Targeting the PI3K/AKT signaling pathway with PNU120596 protects against LPS-induced acute lung injury.

OBJECTIVES: This study investigated the potential therapeutic benefits of PNU120596, a positive allosteric modulator of the α7 nicotinic acetylcholine receptor (α7nAChR), in mitigating acute lung injury (ALI) induced by lipopolysaccharide (LPS) in a mouse model. Specifically, we sought to examine the impact of PNU120596 on the PI3K/AKT signaling pathway in the context of ALI. METHODS: ALI was induced in mice by LPS administration, and the protective effects of PNU120596 were assessed. Lung injury, lung function, and the inflammatory response were evaluated. Additionally, the activation of the PI3K/AKT signaling pathway was examined, along with the levels of inflammatory factors and oxidative stress markers. KEY FINDINGS: PNU120596 significantly ameliorated LPS-induced lung injury, improved lung function, and reduced the inflammatory response in the mouse model of ALI. Furthermore, we observed that PNU120596 inhibited the activation of the PI3K/AKT signaling pathway, which was associated with decreased levels of inflammatory factors and oxidative stress markers. CONCLUSIONS: PNU120596 exhibits promising therapeutic potential for the treatment of acute lung injury, potentially by targeting the PI3K/AKT signaling pathway. These findings suggest that modulation of the α7 nicotinic acetylcholine receptor with PNU120596 may offer a viable strategy for the management of ALI, warranting further investigation and potential clinical applications.

Portable and simultaneous detection of four respiratory pathogens through a microfluidic LAMP and real-time fluorescence assay.

Respiratory pathogen infections are seasonally prevalent and are likely to cause co-infections or serial infections during peak periods of infection. Since they often cause similar symptoms, simultaneous and on-site detection of respiratory pathogens is essential for accurate diagnosis and efficient treatment of these infectious diseases. However, molecular diagnostic techniques for multiple pathogens in this field are lacking. Herein, we developed a microfluidic LAMP and real-time fluorescence assay for rapid detection of multiple respiratory pathogens using a ten-channel microfluidic chip with pathogen primers pre-embedded in the chip reaction well. The microfluidic chip provided a closed reaction environment, effectively preventing aerosol contamination and improving the accuracy of the detection results. Its corresponding detection instrument could automatically collect and display the fluorescence curve in real time, which was more conducive to the interpretation of results. The results showed that the developed method could specifically recognize the nucleic acid of influenza A(H1N1), Mycoplasma pneumoniae, respiratory syncytial virus type A, and SARS-CoV-2 with low detection limits of 104 copies per mL or 103 copies per mL. The test results on clinical samples demonstrated that the developed method has high sensitivity (92.00%) and high specificity (100.00%) and even has the capability to differentiate mixed-infection samples. With simple operation and high detection efficiency, the present portable and simultaneous detection assay could significantly improve the efficiency of on-site detection of respiratory infectious diseases and promote the accurate treatment, efficient prevention and control of the diseases.

A multifunctional evanescent wave biosensor for the universal assay of SARS-CoV-2 variants and affinity analysis of coronavirus spike protein-hACE2 interactions.

The conventional detection model of passive adaptation to pathogen mutations, i.e., developing assays using corresponding antibodies or nucleic acid probes, is difficult to address frequent outbreaks of emerging infectious diseases. In particular, adaptive mutations observed in coronaviruses, which increase the affinity of the spike protein with the human cellular receptor hACE2, play pivotal roles in the transmission and immune evasion of coronaviruses. Herein, we developed a multifunctional optical fiber evanescent wave biosensor for the universal assay of coronavirus and affinity analysis of the spike protein interacting with hACE2, namely, My-SPACE. By competitively binding with Cy5.5-hACE2 between coronavirus spike proteins in mobile buffer and that modified on optical fibers from the SARS-CoV-2 wild type, My-SPACE could automatically detect SARS-CoV-2 and its variants within 10 min. My-SPACE demonstrated greater sensitivity and faster results than ELISA for SARS-CoV-2 variants, achieving 100% specificity and 94.10% sensitivity in detecting the Omicron variant in 18 clinical samples. Moreover, the interaction between hACE2 and the coronavirus spike protein was accurately characterized across SARS-CoV-2 mutants, SARS-CoV and hCoV-NL63. The accuracy of the affinity determined by My-SPACE was verified by SPR. This approach enables preliminary assessment of the transmissibility and hazards of emerging coronaviruses. The sensor fibers of My-SPACE can be reused more than 40 times, and the device is compact and easy to use; moreover, it is available as a rapid and cost-effective on-site detection tool adapted to coronavirus variability and as an effective assessment platform for early warning of coronavirus transmission risk.

