Phage defence system CBASS is regulated by a prokaryotic E2 enzyme that imitates the ubiquitin pathway.

The cyclic-oligonucleotide-based anti-phage signalling system (CBASS) is a type of innate prokaryotic immune system. Composed of a cyclic GMP-AMP synthase (cGAS) and CBASS-associated proteins, CBASS uses cyclic oligonucleotides to activate antiviral immunity. One major class of CBASS contains a homologue of eukaryotic ubiquitin-conjugating enzymes, which is either an E1-E2 fusion or a single E2. However, the functions of single E2s in CBASS remain elusive. Here, using biochemical, genetic, cryo-electron microscopy and mass spectrometry investigations, we discover that the E2 enzyme from Serratia marcescens regulates cGAS by imitating the ubiquitination cascade. This includes the processing of the cGAS C terminus, conjugation of cGAS to a cysteine residue, ligation of cGAS to a lysine residue, cleavage of the isopeptide bond and poly-cGASylation. The poly-cGASylation activates cGAS to produce cGAMP, which acts as an antiviral signal and leads to cell death. Thus, our findings reveal a unique regulatory role of E2 in CBASS.

Effects of endocrine disrupting chemicals and their interactions with genetic risk scores on cardiometabolic traits.

Ubiquitous non-persistent endocrine disrupting chemicals (EDCs) have inconsistent associations with cardiometabolic traits. Additionally, large-scale genome-wide association studies (GWASs) have yielded many genetic risk variants for cardiometabolic traits and diseases. This study aimed to investigate the associations between a wide range of EDC exposures (parabens, bisphenols, and phthalates) and 14 cardiometabolic traits and whether these are moderated by their respective genetic risk scores (GRSs). Data were from 1074 participants aged 18 years or older of the Lifelines Cohort Study, a large population-based biobank. GRSs for 14 cardiometabolic traits were calculated based on genome-wide significant common variants from recent GWASs. The concentrations of 15 EDCs in 24-hour urine were measured by isotope dilution liquid chromatography tandem mass spectrometry technology. The main effects of trait-specific GRSs and each of the EDC exposures and their interaction effects on the 14 cardiometabolic traits were examined in multiple linear regression. The present study confirmed significant main effects for all GRSs on their corresponding cardiometabolic trait. Regarding the main effects of EDC exposures, 26 out of 280 EDC-trait tests were significant with explained variances ranging from 0.43 % (MMP- estimated glomerular filtration rate (eGFR)) to 2.37 % (PrP-waist-hip ratio adjusted body mass index (WHRadjBMI)). We confirmed the association of MiBP and MBzP with WHRadjBMI and body mass index (BMI), and showed that parabens, bisphenol F, and many other phthalate metabolites significantly contributed to the variance of WHRadjBMI, BMI, high-density lipoprotein (HDL), eGFR, fasting glucose (FG), and diastolic blood pressure (DBP). Only one association between BMI and bisphenol F was nominally significantly moderated by the GRS explaining 0.36 % of the variance. However, it did not survive multiple testing correction. We showed that non-persistent EDC exposures exerted effects on BMI, WHRadjBMI, HDL, eGFR, FG, and DBP. However no evidence for a modulating role of GRSs was found.

The nuclease-associated short prokaryotic Argonaute system nonspecifically degrades DNA upon activation by target recognition.

Prokaryotic Argonautes (pAgos) play a vital role in host defense by utilizing short nucleic acid guides to recognize and target complementary nucleic acids. Despite being the majority of pAgos, short pAgos have only recently received attention. Short pAgos are often associated with proteins containing an APAZ domain and a nuclease domain including DUF4365, SMEK, or HNH domain. In contrast to long pAgos that specifically cleave the target DNA, our study demonstrates that the short pAgo from Thermocrispum municipal, along with its associated DUF4365-APAZ protein, forms a heterodimeric complex. Upon RNA-guided target DNA recognition, this complex is activated to nonspecifically cleave DNA. Additionally, we found that the TmuRE-Ago complex shows a preference for 5'-OH guide RNA, specifically requires a uridine nucleotide at the 5' end of the guide RNA, and is sensitive to single-nucleotide mismatches between the guide RNA and target DNA. Based on its catalytic properties, our study has established a novel nucleic acid detection method and demonstrated its feasibility. This study not only expands our understanding of the defense mechanism employed by short pAgo systems but also suggests their potential applications in nucleic acid detection.

