Predictors and Outcomes of Help-Seeking Behaviors: A Longitudinal Investigation in Mental Illness.

Millions of people around the world are affected by mental illness, yet a substantive portion of individuals with mental illness do not regularly seek help from medical professionals or utilize mental health services. Help-seeking involves an individual's communicative intention and behaviors to solicit advice and/or treatment and thus is essentially a communicative process. This manuscript reports a longitudinal study that examined predictors and outcomes of help-seeking in mental illness contexts. Three-wave data from 223 participants clinically diagnosed with one or more mental illness conditions were collected and analyzed. Results indicated that expected outcomes of help-seeking from counselors were significantly associated with participants' communication efficacy and target efficacy at Wave 1, which subsequently influenced motivation to seek help and actual help-seeking behaviors at Wave 2. Actual help-seeking behaviors predicted post-traumatic growth and cognitive reappraisal at Wave 3. Importantly, communication efficacy and target efficacy interacted in their effects on help-seeking motivation and behaviors. Theoretical implications for help-seeking communication processes and practical implications for mental health help-seeking are discussed.

Diesel Soot and Amine-Containing Organic Sulfate Aerosols in an Arctic Oil Field.

The rapid decrease in Arctic sea ice is motivating development and increasing oil and gas extraction activities. However, few observations of these local Arctic emissions exist, limiting the understanding of impacts on atmospheric composition and climate. To address this knowledge gap, the chemical composition of atmospheric aerosols was measured within the North Slope of Alaska oil fields during August and September 2016 using an aerosol time-of-flight mass spectrometer (ATOFMS) and a time-of-flight aerosol chemical speciation monitor (ToF-ACSM). Plumes from oil and gas extraction activities were characterized by soot internally mixed with sulfate (matching diesel soot) and organic carbon particles containing aminium sulfate salts. Sea spray aerosol at the coastal site was frequently internally mixed with sulfate and nitrate, from multiphase chemical processing from elevated NOx and SO2 within the oil field. Background (nonplume) air masses were characterized by aged combustion aerosol. No periods of "clean" (nonpolluted) Arctic air were observed. The composition of the nonrefractory aerosol measured with the ACSM was similar during plume and background periods and was consistent with the mass concentrations of nonrefractory particles measured by ATOFMS. Two ultrafine aerosol growth events were observed during oil field background periods and were correlated with fine mode amine-containing particles.

Waterborne and Dietborne Toxicity of Inorganic Arsenic to the Freshwater Zooplankton Daphnia magna.

Waterborne and dietborne exposure are both important sources for the accumulation of inorganic arsenic (iAs) in aquatic organisms. Although the waterborne toxicity of iAs has been extensively investigated, its dietborne toxicity has received little attention. The present study examined the acute and chronic toxicity of arsenate (iAsV) and arsenite (iAsIII) to the freshwater zooplankton species Daphnia magna under both waterborne and dietborne exposure scenarios. The bioaccumulation, speciation, and tissue and subcellular distributions of arsenic were analyzed to understand the mechanisms accounting for differences in toxicity related to different arsenic species, exposure scenarios, and exposure duration. The toxicity of iAs increased with exposure time, and iAsIII was more toxic than iAsV. Moreover, although dietborne iAs had no acute effect on D. magna, it incurred significant toxicity in the chronic-exposure experiment. Nevertheless, the toxicity of dietborne iAs was still lower than that of waterborne iAs regardless of the exposure duration. This difference was found to be caused by the lower bioaccumulation of dietborne iAs, its higher distribution in the gut and in the biologically detoxified subcellular fraction, and greater transformation to the less toxic dimethylarsinic acid. Overall, the dietborne toxicity of iAs should be considered when evaluating the environmental risks posed by arsenic.

Source-specific Exposure to Contradictory Nutrition Information: Documenting Prevalence and Effects on Adverse Cognitive and Behavioral Outcomes.

Communication scholars have raised concerns that the media present contradictory or conflicting information on health, science, and political issues, speculating that such information may have adverse effects on public cognitions, affect, and behaviors. However, the evidence base for the effects of contradictory messages remains thin. Using nutrition as a case example, this study builds upon this nascent literature by employing a three-wave panel dataset from a survey with a nationally representative sample of American adults. We found that exposure to contradictory nutrition messages from television increases nutrition confusion, whereas exposure from print media decreases confusion. Moreover, nutrition confusion was positively associated with nutrition backlash, and nutrition backlash decreased engagement in fruit and vegetable consumption. Implications for campaigns and other communication interventions are discussed.

