Mechanistic insights into cardiovascular effects of ultrafine particle exposure: A longitudinal panel study.

BACKGROUND: Ultrafine particle (UFP) has been linked with higher risks of cardiovascular diseases; however, the biological mechanisms remain to be fully elucidated. OBJECTIVES: This study aims to investigate the cardiovascular responses to short-term UFP exposure and the biological pathways involved. METHODS: A longitudinal panel study was conducted among 32 healthy, non-smoking young adults in Shanghai, China, who were engaged in five rounds of follow-ups between December 2020 and November 2021. Individual exposures were calculated based on the indoor and outdoor real-time measurements. Blood pressure, arterial stiffness, targeted biomarkers, and untargeted proteomics and metabolomics were examined during each follow-up. Linear mixed-effect models were applied to analyze the exposure and health data. The differential proteins and metabolites were used for pathway enrichment analyses. RESULTS: Short-term UFP exposure was associated with significant increases in blood pressure and arterial stiffness. For example, systolic blood pressure increased by 2.10 % (95 % confidence interval: 0.63 %, 3.59 %) corresponding to each interquartile increase in UFP concentrations at lag 0-3 h, while pulse wave velocity increased by 2.26 % (95 % confidence interval: 0.52 %, 4.04 %) at lag 7-12 h. In addition, dozens of molecular biomarkers altered significantly. These effects were generally present within 24 h after UFP exposure, and were robust to the adjustment of co-pollutants. Molecular changes detected in proteomics and metabolomics analyses were mainly involved in systemic inflammation, oxidative stress, endothelial dysfunction, coagulation, and disturbance in lipid transport and metabolism. DISCUSSION: This study provides novel and compelling evidence on the detrimental subclinical cardiovascular effects in response to short-term UFP exposure. The multi-omics profiling further offers holistic insights into the underlying biological pathways.

Structure Engineering of Acridine Donor to Optimize Color Purity of Blue Thermally Activated Delayed Fluorescence Emitters.

9,9-Dimethyl-9,10-dihydroacridine (DMAC) is one of the most widely used electron donor for constructing high-performance thermally activated delayed fluorescence (TADF) emitters. However, DMAC-based emitters often suffer from the imperfect color purity, particularly in blue emitters, due to its strong electron-donating capability. To modulate donor strength, 2,7-F-Ph-DMAC and 2,7-CF3-Ph-DMAC were designed by introducing the electron-withdrawing 2-fluorophenyl and 2-(trifluoromethyl)phenyl at the 2,7-positions of DMAC. These donors were used, in combination with 2,4,6-triphenyl-1,3,5-triazine (TRZ) acceptor, to develop novel TADF emitters 2,7-F-Ph-DMAC-TRZ and 2,7-CF3-Ph-DMAC-TRZ. Compared to the F- or CF3-free reference emitter, both two emitters showed hypsochromic effect in fluorescence and comparable photoluminescence quantum yields without sacrificing the reverse intersystem crossing rate constants. In particular, 2,7-CF3-Ph-DMAC-TRZ based OLED exhibited a blue shift by up to 39 nm and significantly improved Commission International de l'Éclairage (CIE) coordinates from (0.36, 0.55) to (0.22, 0.41), while the external quantum efficiency kept stable at about 22.5%. This donor engineering strategy should be valid for improving the color purity of large amount of acridine based TADF emitters. It can be predicted that pure blue TADF emitters should be feasible if these F- or CF3-modifed acridine donors are combined with other weaker electron acceptors.

Sensory neuron transient receptor potential vanilloid-1 channel regulates angiogenesis through CGRP in vivo.

