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Purpose of Review Air pollution significantly affects health, causing up to 7 million premature deaths annually with an even larger number of hospitalizations and days of sick leave. Climate change could alter the dispersion of primary pollutants, particularly particulate matter, and intensify the formation of secondary pollutants, such as near-surface ozone. The purpose of the review is to evaluate the recent evidence on the impacts of climate change on air pollution and air pollution-related health impacts and identify knowledge gaps for future research. Recent Findings Several studies modelled future ozone and particulate matter concentrations and calculated the resulting health impacts under different climate scenarios. Due to climate change, ozone- and fine particle-related mortalities are expected to increase in most studies; however, results differ by region, assumed climate change scenario and other factors such as population and background emissions. Summary This review explores the relationships between climate change, air pollution and air pollution-related health impacts. The results highly depend on the climate change scenario used and on projections of future air pollution emissions, with relatively high uncertainty. Studies primarily focused on mortality; projections on the effects on morbidity are needed.

Adenosine deaminases acting on RNA (ADAR) are RNA-editing enzymes that may restrict viral infection. We have utilized deep sequencing to determine adenosine to guanine (A→G) mutations, signifying ADAR activity, in clinical samples retrieved from 93 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in the early phase of the COVID-19 pandemic. A→G mutations were detected in 0.035% (median) of RNA residues and were predominantly nonsynonymous. These mutations were rarely detected in the major viral population but were abundant in minor viral populations in which A→G was more prevalent than any other mutation (P < 0.001). The A→G substitutions accumulated in the spike protein gene at positions corresponding to amino acids 505 to 510 in the receptor binding motif and at amino acids 650 to 655. The frequency of A→G mutations in minor viral populations was significantly associated with low viral load (P < 0.001). We additionally analyzed A→G mutations in 288,247 SARS-CoV-2 major (consensus) sequences representing the dominant viral population. The A→G mutations observed in minor viral populations in the initial patient cohort were increasingly detected in European consensus sequences between March and June 2020 (P < 0.001) followed by a decline of these mutations in autumn and early winter (P < 0.001). We propose that ADAR-induced deamination of RNA is a significant source of mutated SARS-CoV-2 and hypothesize that the degree of RNA deamination may determine or reflect viral fitness and infectivity.

The transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of paramount importance in controlling and combating the coronavirus disease 2019 (COVID-19) pandemic. Currently, over 15,000 SARS-CoV-2 single mutations have been recorded, which have a great impact on the development of diagnostics, vaccines, antibody therapies, and drugs. However, little is known about SARS-CoV-2’s evolutionary characteristics and general trend. In this work, we present a comprehensive genotyping analysis of existing SARS-CoV-2 mutations. We reveal that host immune response via APOBEC and ADAR gene editing gives rise to near 65% of recorded mutations. Additionally, we show that children under age five and the elderly may be at high risk from COVID-19 because of their overreaction to the viral infection. Moreover, we uncover that populations of Oceania and Africa react significantly more intensively to SARS-CoV-2 infection than those of Europe and Asia, which may explain why African Americans were shown to be at increased risk of dying from COVID-19, in addition to their high risk of COVID-19 infection caused by systemic health and social inequities. Finally, our study indicates that for two viral genome sequences of the same origin, their evolution order may be determined from the ratio of mutation type, C > T over T > C.

Purpose of Review Health effects of long-term exposure to ambient PM 2.5 vary with regions, and 75% of the deaths attributable to PM 2.5 were estimated in Asia-Pacific in 2017. This systematic review aims to summarize the existing evidence from cohort studies on health effects of long-term exposure to ambient PM 2.5 in Asia-Pacific. Recent Findings In Asia-Pacific, 60 cohort studies were conducted in Australia, Mainland China, Hong Kong, Taiwan, and South Korea. They consistently supported associations of long-term exposure to PM 2.5 with increased all-cause/non-accidental and cardiovascular mortality as well as with incidence of cardiovascular diseases, type 2 diabetes mellitus, kidney diseases, and chronic obstructive pulmonary disease. Evidence for other health effects was limited. Inequalities were identified in PM 2.5 -health associations. Summary To optimize air pollution control and public health prevention, further studies need to assess the health effects of long-term PM 2.5 exposure in understudied regions, the health effects of long-term PM 2.5 exposure on mortality and risk of type 2 diabetes mellitus, renal diseases, dementia and lung cancer, and inequalities in PM 2.5 -health associations. Study design, especially exposure assessment methods, should be improved.