New insights into the fungal community from the raw genomic sequence data of fig wasp Ceratosolen solmsi.

BACKGROUND: To date, biologists have discovered a large amount of valuable information from assembled genomes, but the abundant microbial data that is hidden in the raw genomic sequence data of plants and animals is usually ignored. In this study, the richness and composition of fungal community were determined in the raw genomic sequence data of Ceratosolen solmsi (RGSD-CS). RESULTS: To avoid the interference from sequences of C. solmsi, the unmapped raw data (about 17.1%) was obtained by excluding the assembled genome of C. solmsi from RGSD-CS. Comparing two fungal reference datasets, internal transcribed spacer (ITS) and large ribosomal subunit (LSU) of rRNA, the ITS dataset discovered a more diverse fungal community and was therefore selected as the reference dataset for evaluating the fungal community based on the unmapped raw data. The threshold of 95% sequence identity revealed many more matched fungal reads and fungal richness in the unmapped raw data than those by identities above 95%. Based on the threshold of 95% sequence identity, the fungal community of RGSD-CS was primarily composed of Saccharomycetes (88.4%) and two other classes (Agaricomycetes and Sordariomycetes, 8.3% in total). Compared with the fungal community of other reported fig wasps, Agaricomycetes and Eurotiomycetes were found to be unique to C. solmsi. In addition, the ratio of total fungal reads to RGSD-CS was estimated to be at least 4.8 × 10(-3), which indicated that a large amount of fungal data was contained in RGSD-CS. However, rarefaction measure indicated that a deeper sequencing coverage with RGSD-CS was required to discover the entire fungal community of C. solmsi. CONCLUSION: This study investigated the richness and composition of fungal community in RGSD-CS and provided new insights into the efficient study of microbial diversity using raw genomic sequence data.

TiO2 nanoparticles act as a carrier of Cd bioaccumulation in the ciliate Tetrahymena thermophila.

When nanoparticles can enter a unicellular organism directly, how may they affect the bioaccumulation and toxicity of other pollutants already present in the environment? To answer this question, we conducted experiments with a protozoan Tetrahymena thermophila. The well-dispersed polyacrylate-coated TiO2 nanoparticles (PAA-TiO2-NPs) were used as a representative nanomaterial, and Cd as a conventional pollutant. We found that PAA-TiO2-NPs could get into Tetrahymena cells directly. Such internalization was first induced by low concentrations of Cd, but later suppressed when Cd concentrations were higher than 1 µg/L. Considering its significant adsorption on PAA-TiO2-NPs, Cd could be taken up by T. thermophila in the form of free ion or metal-nanoparticle complexes. The latter route accounted for 46.3% of Cd internalization. During the 5 h depuration period, 4.34-22.1% of Cd was excreted out, which was independent of the concentrations of intracellular Cd and PAA-TiO2-NPs. On the other hand, both free and intracellular Cd concentrations only partly predicted its toxicity at different levels of PAA-TiO2-NPs. This may have resulted from PAA-TiO2-NPs' synergistic effects and the distinct subcellular distribution of Cd taken up via the two routes above. Overall, we should pay attention to the carrier effects of nanoparticles when assessing their environmental risks.

Latino and European American early adolescents' exposure to music with substance-use references: examining parent-child communication as a moderator.

This study hypothesized that frequent exposure to and attention to music with substance-use references would be indirectly related to alcohol, cigarette, or marijuana use through pro-substance-use beliefs (e.g., norms, outcome expectancies, and refusal efficacy). Parent-child communication, however, would attenuate such associations, which would differ by ethnicity. Multigroup mediation and moderation analyses were conducted, using cross-sectional survey data from 253 Latino and 308 European American 6th-8th grades students. For Latino and European American early adolescents, best-friend-injunctive norms and weak refusal efficacy were significant mediators, but not positive outcome expectancies. Descriptive norms were a significant mediator, but only for European American early adolescents. Although targeted parent-child communication and parental mediation did not moderate the associations between the music-exposure variables and the pro-substance-use beliefs variables, targeted parent-child communication attenuated the association between listening to favorite songs and alcohol consumption. Parental mediation attenuated the association between attention to music and alcohol consumption.