Angiogenesis plays a key role in bone regeneration. The role of neurons of peripheral nerves involved in angiogenesis of bone defects needs to be explored. The transient receptor potential vanilloid 1 (TRPV1), a nociceptor of noxious stimuli, is expressed on sensory neurons. Apart from nociception, little is known about the role of sensory innervation in angiogenesis. Calcitonin gene-related peptide (CGRP), a neuropeptide secreted by sensory nerve terminals, has been associated with vascular regeneration. We characterized the reinnervation of vessels in bone repair and assessed the impact of TRPV1-CGRP signaling on early vascularization. We investigated the pro-angiogenic effect of neuronal TRPV1 in the mouse model of femur defect. Micro-CT analysis with Microfil® reagent perfusion demonstrated neuronal TRPV1 activation enhanced angiogenesis by increasing vessel volume, number, and thickness. Meanwhile, TRPV1 activation upregulated the mRNA and protein expression of vascular endothelial growth factor A (VEGF-A), cell adhesion molecule-1 (CD31), and CGRP. Immunostaining revealed the co-localization of TRPV1 and CGRP in dorsal root ganglia (DRG) sensory neurons. By affecting neuronal TRPV1 channels, the release of neuronal and local CGRP was controlled. We demonstrated that TRPV1 influenced on blood vessel development by promoting CGRP release from sensory nerve terminals. Our results showed that neuronal TRPV1 played a crucial role in regulating angiogenesis during bone repair and provided important clinical implications for the development of novel therapeutic approaches for angiogenesis.

Cellulose separation from ramie bone by one step process with green hydrogen peroxide-citric acid.

Ramie bone (RB), an agricultural waste generated in the textile industry, is a vastly productive renewable natural resource with the potential to be used as a source of cellulose. In this study, ramie bone cellulose (RB-CE) was obtained in one step using a simple and ecologically friendly hydrogen peroxide-citric acid (HPCA) treatment procedure that avoided the use of halogenated reagents and strong acids while also streamlining the treatment processes. Various analytical methods were used to investigate the chemical composition and structure, crystallinity, morphology, thermal properties, surface area and hydration properties of cellulose separated at different treatment temperatures. HPCA successfully removed lignin and hemicellulose from RB, according to chemical composition analysis and FTIR. RB-CE had a type I cellulose crystal structure, and the crystallinity improved with increasing treatment temperature, reaching 72.51 % for RB-CE90. The RB-CE showed good thermal stability with degradation temperatures ranging from 294.2 °C to 319.1 °C. Furthermore, RB-CE had a high water/oil binding capacity, with RB-CE90 having WHC and OBC of 9.68 g/g and 7.24 g/g, respectively. The current work serves as a model for the environmentally friendly and convenient extraction of cellulose from biomass, and the cellulose obtained can be employed in the field of food and composite materials.

Pretreatment with low-frequency magnetic fields can improve the functional properties of pea globulin amyloid-like fibrils.

Plant protein fibrils have recently attracted considerable attention due to their superior mechanical and interfacial properties. The objective of this study was to evaluate the feasibility of low-frequency magnetic field (LF-MF) pretreatment in enhancing the conversion and functional characteristics of the amyloid-like fibrils derived from pea globulin (PG), which was considered a sustainable hypoallergenic protein. The results showed that LF-MF-treated PG (MPG) assembled into longer amyloid-like fibrils compared with native PG (NPG). The MPG presented similar gelling, emulsifying, and foaming properties to the NPG, while the fibril samples exhibited significantly improved functional properties. Moreover, the amyloid-like fibrils generated from the MPG (MPGF) showed large aspect ratios accompanied by superior solubility, molecular flexibility, emulsion stability, and gelling properties. The improved functional properties of the amyloid-like fibrils generated from the MPG can provide a promising outlook for expanding the applications of the PG in food, medicine and other fields.

Associations between ultrafine particle pollution and daily outpatient visits for respiratory diseases in Shanghai, China: a time-series analysis.