Purpose of Review Epidemiological studies of health effects of long-term exposure to outdoor air pollution rely on different exposure assessment methods. This review discusses widely used methods with a special focus on new developments. Recent Findings New data and study designs have been applied, including satellite measurements of fine particles and nitrogen dioxide (NO 2 ). The methods to apply satellite data for epidemiological studies are improving rapidly and have already contributed significantly to national-, continental- and global-scale models. Spatiotemporal models have been developed allowing more detailed temporal resolution compared to spatial models. The development of hybrid models combining dispersion models, satellite observations, land use and surface monitoring has improved models substantially. Mobile monitoring designs to develop models for long-term UFP exposure have been conducted. Summary Methods to assess long-term exposure to outdoor air pollution have improved significantly over the past decade. Application of satellite data and mobile monitoring designs is promising new methods.

Background Adenosine-to-inosine (A-to-I) RNA editing is a co-/post-transcriptional modification introducing A-to-G variations in RNAs. There is extensive discussion on whether the flexibility of RNA editing exerts a proteomic diversification role, or it just acts like hardwired mutations to correct the genomic allele. Eusocial insects evolved the ability to generate phenotypically differentiated individuals with the same genome, indicating the involvement of epigenetic/transcriptomic regulation. Methods We obtained the genomes of 104 Hymenoptera insects and the transcriptomes of representative species. Comparative genomic analysis was performed to parse the evolutionary trajectory of a regulatory Ile > Met auto-recoding site in Adar gene. Results At genome level, the pre-editing Ile codon is conserved across a node containing all eusocial hymenopterans. At RNA level, the editing events are confirmed in representative species and shows considerable condition-specificity. Compared to random expectation, the editable Ile codon avoids genomic substitutions to Met or to uneditable Ile codons, but does not avoid mutations to other unrelated amino acids. Conclusions The flexibility of Adar auto-recoding site in Hymenoptera is selectively maintained, supporting the flexible RNA editing hypothesis. We proposed a new angle to view the adaptation of RNA editing, providing another layer to explain the great phenotypical plasticity of eusocial insects.

The APOBEC/AID family is known for its mutator activity, and recent evidence also supports the potential impact of ADARs. Furthermore, the mutator impacts of APOBEC/ADAR mutations have not yet been investigated. Assessment of pancancer TCGA exomes identified enriched somatic variants among exomes with nonsynonymous APOBEC1, APOBEC3B, APOBEC3C , ADAR, and ADARB1 mutations, compared to exomes with synonymous ones. Principal component (PC) analysis reduced the number of potential players to eight in cancer exomes/genomes, and to five in cancer types. Multivariate regression analysis was used to assess the impact of the PCs on each COSMIC mutational signature among pancancer exomes/genomes and particular cancers, identifying several novel links, including SBS17b, SBS18, and ID7 mainly determined by APOBEC1 mRNA levels; SBS40, ID1, and ID2 by age; SBS3 and SBS16 by APOBEC3A/APOBEC3B mRNA levels; ID5 and DBS9 by DNA repair/replication (DRR) defects; and SBS7a-d, SBS38, ID4, ID8, ID13, and DBS1 by ultraviolet (UV) radiation/ ADARB1 mRNA levels. APOBEC/ADAR mutations appeared to potentiate the impact of DRR defects on several mutational signatures, and some factors seemed to inversely affect certain signatures. These findings potentially implicate certain APOBEC/ADAR mutations/mRNA levels in distinct mutational signatures, particularly APOBEC1 mRNA levels in aging-related signatures and ADARB1 mRNA levels in UV radiation-related signatures.

