A dynamic nomogram to predict invasive fungal super-infection during healthcare-associated bacterial infection in intensive care unit patients: an ambispective cohort study in China.

Objectives: Invasive fungal super-infection (IFSI) is an added diagnostic and therapeutic dilemma. We aimed to develop and assess a nomogram of IFSI in patients with healthcare-associated bacterial infection (HABI). Methods: An ambispective cohort study was conducted in ICU patients with HABI from a tertiary hospital of China. Predictors of IFSI were selected by both the least absolute shrinkage and selection operator (LASSO) method and the two-way stepwise method. The predictive performance of two models built by logistic regression was internal-validated and compared. Then external validity was assessed and a web-based nomogram was deployed. Results: Between Jan 1, 2019 and June 30, 2023, 12,305 patients with HABI were screened in 14 ICUs, of whom 372 (3.0%) developed IFSI. Among the fungal strains causing IFSI, the most common was C.albicans (34.7%) with a decreasing proportion, followed by C.tropicalis (30.9%), A.fumigatus (13.9%) and C.glabrata (10.1%) with increasing proportions year by year. Compared with LASSO-model that included five predictors (combination of priority antimicrobials, immunosuppressant, MDRO, aCCI and S.aureus), the discriminability of stepwise-model was improved by 6.8% after adding two more predictors of COVID-19 and microbiological test before antibiotics use (P<0.01).And the stepwise-model showed similar discriminability in the derivation (the area under curve, AUC=0.87) and external validation cohorts (AUC=0.84, P=0.46). No significant gaps existed between the proportion of actual diagnosed IFSI and the frequency of IFSI predicted by both two models in derivation cohort and by stepwise-model in external validation cohort (P=0.16, 0.30 and 0.35, respectively). Conclusion: The incidence of IFSI in ICU patients with HABI appeared to be a temporal rising, and our externally validated nomogram will facilitate the development of targeted and timely prevention and control measures based on specific risks of IFSI.

Establishment of a human TLR4 compound heterozygous knockout hESC line (WAe009-A-N) to model toll-like receptor 4 deficiency by CRISPR/Cas9 system.

Toll-like receptor 4 (TLR4) is a pattern recognition receptor (PRRS) and an important protective immune receptor. TLR4 deficiency can lead to Inflammatory bowel disease. To explore the role of TLR4, we used CRISPR/Cas9 system to produce TLR4 compound heterozygous knockout embryonic stem cells in H9 cell line. The WAe009-A-N has a compound heterozygous 7 bp deletion/8 bp deletion in TLR4 exon 3, which resulted in a frameshift in the translation of TLR4, and TLR4 protein wasn't detectable in this cell line. In addition, the WAe009-A-N with normal karyotype can express pluripotent markers and differentiate into three germ layers in vitro.

Incidence, temporal trends and risk factors of puerperal infection in Mainland China: a meta-analysis of epidemiological studies from recent decade (2010-2020).

BACKGROUND: Puerperal infection (PI) is a severe threat to maternal health. The incidence and risk of PI should be accurately quantified and conveyed for prior decision-making. This study aims to assess the quality of the published literature on the epidemiology of PI, and synthesize them to identify the temporal trends and risk factors of PI occurring in Mainland China. METHODS: This review was registered in PROSPERO (CRD42021267399). Putting a time frame on 2010 to March 2022, we searched Cochrane library, Embase, Google Scholar, MEDLINE, Web of Science, China biology medicine, China national knowledge infrastructure and Chinese medical current contents, and performed a meta-analysis and meta-regression to pool the incidence of PI and the effects of risk factors on PI. RESULTS: A total of 49 eligible studies with 133,938 participants from 17 provinces were included. The pooled incidence of PI was 4.95% (95%CIs, 4.46-5.43), and there was a statistical association between the incidence of PI following caesarean section and the median year of data collection. Gestational hypertension (OR = 2.14), Gestational diabetes mellitus (OR = 1.82), primipara (OR = 0.81), genital tract inflammation (OR = 2.51), anemia during pregnancy (OR = 2.28), caesarean section (OR = 2.03), episiotomy (OR = 2.64), premature rupture of membrane (OR = 2.54), prolonged labor (OR = 1.32), placenta remnant (OR = 2.59) and postpartum hemorrhage (OR = 2.43) have significant association with PI. CONCLUSIONS: Maternal infection remains a crucial complication during puerperium in Mainland China, which showed a nationwide temporal rising following caesarean section in the past decade. The opportunity to prevent unnecessary PI exists in several simple but necessary measures and it's urgent for clinicians and policymakers to focus joint efforts on promoting the bundle of evidence-based practices.