Event-related prefrontal activations during online video game playing are modulated by game mechanics, physiological arousal and the amount of daily playing.

There is a trend to study human brain functions in ecological contexts and in relation to human factors. In this study, functional near-infrared spectroscopy (fNIRS) was used to record real-time prefrontal activities in 42 male university student habitual video game players when they played a round of multiplayer online battle arena game, League of Legends. A content-based event coding approach was used to analyze regional activations in relation to event type, physiological arousal indexed by heart rate (HR) change, and individual characteristics of the player. Game events Slay and Slain were found to be associated with similar HR and prefrontal responses before the event onset, but differential responses after the event onset. Ventrolateral prefrontal cortex (VLPFC) activation preceding the Slay onset correlated positively with HR change, whereas activations in dorsolateral prefrontal cortex (DLPFC) and rostral frontal pole area (FPAr) preceding the Slain onset were predicted by self-reported hours of weekly playing (HoWP). Together, these results provide empirical evidence to support the notion that event-related regional prefrontal activations during online video game playing are shaped by game mechanics, in-game dynamics of physiological arousal and individual characteristics the players.

Toxic effects of the heavy metal Cd on Apis cerana cerana (Hymenoptera: Apidae): Oxidative stress, immune disorders and disturbance of gut microbiota.

Cadmium (Cd) is a toxic non-essential metal element that can enter the honey bee body through air, water and soil. Currently, there is a lack of sufficient research on the effects of Cd on A. cerana cerana, especially the potential risks of long-term exposure to sublethal concentrations. In order to ascertain the toxicological effects of the heavy metal Cd on bees, we performed laboratory-based toxicity experiments on worker bees and conducted analyses from three distinctive facets: antioxidative, immunological, and gut microbiota. The results showed that exposure of bees to high concentrations of Cd resulted in acute mortality, and the increase in mortality was concentration dependent. In long-term exposure to sublethal concentrations, Cd reduced the number of transcripts of antioxidant genes (AccSOD1, AccTPx3 and AccTPx4) and superoxide dismutase activity, causing an increase in malondialdehyde content. Simultaneously, the transcription of immune-related genes (AccAbaecin and AccApidaecin) and acetylcholinesterase activities was inhibited. Furthermore, Cd changes the structural characteristics of bacterial and fungal communities in the gut, disrupting the balance of microbial communities. In conclusion, the health and survival of honey bees are affected by Cd. This study provides a scientific basis for investigating the toxicological mechanisms and control strategies of the heavy metal Cd on honey bees, while facilitating a better understanding and protection of these valuable honey bees.

Effects of abamectin nanocapsules on bees through host physiology, immune function, and gut microbiome.

Pesticide usage is a common practice to increase crop yields. Nevertheless, the existence of pesticide residues in the surrounding environment presents a significant hazard to pollinators, specifically the potential undisclosed dangers related to emerging nanopesticides. This study examines the impact of abamectin nanocapsules (AbaNCs), created through electrostatic self-assembly, as an insecticide on honey bees. It was determined that AbaNCs upregulated detoxification genes, including CYP450, as well as antioxidant and immune genes in honey bees. Furthermore, AbaNCs affected the activity of crucial enzymes such as superoxide dismutase (SOD). Although no apparent damage was observed in bee gut tissue, AbaNCs significantly decreased digestive enzyme activity. Microbiome sequencing revealed that AbaNCs disrupted gut microbiome, resulting in a reduction of beneficial bacteria such as Bifidobacterium and Lactobacillus. Additionally, these changes in the gut microbiome were associated with decreased activity of digestive enzymes, including lipase. This study enhances our understanding of the impact of nanopesticides on pollinating insects. Through the revelation of the consequences arising from the utilization of abamectin nanocapsules, we have identified potential stress factors faced by these pollinators, enabling the implementation of improved protective measures.

Heart Rate Variability during Online Video Game Playing in Habitual Gamers: Effects of Internet Addiction Scale, Ranking Score and Gaming Performance.

