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Water-insoluble organic carbon (WIOC) constitutes a substantial portion of organic carbon (OC) and contributes significantly to light absorption by brown carbon (BrC), playing pivotal roles in climate forcing. China is a hotspot region with high levels of OC and BrC, but information regarding the sources and light-absorbing properties of WIOC on a national scale remains scarce. Here, we investigated the light-absorbing properties and sources of WIOC in 10 representative urban cities in China. On average, WIOC made up 33.4 ± 7.66 % and 40.5 ± 9.73 % of concentrations and light absorption at 365 nm (Abs365) of extractable OC (EX-OC), which includes relatively hydrophobic OC (WIOC and humic-like substances, HULIS-C) and hydrophilic OC (non-humic-like substances, non-HULIS-C). The mass absorption efficiency of WIOC at 365 nm (MAE365) was (1.59 ± 0.55 m2 (g C)−1) comparable to that of HULIS (1.54 ± 0.57 m2 (g C)−1) but significantly higher than non-HULIS (0.71 ± 0.28 m2 (g C)−1), indicating that hydrophobic OC possesses a stronger light-absorbing capacity than hydrophilic OC. Biomass burning (31.0 %) and coal combustion (31.1 %) were the dominant sources of WIOC, with coal combustion sources exhibiting the strongest light-absorbing capacity. Moreover, employing the simple forcing efficiency (SFE300–700 nm) method, we observed that WIOC exhibited the highest SFE300–700 nm (6.57 ± 5.37 W g−1) among the EX-OC fractions. The radiative forcing of EX-OC was predominantly contributed by hydrophobic OC (WIOC – 39.4 ± 15.5 % and HULIS – 39.5 ± 12.1 %). Considering the aromaticity, sources, and atmospheric processes of different carbonaceous components, we propose a light-absorbing carbonaceous continuum, revealing that components enriched with fossil sources tend to possess stronger light-absorbing capacity, higher aromatic levels, increased molecular weights, and greater recalcitrance in the atmosphere. Reducing fossil fuel emissions emerges as an effective means of mitigating both gaseous (CO2) and particulate light-absorbing carbonaceous warming components.

Abstract We assessed the causal relation of four glycemic traits and type 2 diabetes liability with 167 metabolites using Mendelian randomization with various sensitivity analyses and a reverse Mendelian randomization analysis. We extracted instruments for fasting glucose, 2-h glucose, fasting insulin, and glycated hemoglobin from the Meta-Analyses of Glucose and Insulin-related traits Consortium (n = 200,622), and those for type 2 diabetes liability from a meta-analysis of multiple cohorts (148,726 cases, 965,732 controls) in Europeans. Outcome data were from summary statistics of 167 metabolites from the UK Biobank (n = 115,078). Fasting glucose and 2-h glucose were not associated with any metabolite. Higher glycated hemoglobin was associated with higher free cholesterol in small low-density lipoprotein. Type 2 diabetes liability and fasting insulin were inversely associated with apolipoprotein A1, total cholines, lipoprotein subfractions in high-density-lipoprotein and intermediate-density lipoproteins, and positively associated with aromatic amino acids. These findings indicate hyperglycemia-independent patterns and highlight the role of insulin in type 2 diabetes development. Further studies should evaluate these glycemic traits in type 2 diabetes diagnosis and clinical management.

Organosulfur compounds (OrgSs), especially organosulfates, have been widely reported to be present in large quantities in particulate organic matter found in various atmospheric environments. Despite hundreds of organosulfates and their formation mechanisms being previously identified, a large fraction of OrgSs remain unexplained at the molecular level, and a better understanding of their formation pathways and critical environmental parameters is required to explain the variations in their concentrations. In this study, the abundance and molecular composition of OrgSs in fine particulate samples collected in Guangzhou were reported. The results revealed that the ratio of the annual average mass of organic sulfur to total particulate sulfur was 33 ± 12 %, and organic sulfur had positive correlations with SO2 (r=0.37, p) and oxidant (NOx + O3, r=0.40, p). A Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analysis revealed that more than 80 % of the sulfur-containing formulas detected in the samples had the elemental composition of o/(4s+3n)≥1, indicating that they were largely in the form of oxidized organosulfates or nitrooxy organosulfates. Many OrgSs that were previously tentatively identified as having biogenic or anthropogenic origins were also present in freshly emitted aerosols derived from combustion sources. The results indicated that the formation of OrgSs through an epoxide intermediate pathway could account for up to 46 % of OrgSs from an upper bound estimation, and the oxidant levels could explain 20 % of the variation in the mass of organic sulfur. The analysis of our large dataset of FT-ICR MS results suggested that relative humidity, oxidation of biogenic volatile organic compounds via ozonolysis, and NOx-related nitrooxy organosulfate formation were the major reasons for the molecular variation of OrgSs, possibly highlighting the importance of the acid-catalyzed ring-opening of epoxides, oxidation processes, and heterogeneous reactions involving either the uptake of SO2 or the heterogeneous oxidation of particulate organosulfates into additional unrecognized OrgSs.