Previous epidemiological studies have linked short-term exposure to particulate matter with outpatient visits for respiratory diseases. However, evidence on ultrafine particle (UFP) is still scarce in China. To investigate the association between short-term UFP exposure and outpatient visits for respiratory diseases as well as the corresponding lag patterns, information on outpatient visits for main respiratory diseases during January 1, 2017, to December 31, 2019 was collected from electronic medical records of two large tertiary hospitals in Shanghai, China. Generalized additive models employing a Quasi-Poisson distribution were employed to investigate the relationships between UFP and respiratory diseases. We computed the percentage change and its corresponding 95% confidence interval (CI) for outpatient visits related to respiratory diseases per interquartile range (IQR) increase in UFP concentrations. Based on a total of 1,034,394 hospital visits for respiratory diseases in Shanghai, China, we found that the strongest associations of total UFP with acute upper respiratory tract infection (AURTI), bronchitis, chronic obstructive pulmonary disease (COPD), and pneumonia occurred at lag 03, 03, 0, and 03 days, respectively. Each IQR increase in the total UFP concentrations was associated with increments of 9.02% (95% CI: 8.64-9.40%), 3.94% (95% CI: 2.84-5.06%), 4.10% (95% CI: 3.01-5.20%), and 10.15% (95% CI: 9.32-10.99%) for AURTI, bronchitis, COPD, and pneumonia, respectively. Almost linear concentration-response relationship curves without apparent thresholds were observed between total UFP and outpatient-department visits for four respiratory diseases. Stratified analyses illustrated significantly stronger associations of total UFP with AURTI, bronchitis, and pneumonia among female patients, while that with COPD was stronger among male patients. After adjustment of criteria air pollutants, these associations all remained robust. This time-series study indicates that short-term exposure to UFP was associated with increased risk of hospital visits for respiratory diseases, underscoring the importance of reducing ambient UFP concentrations for respiratory diseases control and prevention.

Effects of main active components of rosemary on growth performance, meat quality and lipid metabolism in finishing pigs.

Rosemary extracts have been widely used as feed additives in recent years. This study aimed to investigate the effects of rosmarinic acid (RA) and ursolic acid (UA), the main active components of rosemary, on growth performance, meat quality and lipid metabolism in finishing pigs. A total of 72 finishing pigs (Landrace; initial age of 150 d) were randomly divided into 3 treatments with 8 replicates of 3 pigs each, and fed a basal diet or diet containing 500 mg/kg of RA or UA. The results showed that dietary supplementation of RA or UA had no significant effect on the growth performance and carcass traits of finishing pigs (P > 0.05). However, both RA and UA significantly increased the triglyceride (TG) level in soleus muscle (P < 0.001). Supplementation of RA increased the expression of genes related to lipogenesis and transport including fatty acid synthase (FAS) (P < 0.001), sterol regulatory element binding protein-1c (SREBP1c) (P < 0.001) and peroxisome proliferator-activated receptor γ (PPARγ) (P < 0.05), while UA increased the expression of fatty acid transport protein 1 (FATP1), a gene related to lipid uptake (P < 0.05). However, RA reduced the expression of adipogenesis-related gene acetyl-coenzyme A carboxylase α (ACCα) (P < 0.01). Characterization of cecal microbiota indicated that RA increased the microbial richness (chao 1, P < 0.001) and diversity (observed species, P < 0.01). Further analysis of the genera revealed that RA increased the relative abundance of Bacteroides and g-UCG-005 (P < 0.05), and UA enriched Prevotella (P < 0.001). Correlation analysis showed that g-UCG-005 was positively correlated with the expression of FAS, carnitine palmitoyl transferase 1B (CPT1B), SREBP1c and PPARγ (P < 0.01). In conclusion, dietary supplementation of RA or UA may increase fat deposition in muscle of finishing pigs by regulating lipid metabolism and gut microbiota.

The influence of tag sequence on recombinant humanized collagen (rhCol) and the evaluation of rhCol on Schwann cell behaviors.

Recombinant humanized collagen (rhCol) was an extracellular matrix (ECM)-inspired biomimetic biomaterial prepared by biosynthesis technology, which was considered non-allergenic and could possibly activate tissue regeneration. The influence of tag sequence on both structures and performances of rhCol type III (rhCol III) was investigated, and the effect of rhCol III on cell behaviors was evaluated and discussed using Schwann cells (SCs) as in vitro model that was critical in the repair process after peripheral nerve injury. The results demonstrated that the introduction of tag sequence would influence both advanced structures and properties of rhCol III, while rhCol III regulated SCs adhesion, spreading, migration and proliferation. Also, both nerve growth factor and brain-derived neurotrophic factor increased when exposed to rhCol III. As the downstream proteins of integrin-mediated cell adhesions, phosphorylation of focal adhesion kinase and expression of vinculin was up-regulated along with the promotion of SCs adhesion and migration. The current findings contributed to a better knowledge of the interactions between rhCol III and SCs, and further offered a theoretical and experimental foundation for the development of rhCol III-based medical devices and clinical management of peripheral nerve injury.

