Search

Additive manufacturing (AM) or industrial 3D printing uses cutting-edge technologies and materials to produce a variety of complex products. However, the effects of the unintentionally emitted AM (nano)particles (AMPs) on human cells following inhalation, require further investigations. The physicochemical characterization of the AMPs, extracted from the filter of a Laser Powder Bed Fusion (L-PBF) 3D printer of iron-based materials, disclosed their complexity, in terms of size, shape, and chemistry. Cell Painting, a high-content screening (HCS) assay, was used to detect the subtle morphological changes elicited by the AMPs at the single cell resolution. The profiling of the cell morphological phenotypes, disclosed prominent concentration-dependent effects on the cytoskeleton, mitochondria, and the membranous structures of the cell. Furthermore, lipidomics confirmed that the AMPs induced the extensive membrane remodeling in the lung epithelial and macrophage co-culture cell model. To further elucidate the biological mechanisms of action, the targeted metabolomics unveiled several inflammation-related metabolites regulating the cell response to the AMP exposure. Overall, the AMP exposure led to the internalization, oxidative stress, cytoskeleton disruption, mitochondrial activation, membrane remodeling, and metabolic reprogramming of the lung epithelial cells and macrophages. We propose the approach of integrating Cell Painting with metabolomics and lipidomics, as an advanced nanosafety methodology, increasing the ability to capture the cellular and molecular phenotypes and the relevant biological mechanisms to the (nano)particle exposure.

BACKGROUND: Heart sound auscultation, due to it being a non-invasive, convenient, and relatively low-cost technique, remains the dominant method for detection of cardiovascular disease. METHODS: In this paper, we present a method for identifying abnormal heart sounds based on a novel Dense Feature Selection Convolution Network framework (Dense-FSNet). The Dense-FSNet is comprised of multiple, circular dense connectivity modules, called Clique Blocks. These Clique Blocks can allow low-level and high-level features to stimulate each other for cyclic updates, which subsequently enhances the information flow among layers. Inspired by the channel-wise attention mechanism from Squeeze-and-Excitation Networks (SENet), we adopted squeeze-and-excitation block to avoid the progressive growth of parameters. The effect of the model was assessed using the accuracy, specificity, sensitivity, and area under the curve (AUC) values. To improve model performance, in addition to the structures mentioned above, we incorporated a multi-scale attention mechanism into our framework. RESULTS: Using this attention mechanism, our model was able to achieve adaptively spatial feature fusion by adjusting a hyper-feature that contains higher level visual information and lower-level features including edge details and context information. It is worth noting that data balance technology was also used in the process of building the model, and notable results have been achieved. CONCLUSIONS: Experience using the PhysioNet/CinC 2016 dataset shows that our proposed Dense-FSNet models achieve state of the art levels in the classification and detection of abnormal heart sounds.

Silica nanoparticles (SiNPs), one of the most produced nanoparticles (NPs) in the world, are used in all aspects of life. The increased application of SiNPs, especially in medicine, has raised considerable concern regarding their toxicological impact. Previous studies have shown that SiNPs can pass through the reproductive barrier and cause reproductive organ dysfunction by destroying Sertoli cells, Leydig cells, and germ cells. However, little is known about the mechanism of SiNPs-induced reproductive toxicity. In the present study, 5-week-old male mice were intraperitoneally administered SiNPs per day for 1 week at a dose of 0.2 mg per mouse. The results showed that SiNPs could cause damage to the structure of the testis and the epididymis and change the reproductive organ coefficients, leading to decreases of 56.1% and 55.3% in the rates of sperm concentration and motility and an increase of 168.8% in the rate of sperm abnormality. Moreover, the serum testosterone level obviously decreased from 18.77 to 5.23 µg/ml after exposure, and the transcription statuses of some key genes involved in the synthesis and transport of testosterone in the testis were also affected. Additional experiments showed that SiNPs exposure during puberty induced oxidative stress and an inflammatory response, as shown by the changed activity of superoxide dismutase (SOD), increased contents of malondialdehyde (MDA), and excess expression of proinflammatory factors, including TNF-α and IL-1β. Furthermore, the administration of SiNPs caused DNA damage and cell apoptosis, which were presented by the increased apoptotic cells in the sections of testis and epididymis and activation of the TNF-α/TNFR I-mediated pro-apoptotic pathway. In conclusion, these results indicate that SiNPs exposure during puberty significantly damaged the structure and function of the testis and epididymis by inducing oxidative stress and cell apoptosis. This study provides novel insight into SiNPs-induced reproductive toxicity during puberty, which warrants a more careful assessment of SiNPs before their application in juvenile supplies.