Twitter has been an important platform for people to discuss and share health-related information. It provides a massive amount of data for real-time monitoring of infectious diseases (such as COVID-19) and freeing disease-prevention organizations from the tedious labor involved in public health surveillance. Personal health mention (PHM) detection is one of the critical methods to keep up-to-date on an epidemic’s condition; it attempts to identify a person’s health condition based on online text information. This paper explores PHM identification for COVID-19 through Twitter. We built a COVID-19 PHM data set containing tweets annotated with four types of COVID-19-related health conditions. A masked attention model was devised to classify the tweets as self-mention, other-mention, awareness, and non-health. We obtained promising results on the PHM identification task. The classification results facilitate timely health monitoring and surveillance for digital epidemiology. We also evaluate how the attention mechanism and training method affect the model’s predictive performance.

Chromophores represent an important portion of light-absorbing species, i.e., brown carbon. Yet knowledge of what and how chromophores contribute to aerosol light absorption is still sparse. To address this problem, we examined soluble independent chromophores in a set of year-round aerosol samples from Bangkok. The water-soluble fluorescent chromophores identified via excitation–emission matrix (EEM) spectroscopy and follow-up parallel factor analysis could be mainly assigned as humic-like substances and protein-like substances, which differed in their EEM pattern from that of the methanol-soluble fraction. The emission wavelength of fluorescent chromophores in environmental samples tended to increase compared with that of the primary combustion emission, which could be attributed to secondary formation or the aging process. Fluorescent indices inferred that these light-absorbing chromophores were not significantly humified and comprised a mixture of organic matter of terrestrial and microbial origin, which exhibited a different characteristic from primary biomass burning and coal-combustion results. A multiple linear regression analysis revealed that larger fluorescent chromophores that were oxygen-rich and highly aromatic with high molecular weights were the key contributors of light absorption, preferably at longer emission wavelengths (λmax⁡ > 500 nm). Positive matrix factorization analysis further suggested that up to 50 % of these responsible chromophores originated from biomass burning emissions.

Brown carbon (BrC) plays an essential impact on radiative forcing due to its ability to absorb sunlight. In this study, the optical properties and molecular characteristics of water-soluble and methanol-soluble organic carbon (OC; MSOC) emitted from the simulated combustion of biomass and coal fuels and vehicle emissions were investigated using ultraviolet–visible (UV–vis) spectroscopy, excitation–emission matrix (EEM) spectroscopy, and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) coupled with electrospray ionization (ESI). The results showed that these smoke aerosol samples from biomass burning (BB) and coal combustion (CC) had a higher mass absorption efficiency at 365 nm (MAE365) than vehicle emission samples. A stronger MAE365 value was also found in MSOC than water-soluble organic carbon (WSOC), indicating low polar compounds would possess a higher light absorption capacity. Parallel factor (PARAFAC) analysis identified six types of fluorophores (P1–6) in WSOC including two humic-like substances (HULIS-1) (P1 and P6), three protein-like substances (PLOM) (P2, P3, and P5), and one undefined substance (P4). HULIS-1 was mainly from aging vehicle exhaust particles; P2 was only abundant in BB aerosols; P3 was ubiquitous in all tested aerosols; P4 was abundant in fossil burning aerosols; and P5 was more intense in fresh vehicle exhaust particles. The MSOC chromophores (six components; C1–6) exhibited consistent characteristics with WSOC, suggesting the method could be used to indicate the origins of chromophores. FT-ICR mass spectra showed that CHO and CHON were the most abundant components of WSOC, but S-containing compounds appeared in a higher abundance in CC aerosols and vehicle emissions than BB aerosols, while considerably fewer S-containing compounds largely with CHO and CHON were detected in MSOC. The unique formulas of different sources in the van Krevelen (VK) diagram presented different molecular distributions. To be specific, BB aerosols with largely CHO and CHON had a medium H ∕ C and low O ∕ C ratio, while CC aerosols and vehicle emissions largely with S-containing compounds had an opposite H ∕ C and O ∕ C ratio. Moreover, the light absorption capacity of WSOC and MSOC was positively associated with the unsaturation degree and molecular weight in the source aerosols. The above results are potentially applicable to further studies on the EEM-based or molecular-characteristic-based source apportionment of chromophores in atmospheric aerosols.