Triphenylene-Based Emitters with Hybridized Local and Charge-Transfer Characteristics for Efficient Nondoped Blue OLEDs with a Narrowband Emission and a Small Efficiency Roll-Off.

Developing high-efficiency nondoped blue organic light-emitting diodes (OLEDs) with high color purity and low-efficiency roll-off is vital for display and lighting applications. Herein, we developed two asymmetric D-π-A blue emitters, PIAnTP and PyIAnTP, in which triphenylene is first utilized as a functional acceptor. The relatively weak charge transfer (CT) properties, rigid molecular structures, and multiple supramolecular interactions in PIAnTP and PyIAnTP can significantly enhance the fluorescence efficiency and suppress the structural relaxations to obtain a narrowband blue emission. The photophysical experiments and theoretical simulations reveal that they both exhibit a typical hybridized local and charge-transfer (HLCT) excited state and achieve high external quantum efficiency (EQE) via a "hot exciton" channel. As a result, PIAnTP- and PyIAnTP-based nondoped devices realize blue emission at 456 and 464 nm, corresponding to CIE coordinates of (0.16, 0.14) and (0.16, 0.19), narrow full width at half-maximums of 52 and 60 nm, and the high EQEs of 8.36 and 8.69%, respectively. More importantly, the PIAnTP- and PyIAnTP-based nondoped devices show small EQE roll-offs of only 5.9 and 2.4% at 1000 cd m-2, respectively. These results signify an advance in designing a highly efficient blue emitter for nondoped OLEDs.

Cold Spells and the Onset of Acute Myocardial Infarction: A Nationwide Case-Crossover Study in 323 Chinese Cities.

BACKGROUND: Few studies have explored the relationships between cold spells and acute myocardial infarction (AMI) using the information of symptom onset. OBJECTIVES: We assessed the impact of cold spells on AMI onset and the potential effect modifiers. METHODS: We conducted a time-stratified case-crossover study among 456,051 eligible patients with AMI from 2,054 hospitals in 323 Chinese cities between January 2015 and June 2021 during cold seasons (November to March). Nine definitions of cold spells were used by combining three relative temperature thresholds (i.e., lower than the 7.5th, 5th, and 2.5th percentiles) and three durations of at least 2-4 consecutive d. Conditional logistic regressions with distributed lag models were applied to evaluate the cumulated effects of cold spells on AMI onset over lags 0-6 d, after adjusting for daily mean temperature. RESULTS: The associations generally appeared on lag 1 d, peaked on lag 3 d, and became nonsignificant approximately on lag 5 d. Cold spells defined by more stringent thresholds of temperature were associated with higher risks of AMI onset. For cold spell days defined by a daily mean temperature of ≤7.5th percentile and durations of ≥2d, ≥3d, and ≥4d, the percentage changes in AMI risk were 4.24% [95% confidence interval (CI): 2.31%, 6.20%], 3.48% (95% CI: 1.62%, 5.38%), and 2.82% (95% CI: 0.98%, 4.70%), respectively. Significant AMI risks associated with cold spells were observed among cases from regions without centralized heating, whereas null or much weaker risks were found among those from regions with centralized heating. Patients ≥65 years of age were more susceptible to cold spells. DISCUSSION: This national case-crossover study presents compelling evidence that cold spells could significantly increase the risk of AMI onset. https://doi.org/10.1289/EHP11841.

Neuronal TRPV1-CGRP axis regulates bone defect repair through Hippo signaling pathway.