Previous studies have demonstrated that individuals with internet gaming disorder (IGD) display abnormal autonomic activities at rest and during gameplay. Here, we examined whether and how in-game autonomic activity is modulated by human characteristics and behavioral performance of the player. We measured heart rate variability (HRV) in 42 male university student habitual gamers (HGs) when they played a round of League of Legends game online. Short-term HRV indices measured in early, middle and late phases of the game were compared between the players at high risk of developing IGD and those at low risk, as assessed by the revised Chen Internet addiction scale (CIAS-R). Multiple linear regression (MLR) was used to identify significant predictors of HRV measured over the whole gameplay period (WG), among CIAS-R, ranking score, hours of weekly playing and selected in-game performance parameters. The high-risk players showed a significantly higher low-frequency power/high-frequency power ratio (LF/HF) relative to the low-risk players, regardless of game phase. MLR analysis revealed that LF/HF measured in WG was predicted by, and only by, CIAS-R. The HRV indicators of sympathetic activity were found to be predicted only by the number of slain in WG (NSlain), and the indicators of parasympathetic activity were predicted by both CIAS-R and NSlain. Collectively, the results demonstrated that risk of developing IGD is associated with dysregulated autonomic balance during gameplay, and in-game autonomic activities are modulated by complex interactions among personal attributes and in-game behavioral performance of the player, as well as situational factors embedded in game mechanics.

Povetacicept, an Enhanced Dual APRIL/BAFF Antagonist That Modulates B Lymphocytes and Pathogenic Autoantibodies for the Treatment of Lupus and Other B Cell-Related Autoimmune Diseases.

OBJECTIVE: Dysregulated APRIL/BAFF signaling is implicated in the pathogenesis of multiple autoimmune diseases, including systemic lupus erythematosus and lupus nephritis. We undertook this study to develop and evaluate a high-affinity APRIL/BAFF antagonist to overcome the clinical limitations of existing B cell inhibitors. METHODS: A variant of TACI-Fc generated by directed evolution showed enhanced binding for both APRIL and BAFF and was designated povetacicept (ALPN-303). Povetacicept was compared to wild-type (WT) TACI-Fc and related molecules in vitro and in vivo. RESULTS: Povetacicept inhibited APRIL and BAFF more effectively than all evaluated forms of WT TACI-Fc and selective APRIL and BAFF inhibitors in cell-based reporter assays and primary human B cell assays, mediating potent suppression of B cell proliferation, differentiation, and immunoglobulin (Ig) secretion. In mouse immunization models, povetacicept significantly reduced serum immunoglobulin titers and antibody-secreting cells more effectively than anti-CD20 monoclonal antibodies, WT TACI-Fc, or APRIL and BAFF inhibitors. In the NZB × NZW mouse lupus nephritis model, povetacicept significantly enhanced survival and suppressed proteinuria, anti-double-stranded DNA antibody titers, blood urea nitrogen, glomerulonephritis, and renal immunoglobulin deposition. In the bm12 mouse lupus model, povetacicept significantly reduced splenic plasmablasts, follicular helper T cells, and germinal center B cells. In non-human primates, povetacicept was well tolerated, exhibited high serum exposure, and significantly decreased serum IgM, IgA, and IgG levels after a single dose. CONCLUSION: Enhanced APRIL and BAFF inhibition by povetacicept led to greater inhibition of B cell populations critical for autoantibody production compared to WT TACI-Fc and CD20-, APRIL-, or BAFF-selective inhibitors. Potent, dual inhibition by povetacicept has the potential to significantly improve clinical outcomes in autoantibody-related autoimmune diseases.

Intestinal Bacterial Diversity and Functional Analysis of Three Lepidopteran Corn Ear Worm Larvae.

Insects, as the most abundant animal group on earth, and their symbionts help their hosts to adapt to various environments. Conogethes punctiferalis, Ostrinia furnacalis and Helicoverpa armigera are three main pests co-occurring in the ear stage of corn, which significantly affect the yield and quality of corn. The purpose of this study was to compare the diversity and function of the intestinal bacteria of the three co-occurring lepidopteran pests, C. punctiferalis, O. furnacalis and H. armigera, and to explore the reason of their prevalence from the microbiota's view. Our results showed the difference of diversity and abundance of the gut bacteria of three co-occurring lepidopteran pests at the ear stage. Proteobacteria and Firmicutes were the dominant phyla, and the Enterobacteriaceae and Enterococcaceae were the dominant families in the three pests. Compared with the other two pests, Bacteroidetes was found much more in C. punctiferalis. In addition, C. punctiferalis showed more correlation and similarity in bacteria composition with corn endophytic bacteria, as well as had obvious advantages in metabolic, environmental information processing, cellular processes and organic systems function pathways. Our findings may provide insight into the prevalence of corn earworm larvae from the perspective of gut microbiota and function prediction.