A genome-wide association study of 24-hour urinary excretion of endocrine disrupting chemicals.

Ubiquitous exposure to environmental endocrine disrupting chemicals (EDCs) instigates a major public health problem, but much remains unknown on the inter-individual differences in metabolism and excretion of EDCs. To examine this we performed a two-stage genome-wide association study (GWAS) for 24-hour urinary excretions of four parabens, two bisphenols, and nine phthalate metabolites. Results showed five genome-wide significant (p-value < 5x10-8) and replicated single nucleotide polymorphisms (SNPs) representing four independent signals that associated with mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP). Three of the four signals were located on chromosome 10 in a locus harboring the cytochrome P450 (CYP) genes CYP2C9, CYP2C58P, and CYP2C19 (rs117529685, pMECPP = 5.38x10-25; rs117033379, pMECPP = 1.96x10-19; rs4918798, pMECPP = 4.01x10-71; rs7895726, pMEHHP = 1.37x10-15, r2 with rs4918798 = 0.93). The other signal was on chromosome 6 close to the solute carrier (SLC) genes SLC17A1, SLC17A3, SLC17A4, and SCGN (rs1359232, pMECPP = 7.6x10-16). These four SNPs explained a substantial part (8.3 % - 9.2 %) of the variance in MECPP in the replication cohort. Bioinformatics analyses supported a likely causal role of CYP2C9 and SLC17A1 in metabolism and excretion of MECPP and MEHHP. Our results provide biological insights into mechanisms of phthalate metabolism and excretion with a likely causal role for CYP2C9 and SLC17A1.

Prokaryotic Gabija complex senses and executes nucleotide depletion and DNA cleavage for antiviral defense.

The Gabija complex is a prokaryotic antiviral system consisting of the GajA and GajB proteins. GajA was identified as a DNA nicking endonuclease but the functions of GajB and the complex remain unknown. Here, we show that synergy between GajA-mediated DNA cleavage and nucleotide hydrolysis by GajB initiates efficient abortive infection defense against virulent bacteriophages. The antiviral activity of GajA requires GajB, which senses DNA termini produced by GajA to hydrolyze (d)A/(d)GTP, depleting essential nucleotides. This ATPase activity of Gabija complex is only activated upon DNA binding. GajA binds to GajB to form stable complexes in vivo and in vitro. However, a functional Gabija complex requires a molecular ratio between GajB and GajA below 1:1, indicating stoichiometric regulation of the DNA/nucleotide processing complex. Thus, the Gabija system exhibits distinct and efficient antiviral defense through sequential sensing and activation of nucleotide depletion and DNA cleavage, causing a cascade suicide effect.

Effect of Several Naja atra Antivenom Injection Methods on the Rabbit Model of Naja naja atra Bite Poisoning.

Snakebite is a global public health concern, which often occurs in tropical and subtropical underdeveloped areas, but it is often neglected. In the southern China, Naja naja atra (Chinese cobra) is a common venomous snake that causes swelling and necrosis of local tissues, even amputation and death. Currently, the main therapy is the administration of Naja atra antivenom, which greatly reduces mortality. However, the antivenom is not particularly effective in the improvement of local tissue necrosis. Clinically, antivenom is mainly administered intravenously. We speculated that the method of injection influences the efficacy of antivenom. In this study, the rabbit model was used to explore the effects of different antivenom injection methods on systemic and local poisoning symptoms. If topical injection of antivenom contributes to ameliorate tissue necrosis, then we need to reconsider the use of Naja atra antivenom.