Etiology and clinical features of infection-associated plastic bronchitis in children.

OBJECTIVE: To investigate the etiological characteristics of plastic bronchitis (PB) caused by pulmonary infections in children and to identify any differences in the clinical features of PB cases caused by different pathogens. METHOD: We collected data on children diagnosed with PB and admitted to the Respiratory Department at Soochow University Children's Hospital between July 2021 and March 2023 utilizing electronic bronchoscopy. We analyzed clinical characteristics and the species of pathogens causing the illness in these children. RESULT: A total of 45 children were enrolled. The main clinical symptoms observed were cough (100%), fever (80%), shortness of breath (28.9%), and wheezing (20.0%). Pathogens were identified in 38 (84.4%) patients. Mycoplasma pneumoniae (MP) had the highest detection rate at 53.3%, followed by the Boca virus at 26.7%. MP-induced PB typically occurs in older children with an average age of 7.46 ± 2.36 years, with the main symptoms including high fever (85.7%) and local hyporespiration (42.9%). In contrast, Boca virus-induced PB tends to occur in younger children, with the main symptoms of moderate fever (54.5%), and wheezing (54.5%). The MP group exhibited a higher incidence of both internal and external pulmonary complications, including pleural effusion (42.9%), elevated aspartate aminotransferase (52.4%), lactic dehydrogenase (76.2%), and D-D dimer (90.5%). Conversely, the Boca virus group primarily showed pulmonary imaging of atelectasis (81.8%), with no pleural effusion. The average number of bronchoscopic interventions in the MP group was 2.24 ± 0.62, which was significantly higher than that required in the Boca virus group (1.55 ± 0.52). During the second bronchoscopy, 57.1% of children in the MP group still had visible mucus plugs, while none were observed in the Boca virus group. CONCLUSION: MP and Boca virus are the primary pathogens responsible for PB among children. The clinical manifestations of PB typically vary significantly based on the pathogen causing the condition.

Neural Maximum a Posteriori Estimation on Unpaired Data for Motion Deblurring.

Real-world dynamic scene deblurring has long been a challenging task since paired blurry-sharp training data is unavailable. Conventional Maximum A Posteriori estimation and deep learning-based deblurring methods are restricted by handcrafted priors and synthetic blurry-sharp training pairs respectively, thereby failing to generalize to real dynamic blurriness. To this end, we propose a Neural Maximum A Posteriori (NeurMAP) estimation framework for training neural networks to recover blind motion information and sharp content from unpaired data. The proposed NeruMAP consists of a motion estimation network and a deblurring network which are trained jointly to model the (re)blurring process (i.e. likelihood function). Meanwhile, the motion estimation network is trained to explore the motion information in images by applying implicit dynamic motion prior, and in return enforces the deblurring network training (i.e. providing sharp image prior). The proposed NeurMAP is an orthogonal approach to existing deblurring neural networks, and is the first framework that enables training image deblurring networks on unpaired datasets. Experiments demonstrate our superiority on both quantitative metrics and visual quality over State-of-the-art methods.

Economic burden attributable to healthcare-associated infections in tertiary public hospitals of Central China: a multi-centre case-control study.

Healthcare-associated infection (HAI) is a major cause of morbidity, mortality and cost, which vary widely by region and hospital. In this case-control study, we calculated losses attributable to HAI in central China. A total of 2976 patients in 10 hospitals were enrolled, and the incidence rate of HAI (range, 0.88-4.15%) was significantly, but negatively associated with the cost per 1000 beds of its prevention (range, $24 929.76-$53 146.41; r = -0.76). The per capita economic loss attributable to HAIs was $2047.07 (interquartile range, $327.63-$6429.17), mainly from the pharmaceutical cost (median, $1044.39). The HAIs, which occurred in patients with commercial medical insurance, affected the haematologic system and caused by Acinetobacter baumannii, contributed most to the losses (median, $3881.55, $4734.20 and $9882.75, respectively). Furthermore, the economic losses attributable to device-associated infections and hospital-acquired multi-drug resistant bacteria were two to four times those of the controls. The burden attributable to HAI is heavy, and opportunities for easing this burden exist in several areas, including that strengthening antibiotic stewardship and practicing effective bundle of HAI prevention for patients carrying high-risk factors, for example, elders or those with catheterisations in healthcare institutions, and accelerating the medical insurance payment system reform based on diagnosis-related groups by policy-making departments.