Transient receptor potential vanilloid type 1 (TRPV1) is highly expressed on sensory neurons where it serves as a polymodal receptor for detecting physical and chemical stimuli. However, the role of TRPV1 in bone metabolism remains largely unclear. This study aimed to investigate the underlying mechanism of neuronal TRPV1 in regulating bone defect repair. In vivo experiment verified that TRPV1 activation could trigger dorsal root ganglion (DRG) producing the neuropeptide calcitonin gene-related peptide (CGRP) in mice. The accelerated bone healing of femoral defect in this process was observed compared to the control group (p < 0.05). Conversely, Trpv1 knockdown led to reduced CGRP expression in DRG and nerves innervating femur bone tissue, following impaired bone formation and osteogenic capability in the defect region (p < 0.05), which could be rescued by local CGRP treatment. In vitro, results revealed that TRPV1 function in DRG neurons contributed essentially to the regulation of osteoblast physiology through affecting the production and secretion of CGRP. The capsaicin-activated neuronal TRPV1-CGRP axis could enhance the proliferation, migration and differentiation of osteoblasts (p < 0.05). Furthermore, we found that the promoting role of neuronal TRPV1 in osteogenesis was associated with Hippo signaling pathway, reflected by the phosphorylation protein level of large tumor suppressor 1 (LATS1), MOB kinase activator 1 (MOB1) and Yes-associated protein (YAP), as well as the subcellular location of YAP. Our study clarified the effects and intrinsic mechanisms of neuronal TRPV1 on bone defect repair, which might offer us a therapeutic implication for bone disorders.

The COMPASS Complex Regulates Fungal Development and Virulence through Histone Crosstalk in the Fungal Pathogen Cryptococcus neoformans.

The Complex of Proteins Associated with Set1 (COMPASS) methylates lysine K4 on histone H3 (H3K4) and is conserved from yeast to humans. Its subunits and regulatory roles in the meningitis-causing fungal pathogen Cryptococcus neoformans remain unknown. Here we identified the core subunits of the COMPASS complex in C. neoformans and C. deneoformans and confirmed their conserved roles in H3K4 methylation. Through AlphaFold modeling, we found that Set1, Bre2, Swd1, and Swd3 form the catalytic core of the COMPASS complex and regulate the cryptococcal yeast-to-hypha transition, thermal tolerance, and virulence. The COMPASS complex-mediated histone H3K4 methylation requires H2B mono-ubiquitination by Rad6/Bre1 and the Paf1 complex in order to activate the expression of genes specific for the yeast-to-hypha transition in C. deneoformans. Taken together, our findings demonstrate that putative COMPASS subunits function as a unified complex, contributing to cryptococcal development and virulence.

Fine and coarse particulate air pollution and hospital admissions for a wide range of respiratory diseases: a nationwide case-crossover study.

BACKGROUND: The associations between fine and coarse particulate matter (PM2.5 and PM2.5-10) air pollution and hospital admissions for full-spectrum respiratory diseases were rarely investigated, especially for age-specific associations. We aim to estimate the age-specific associations of short-term exposures to PM2.5 and PM2.5-10 with hospital admissions for full-spectrum respiratory diseases in China. METHODS: We conducted an individual-level case-crossover study based on a nationwide hospital-based registry including 153 hospitals across 20 provincial regions in China in 2013-20. We applied conditional logistic regression models and distributed lag models to estimate the exposure- and lag-response associations. RESULTS: A total of 1 399 955 hospital admission records for various respiratory diseases were identified. The associations of PM2.5 and PM2.5-10 with total respiratory hospitalizations lasted for 4 days, and an interquartile range increase in PM2.5 (34.5 µg/m3) and PM2.5-10 (26.0 µg/m3) was associated with 1.73% [95% confidence interval (95% CI): 1.34%, 2.12%)] and 1.70% (95% CI: 1.31%, 2.10%) increases, respectively, in total respiratory hospitalizations over lag 0-4 days. Acute respiratory infections (i.e. pneumonia, bronchitis and bronchiolitis) were consistently associated with PM2.5 or PM2.5-10 exposure across different age groups. We found the disease spectrum varied by age, including rarely reported findings (i.e. acute laryngitis and tracheitis, and influenza) among children and well-established associations (i.e. chronic obstructive pulmonary disease, asthma, acute bronchitis and emphysema) among older populations. Besides, the associations were stronger in females, children and older populations. CONCLUSIONS: This nationwide case-crossover study provides robust evidence that short-term exposure to both PM2.5 and PM2.5-10 was associated with increased hospital admissions for a wide range of respiratory diseases, and the spectra of respiratory diseases varied by age. Females, children and older populations were more susceptible.