A Unique m6A-Dependent Restriction Endonuclease from an Archaeal Virus.

Prokaryotes possess numerous diverse defense systems to resist viral infections, while some viruses have also evolved antiviral defense systems to exclude other viruses in cases of multiple infections. Here, we report the first virus-derived modification-dependent restriction endonuclease (HHPV4I) from the archaeal virus HHPV4 (Haloarcula hispanica pleomorphic virus 4). HHPV4I contains an SRA domain, a winged helix (wH) domain, and an HNH domain; recognizes the Gm6ATC site; and specifically binds to Gm6ATC site-containing DNA. Both the wH domain and the HNH domain are responsible for DNA binding. Unlike the well-known m6A-specific restriction enzyme DpnI, HHPV4I only efficiently cleaves DNA with a fully methylated Gm6ATC site and cleaves DNA both upstream and downstream of the Gm6ATC sites on both DNA strands. Furthermore, HHPV4I preferentially cleaves DNA between VR bases (V = A/G/C, R = A/G) 4 to 20 nt away from the Gm6ATC site. Thus, the cleavage pattern of HHPV4I is distinct from those of all of the presently characterized restriction endonucleases. Mutations in the wH domain of HHPV4I do not alter m6A-dependent endonuclease activity, but they decrease recognition sequence specificity, thus expanding the cleaving capacity to more m6A-containing DNA sequences. The wH domain provides a target for searching, developing, and engineering novel m6A-dependent endonucleases. IMPORTANCE Many modification-dependent restriction endonucleases (MDREs) were identified in prokaryotes and recognized modified cytosine bases, such as 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), and glucosyl-5-hydroxymethylcytosine (g5hmC). The first virus-derived MDRE (HHPV4I) from the archaeal virus HHPV4 was identified in this study. The viral MDRE suggested a new strategy employed by the virus to exclude other viruses in the case of multiple replications. HHPV4I is a novel N6-methyladenine (m6A)-dependent restriction endonuclease, while the cleavage pattern of HHPV4I is distinct from the well-known m6A-dependent restriction endonuclease DpnI. HHPV4I recognizes Gm6ATC sites and cleaves DNA both upstream and downstream of the Gm6ATC sites on both DNA strands. It preferentially cleaves DNA between VR bases (V = A/G/C, R = A/G) 4 to 20 nt away from the Gm6ATC sites. Furthermore, mutations in the HHPV4I wH domain can alter the sequence specificity without impeding the m6A-dependent DNA cleavage activity, providing a target for engineering more m6A-dependent endonucleases with different sequence specificities.

Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose.

The genetic regulation of post-prandial glucose levels is poorly understood. Here, we characterise the genetic architecture of blood glucose variably measured within 0 and 24 h of fasting in 368,000 European ancestry participants of the UK Biobank. We found a near-linear increase in the heritability of non-fasting glucose levels over time, which plateaus to its fasting state value after 5 h post meal (h2 = 11%; standard error: 1%). The genetic correlation between different fasting times is > 0.77, suggesting that the genetic control of glucose is largely constant across fasting durations. Accounting for heritability differences between fasting times leads to a ~16% improvement in the discovery of genetic variants associated with glucose. Newly detected variants improve the prediction of fasting glucose and type 2 diabetes in independent samples. Finally, we meta-analysed summary statistics from genome-wide association studies of random and fasting glucose (N = 518,615) and identified 156 independent SNPs explaining 3% of fasting glucose variance. Altogether, our study demonstrates the utility of random glucose measures to improve the discovery of genetic variants associated with glucose homeostasis, even in fasting conditions.

Psychrophilic phage VSW-3 RNA polymerase reduces both terminal and full-length dsRNA byproducts in in vitro transcription.