Atomistic mechanism of phase transformation between topologically close-packed complex intermetallics.

Understanding how topologically close-packed phases (TCPs) transform between one another is one of the challenging puzzles in solid-state transformations. Here we use atomic-resolved tools to dissect the transition among TCPs, specifically the µ and P (or σ) phases in nickel-based superalloys. We discover that the P phase originates from intrinsic (110) faulted twin boundaries (FTB), which according to first-principles calculations is of extraordinarily low energy. The FTB sets up a pathway for the diffusional in-flux of the smaller 3d transition metal species, creating a Frank interstitial dislocation loop. The climb of this dislocation, with an unusual Burgers vector that displaces neighboring atoms into the lattice positions of the product phase, accomplishes the structural transformation. Our findings reveal an intrinsic link among these seemingly unrelated TCP configurations, explain the role of internal lattice defects in facilitating the phase transition, and offer useful insight for alloy design that involves different complex phases.

Plant-Derived Exosomes as a Drug-Delivery Approach for the Treatment of Inflammatory Bowel Disease and Colitis-Associated Cancer.

Inflammatory bowel disease (IBD) is a chronic recurrent intestinal disease and includes Crohn's disease (CD) and ulcerative colitis (UC). Due to the complex etiology of colitis, the current treatments of IBD are quite limited and are mainly concentrated on the remission of the disease. In addition, the side effects of conventional drugs on the body cannot be ignored. IBD also has a certain relationship with colitis-associated cancer (CAC), and inflammatory cells can produce a large number of tumor-promoting cytokines to promote tumor progression. In recent years, exosomes from plants have been found to have the ability to load drugs to target the intestine and have great potential for the treatment of intestinal diseases. This plant-derived exosome-targeting delivery system can load chemical or nucleic acid drugs and deliver them to intestinal inflammatory sites stably and efficiently. This review summarizes the pathophysiological characteristics of IBD and CAC as well as the application and prospect of plant exosomes in the treatment of IBD and CAC.

Exposure Trajectory Recovery From Motion Blur.

Motion blur in dynamic scenes is an important yet challenging research topic. Recently, deep learning methods have achieved impressive performance for dynamic scene deblurring. However, the motion information contained in a blurry image has yet to be fully explored and accurately formulated because: (i) the ground truth of dynamic motion is difficult to obtain; (ii) the temporal ordering is destroyed during the exposure; and (iii) the motion estimation from a blurry image is highly ill-posed. By revisiting the principle of camera exposure, motion blur can be described by the relative motions of sharp content with respect to each exposed position. In this paper, we define exposure trajectories, which represent the motion information contained in a blurry image and explain the causes of motion blur. A novel motion offset estimation framework is proposed to model pixel-wise displacements of the latent sharp image at multiple timepoints. Under mild constraints, our method can recover dense, (non-)linear exposure trajectories, which significantly reduce temporal disorder and ill-posed problems. Finally, experiments demonstrate that the recovered exposure trajectories not only capture accurate and interpretable motion information from a blurry image, but also benefit motion-aware image deblurring and warping-based video extraction tasks. Codes are available on https://github.com/yjzhang96/Motion-ETR.

Quantitative analysis of coal quality by laser-induced breakdown spectroscopy assisted with different chemometric methods.