The molecular compositions of polar organic compounds (POCs) in particles emitted from various vessels and excavators were characterized using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), and possible molecular structures of POCs were proposed. POCs were extracted with purified water and sorted by elemental composition into three groups: CHO, CHON, and S-containing compounds (CHONS and CHOS). The results show the following. (i) CHO (accounting for 49 % of total POCs in terms of peak response) was the most abundant group for all tested off-road engines, followed by CHON (33 %) and CHOS (35 %) for diesel and HFO (heavy-fuel-oil)-fueled off-road engines. (ii) The abundance and structure of the CHON group in water extracts were different in terms of engine type and load. The relative peak response of CHON was the highest for excavator emissions in working mode, compared to the idling and moving modes. Furthermore, dinitrophenol and methyl dinitrophenol were potentially the most abundant emission species for high-rated speed excavators, while nitronaphthol and methyl nitronaphthol were more important for low-rated speed vessels. (iii) The composition and structure of the S-containing compounds were directly influenced by fuel oil characteristics (sulfur content and aromatic ring), with more condensed aromatic rings in the S-containing compounds proposed in HFO-fueled vessel emissions. More abundant aliphatic chains were inferred in diesel equipment emissions. Overall, higher fractions of condensed hydrocarbons and aromatic rings in POCs emitted from vessels using HFO cause strong optical absorption capacity. Different structures in POCs could provide a direction for qualitative and quantitative analysis of organic compounds as tracers to distinguish these emissions from diesel or HFO-fueled off-road engines.

Estimating exposure to fine Particulate Matter (PM2.5) requires surface with high spatial resolution. Aerosol optical depth (AOD) is one of MODIS products, being used to monitor PM2.5 concentration on ground level indirectly. In this research, AOD was derived in fine spatial resolution of 1×1 Km by utilizing an algorithm developed in which local aerosol models and conditions were took into account. Afterwards, due to spatial varying the relation between AOD-PM2.5, a regional scale geographically weighted regression model (GWR) was developed to derive daily seamless surface concentration of PM2.5 over Beijing, Tianjin and Hebei. For this purpose , various combinations of explanatory variables were investigated in the base of data availability, among which the best one includes AOD, PBL height, mean value of RH in boundary layer, mean value of temperature in boundary layer, wind speed and pressure was selected for the proposed GWR model over study area. The results show that, our model produces surface concentration of PM2.5 with annual RMSE of 18.6μg/m3. Besides, the feasibility of our model in estimating air pollution level was also assessed and high compatibility between model and ground monitoring was observed, which demonstrates the capability of the MODIS AOD and proposed model to estimate ground level PM2.5.

Brown carbon (BrC) draws increasing attention due to its effects on climate and other environmental factors. In China, household coal burned for heating and cooking purposes releases huge amounts of carbonaceous particles every year; however, BrC emissions have rarely been estimated in a persuasive manner due to the unavailable emission characteristics. Here, seven coals jointly covering geological maturity from low to high were burned in four typical stoves as both chunk and briquette styles. The optical integrating sphere (IS) method was applied to measure the emission factors (EFs) of BrC and black carbon (BC) via an iterative process using the different spectral dependence of light absorption for BrC and BC and using humic acid sodium salt (HASS) and carbon black (CarB) as reference materials. The following results have been found: (i) the average EFs of BrC for anthracite coal chunks and briquettes are 1.08 ± 0.80 and 1.52 ± 0.16 g kg−1, respectively, and those for bituminous coal chunks and briquettes are 8.59 ± 2.70 and 4.01 ± 2.19 g kg−1, respectively, reflecting a more significant decline in BrC EFs for bituminous coals than for anthracites due to briquetting. (ii) The BrC EF peaks at the middle of coal's geological maturity, displaying a bell-shaped curve between EF and volatile matter (Vdaf). (iii) The calculated BrC emissions from China's residential coal burning amounted to 592 Gg (1 Gg = 109 g) in 2013, which is nearly half of China's total BC emissions. (iv) The absorption Ångström exponents (AAEs) of all coal briquettes are higher than those of coal chunks, indicating that the measure of coal briquetting increases the BrC ∕ BC emission ratio and thus offsets some of the climate cooling effect of briquetting. (v) In the scenario of current household coal burning in China, solar light absorption by BrC (350–850 nm in this study) accounts for more than a quarter (0.265) of the total absorption. This implies the significance of BrC to climate modeling.