Functional properties, structural characteristics, and anti-complementary activities of two degraded polysaccharides from strawberry fruits.

Two low-molecular-weight polysaccharides (DPSP50 and DPSP70) were obtained using hydrogen peroxide-vitamin C (H2O2-Vc) treatment at 50 °C and 70 °C, respectively. Both DPSP50 and DPSP70 comprised the same six monosaccharides in different ratios, and their molecular weights (Mws) were 640 kDa and 346 kDa, respectively. Functional properties analyses demonstrated that DPSP50 and DPSP70 each had an excellent water holding capacity, oil absorption capacity, and emulsion properties, as well as shear-thinning characteristics and viscoelastic properties. Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopic assays confirmed the existence of α-, ß-pyranose rings and the same six sugar residues in DPSP50 and DPSP70. The results of Congo red test, scanning electron microscopy (SEM), and X-ray diffraction (XRD) demonstrated that DPSP50 and DPSP70 did not contain triple-helix conformations, but were amorphous aggregates with flake-like shape and rough surface. Additionally, both DPSP50 and DPSP70 showed strong anti-complementary activities through the classical pathway and the alternative pathway. The results support the potential utility of these degraded polysaccharides from strawberry fruits in functional foods and medicines.

Insights into anthropogenic impact on atmospheric inorganic aerosols in the largest city of the Tibetan Plateau through multidimensional isotope analysis.

Particulate inorganic nitrogen aerosols (PIN) significantly influence air pollution and pose health risks worldwide. Despite extensive observations on ammonium (pNH4+) and nitrate (pNO3-) aerosols in various regions, their key sources and mechanisms in the Tibetan Plateau remain poorly understood. To bridge this gap, this study conducted a sampling campaign in Lhasa, the Tibetan Plateau's largest city, with a focus on analyzing the multiple isotopic signatures (δ15N, ∆17O). These isotopes were integrated into a Bayesian mixing model to quantify the source contributions and oxidation pathways for pNH4+ and pNO3-. Our results showed that traffic was the largest contributor to pNH4+ (31.8 %), followed by livestock (25.4 %), waste (21.8 %), and fertilizer (21.0 %), underscoring the impact of vehicular emissions on urban NH3 levels in Lhasa. For pNO3-, coal combustion emerged as the largest contributor (27.3 %), succeeded by biomass burning (26.3 %), traffic emission (25.3 %), and soil emission (21.1 %). In addition, the ∆17O-based model indicated a dominant role of NO2 + OH (52.9 %) in pNO3- production in Lhasa, which was similar to previous observations. However, it should be noted that the NO3 + volatile organic component (VOC) contributed up to 18.5 % to pNO3- production, which was four times higher than the Tibetan Plateau's background regions. Taken together, the multidimensional isotope analysis performed in this study elucidates the pronounced influence of anthropogenic activities on PIN in the atmospheric environment of Lhasa.

Characterization of ammonia emissions from light-duty gasoline vehicles based on real-world driving and dynamometer measurements.

Ammonia (NH3) contributes significantly to the formation of particulate matter, and vehicles represent a major source of NH3 in urban areas. However, there remains a lack of comprehensive understanding regarding the emission characteristics of NH3 from vehicles. This study conducted real-world driving emission (RDE) measurements and dynamometer measurements on 33 light-duty gasoline vehicles (LDGVs) to investigate their emission characteristics and impact factors. The tested vehicles include China 3 to China 6 emission standards. The results show that the average NH3 emission factors of LDGVs decreased by >80 % from China 3 to China 6 emission standards. The results obtained from dynamometer measurements reveal that independent from other conventional pollutants (such as HCHO and NOx), NH3 emissions do not exhibit significant emission peaks during the hot- or cold-start phase. The RDE measurement covers a more comprehensive range of the vehicle's real-world driving conditions, resulting in higher NH3 emission factors compared with dynamometer measurements. The analysis of RDE measurements revealed that NH3 emissions are influenced by vehicle speeds and accelerations. Acceleration processes contribute approximately 50 % of total NH3 emissions over a driving period. Finally, using real driving speed, acceleration, and road gradient as input parameters, an NH3 emission rate model based on vehicle specific power was developed. This emission rate model enables a more precise reflection of LDGVs' NH3 emissions of LDGVs across diverse driving conditions and provides valuable data support for high-resolution inventories of vehicle NH3 emissions.