Influence of humic acid and fluvic acid on the altered toxicities of arsenite and arsenate toward two freshwater algae.

Arsenic pollution in freshwater poses a serious threat to aquatic organisms. However, dissolved organic matter (DOM) in water can modulate arsenic environmental toxicity by either suppressing or promoting its bioaccumulation. In this study, we investigated the toxicity, bioaccumulation, and biotransformation of inorganic arsenic (arsenite AsIII and arsenate AsV) combined with two types of DOM, i.e., humic acid (HA) and fulvic acid (FA), in the algae Chlamydomonas reinhardtii and Ochromonas danica. C. reinhardtii has a cell wall and cannot bioaccumulate arsenic complexation, whereas O. danica has no cell wall. Without DOM, AsV was more toxic than AsIII for C. reinhardtii, and AsV was less toxic than AsIII for O. danica. HA and FA addition reduced AsV and AsIII toxicities; the larger molecular weight (Mw) of HA contributed to the reduction in toxicity to an even greater extent, and reduced arsenic accumulation while promoting the biotransformation ability of C. reinhardtii, which has a cell wall. However, HA and FA addition increased AsV and AsIII toxicities and arsenic accumulation while relatively enhancing the biotransformation ability of O. danica, which has no cell wall. Coupling toxicity, bioaccumulation, and biotransformation, DOM (HA and FA) contributed to the altered toxicity of freshwater algae to AsV and AsIII through reduced/increased arsenic accumulation and enhanced biotransformation. Overall, our study considered the combined toxicity of inorganic arsenic and DOM in phytoplankton, helping estimate the potential environmental risk of arsenic in aqueous environments.

Proper irrigation amount for eggplant cultivation in a solar greenhouse improved plant growth, fruit quality and yield by influencing the soil microbial community and rhizosphere environment.

Water scarcity is a worldwide problem, and in order to obtain plenty of production, agricultural irrigation water accounts for a large portion. Many studies have shown that the interaction of root microorganisms and soil can promote crop growth. Developing ways to reduce irrigation to maintain soil fertility and ensure crop yield by regulating the root microenvironment is an important research goal. Here, we developed a reasonable irrigation plan for eggplant cultivation in a solar greenhouse. The maximum theoretical amount of water demand during eggplant planting obtained from a previous study was used as the control (CK), and the irrigation in the treatments was reduced by 10, 20 and 30% relative to this amount. The 10% irrigation reduction treatment (T1) significantly improved soil nutrients and increased soil catalase, urease and alkaline phosphatase activities (p < 0.05). Further analysis of rhizosphere microorganisms revealed the highest richness and diversity of the microbial community under the T1 treatment, with Bacilli as the most abundant bacteria and Aspergillaceae as the most abundant fungi and lower relative abundances of Chloroflexi and Acidobacteria (p < 0.05). Changes in microbial community structure under the influence of different irrigation treatments resulted in improvements in rhizosphere N cycling and nutrient catabolism. The plant-microbe interactions led to significant increases in eggplant plant height, root vigour, root surface area, leaf chlorophyll a, leaf net photosynthetic rate, water use efficiency, transpiration rate, and stomatal conductance under the T1 treatment compared to the CK treatment; soluble sugar, soluble protein and free amino acid contents in eggplant fruit increased by 10.8, 12.3 and 6.7%, respectively; and yield increased by 3.9%. Our research proved that the 10% irrigation reduction treatment (T1) could improve microbial community richness and fruit yield, which would improve irrigation efficiency and cost reduction in agriculture.

Suaeda salsa Root-Associated Microorganisms Could Effectively Improve Maize Growth and Resistance under Salt Stress.