Many antibiotics, either directly or indirectly, cause DNA damage thereby activating the bacterial DNA damage (SOS) response. SOS activation results in expression of genes involved in DNA repair and mutagenesis, and the regulation of the SOS response relies on two key proteins, LexA and RecA. Genetic studies have indicated that inactivating the regulatory proteins of this response sensitizes bacteria to antibiotics and slows the appearance of resistance. However, advancement of small molecule inhibitors of the SOS response has lagged, despite their clear promise in addressing the threat of antibiotic resistance. Previously, we had addressed this deficit by performing a high throughput screen of ∼1.8 million compounds that monitored for inhibition of RecA-mediated auto-proteolysis of Escherichia coli LexA, the reaction that initiates the SOS response. In this report, the refinement of the 5-amino-1-(carbamoylmethyl)-1H-1,2,3-triazole-4-carboxamide scaffold identified in the screen is detailed. After development of a modular synthesis, a survey of key activity determinants led to the identification of an analog with improved potency and increased breadth, targeting auto-proteolysis of LexA from both E. coli and Pseudomonas aeruginosa. Comparison of the structure of this compound to those of others in the series suggests structural features that may be required for activity and cross-species breadth. In addition, the feasibility of small molecule modulation of the SOS response was demonstrated in vivo by the suppression of the appearance of resistance. These structure activity relationships thus represent an important step toward producing Drugs that Inhibit SOS Activation to Repress Mechanisms Enabling Resistance (DISARMERs).

Fine carbonaceous aerosols (CAs) is the key factor influencing the currently filthy air in megacities in China, yet few studies simultaneously focus on the origins of different CAs species using specific and powerful source tracers. Here, we present a detailed source apportionment for various CAs fractions, including organic carbon (OC), water-soluble OC (WSOC), water-insoluble OC (WIOC), elemental carbon (EC) and secondary OC (SOC) in the largest cities of North (Beijing, BJ) and South China (Guangzhou, GZ), using the measurements of radiocarbon and anhydrosugars. Results show that non-fossil fuel sources such as biomass burning and biogenic emission make a significant contribution to the total CAs in Chinese megacities: 56 ± 4 in BJ and 46 ± 5 % in GZ, respectively. The relative contributions of primary fossil carbon from coal and liquid petroleum combustions, primary non-fossil carbon and secondary organic carbon (SOC) to total carbon are 19, 28 and 54 % in BJ, and 40, 15 and 46 % in GZ, respectively. Non-fossil fuel sources account for 52 in BJ and 71 % in GZ of SOC, respectively. These results suggest that biomass burning has a greater influence on regional particulate air pollution in North China than in South China. We observed an unabridged haze bloom-decay process in South China, which illustrates that both primary and secondary matter from fossil sources played a key role in the blooming phase of the pollution episode, while haze phase is predominantly driven by fossil-derived secondary organic matter and nitrate.