Atherosclerosis, gut microbiome, and exercise in a meta-omics perspective: a literature review.

Background: Cardiovascular diseases are the leading cause of death worldwide, significantly impacting public health. Atherosclerotic cardiovascular diseases account for the majority of these deaths, with atherosclerosis marking the initial and most critical phase of their pathophysiological progression. There is a complex relationship between atherosclerosis, the gut microbiome's composition and function, and the potential mediating role of exercise. The adaptability of the gut microbiome and the feasibility of exercise interventions present novel opportunities for therapeutic and preventative approaches. Methodology: We conducted a comprehensive literature review using professional databases such as PubMed and Web of Science. This review focuses on the application of meta-omics techniques, particularly metagenomics and metabolomics, in studying the effects of exercise interventions on the gut microbiome and atherosclerosis. Results: Meta-omics technologies offer unparalleled capabilities to explore the intricate connections between exercise, the microbiome, the metabolome, and cardiometabolic health. This review highlights the advancements in metagenomics and metabolomics, their applications in research, and examines how exercise influences the gut microbiome. We delve into the mechanisms connecting these elements from a metabolic perspective. Metagenomics provides insight into changes in microbial strains post-exercise, while metabolomics sheds light on the shifts in metabolites. Together, these approaches offer a comprehensive understanding of how exercise impacts atherosclerosis through specific mechanisms. Conclusions: Exercise significantly influences atherosclerosis, with the gut microbiome serving as a critical intermediary. Meta-omics technology holds substantial promise for investigating the gut microbiome; however, its methodologies require further refinement. Additionally, there is a pressing need for more extensive cohort studies to enhance our comprehension of the connection among these element.

Severe photochemical pollution formation associated with strong HONO emissions from dew and guttation evaporation.

The unknown daytime source of HONO has been extensively investigated due to unexplained atmospheric oxidation capacity and current modelling bias, especially during cold seasons. In this study, abrupt morning increases in atmospheric HONO at a rural site in the North China Plain (NCP) were observed almost on daily basis, which were closely linked to simultaneous rises in atmospheric water vapor content and NH3 concentrations. Dew and guttation water formation was frequently observed on wheat leaves, from which water samples were taken and chemically analyzed for the first time. Results confirmed that such natural processes likely governed the daily nighttime deposition and daytime release of HONO and NH3, which have not been considered in the numerous HONO budget studies investigating its large missing daytime source in the NCP. The dissolved HONO and NH3 in leaf surface water droplets reached 1.4 and 23 mg L-1 during the morning on average, resulting in averaged atmospheric HONO and NH3 increases of 0.89 ± 0.61 and 43.7 ± 29.3 ppb during morning hours, with relative increases of 186 ± 212 % and 233 ± 252 %, respectively. The high atmospheric oxidation capacity contained within HONO was stored in near surface liquid water (such as dew, guttation and soil surface water) during nighttime, which prevented its atmospheric dispersion after sunset and protected it from photodissociation during early morning hours. HONO was released in a blast during later hours with stronger solar radiation, which triggered and then accelerated daytime photochemistry through the rapid photolysis of HONO and subsequent OH production, especially under high RH conditions, forming severe secondary gaseous and particulate pollution. Results of this study demonstrate that global ecosystems might play significant roles in atmospheric photochemistry through nighttime dew formation and guttation processes.

An increase in a long noncoding RNA ANRIL in peripheral plasma is an indicator of stable angina.

INTRODUCTION: Stable angina develops during physical activity or stress, and it is typically an aspect of Coronary Heart Disease (CHD) that can lead to arrhythmia, heart failure and even sudden death. ANRIL, an Antisense Noncoding RNA gene in the INK4 Locus, is associated with multiple disorders including CHD; however, expressional levels of ANRIL in between patients with stable angina and myocardial infarction, one of the acute coronary syndrome, have not been clarified yet. METHODS: The authors enrolled 62 patients with myocardial infarction and 59 with stable angina before primary percutaneous coronary intervention, as well as 48 healthy volunteers. Their peripheral blood was collected for analysis of ANRIL and cardiac troponin I, a traditional diagnostic index of CHD by real-time PCR. RESULTS: The data showed that ANRIL is a better diagnostic indicator than cardiac troponin I in patients with stable angina and that the levels of ANRIL are higher in patients with stable angina than those with the myocardial infarction. DISCUSSION: The levels of ANRIL in peripheral plasma could be used as a good biomarker for stable angina.