The widespread use of silica nanoparticles (SiNPs) has increased the risk of human exposure, which raised concerns about their adverse effects on human health, especially the reproductive system. Previous studies have shown that SiNPs could cause damage to reproductive organs, but the specific mechanism is still unclear. In this study, to investigate the underlying mechanism of male reproductive toxicity induced by SiNPs, 40 male mice at the age of 8 weeks were divided into two groups and then intraperitoneally injected with vehicle control or 10 mg/kg SiNPs per day for one week. The results showed that SiNPs could damage testicular structure, perturb spermatogenesis and reduce serum testosterone levels, leading to a decrease in sperm quality and quantity. In addition, the ROS level in the testis of exposed mice was significantly increased, followed by imbalance of the oxidative redox status. Further study revealed that exposure to SiNPs led to cell cycle arrest and apoptosis, as shown by downregulation of the expression of positive cell cycle regulators and the activation of TNF-α/TNFR Ⅰ-mediated apoptotic pathway. The results demonstrated that SiNPs could cause testicles injure via inducing oxidative stress and DNA damage which led to cell cycle arrest and apoptosis, and thereby resulting in spermatogenic dysfunction.

Background Diabetes is a chronic disease, and it could affect both health and quality of life (QOL). A lot of studies have reported some predictors of QOL of type 2 diabetes patients. While their results were not completely consistent. So the aim of our study was finding out the related factors (including characteristics related to the disease, life styles and mental health factors) of QOL of type 2 diabetes patients. Methods We searched Cochrane library, EmBase, PubMed and CNKI databases for published studies that evaluated the related factors of QOL of type 2 diabetes patients by using a proper statistic method and had effect sizes (OR or β) and 95% confidence intervals from January 1st 2000 to May 31st 2016. Any study types were acceptable, and we excluded the reviews, letters, editorials and pooled analyses. The data were analyzed using STATA software (Version 12.0; Stata Corporation). Effect sizes and 95% confidence intervals were calculated to evaluate the relationship between these factors and QOL. Results Eighteen studies were included into our systematic review and meta-analysis, totaling 57,109 type 2 diabetes patients. Do more physical exercises (The pooled ORs ranged from 0.635 to 0.825 for different scales, less than 1.00), glucose check more frequently [pooled OR (95%CI): 0.175 (0.041, 0.756)] were associated with a better QOL. Presence of complications (The pooled ORs ranged from 1.462 to 3.038 for different scales, more than 1.00), presence of hypertension [pooled OR (95%CI): 1.389 (1.173, 1644)], longer duration of diabetes [pooled OR (95%CI): 1.865 (1.088, 3.197)], diet with more red meat [pooled OR (95%CI): 2.085 (1.063, 4.089)] and depression (The pooled ORs ranged from 3.003 to 11.473 for different scales, higher than 1.00) were associated with a worse QOL. Conclusion The results of this study show that physical exercise, glucose check frequently, complications, hypertension, duration of diabetes, diet with more red meat, and depression were associated with the QOL of type 2 diabetes patients.

Background/Aims: There is increasing evidence that exposure to air pollutants, including particulate matter (PM2.5, PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2), might aggravate preexisting skin diseases such as eczema and urticaria. Here we investigated if a possible link exists between air pollution and acne vulgaris. We assessed the association between ambient air pollutant concentrations and the number of visits of patients for acne vulgaris to a dermatological outpatient clinic in Beijing, China, from April 1, 2012 to April 30, 2014. Methods: In this time period, 59,325 outpatient visits were recorded because of acne vulgaris. Daily air pollution parameters for PM10, PM2.5, SO2, and NO2 were obtained from the Beijing Municipal Environmental Monitoring Center. Results: Increased concentrations of ambient PM2.5, PM10, and NO2 were significantly associated with increased numbers of outpatient visits for acne vulgaris over the 2 years. These effects could be observed for NO2 in a single-pollutant model and for PM2.5, PM10, and NO2 in 2-pollutant models, which are closer to real-life exposure. Of note, these effects were specific because they were not observed for increased SO2 concentrations, which even showed negative correlations in all test models. Conclusion: This study provides indirect evidence for a link between acne vulgaris and air pollution.

BACKGROUND: A few models have been proposed for the prediction of the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP), but many include factors that are not assessed routinely. Herein, we intend to develop and validate a predictive model for the occurrence of PEP. METHODS: Data of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) from January 01, 2016 to May 16, 2019 (training set and internal test set) and from May 17, 2019 to December 25, 2019 (external test set) were retrospectively collected. The performance of the model was validated in the two validation cohorts. RESULTS: A total of 342 patients were included for the external test set, and 47 (13.7%) developed PEP. The variables included in the scoring system were gastrectomy history, high direct bilirubin (DBIL), high albumin (ALB), villous type of papillary orifice, nodular type of papillary orifice, pancreatic guidewire passages, precut sphincterotomy, and high operator experience. A total score >5 indicated high risk. In the external test set, the area under the curve (AUC) was 0.718, the sensitivity was 0.723, and the specificity was 0.676. In the external test set, the probability of PEP was 6.1%, 17.0%, and 37.5% in patients with low (5) risk scores, respectively. CONCLUSIONS: This study established a scoring system for predicting the risk of PEP using routinely measured clinical variables. Its application in routine work warrants further investigation.