Rapid and accurate measurement of coal quality has great significance for efficient use of coal at thermal power plants. Laser-induced breakdown spectroscopy (LIBS) combined with chemometric methods has many unique advantages in coal analysis. In this study, four calibration models, based on partial least squares regression (PLSR), support vector regression (SVR), artificial neural network (ANN), and principal component regression (PCR), were applied assisted by the LIBS technique for the quantitative analysis of coal quality. In order to find the optimal calibration method with LIBS for coal analysis, the spectral data of 40 standard coal samples with pressed-pellet pretreatment were acquired through a LIBS experimental setup, and the modeling efficiency and prediction accuracy of the four chemometric methods were compared based on these spectral data. As a result, the modeling efficiency of PLSR was found to be the highest, that of SVR was the lowest, and that of ANN ranked third. In terms of prediction performance, ANN was found to work better than the other three chemometric methods, and the average absolute error (AAE) of prediction of ash content, volatile matter content and calorific value were 0.69%, 0.87%, and 0.56 MJ kg-1, respectively. ANN can seek the best compromise of modeling efficiency and prediction accuracy and is demonstrated to be an optimal multivariate calibration method with LIBS for online measurement of coal quality at thermal power plants.

NR4A1 regulates cerebral ischemia-induced brain injury by regulating neuroinflammation through interaction with NF-κB/p65.

Stroke is reported as a leading cause of mortality and disability in the world. Neuroinflammation is significantly induced responding to ischemic stroke, and this process is accompanied with microglial activation. However, the pathogenesis contributing to ischemic stroke remains unclear. NR4A1 (Nur77) is a nuclear receptor that is expressed in macrophages, playing a significant role in regulating inflammatory response. In the present study, we attempted to explore the effects of NR4A1 on ischemic stroke using in vivo and in vitro studies. Results suggested that NR4A1 expression in microglia was markedly increased after cerebral ischemic damage. Then, we found that NR4A1 knockout attenuated ischemia-triggered infarction volume and neuron injury. Also, cognitive impairments were improved in ischemic mice with NR4A1 deficiency, resulting in functional improvements. Moreover, M1 polarization in microglia and neutrophil recruitment was significantly alleviated by NR4A1 deletion, as evidenced by the reduced expression of M1 markers, chemokines, as well as intracellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO) levels. Importantly, we found that NR4A1 could interact with nuclear factor-κB (NF-κB)/p65 based on in vivo and in vitro results. Suppressing p65 activation by the use of its inhibitor clearly reduced the NR4A1 expression, M1 polarization and neutrophil recruitments, while rescued the expression of anti-inflammatory factors in microglia treated with oxygen-glucose deprivation (OGD). Therefore, NR4A1 suppression in microglia restrained neuroinflammation through interacting with NF-κB/p65 to attenuate ischemic stroke.

Seasonal modification of the associations of exposure to polycyclic aromatic hydrocarbons or phthalates of cellular aging.

Exposure to polycyclic aromatic hydrocarbons (PAHs) and phthalates link to oxidative stress and inflammatory response, which exert cellular aging. However, modification effect of seasonal factor on the association of PAHs or phthalates exposure with relative telomere length (RTL) or mitochondrial DNA copy number (mtDNA-CN) has remained unclear. In this pilot study, 106 subjects were from an urban population (n = 1240) who lived in the two districts in Wuhan city, China. Participants completed physical examinations and provided 191 blood samples for RTL and mtDNA-CN analysis and 627 urine samples for monohydroxylated-PAHs (OH-PAHs) and phthalate metabolites measurements in the winter and summer seasons. We assessed the associations of urinary OH-PAHs or phthalates metabolites with RTL or mtDNA-CN by linear regression analysis and linear mixed-effect models. We found that urinary OH-PAHs were positively associated with mtDNA-CN at lag 2 day and 3-day moving average, but negatively related to RTL at lag 0, lag 1 and lag 2 day and 3-day moving average (p < 0.05). Urinary phthalate metabolites were negatively associated with mtDNA lag 0, lag 1 and lag 2 day and 3-day moving average, but positively related to RTL at lag 0 day (p < 0.05). Seasonal factor modified the association of urinary OH-PAHs with mtDNA-CN as well as urinary phthalate metabolites with RTL. In vitro experiment showed that under certain conditions, benzo[a]pyrene increased mtDNA-CN at 48 h and di (2-ethylhexyl) phthalate did RTL at 24 h in HepG2 cells. Seasonal variations in the metabolisms of PAHs or phthalates in human body may affect the relation of PAHs or phthalates exposure with cellular aging.

Novel preparation of Au nanoparticles loaded Laponite nanoparticles/ECM injectable hydrogel on cardiac differentiation of resident cardiac stem cells to cardiomyocytes.