Speeding lectures to make time for retrieval practice: Can we improve the efficiency of interpolated testing?

Testing is increasingly recognized as an important tool in learning. One form of testing often used in lectures, particularly recorded lectures, is interpolated testing wherein tests are interspersed throughout the lecture. Like testing in general, interpolated testing appears to benefit performance on content tests among other outcome variables (e.g., mind wandering). While beneficial, adding testing also increases instructional time. In the present investigation, we examine one strategy to mitigate the costs of this increase in instructional time in the context of recorded lectures. Specifically, we examine the interaction between increasing the playback speed of a recorded lecture and adding interpolated tests. Results demonstrate that the conjoint effects of these two interventions are largely additive. That is, the benefit of testing was as robust in a normal speed lecture and a lecture that was sped up 1.5×. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Leverage of nuclease-deficient CasX for preventing pathological angiogenesis.

Gene editing with a CRISPR/Cas system is a novel potential strategy for treating human diseases. Pharmacological inhibition of phosphoinositide 3-kinase (PI3K) δ suppresses retinal angiogenesis in a mouse model of oxygen-induced retinopathy. Here we show that an innovative system of adeno-associated virus (AAV)-mediated CRISPR/nuclease-deficient (d)CasX fused with the Krueppel-associated box (KRAB) domain is leveraged to block (81.2% ± 6.5%) in vitro expression of p110δ, the catalytic subunit of PI3Kδ, encoded by Pik3cd. This CRISPR/dCasX-KRAB (4, 269 bp) system is small enough to be fit into a single AAV vector. We then document that recombinant AAV serotype (rAAV)1 efficiently transduces vascular endothelial cells from pathologic retinal vessels, which show high expression of p110δ; furthermore, we demonstrate that blockade of retinal p110δ expression by intravitreally injected rAAV1-CRISPR/dCasX-KRAB targeting the Pik3cd promoter prevents (32.1% ± 5.3%) retinal p110δ expression as well as pathological retinal angiogenesis in a mouse model of oxygen-induced retinopathy. These data establish a strong foundation for treating pathological angiogenesis by AAV-mediated CRISPR interference with p110δ expression.

METTL3-mediated m6A modification of pri-miR-148a-3p affects prostate cancer progression by regulating TXNIP.

OBJECTIVE: Prostate cancer (PCa) severely affects men's health worldwide. The mechanism of methyltransferase-like 3 (METTL3) in affecting PCa development by regulating miR-148a-3p expression via N6-methyladenosine (m6A) modification was investigated. METHODS: METTL3, miR-148a-3p, and thioredoxin interacting protein (TXNIP) levels were determined using RT-qPCR and Western blotting. The m6A modification level of miR-148a-3p was observed by Me-RIP assay. Bioinformatics website predicted miR-148a-3p and TXNIP levels in PCa and their correlation, and the binding site between them was verified by dual-luciferase assay. The proliferation, migration, invasion, and apoptosis of PCa cells were examined by CCK-8 assay, Transwell assay, and flow cytometry. A transplanted tumor model was established in nude mice to observe the tumor growth ability, followed by determination of TXNIP levels in tumor tissues by immunohistochemistry. RESULTS: METTL3 interference restrained the proliferation, migration, and invasion and promoted apoptosis of PCa cells. METTL3 up-regulated miR-148a-3p by promoting the m6A modification of pri-miR-148a-3p in PCa cells. miR-148a-3p overexpression nullified the inhibitory actions of silencing METTL3 on PCa cell growth. miR-148a-3p facilitated PCa cell growth by silencing TXNIP. METTL3 interference inhibited tumor growth by down-regulating miR-148a-3p and up-regulating TXNIP. CONCLUSION: METTL3 promoted miR-148a-3p by mediating the m6A modification of pri-miR-148a-3p, thereby targeting TXNIP, interfering with METTL3 to inhibit the proliferation, migration and invasion of PCa cells, promote apoptosis, and inhibit tumor growth in nude mice.

Sources, size-resolved deposition in the human respiratory tract and health risks of submicron black carbon in urban atmosphere in Pearl River Delta, China.