Hourly air pollution exposure and the onset of symptomatic arrhythmia: an individual-level case-crossover study in 322 Chinese cities.

BACKGROUND: Few studies have explored the relationship between air pollution and arrhythmia onset at the hourly level. We aimed to examine the association of exposure to air pollution with the onset of acute symptomatic arrhythmia at an hourly level. METHODS: We conducted a nationwide, time-stratified, case-crossover study in China between 2015 and 2021. We obtained hourly information on the onset of symptomatic arrhythmia (including atrial fibrillation, atrial flutter, atrial and ventricular premature beats and supraventricular tachycardia) from the Chinese Cardiovascular Association Database - Chest Pain Center (including 2025 certified hospitals in 322 cities). We obtained data on hourly concentrations of 6 air pollutants from the nearest monitors, including fine particles (PM2.5), coarse particles (PM2.5-10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone. For each patient, we matched the case period to 3 or 4 control periods during the same hour, day of week, month and year. We used conditional logistic regression models to analyze the data. RESULTS: We included a total of 190 115 patients with acute onset of symptomatic arrhythmia. Air pollution was associated with increased risk of onset of symptomatic arrhythmia within the first few hours of exposure; this risk attenuated substantially after 24 hours. An interquartile range increase in PM2.5, NO2, SO2 and CO in the first 24 hours after exposure (i.e., lag period 0-24 h) was associated with significantly higher odds of atrial fibrillation (1.7%-3.4%), atrial flutter (8.1%-11.4%) and supraventricular tachycardia (3.4%-8.9%). Exposure to PM2.5-10 was associated with significantly higher odds of atrial flutter (8.7%) and supraventricular tachycardia (5.4%), and exposure to ozone was associated with higher odds of supraventricular tachycardia (3.4%). The exposure-response relationships were approximately linear, without discernible concentration thresholds. INTERPRETATION: Exposure to air pollution was associated with the onset of symptomatic arrhythmia shortly after exposure. This finding highlights the importance of further reducing air pollution and taking prompt protective measures for susceptible populations during periods of elevated levels of air pollutants.

Respiratory Effects of Traffic-Related Air Pollution: A Randomized, Crossover Analysis of Lung Function, Airway Metabolome, and Biomarkers of Airway Injury.

BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been associated with increased risks of respiratory diseases, but the biological mechanisms are not yet fully elucidated. OBJECTIVES: Our aim was to evaluate the respiratory responses and explore potential biological mechanisms of TRAP exposure in a randomized crossover trial. METHODS: We conducted a randomized crossover trial in 56 healthy adults. Each participant was exposed to high- and low-TRAP exposure sessions by walking in a park and down a road with high traffic volume for 4 h in random order. Respiratory symptoms and lung function, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), the ratio of FEV1 to FVC, and maximal mid-expiratory flow (MMEF), were measured before and after each exposure session. Markers of 8-isoprostane, tumor necrosis factor-α (TNF-α), and ezrin in exhaled breath condensate (EBC), and surfactant proteins D (SP-D) in serum were also measured. We used linear mixed-effects models to estimate the associations, adjusted for age, sex, body mass index, meteorological condition, and batch (only for biomarkers). Liquid chromatography-mass spectrometry was used to profile the EBC metabolome. Untargeted metabolome-wide association study (MWAS) analysis and pathway enrichment analysis using mummichog were performed to identify critical metabolomic features and pathways associated with TRAP exposure. RESULTS: Participants had two to three times higher exposure to traffic-related air pollutants except for fine particulate matter while walking along the road compared with in the park. Compared with the low-TRAP exposure at the park, high-TRAP exposure at the road was associated with a higher score of respiratory symptoms [2.615 (95% CI: 0.605, 4.626), p=1.2×10-2] and relatively lower lung function indicators [-0.075L (95% CI: -0.138, -0.012), p=2.1×10-2] for FEV1 and -0.190L/s (95% CI: -0.351, -0.029; p=2.4×10-2) for MMEF]. Exposure to TRAP was significantly associated with changes in some, but not all, biomarkers, particularly with a 0.494-ng/mL (95% CI: 0.297, 0.691; p=9.5×10-6) increase for serum SP-D and a 0.123-ng/mL (95% CI: -0.208, -0.037; p=7.2×10-3) decrease for EBC ezrin. Untargeted MWAS analysis revealed that elevated TRAP exposure was significantly associated with perturbations in 23 and 32 metabolic pathways under positive- and negative-ion modes, respectively. These pathways were most related to inflammatory response, oxidative stress, and energy use metabolism. CONCLUSIONS: This study suggests that TRAP exposure might lead to lung function impairment and respiratory symptoms. Possible underlying mechanisms include lung epithelial injury, inflammation, oxidative stress, and energy metabolism disorders. https://doi.org/10.1289/EHP11139.

