the prevalence of PIM use in older people with diabetes and identify potential risk factors influencing the development of PIM use. METHODS: This was a cross-sectional study conducted in an outpatient setting in Beijing, China, using Chinese criteria. The prevalence of PIM use, polypharmacy, and comorbidities in older adults with diabetes in an outpatient setting was measured. Logistic models were employed to investigate the association among polypharmacy, comorbidities, and PIM use. RESULTS: The prevalence of PIM use and polypharmacy was 50.1% and 70.8%, respectively. The most common comorbidities were hypertension (68.0%), hyperlipemia (56.6%), and stroke (36.3%), and the top three inappropriately used medications were insulin (22.0%), clopidogrel (11.9%), and eszopiclone (9.81%). Age (OR 1.025; 95% CI 1.009, 1.042), the number of diagnoses (OR 1.172; 95% CI 1.114, 1.232), coronary heart disease (OR 1.557; 95% CI 1.207, 2.009), and polypharmacy (OR 1.697; 95% CI 1.252, 2.301) were associated with PIM use. CONCLUSIONS: Given the higher rate of PIM use among older adults with diabetes, strategies and interventions targeting this population are needed to minimize PIM use.

Influences of El Niño-Southern Oscillation on summertime ozone pollution over central-eastern China during 1950-2014.

Summertime ozone pollution has become increasingly severe over many parts of China in recent years. Due to lack of historical ozone observations, few studies have analyzed the linkage between natural climate variability and ozone levels for a long time series. This study uses the simulation datasets from CMIP6 to explore the effects of El Niño-Southern Oscillation (ENSO) on summertime (June/July/August) surface ozone concentrations in central-eastern China (CEC; 20°N-42°N, 100°E-123°E) during the period of 1950-2014. Our results show that, after excluding the emission-related trend, the detrended summertime daily mean surface ozone concentrations averaged over CEC in El Niño years (30.69 ppb) are higher than those in La Niña events (29.34 ppb). Compared to the summertime mean ozone of 1950-2014 (30.25 ppb), the maximum anomalies in CMIP6 are 2.88 ppb (9.52% higher) and - 5.52 ppb (18.25% lower) in El Niño and La Niña years, respectively. In addition, the summertime MDA8 ozone of CEC is significantly correlated with the central-eastern equatorial Pacific SST (5°N-5°S, 170°W-120°W) (R = 0.29, P-value = 0.02). Such ozone increases/declines in El Niño/La Niña years are also found in satellite observations of OMI ozone. The results show that the ENSO affects the large-scale circulations over central-eastern China, which regulate the regional atmospheric stability and meteorological conditions (including horizontal wind fields, geopotential height, vertical velocity, surface air temperature, and precipitation) to influence the efficiency of ozone photochemical formation and transport. Our study makes better estimation and attribution of future surface ozone pollution in China.

Distracted driving behavior in patients with insomnia.

Insomnia is one of the most common sleep disorders and is characterized by a subjective perception of difficulty falling asleep. Drivers with insomnia are vulnerable to distraction and exhibit higher levels of risk while driving. This study investigated the effect of two sources of in-vehicle distractions on the driving performance of drivers with insomnia and good sleepers by analyzing different driving behavior measures. Twenty-one drivers with insomnia and twenty-one healthy volunteers were recruited to complete simulated driving dual tasks. The primary task required the participants to perform: (a) a lane-keeping task, and (b) a lane-change task. The secondary task required the participants to deal with: (a) baseline (non-task), (b) internal distraction task, and (c) external distraction task. The internal distraction task required participants to complete quantitative reasoning tasks, while the external distraction task was a 0-back test. The relationship between distracted driving ability and cognitive function was also investigated. The results demonstrate that for lane-keeping tasks, drivers with insomnia had significantly higher standard deviations (SD) for speed, throttle position, acceleration, and lateral position than healthy drivers under internal distraction, but the driving performance did not differ significantly between groups under internal distraction or baseline. In the lane-change task, drivers with insomnia had higher SDs for steering wheel angle, steer angular velocity, lateral acceleration, and lateral speed than healthy drivers under external distraction. Moreover, external distraction impaired driving behavior in the healthy group, while internal distraction impaired driving ability in both groups. Healthy drivers with cognitive impairment displayed impaired lane-keeping abilities under internal distractions and impaired lane-changing abilities under external distractions. Driving performance in the insomnia group was not significantly associated with cognitive function. The results demonstrate that insomnia and distraction impair driving ability, and driver performance is affected differently by the distraction source (internal or external). The driving ability of healthy drivers with decreased cognition was impaired, but not that of insomniacs.The findings of this study provide new insights for preventing and estimating the potential influence of distracted driving behavior in individuals with insomnia.