Black carbon (BC) has a significantly negative impact on air quality, climate and human health. Here we investigated the sources and health effects of BC in urban area of the Pearl River Delta (PRD) based on online data measured by Aerodyne soot particle high-resolution time of flight aerosol mass spectrometer (SP-AMS). In urban PRD, BC particles mainly came from vehicle emissions especially heavy-duty vehicle exhausts (contributing 42.9 % of total BC mass concentration), long-range transport (27.6 %), and aged biomass combustion emissions (22.3 %). Indicated by source analysis using simultaneous aethalometer data, BC associated with local secondary oxidation and transport may also be originated from fossil fuel combustion, especially traffic sources in urban and surrounding areas. Size-resolved BC mass concentrations provided by SP-AMS, for the first time to our best knowledge, were used to calculate BC deposition in the human respiratory tract (HRT) of different populations (children, adults, and the elderly) by the Multiple-Path Particle Dosimetry (MPPD) model. We found that submicron BC was deposited more in the pulmonary (P) region (49.0-53.2 % of the total BC deposition dose), while less in the tracheobronchial (TB, 35.6-37.2 %) and head (HA, 11.2-13.8 %) regions. Adults suffered the highest BC deposition (1.19 µg day-1) than the elderly (1.09 µg day-1) and children (0.25 µg day-1). BC deposition rate was greater at night (especially 18:00-24:00) than during the daytime. The maximum deposition in the HRT was found for BC particles around 100 nm, mainly in deeper respiratory regions (TB and P), which may cause more serious health effects. Adults and the elderly group are confronted with the notable carcinogenic risk of BC in the urban PRD, up to 29 times higher than the threshold. Our study emphasizes the need to control BC pollution in the urban area, especially nighttime vehicle emissions.

Quantitative evaluation for the sources and aging processes of organic aerosols in urban Guangzhou: Insights from a comprehensive method of dual­carbon isotopes and macro tracers.

Organic carbon aerosol (OC) is a pivotal component of PM2.5 in the atmospheric environment, yet its emission sources and atmospheric behaviors remain poorly constrained in many regions. In this study, a comprehensive method based on the combination of dual­carbon isotopes (13C and 14C) and macro tracers was employed in the PRDAIO campaign performed in the megacity of Guangzhou, China. The 14C analysis showed that 60 ± 9 % of OC during the sampling campaign was associated with non-fossil sources such as biomass burning activities and biogenic emissions. It should be noted that this non-fossil contribution in OC would significantly decrease when the air masses came from the eastern cities. Overall, we found that non-fossil secondary OC (SOCNF) was the largest contributor (39 ± 10 %) to OC, followed by fossil secondary OC (SOCFF: 26 ± 5 %), fossil primary OC (POCFF: 14 ± 6 %), biomass burning OC (OCbb: 13 ± 6 %) and cooking OC (OCck: 8 ± 5 %). Also, we established the dynamic variation of 13C as a function of aged OC and the volatile organic compounds (VOCs) oxidized OC to explore the impact of aging processes on OC. Our pilot results showed that atmospheric aging was highly sensitive to the emission sources of seed OC particles, with a higher aging degree (86 ± 4 %) when more non-fossil OC particles were transferred from the northern PRD.

Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics.

N6-methyladenosine (m6A) is a representative of RNA methylation modification, which plays a critical role in the epigenetic modification process of regulating human diseases. As a key protein for m6A, methyltransferase 3 (METTL3) had been identified to be associated with a variety of diseases. The publications related to METTL3 were searched in the Web of Science Core Collection from the earliest mention to July 1st, 2022. Being screened by the retrieval strategy, a total of 1,738 articles related to METTL3 were retrieved. Much of our work focused on collecting the data of annual publication outputs, high-yielding countries/regions/authors, keywords, citations, and journals frequently published for qualitative and quantitative analysis. We found that diseases with high correlations to METTL3 not only included various known cancers but also obesity and atherosclerosis. In addition to m6A-related enzyme molecules, the most frequent key molecules were MYC proto-oncogene (C-MYC), Enhancer of zeste homolog 2 (EZH2), and Phosphatase and tensin homolog deleted on chromosome 10 (PTEN). METTL3 and methyltransferase 14 (METTL14) may function through opposite regulatory pathways in the same disease. "Leukemia," "Liver Cancer," and "Glioblastoma" were speculated to be potential hotspots in METTL3 related study. The number of publications had significantly surged year by year, demonstrating the growing importance of the research on epigenetic modification in the pathology of various diseases.