Root-associated microorganisms are widely recognized as playing an important role in mitigating stress-induced damage to plants, but the responses of rhizosphere microbial communities after inoculation and their relationship with plant responses remain unclear. In this study, the bacterium Providencia vermicola BR68 and the fungus Sarocladium kiliense FS18 were selected from among 91 strains isolated from the halophyte Suaeda salsa to interact with maize seedlings under salt stress. The results showed that compared with NaCl-only treatment, inoculation with strains BR68 and FS18 significantly improved the growth, net photosynthetic rate, and antioxidant enzyme activities of maize; significantly reduced proline content and generation rate of reactive oxygen species (ROS); and alleviated oxidative stress and osmotic stress. Moreover, inoculation with these two strains increased the activities of soil microbiome enzymes such as sucrase, catalase, and fluorescein diacetate hydrolase, which improved maize physiologies and promoted maize growth under salt stress. In addition, these inoculated strains significantly affected the abundance of certain genera, and the correlation trends for these genera with soil properties and maize physiologies were similar to those of these inoculated strains. Strain BR68 was indirectly associated with bacterial communities through BR-specific biomarkers, and bacterial communities and soil properties explained most of the variation in maize physiologies and growth. Inoculation of strain FS18 was directly associated with variations in soil properties and maize physiologies. The two strains improved maize growth under salt stress and alleviated stress damage in maize in different ways. The links among salt-tolerant microorganisms, soil, and plants established in this study can inform strategies for improving crop cultivation in salinized lands. IMPORTANCE This study demonstrates that halophyte root-associated microorganisms can promote crop tolerance to salt stress and clarify the mechanism by which the strains work in rhizosphere soil. The links among salt-tolerant microorganisms, soil, and plants established in this study can inform strategies for improving crop cultivation in salinized lands.

Arsenic bioaccumulation and biotransformation in aquatic organisms.

Arsenic exists universally in freshwater and marine environments, threatening the survival of aquatic organisms and human health. To elucidate arsenic bioaccumulation and biotransformation processes in aquatic organisms, this review evaluates the dissolved uptake, dietary assimilation, biotransformation, and elimination of arsenic in aquatic organisms and discusses the major factors influencing these processes. Environmental factors such as phosphorus concentration, pH, salinity, and dissolved organic matter influence arsenic absorption from aquatic systems, whereas ingestion rate, gut passage time, and gut environment affect the assimilation of arsenic from foodstuffs. Arsenic bioaccumulation and biotransformation mechanisms differ depending on specific arsenic species and the involved aquatic organism. Although some enzymes engaged in arsenic biotransformation are known, deciphering the complicated synthesis and degradation pathway of arsenobetaine remains a challenge. The elimination of arsenic involves many processes, such as fecal excretion, renal elimination, molting, and reproductive processes. This review facilitates our understanding of the environmental behavior and biological fate of arsenic and contributes to regulation of the environmental risk posed by arsenic pollution.

Identifying the roles of imine and alkyne linkages in determining the photocatalytic hydrogen evolution over thiadiazole-based covalent organic frameworks.

Covalent organic frameworks (COFs) have emerged as an extremely promising material for photocatalytic water splitting for hydrogen production. However, their photocatalytic performance is seriously affected by the properties of their donors, acceptors and linkages. So far, few studies have been reported on the key roles of the linkages of a specific COF in improving its photocatalytic hydrogen production performance. Herein, this study designed and synthesized two thiadiazole-based COFs linked by imine and alkyne bonds. The results show that the photocatalytic hydrogen production performance of imine-linked COFs (TeTz-COF1) is 19.6 times higher than that of alkyne-linked COFs (TeTz-COF2). Impressively, TeTz-COF1 achieves an apparent quantum efficiency of 3.5% at 475 nm due to the presence of imine bonds. The experimental results confirm that TeTz-COF1 with imine linkages shows higher photocurrent density, lower photocurrent resistance, and longer fluorescence lifetime than TeTz-COF2 with alkyne linkages. Meanwhile, the well-defined density functional theory (DFT) calculations further suggest that both the imine bond and the acetylene bond belong to the HOMO orbitals. Particularly, the imine bonds endow TeTz-COF1 with more delocalized orbital occupation and smaller work functions, thus leading to its lower excited state energy, stronger carrier separation ability and faster electron migration capability. Both theoretical analysis and the experimental results prove that the presence of imine bonds in TeTz-COF1 can enable the efficient separation and fast transport of photogenerated carriers and high reducing ability of photogenerated electrons. This work may provide important guiding significance for the development of new COFs in the direction of photocatalytic water splitting for hydrogen production.

PM2.5 composition and sources in the San Joaquin Valley of California: A long-term study using ToF-ACSM with the capture vaporizer.