Cardiac tissue engineering offers a facile biomedical technology to develop a cardiac tissue regeneration or tissue repair by involving combinations of effective biomaterials and nanomaterials with engineering strategies. The cardiac regenerative materials were fabricated by electrically active nanoparticles onto the biocompatible matrix to inspire low-resistance electrical signal in the native heart tissues. In the current report, we investigated on the improvement of cardiac functionally inspired conductive injectable hydrogel fabricated from the electroactive gold (Au) and laponite (Lap) nanoparticles loaded myocardial extracellular matrix (ECM) to enhance the functional and biological properties of cardiomyocytes. The incorporation of nanoformulations into the ECM was maintained the functionality behaviors and maintenance of electrical conductivity into cardiomyocytes. The effects of nanoparticles onto the ECM were provided decreasing porous structure and interconnected pores in the hydrogel structure for the favorable environment of cardiac tissues. The biological analysis of cell survival and immunostaining studies of cardiomyocytes established that Au loaded Lap/ECM hydrogel improve cell compatibility and phenotypes maturation of cardiac specific proteins. The combination of electrically active nanoformulations and biologically active ECM was enhanced the cell expression of cardiac specific markers (SAC, cTnl and Cx43), indicating the potential role of nanoparticles loaded ECM hydrogel as an appropriate cardiac regenerative material for the repair of infarcted myocardium.

Seasonal variations of tris (2-chloroethyl) phosphate and cytotoxicity of organic extracts in water samples from Wuhan, China.

Tris (2-chloroethyl) phosphate (TCEP) is a typical phosphate flame retardant. Its potential adverse health effects have recently aroused concern. We investigated the seasonal variations of TCEP concentrations in the raw, finished and tap water samples from two drinking water treatment plants (DWTPs) in China, and evaluated the cytotoxicity and apoptosis/necrosis of organic extracts (OEs) in water samples. We enriched TCEP and OEs in water samples by solid-phase extraction method. The TCEP concentrations in water samples were determined by gas chromatography-mass spectrometry. Normal human liver cell line L02 was treated with OEs in the water samples, and then the cytotoxicity and apoptosis/necrosis were measured by 3-(4, 5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and flow cytometry, respectively. The results showed that cytotoxicities of OEs in raw water samples from both DWTPs in summer and winter were stronger than those in spring and autumn, cytotoxicity of OEs in finished and tap water samples from both DWTPs in summer and autumn were stronger than those in spring and winter. In all seasons, the maximal concentrations (100 mL water/mL cell culture) of OEs in the raw water samples from both DWTPs induced late apoptosis/necrosis. The reasons for seasonal variations of TCEP in water samples and potential toxic effects of other pollutants in the water samples need to be further investigated.

Dose-response relationships between urinary phthalate metabolites and serum thyroid hormones among waste plastic recycling workers in China.

BACKGROUND: Exposure to phthalates may affect thyroid hormone status. However, there were inconsistent observations for the associations of phthalates exposure with altered thyroid hormones. OBJECTIVES: The aim of this study was to investigate effects of urinary excretion of phthalate metabolites on the levels of thyroid hormones among workers engaged in waste plastic recycling in China. METHODS: We measured serum levels of thyroid hormones and urinary levels of eight phthalate metabolites among 317 participants (165 workers engaged in waste plastic recycling and 152 farmers), analyzed relationships between urinary phthalate metabolites and thyroid function parameters by multivariate linear regression analysis and structural equation modelling as well as assessed the dose-response relationships between them by restricted cubic spline functions. RESULTS: Maximum urinary values of eight phthalate metabolites in the occupational exposed workers were higher than the controls. Compared with the controls, the workers had higher levels of urinary monobenzyl phthalate (MBzP, 1.12 vs. 0.92 µg/g creatinine), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP, 38.84 vs. 32.55 µg/g creatinine), mono-n-octyl phthalate (MOP, .11 vs. 0.09 µg/g creatinine), serum total triiodothyronine (T3, 1.04 vs. 0.92 ng/mL) and the T3 to thyroxine (T4) ratio (1.44 vs. 1.09) (all P < 0.05). The results from structural equation modelling analysis showed that phthalates metabolites were positively associated with total T3 (ß = 0.044, SE = 0.021, P < 0.05) or the T3/T4 ratio (ß = 0.053, SE = 0.022, P < 0.05) among all participants. Among the workers, there were the non-monotonic dose-response associations between urinary monomethyl phthalate (MMP) and serum total T3 or the T3/T4 ratio, as well as between urinary monoethyl phthalate (MEP) and the T3/T4 ratio (all P < 0.05). CONCLUSIONS: The dose-response relationships between urinary phthalate metabolites and thyroid hormone parameters may be non-monotonic among the workers. Further investigations are needed to corroborate these findings.