Global Trends of Lipid Metabolism Research in Epigenetics Field: A Bibliometric Analysis from 2012-2021.

Most common diseases are characterized by metabolic changes, among which lipid metabolism is a hotspot. Numerous studies have demonstrated a strong correlation between epigenetics and lipid metabolism. This study of publications on the epigenetics of lipid metabolism searched in the Web of Science Core Collection from 2012 to 2022, and a total of 3685 publications were retrieved. Much of our work focused on collecting the data of annual outputs, high-yielding countries and authors, vital journals, keywords and citations for qualitative and quantitative analysis. In the past decade, the overall number of publications has shown an upward trend. China (1382, 26.69%), the United States (1049, 20.26%) and Italy (206, 3.98%) were the main contributors of outputs. The Chinese Academy of Sciences and Yale University were significant potential cooperation institutions. Articles were mainly published in the "International Journal of Molecular Sciences". In addition to typical liver-related diseases, "ferroptosis", "diabetes" and "atherosclerosis" were identified as potential research topics. "NF-κB" and "oxidative stress" were referred to frequently in publications. METTL3 and ALKBH5 were the most discussed m6A-related enzymes in 2022. Our study revealed research hotspots and new trends in the epigenetics of lipid metabolism, hoping to provide significant information and inspiration for researchers to further explore new directions.

Characterizing Operating Condition-Based Formaldehyde Emissions of Light-Duty Diesel Trucks in China Using a PEMS-HCHO System.

Formaldehyde (HCHO) plays a critical role in atmospheric photochemistry and public health. While existing studies have suggested that vehicular exhaust is an important source of HCHO, the operating condition-based diesel truck HCHO emission measurements remain severely limited due to the limited temporal resolution and accuracy of measurement techniques. In this study, we characterized the second-by-second HCHO emissions from 29 light-duty diesel trucks (LDDTs) in China over dynamometer and real-world driving tests using a portable online HCHO emission measurement system (PEMS-HCHO), considering various operating conditions. Our results suggested that the HCHO emissions from LDDTs might be underestimated by the widely used offline DNPH-HPLC method. The HCHO emissions at a 200 s cold start from China V LDDT can be up to 50 mg/start. Different driving conditions over dynamometer and real-world driving tests led to a 2-4 times difference in the HCHO emission factors (EFs). Under real-world hot-running conditions, the HCHO EFs of China III, IV, V, and VI LDDTs were 43.5 ± 35.7, 10.6 ± 14.2, 8.8 ± 5.1, and 3.2 ± 1.2 mg/km, respectively, which significantly exceeded the latest California low emission vehicle III HCHO emission standard (2.5 mg/km). These findings highlighted the significant impact of vehicle operating conditions on HCHO emissions and the urgency of regulating HCHO emissions from LDDTs in China.

Vertical measurements of stable nitrogen and oxygen isotope composition of fine particulate nitrate aerosol in Guangzhou city: Source apportionment and oxidation pathway.

Nowadays, the emission source and formation mechanism of fine particulate nitrate (pNO3-) in China are mired in controversy. In this study, the stable nitrogen isotope (δ15N-NO3-) and triple oxygen isotope (Δ17O-NO3-) were determined for the pNO3- samples collected at three heights under different atmospheric oxidation capacity (AOC) (Ox = O3 + NO2: 107 ± 29 µg m-3 at ground, 102 ± 28 µg m-3 at 118 m, 122 ± 23 µg m-3 at 488 m) conditions during the sampling period based on the Canton Tower, Guangzhou, China. The Bayesian mixing model showed that coal combustion was the largest contributor to pNO3- in this city, followed by biomass burning, vehicle exhaust, and soil emission. Interestingly, we found that vertical NOx and pNO3- concentrations displayed an opposite pattern owing to the different formation mechanisms among heights. The average contributions of oxidation pathways for (NO2 + OH, P1), (NO3 + DMS/HC, P2), and (N2O5 + H2O, P3) were 61 %, 12 %, and 27 % at the ground, respectively, and these values would vary greatly among heights. These results implied that both AOC and NOx loading played an important role in pNO3- production. The pNO3- displayed a positive correlation with NOx (r = 0.95) with an enhanced contribution of the P1 pathway under the relatively high AOC condition. However, pNO3- has a negative correlation with NOx (r = -0.99) with a rise of heterogeneous reaction (P2 and P3) under the relatively low AOC condition. Therefore, the current emission control strategy for air pollution in China needs to consider the AOC conditions among regions to effectively mitigate particulate air pollution.