RNA research and applications are underpinned by in vitro transcription (IVT), but RNA impurities resulting from the enzymatic reagents severely impede downstream applications. To improve the stability and purity of synthesized RNA, we have characterized a novel single-subunit RNA polymerase (RNAP) encoded by the psychrophilic phage VSW-3 from a plateau lake. The VSW-3 RNAP is capable of carrying out in vitro RNA synthesis at low temperatures (4-25°C). Compared to routinely used T7 RNAP, VSW-3 RNAP provides a similar yield of transcripts but is insensitive to class II transcription terminators and synthesizes RNA without redundant 3'-cis extensions. More importantly, through dot-blot detection with the J2 monoclonal antibody, we found that the RNA products synthesized by VSW-3 RNAP contained a much lower amount of double-stranded RNA byproducts (dsRNA), which are produced by transcription from both directions and are significant in T7 RNAP IVT products. Taken together, the VSW-3 RNAP almost eliminates both terminal loop-back dsRNA and full-length dsRNA in IVT and thus is especially advantageous for producing RNA for in vivo use.

Corrigendum: Molecular Dissection of the Primase and Polymerase Activities of Deep-Sea Phage NrS-1 Primase-Polymerase.

[This corrects the article DOI: 10.3389/fmicb.2021.766612.].

Molecular Dissection of the Primase and Polymerase Activities of Deep-Sea Phage NrS-1 Primase-Polymerase.

PrimPols are a class of primases that belong to the archaeo-eukaryotic primase (AEP) superfamily but have both primase and DNA polymerase activities. Replicative polymerase from NrS-1 phage (NrSPol) is a representative of the PrimPols. In this study, we identified key residues for the catalytic activity of NrSPol and found that a loop in NrSPol functionally replaces the zinc finger motif that is commonly found in other AEP family proteins. A helix bundle domain (HBD), conserved in the AEP superfamily, was recently reported to bind to the primase recognition site and to be crucial for initiation of primer synthesis. We found that NrSPol can recognize different primase recognition sites, and that the initiation site for primer synthesis is not stringent, suggesting that the HBD conformation is flexible. More importantly, we found that although the HBD-inactivating mutation impairs the primase activity of NrSPol, it significantly enhances the DNA polymerase activity, indicating that the HBD hinders the DNA polymerase activity. The conflict between the primase activity and the DNA polymerase activity in a single protein with the same catalytic domain may be one reason for why DNA polymerases are generally unable to synthesize DNA de novo.

Association between αß and γδ T-cell subsets and clinicopathological characteristics in patients with breast cancer.

The aim of the present study was to discuss the effect of surgery on the T-lymphocyte subsets of patients with breast cancer (BC) and investigate the association between peripheral blood αß and γδ T-cell counts and the clinicopathological characteristics of BC. The CD3+, CD4+, CD8+ and γδ T-cell subsets in the peripheral blood of healthy volunteers and Patients with BC before and after surgery were determined using flow cytometry. The association between αß and γδ T-cell counts in the peripheral blood and clinicopathological characteristics was analyzed by comparing the differences in the αß and γδ T-cell counts in the peripheral blood of Patients with BC before and after surgery with those of healthy volunteers and combining with clinicopathological data. The CD3+, CD4+ and γδ T-cell counts in the peripheral blood of Patients with BC were lower compared with those in healthy volunteers (P=0.0077, 0.0116 and 0.0003, respectively), whereas the number of CD8+ cells was higher (P=0.0241). The CD3+, CD4+ and γδ T-cell counts and the CD4+/CD8+ ratio after surgery were significantly higher compared with those before surgery (P=0.0109, 0.0031, 0.0165 and 0.018, respectively). There was no significant difference between the number of CD8+ cells before and after surgery (P=0.0053), but the number of CD8+ cells was higher in healthy volunteers compared with that in Patients with BC (P<0.05). Moreover, the CD3+ cell number was higher in patients with TNM stage II/III compared with those with TNM stage I disease (P=0.187 and 0.022, respectively), and the peripheral blood CD4+/CD8+ ratio and number of γδ T cells were lower in stage III compared with stage I Patients with BC (P=0.0065 and 0.0176, respectively). Histological grading demonstrated that the CD4+/CD8+ ratio and number of γδ T cells in patients with stage III BC were lower compared with those with stage I BC (P=0.02 and 0.0128, respectively). The γδ T-cell count in patients with luminal A and B subtypes was significantly higher compared with that in patients with basal-like subtype (P=0.004 and 0.0104, respectively). The CD3+, CD4+ and γδ T-cell counts were significantly lower in patients with lymph node (LN) metastasis compared with those without LN metastasis, and the CD8+ cell number was lower in patients without LN metastasis compared with that in patients with >10 LN metastases (P=0.0086, 0.0000 and 0.00468, respectively). The CD8+ cell count in patients without LN metastasis was lower compared with that in patients with 4-9 and >10 LN metastases (P=0.0435 and 0.0283, respectively). Surgery affects the T-lymphocyte subpopulations in patients with BC, and αß and γδ T-cell counts may increase following mastectomy. Therefore, measurement of peripheral blood lymphocyte subsets is crucial for understanding the immune function status of Patients with BC with differences in TNM stage, histological grade, cell subtypes and LN metastases, and may provide a basis for the application of T-cell subsets in the comprehensive treatment of BC.