Transferring From Textual Entailment to Biomedical Named Entity Recognition.

Biomedical Named Entity Recognition (BioNER) aims at identifying biomedical entities such as genes, proteins, diseases, and chemical compounds in the given textual data. However, due to the issues of ethics, privacy, and high specialization of biomedical data, BioNER suffers from the more severe problem of lacking in quality labeled data than the general domain especially for the token-level. Facing the extremely limited labeled biomedical data, this work studies the problem of gazetteer-based BioNER, which aims at building a BioNER system from scratch. It needs to identify the entities in the given sentences when we have zero token-level annotations for training. Previous works usually use sequential labeling models to solve the NER or BioNER task and obtain weakly labeled data from gazetteers when we don't have full annotations. However, these labeled data are quite noisy since we need the labels for each token and the entity coverage of the gazetteers is limited. Here we propose to formulate the BioNER task as a Textual Entailment problem and solve the task via Textual Entailment with Dynamic Contrastive learning (TEDC). TEDC not only alleviates the noisy labeling issue, but also transfers the knowledge from pre-trained textual entailment models. Additionally, the dynamic contrastive learning framework contrasts the entities and non-entities in the same sentence and improves the model's discrimination ability. Experiments on two real-world biomedical datasets show that TEDC can achieve state-of-the-art performance for gazetteer-based BioNER.

Low ambient temperature increases the risk and burden of atrial fibrillation episodes: A nationwide case-crossover study in 322 Chinese cities.

BACKGROUND: Non-optimum ambient temperature has recently been acknowledged as an independent risk factor for disease burden, but its impact on atrial fibrillation (AF) episodes was rarely evaluated. OBJECTIVES: To examine the associations between ambient non-optimum temperature and symptom onset of AF episodes and calculate the corresponding disease burden. METHODS: We conducted an individual-level, time-stratified, case-crossover analysis based on a nationwide registry, which comprises of 94,711 eligible AF patients from 1993 hospitals in 322 Chinese cities from January 2015 to December 2021. Multiple moving 24 h average temperatures prior to the symptom onset of AF episodes were calculated as lag days. The associations were analyzed using conditional logistic regression combined with distributed lag non-linear models with a duration of lag 0-7 days, after controlling for criteria air pollutants. Stratification analyses were performed to explore possible effect modifiers. RESULTS: There was a monotonically increasing relationship of AF onset risk with decreasing temperature. The excess AF risk occurred at lag 1 d and lasted for 5 days. Nationally, the cumulative relative risk of AF episode onset associated with extremely low temperature (-9.3 °C) over lag 0-7 d was 1.25 (95 % confidence interval: 1.08, 1.45), compared with the reference temperature (31.5 °C). The exposure-response curve was steeper in the south than in the north where there was levelling-off at lower temperature. Nationally, 7.59 % of acute AF episodes could be attributable to non-optimum temperatures. The attributable fraction was larger for southern residents, males and patients <65 years. CONCLUSION: This nationwide study provides novel and robust evidence that declining ambient temperature could increase the risk of AF episode onset. We also provide the first-hand evidence that a considerable proportion of acute AF episodes could be attributable to non-optimum temperatures.