Association of polycyclic aromatic hydrocarbons exposure with atherosclerotic cardiovascular disease risk: A role of mean platelet volume or club cell secretory protein.

BACKGROUND: Inflammation may play an important role in the association between exposure to polycyclic aromatic hydrocarbons (PAHs) and atherosclerotic cardiovascular disease (ASCVD) risk. However, the underlying mechanisms remain unclear. OBJECTIVES: To investigate the association of PAHs exposure with ASCVD risk and effects of mean platelet volume (MPV) or Club cell secretory protein (CC16) on the association. METHODS: A total of 2022 subjects (689 men and 1333 women) were drawn from the baseline Wuhan residents of the Wuhan-Zhuhai Cohort study. Data on demography and the physical examination were obtained from each participant. Urinary monohydroxy PAH metabolites (OH-PAHs) levels were measured by a gas chromatography-mass spectrometry. We estimated the association between each OH-PAHs and the 10-year ASCVD risk or coronary heart disease (CHD) risk using logistic regression models, and further analyze the mediating effect of MPV or plasma CC16 on the association by using structural equation modeling. RESULTS: The results of multiple logistic regression models showed that some OH-PAHs were positively associated with ASCVD risk but not CHD risk, including 2-hydroxyfluoren (ß = 1.761; 95% CI: 1.194-2.597), 9-hydroxyfluoren (ß = 1.470; 95% CI: 1.139-1.898), 1-hydroxyphenanthrene (ß = 1.480; 95% CI: 1.008-2.175) and ΣOH-PAHs levels (ß = 1.699; 95% CI: 1.151-2.507). The analysis of structural equation modeling shows that increased MPV and increased plasma CC16 levels contributed 13.6% and 15.1%, respectively, to the association between PAHs exposure and the 10-year ASCVD risk (p < 0.05). CONCLUSIONS: Exposure to PAHs may increase the risk of atherosclerosis, which was partially mediated by MPV or CC16.

Obesity mediated the association of exposure to polycyclic aromatic hydrocarbon with risk of cardiovascular events.

Exposure to polycyclic aromatic hydrocarbons (PAHs) could cause high blood pressure (BP) and increased risk for atherosclerotic cardiovascular disease (ASCVD). However, the mechanisms underlying the relationship between them were unclear. We investigated potential mediation effect of obesity on the association of exposure to PAHs with high BP and increased risk for ASCVD. In the repeated measures study, 106 community-dwelling residents in Wuhan, China finished the physical examination in the winter and summer seasons, eight urinary PAHs metabolites were measured. Associations of urinary PAHs with high BP and increased risk for ASCVD were assessed using either linear mixed effect models or generalized estimating equations models. Mediation analysis was performed to evaluate the mediating effect of obesity on the association of urinary PAHs metabolites with high BP or increased risk of ASCVD. We observed the positive association between urinary PAHs metabolites and BP or the odds ratios for high BP (all P<0.05). Additionally, each one-unit increase in ln-transformed urinary levels of 4-hydroxyphenanthrene or the total of PAH metabolites was associated with a 12.63% or 11.91% increase in the estimated 10-year ASCVD risk (both P<0.05). The waist-to-height ratio mediated 29.0% of the association of urinary 4-hydroxyphenanthrene with increased risk of ASCVD (P<0.05). The findings suggest that PAHs exposure may be associated with elevated BP and an increased risk of ASCVD. Obesity may partially mediate the association between PAHs exposure and higher BP or increased risk of ASCVD.

Tris (2-chloroethyl) phosphate induces senescence-like phenotype of hepatocytes via the p21Waf1/Cip1-Rb pathway in a p53-independent manner.