The San Joaquin Valley (SJV) of California has suffered persistent particulate matter (PM) pollution despite many years of control efforts. To further understand the chemical drivers of this problem and to support the development of State Implementation Plan for PM, a time-of-flight aerosol chemical speciation monitor (ToF-ACSM) outfitted with a PM2.5 lens and a capture vaporizer has been deployed at the Fresno-Garland air monitoring site of the California Air Resource Board (CARB) since Oct. 2018. The instrument measured non-refractory species in PM2.5 continuously at 10-min resolution. In this study, the data acquired from Oct. 2018 to May 2019 were analyzed to investigate the chemical characteristics, sources and atmospheric processes of PM2.5 in the SJV. Comparisons of the ToF-ACSM measurement with various co-located aerosol instruments show good agreements. The inter-comparisons indicated that PM2.5 in Fresno was dominated by submicron particles during the winter whereas refractory species accounted for a major fraction of PM2.5 mass during the autumn associated with elevated PM10 loadings. A rolling window positive matrix factorization analysis was applied to the organic aerosol (OA) mass spectra using the Multilinear Engine (ME-2) algorithm. Three distinct OA sources were identified, including vehicle emissions, local and regional biomass burning, and formation of oxygenated species. There were significant seasonal variations in PM2.5 composition and sources. During the winter, residential wood burning and oxidation of nitrogen oxides were major contributors to the occurrence of haze episodes with PM2.5 dominated by biomass burning OA and nitrate. In autumn, agricultural activities and wildfires were found to be the main cause of PM pollution. PM2.5 concentrations decreased significantly after spring and were dominated by oxygenated OA during March to May. Our results highlight the importance of using seasonally dependent control strategies to mitigate PM pollution in the SJV.

Acazicolcept (ALPN-101), a dual ICOS/CD28 antagonist, demonstrates efficacy in systemic sclerosis preclinical mouse models.

BACKGROUND: Uncontrolled immune response with T cell activation has a key role in the pathogenesis of systemic sclerosis (SSc), a disorder that is characterized by generalized fibrosis affecting particularly the lungs and skin. Costimulatory molecules are key players during immune activation, and recent evidence supports a role of CD28 and ICOS in the development of fibrosis. We herein investigated the efficacy of acazicolcept (ALPN-101), a dual ICOS/CD28 antagonist, in two complementary SSc-related mouse models recapitulating skin fibrosis, interstitial lung disease, and pulmonary hypertension. METHODS: Expression of circulating soluble ICOS and skin-expressed ICOS was investigated in SSc patients. Thereafter, acazicolcept was evaluated in the hypochlorous acid (HOCL)-induced dermal fibrosis mouse model and in the Fra-2 transgenic (Tg) mouse model. In each model, mice received 400 µg of acazicolcept or a molar-matched dose of an Fc control protein twice a week for 6 weeks. After 6 weeks, skin and lung were evaluated. RESULTS: ICOS was significantly increased in the sera from SSc patients and in SSc skin biopsies as compared to samples from healthy controls. Similar body weight changes were observed between Fc control and acazicolcept groups in both HOCL and Fra-2 Tg mice suggesting a good tolerance of acazicolcept treatment. In mice challenged with HOCL, acazicolcept induced a significant decrease in dermal thickness, collagen content, myofibroblast number, and inflammatory infiltrates characterized by B cells, T cells, neutrophils, and macrophages. In the Fra-2 Tg mouse model, acazicolcept treatment reduced lung collagen content, fibrillar collagen, histological fibrosis score, and right ventricular systolic pressure (RVSP). A reduction in frequency of CD4+ and T effector memory cells and an increase in the percentage of CD4+ T naïve cells in spleen and lung of acazicolcept-treated Fra-2 Tg mice was observed as compared to Fc control-treated Fra-2 Tg mice. Moreover, acazicolcept reduced CD69 and PD-1 expression on CD4+ T cells from the spleen and the lung. Target engagement by acazicolcept was demonstrated by blockade of CD28 and ICOS detection by flow cytometry in treated mice. CONCLUSIONS: Our results confirm the importance of costimulatory molecules in inflammatory-driven fibrosis. Our data highlight a key role of ICOS and CD28 in SSc. Using complementary models, we demonstrated that dual ICOS/CD28 blockade by acazicolcept decreased dermal and pulmonary fibrosis and alleviated pulmonary hypertension. These results pave the way for subsequent research on ICOS/CD28-targeted therapies.