Synthesis of a BINOL-Based C3 Symmetric Schiff Base and Its Fluorescence Response to Zn2.

A novel C3 symmetric 1,1'-bi-2-naphthol-based Schiff base (R,R,R)-6 has been synthesized which shows highly selective fluorescence enhancement with Zn2+ among 21 metal cations examined. Its sensitivity and selectivity are found to be greater than other related C2 (1) and C1 [(R)-9] symmetric compounds in the fluorescent recognition of Zn2+ . The mechanistic study reveals that the selective fluorescence enhancement of the probe can be attributed to the formation of a unimolecular multidentate 6-coordinated Zn2+ complex.

Genome-Wide Profiling of Exosomal Long Noncoding RNAs Following Air Pollution Exposure: A Randomized, Crossover Trial.

Changes in human genome-wide long noncoding RNAs (lncRNAs) associated with air pollution are unknown. This study aimed to investigate the effect of air pollution on human exosomal lncRNAs. A randomized, crossover trial was conducted among 35 healthy adults. Participants were allocated to 4 h exposure in road (high air pollution) and park (low air pollution) sessions in random order with a 2 week washout period. RNA sequencing was performed to measure lncRNAs. Differential lncRNAs were identified using a linear mixed-effect model. Mean concentrations of air pollutants such as ultrafine particles (UFP), black carbon (BC), carbon monoxide (CO), and nitrogen dioxide (NO2) were 2-3 times higher in the road than those in the park. Fifty-five lncRNAs [false discovery rate (FDR) < 0.05] including lncRNA NORAD, MALAT1, and H19 were changed in response to air pollution exposure. We found that 54 lncRNAs were associated with CO, 49 lncRNAs with UFP, 49 lncRNAs with BC, 48 lncRNAs with NO2, and 4 lncRNAs with PM2.5 (FDR < 0.05). These differential lncRNAs participated in dozens of pathways including cardiovascular signaling, epithelial cell proliferation, inflammation, and transforming growth factor. This trial for the first time profiled changes of human exosomal lncRNAs following air pollution. Our findings revealed multiple biological processes moderated by lncRNAs and provided epigenetic insights into cardiovascular effects of air pollution.

Hourly Ultrafine Particle Exposure and Acute Myocardial Infarction Onset: An Individual-Level Case-Crossover Study in Shanghai, China, 2015-2020.

Associations between ultrafine particles (UFPs) and hourly onset of acute myocardial infarction (AMI) have rarely been investigated. We aimed to evaluate the impacts of UFPs on AMI onset and the lag patterns. A time-stratified case-crossover study was performed among 20,867 AMI patients from 46 hospitals in Shanghai, China, between January 2015 and December 2020. Hourly data of AMI onset and number concentrations of nanoparticles of multiple size ranges below 0.10 µm (0.01-0.10, UFP/PNC0.01-0.10; 0.01-0.03, PNC0.01-0.03; 0.03-0.05, PNC0.03-0.05; and 0.05-0.10 µm, PNC0.05-0.10) were collected. Conditional logistic regressions were applied. Transient exposures to these nanoparticles were significantly associated with AMI onset, with almost linear exposure-response curves. These associations occurred immediately after exposure, lasted for approximately 6 h, and attenuated to be null thereafter. Each interquartile range increase in concentrations of total UFPs, PNC0.01-0.03, PNC0.03-0.05, and PNC0.05-0.10 during the preceding 0-6 h was associated with increments of 3.29, 2.08, 2.47, and 2.93% in AMI onset risk, respectively. The associations were stronger during warm season and at high temperatures and were robust after adjusting for criteria air pollutants. Our findings provide novel evidence that hourly UFP exposure is associated with immediate increase in AMI onset risk.