The Lnc-RNA APPAT Suppresses Human Aortic Smooth Muscle Cell Proliferation and Migration by Interacting With MiR-647 and FGF5 in Atherosclerosis.

PURPOSE: LncRNA-Atherosclerotic plaque pathogenesis-associated transcript (APPAT) could be detected in circulating blood and has been demonstrated to correlate with the development of atherosclerosis in our previous work. It could be a potential noninvasive biomarker for earlier diagnoses of clinical cardiovascular disease. Moreover, the expression of miR-647 increased in ox-LDL-treated vascular smooth muscle cells and peripheral blood of patients with coronary heart disease. A negative correlation between APPAT and miR-647 was confirmed, and FGF5 was screened as molecular target of miR-647. However, it is largely unclear how APPAT, miR-647, and FGF5 interact and function in disease development. Here, we aim to explore the underlying molecular mechanism in this progression. MATERIALS AND METHODS: APPAT, miR-647, and FGF5 expression levels were detected by quantitative reverse transcription polymerase chain reaction; cell proliferation was detected by EdU incorporation assay; cell migration was detected by wound-healing assay; the molecular interaction of APPAT/FGF5 with miR-647 was verified by dual-luciferase reporter assay; the western blot was performed to determine the gene expression at protein levels; subcellular localizations of APPAT and miR-647 were observed by fluorescence in situ hybridization; cytosolic and nucleus fractionation assay was performed to further detect the distribution of miR-647. RESULTS: APPAT and miR-647 have inverse effects on human aortic smooth muscle cells' (HASMCs) proliferation and migration. APPAT negatively regulated the cell activity, whereas miR-647 did it in a positive way (p<0.05). Three pairs of molecular interplay were found: mutual negative regulation between APPAT and miR-647, APPAT downregulated FGF5, miR-647 regulation on FGF5 (p<0.05). Subcellular location assay confirmed the molecular interaction of APPAT and miR-647. CONCLUSIONS: APPAT could suppress the migration and proliferation of ox-LDL-treated HASMCs via interacting with miR-647 and FGF5. We revealed a nontypical competing endogenous RNA mechanism of long noncoding RNA in the progression of atherosclerosis.

Optimization of ultrasound-assisted aqueous two-phase extraction of polysaccharides from seabuckthorn fruits using response methodology, physicochemical characterization and bioactivities.

BACKGROUND: Seabuckthorn fruits contains many active subtances, among them, the seabuckthorn polysaccharide is one of the main active ingredients, and exhibits diverse bioactivities. The extraction of polysaccharides from seabuckthorn fruits is the most important step for their wide applications. Ultrasound-assisted aqueous two-phase extraction (UA-ATPE) is a promising green method for extracting polysaccharides. Additionally, physicochemical characterization and antioxidant activities can evaluate the potential functions and applications in the food and medicine industries. RESULTS: Based on the single-factor experiments, 20.70% (w/w) ammonium sulfate ((NH4 )2 SO4 ) and 27.56% (w/w) ethanol were determined as the suitable composition for aqueous two-phase. The optimum conditions of UA-ATPE obtained by response surface methodology were as follows: ultrasonic power (390 W), extraction time (41 min), liquid-to-material ratio (72: 1 mL/g), and the total yield of the polysaccharides reached 34.14 ± 0.10%, The molecular weights of the purified upper-phase seabuckthorn polysaccharide (PUSP) and the purified lower-phase seabuckthorn polysaccharide (PLSP) were 65 525 and 26 776 Da, respectively. PUSP and PLSP contained the same six monosaccharides (galacturonic acid, rhamnose, xylose, mannose, glucose and galactose), but with different molar ratios. Furthermore, PUSP and PLSP displayed certain viscoelastic property, had no triple helical structure, possessed different thermal stability, surface morphology and conformation in aqueous solution. PUSP and PLSP displayed strong antioxidant properties by the assays of scavenging ability of ABTS+ ·, the protection of DNA damage and erythrocyte hemolysis. CONCLUSION: UA-ATPE significantly increased the yield of seabuckthorn polysaccharides. PUSP and PLSP were different in many aspects, such as molar ratio, surface shape and antioxidant activities. Seabuckthornpolysaccharides possess great potential in medicine and functional foods. © 2022 Society of Chemical Industry.