Biochemical pathways are often genetically encoded as simple transcription regulation networks, where one transcription factor regulates the expression of multiple genes in a pathway. The relative timing of each promoter's activation and shut-off within the network can impact physiology. In the DNA damage repair pathway (known as the SOS response) of Escherichia coli, approximately 40 genes are regulated by the LexA repressor. After a DNA damaging event, LexA degradation triggers SOS gene transcription, which is temporally separated into subsets of 'early', 'middle', and 'late' genes. Although this feature plays an important role in regulating the SOS response, both the range of this separation and its underlying mechanism are not experimentally defined. Here we show that, at low doses of DNA damage, the timing of promoter activities is not separated. Instead, timing differences only emerge at higher levels of DNA damage and increase as a function of DNA damage dose. To understand mechanism, we derived a series of synthetic SOS gene promoters which vary in LexA-operator binding kinetics, but are otherwise identical, and then studied their activity over a large dose-range of DNA damage. In distinction to established models based on rapid equilibrium assumptions, the data best fit a kinetic model of repressor occupancy at promoters, where the drop in cellular LexA levels associated with higher doses of DNA damage leads to non-equilibrium binding kinetics of LexA at operators. Operators with slow LexA binding kinetics achieve their minimal occupancy state at later times than operators with fast binding kinetics, resulting in a time separation of peak promoter activity between genes. These data provide insight into this remarkable feature of the SOS pathway by demonstrating how a single transcription factor can be employed to control the relative timing of each gene's transcription as a function of stimulus dose.

Malat1 is a long noncoding RNA with a wide array of functions, including roles in regulating cancer cell migration and metastasis. However, the nature of its involvement in control of these oncogenic processes is incompletely understood. In the present study, we investigate the role of Malat1 and the effects of Malat1 KO in a breast cancer cell model. Our selection of Malat1 as the subject of inquiry followed initial screening experiments seeking to identify lncRNAs which are altered in the presence or absence of Nischarin, a gene of interest previously discovered by our lab. Nischarin is a well characterized tumor suppressor protein and actively represses cell proliferation, migration, and invasion in breast cancer. Our microarray screen for lncRNAs revealed multiple lncRNAs to be significantly elevated in cells ectopically expressing Nischarin compared to control cancer cells, which have only marginal Nisch expression. Using these cells, we assess how the link between Nischarin and Malat1 affects cancer cell function, finding that Malat1 confers an inhibitory effect on cell growth and migration which is lost following Malat1 KO, but in a Nisch-dependent context. Specifically, Malat1 KO in the background of low Nischarin expression had a limited effect on cell functions, while Malat1 KO in cells with high levels of Nischarin led to significant increases in cell proliferation and migration. In summary, this project provides further clarity concerning the function of Malat1, specifically in breast cancer, while also indicating that the Nischarin expression context is an important factor in the determining how Malat1 activity is governed in breast cancer.

ABSTRACT The bacterial SOS response is a DNA damage repair network that is strongly implicated in both survival and acquired drug resistance under antimicrobial stress. The two SOS regulators, LexA and RecA, have therefore emerged as potential targets for adjuvant therapies aimed at combating resistance, although many open questions remain. For example, it is not well understood whether SOS hyperactivation is a viable therapeutic approach or whether LexA or RecA is a better target. Furthermore, it is important to determine which antimicrobials could serve as the best treatment partners with SOS-targeting adjuvants. Here we derived Escherichia coli strains that have mutations in either lexA or recA genes in order to cover the full spectrum of possible SOS activity levels. We then systematically analyzed a wide range of antimicrobials by comparing the mean inhibitory concentrations (MICs) and induced mutation rates for each drug-strain combination. We first show that significant changes in MICs are largely confined to DNA-damaging antibiotics, with strains containing a constitutively repressed SOS response impacted to a greater extent than hyperactivated strains. Second, antibiotic-induced mutation rates were suppressed when SOS activity was reduced, and this trend was observed across a wider spectrum of antibiotics. Finally, perturbing either LexA or RecA proved to be equally viable strategies for targeting the SOS response. Our work provides support for multiple adjuvant strategies, while also suggesting that the combination of an SOS inhibitor with a DNA-damaging antibiotic could offer the best potential for lowering MICs and decreasing acquired drug resistance. IMPORTANCE Our antibiotic arsenal is becoming depleted, in part, because bacteria have the ability to rapidly adapt and acquire resistance to our best agents. The SOS pathway, a widely conserved DNA damage stress response in bacteria, is activated by many antibiotics and has been shown to play central role in promoting survival and the evolution of resistance under antibiotic stress. As a result, targeting the SOS response has been proposed as an adjuvant strategy to revitalize our current antibiotic arsenal. However, the optimal molecular targets and partner antibiotics for such an approach remain unclear. In this study, focusing on the two key regulators of the SOS response, LexA and RecA, we provide the first comprehensive assessment of how to target the SOS response in order to increase bacterial susceptibility and reduce mutagenesis under antibiotic treatment.