Purpose of Review We reviewed recent peer-reviewed literature on three categories of individual- and household-level interventions against air pollution: air purifiers, facemasks, and behavior change. Recent Findings High-efficiency particulate air/arresting (HEPA) filter air purifier use over days to weeks can substantially reduce fine particulate matter (PM 2.5 ) concentrations indoors and improve subclinical cardiopulmonary health. Modeling studies suggest that the population-level benefits of HEPA filter air purification would often exceed costs. Well-fitting N95 and equivalent respirators can reduce PM 2.5 exposure, with several randomized crossover studies also reporting improvements in subclinical cardiovascular health. The health benefits of other types of face coverings have not been tested and their effectiveness in reducing exposure is highly variable, depends largely on fit, and is unrelated to cost. Behavior modifications may reduce exposure, but there has been little research on health impacts. Summary There is now substantial evidence that HEPA filter air purifiers reduce indoor PM 2.5 concentrations and improve subclinical health indicators. As a result, their use is being recommended by a growing number of government and public health organizations. Several studies have also reported subclinical cardiovascular health benefits from well-fitting respirators, while evidence of health benefits from other types of facemasks and behavior changes remains very limited. In situations when emissions cannot be controlled at the source, such as during forest fires, individual- or household-level interventions may be the primary option. In most cases, however, such interventions should be supplemental to emission reduction efforts that benefit entire communities.

MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cancer, cardiovascular and metabolic diseases, relies highly on miRNAs. However, deciphering the precise roles of specific miRNAs in these pathophysiological contexts is challenging due to the high levels of complexity of their actions. Indeed, regulation of mRNA expression by miRNAs is frequently cell/organ specific; highly dependent on the stress and metabolic status of the organism; and often poorly correlated with miRNA expression levels. Such biological features of miRNAs suggest that various regulatory mechanisms control not only their expression, but also their activity and/or bioavailability. Several mechanisms have been described to modulate miRNA action, including genetic polymorphisms, methylation of miRNA promoters, asymmetric miRNA strand selection, interactions with RNA-binding proteins (RBPs) or other coding/non-coding RNAs. Moreover, nucleotide modifications (A-to-I or C-to-U) within the miRNA sequences at different stages of their maturation are also critical for their functionality. This regulatory mechanism called “RNA editing” involves specific enzymes of the adenosine/cytidine deaminase family, which trigger single nucleotide changes in primary miRNAs. These nucleotide modifications greatly influence a miRNA’s stability, maturation and activity by changing its specificity towards target mRNAs. Understanding how editing events impact miRNA’s ability to regulate stress responses in cells and organs, or the development of specific pathologies, e.g., metabolic diseases or cancer, should not only deepen our knowledge of molecular mechanisms underlying complex diseases, but can also facilitate the design of new therapeutic approaches based on miRNA targeting. Herein, we will discuss the current knowledge on miRNA editing and how this mechanism regulates miRNA biogenesis and activity.

Prostate cancer antigen 3 ( PCA3 ) is the most specific prostate cancer biomarker but its function remains unknown. Here we identify PRUNE2 , a target protein-coding gene variant, which harbors the PCA3 locus, thereby classifying PCA3 as an antisense intronic long noncoding (lnc)RNA. We show that PCA3 controls PRUNE2 levels via a unique regulatory mechanism involving formation of a PRUNE2/PCA3 double-stranded RNA that undergoes adenosine deaminase acting on RNA (ADAR)-dependent adenosine-to-inosine RNA editing. PRUNE2 expression or silencing in prostate cancer cells decreased and increased cell proliferation, respectively. Moreover, PRUNE2 and PCA3 elicited opposite effects on tumor growth in immunodeficient tumor-bearing mice. Coregulation and RNA editing of PRUNE2 and PCA3 were confirmed in human prostate cancer specimens, supporting the medical relevance of our findings. These results establish PCA3 as a dominant-negative oncogene and PRUNE2 as an unrecognized tumor suppressor gene in human prostate cancer, and their regulatory axis represents a unique molecular target for diagnostic and therapeutic intervention.