Nitrobenzene is an important raw material and product, which presents a heavy threat to the ecosystem. The potential impacts of nitrobenzene on sediment oxygen demand (SOD) were studied in lake sediment simulating reactors receiving relatively low inputs of nitrobenzene. Oxygen microprofiles were measured in these sediment reactors using microelectrodes. After an initial microprofile measurement as a control, nitrobenzene was added to the overlying water resulting in concentrations of 0, 50, 100, and 150 μg/L. Microprofiles were measured on day 1,2,4 and 7 following the addition of nitrobenzene. SODs were determined from the microprofiles using a reaction-diffusion model. Results showed that the SODs increased relative to the initial values measured in the pre-treatment period in reactors exposed to all nitrobenzene concentrations on day 1. However, the values decreased gradually on the following days, which eventually resulted in a 50% loss in SODs after 7 days of exposure to nitrobenzene in all reactors. In addition, the inhibition effect of nitrobenzene on SOD exhibited a weak relationship with its concentration. The microscopic observation and count of algae in the sediment showed that the exposure to nitrobenzene did not change the composition of algae greatly, however, it decreased the number of dominant algae species sharply after 7 days of exposure. These results suggested that nitrobenzene could significantly alter SOD in lakes, which could ultimately affect the pollutant recovery in aquatic-sediment systems.

This study explored the association between particulate matter with an aerodynamic diameter of less than 10 μm (PM10) and the cause-specific respiratory mortality. We used the ordinary kriging method to estimate the spatial characteristics of ambient PM10 at 1-km × 1-km resolution across Beijing during 2008-2009 and subsequently fit the exposure-response relationship between the estimated PM10 and the mortality due to total respiratory disease, chronic lower respiratory disease, chronic obstructive pulmonary disease (COPD), and pneumonia at the street or township area levels using the generalized additive mixed model (GAMM). We also examined the effects of age, gender, and season in the stratified analysis. The effects of ambient PM10 on the cause-specific respiratory mortality were the strongest at lag0-5 except for pneumonia, and an inter-quantile range increase in PM10 was associated with an 8.04 % (95 % CI 4.00, 12.63) increase in mortality for total respiratory disease, a 6.63 % (95 % CI 1.65, 11.86) increase for chronic lower respiratory disease, and a 5.68 % (95 % CI 0.54, 11.09) increase for COPD, respectively. Higher risks due to the PM10 exposure were observed for females and elderly individuals. Seasonal stratification analysis showed that the effects of PM10 on mortality due to pneumonia were stronger during spring and autumn. While for COPD, the effect of PM10 in winter was statistically significant (15.54 %, 95 % CI 5.64, 26.35) and the greatest among the seasons. The GAMM model evaluated stronger associations between concentration of PM10. There were significant associations between PM10 and mortality due to respiratory disease at the street or township area levels. The GAMM model using high-resolution PM10 could better capture the association between PM10 and respiratory mortality. Gender, age, and season also acted as effect modifiers for the relationship between PM10 and respiratory mortality.

Calcineurin is a conserved calcium/calmodulin-dependent serine/threonine-specific protein phosphatase that acts in cell stress responses. Calcineurin is essential for growth at 37°C and for virulence of the human fungal pathogen Cryptococcus neoformans , but its substrates remain unknown. The C2 domain-containing, phospholipid-binding protein Cts1 was previously identified as a multicopy suppressor of a calcineurin mutation in C. neoformans . Here we further characterize the function of Cts1 and the links between Cts1 and calcineurin. GFP-Cts1 localizes to cytoplasmic puncta and colocalizes with the endosomal marker FM4-64. The cts1 Δ mutant shows a distinct FM4-64 staining pattern, suggesting involvement of Cts1 in endocytic trafficking. In large budded cells, GFP-Cts1 localizes transiently at the mother bud neck, as a single ring that undergoes contraction. mCherry-Cts1 colocalizes with the GFP-tagged calcineurin catalytic subunit Cna1 at sites of mRNA processing at 37°C, suggesting that Cts1 and calcineurin function coordinately during thermal stress. GFP-Cts1 exhibits slower electrophoretic mobility for cells grown at 37°C than for cells grown at 24°C, and the shift to a higher molecular weight is more pronounced in the presence of the calcineurin inhibitor FK506. In vitro treatment with calf intestinal alkaline phosphatase (CIP) restores faster electrophoretic mobility to GFP-Cts1, suggesting that Cts1 is phosphorylated at 37°C and may be dephosphorylated in a calcineurin-dependent manner. mCherry-Cts1 also coimmunoprecipitates with GFP-Cna1, with greater complex formation at 37°C than at 24°C. Taken together, these findings support potential roles for Cts1 in endocytic trafficking, mRNA processing, and cytokinesis and suggest that Cts1 is a substrate of calcineurin during high-temperature stress responses.

Sex pheromone biosynthesis in the Asian corn borer Ostrinia furnacalis was studied by topical application of deuterium labelled fatty acids to the pheromone gland. The incorporation of the labelled acids into pheromone components and precursors was determined by gas chromatography with flame ionization detection and mass spectrometry in the selected ion monitoring mode. The labelling experiments suggest that the pheromone components (E)‐ and (Z)‐12‐tetradecenyl acetates are biosynthesized from palmitic acid by δ14 desaturation, followed by chain shortening (β‐oxidation), reduction, and acetylation. This is the first confirmation of a Δ14 desaturase in an eukaryotic system.