Tris (2-chloroethyl) phosphate (TCEP) has been widely used as a plasticizer and flame retardant. TCEP as a potential carcinogen is often detected in the occupational and nature environments. To investigate effects of TCEP on human hepatocytes, we assessed cell growth rate, cellular membrane integrity, senescence-associated ß-galactosidase (SA-ß-Gal) activity and analyzed expression of regulators involved in the p53-p21Waf1/Cip1-Rb pathway in TCEP-treated L02 cells. The results showed TCEP increased the percentage of SA-ß-Gal positive cells, decreased IL-6 levels, down-regulated the regulators of p38MAPK-NF-κB pathways, but up-regulated the regulators of p21Waf1/Cip1-Rb pathway in L02 cells. Furthermore, we measured the SA-ß-Gal activity and expression of regulators involved in the p53-p21Waf1/Cip1-Rb pathway in L02-p53 cells and p53-null Hep3B cells. Similar results were found in L02-p53 cells and Hep3B cells. The findings demonstrated that TCEP induced senescence-like growth arrest via the p21Waf1/Cip1-Rb pathway in a p53-independent manner, without activation of the IL-6/IL6R, p38MAPK-NF-κB pathways in hepatocytes.

Exposure to polycyclic aromatic hydrocarbons and central obesity enhanced risk for diabetes among individuals with poor lung function.

Some studies have shown an association between obesity or exposure to polycyclic aromatic hydrocarbons (PAHs) and the risk of diabetes. This study aimed to investigate the interaction of obesity and urinary monohydroxy-PAHs (OH-PAHs) on diabetes. Individuals (n = 2716) were drawn from the baseline survey of the Wuhan-Zhuhai Cohort Study. They completed the physical examination, measurements of lung function, biochemical indices and urinary OH-PAHs levels. Additive effect of obesity and urinary ΣOH-PAHs levels on diabetes was assessed by calculating the relative excess risk due to interaction (RERI) and the attributable proportion (AP) due to interaction. Several urinary OH-PAHs were positively associated with diabetes in individuals with central obesity or normal weight (p < 0.05 for all). Among individuals with poor lung function, the RERI between urinary ΣOH-PAHs and waist circumstance (WC, RERI: 0.866, 95% CI: -0.431, 2.164, p = 0.192) or waist-to-height ratio (WHtR, RERI: 1.091, 95% CI: -0.124, 2.305, p = 0.078) was found; the AP due to the interaction between urinary ΣOH-PAHs and WC or WHtR was 0.383 (95% CI: -0.07, 0.80, p = 0.086) or 0.465 (95% CI: 0.019, 0.912, p = 0.04). The results indicated that central obesity may enhance the effect of exposure to background PAHs on diabetes in individuals with poor lung function.

Association of individual-level concentrations and human respiratory tract deposited doses of fine particulate matter with alternation in blood pressure.

Fine particulate matter (PM2.5) contributes to the risk of cardiovascular events, partially owing to its deposition in the human respiratory tract. To investigate short-term effects of ambient PM2.5 exposure on alternation of blood pressure (BP), this study was conducted during the winter-summer period between 2014 and 2015. The study included 106 community residents in Wuhan city, China. We repeatedly monitored the household and outdoor PM2.5 concentrations as well as individual-level PM2.5 in each season, and then assessed personal PM2.5 exposure (including deposited doses of PM2.5 in the human respiratory tract) by using different methodology (such as using a dosimetry model). All participants took part in the physical examination, including the inflammatory indicators, BP and lung function parameters measurements. Subsequently, we assessed the health damage of exposure to PM2.5 using generalized additive models. We observed increased BP at 2-day lag for an interquartile range increase in ambient fixed-site, households, individual-level PM2.5 exposure and the corresponding lung deposited doses of each exposure concentration (p < 0.05), decreased BP at 3-day lag for an interquartile range increase in ambient fixed-site, households PM2.5 and the corresponding lung deposited doses of each exposure concentration (p < 0.05). The estimated deposited doses of PM2.5 by the deposition fractions in this study and the referenced deposition fractions by previous reported method were equivalent associated with alternation in BP. In conclusion, lung deposited dose of PM2.5 as a quantitative indicator may be used to assess adverse cardiovascular effects following the systemic inflammation. However, we require careful assessment of acute adverse cardiovascular effects using ambient fixed-site PM2.5 after short-term PM2.5 exposure.