An epigenome-wide association study identifies multiple DNA methylation markers of exposure to endocrine disruptors.

BACKGROUND: Exposure to environmental endocrine disrupting chemicals (EDCs) may play an important role in the epidemic of metabolic diseases. Epigenetic alterations may functionally link EDCs with gene expression and metabolic traits. OBJECTIVES: We aimed to evaluate metabolic-related effects of the exposure to endocrine disruptors including five parabens, three bisphenols, and 13 metabolites of nine phthalates as measured in 24-hour urine on epigenome-wide DNA methylation. METHODS: A blood-based epigenome-wide association study was performed in 622 participants from the Lifelines DEEP cohort using Illumina Infinium HumanMethylation450 methylation data and EDC excretions in 24-hour urine. Out of the 21 EDCs, 13 compounds were detected in >75% of the samples and, together with bisphenol F, were included in these analyses. Furthermore, we explored the putative function of identified methylation markers and their correlations with metabolic traits. RESULTS: We found 20 differentially methylated cytosine-phosphate-guanines (CpGs) associated with 10 EDCs at suggestive p-value < 1 × 10-6, of which four, associated with MEHP and MEHHP, were genome-wide significant (Bonferroni-corrected p-value < 1.19 × 10-7). Nine out of 20 CpGs were significantly associated with at least one of the tested metabolic traits, such as fasting glucose, glycated hemoglobin, blood lipids, and/or blood pressure. 18 out of 20 EDC-associated CpGs were annotated to genes functionally related to metabolic syndrome, hypertension, obesity, type 2 diabetes, insulin resistance and glycemic traits. CONCLUSIONS: The identified DNA methylation markers for exposure to the most common EDCs provide suggestive mechanism underlying the contributions of EDCs to metabolic health. Follow-up studies are needed to unravel the causality of EDC-induced methylation changes in metabolic alterations.

Identification, Heritability, and Relation With Gene Expression of Novel DNA Methylation Loci for Blood Pressure.

We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-related CpG sites with P<1×10-5. In silico replication in the CHARGE consortium of 17 010 individuals validated 16 of these CpG sites. Out of the 16 CpG sites, 13 showed novel association with BP. Conversely, out of the 126 CpG sites identified as being associated (P<1×10-7) with BP in the CHARGE consortium, 21 were replicated in the current study. Methylation levels of all the 34 CpG sites that were cross-validated by the current study and the CHARGE consortium were heritable and 6 showed association with gene expression. Furthermore, 9 CpG sites also showed association with BP with P<0.05 and consistent direction of the effect in the meta-analysis of the Finnish Twin Cohort (199 twin pairs and 4 singletons; 61% monozygous) and the Netherlands Twin Register (266 twin pairs and 62 singletons; 84% monozygous). Bivariate quantitative genetic modeling of the twin data showed that a majority of the phenotypic correlations between methylation levels of these CpG sites and BP could be explained by shared unique environmental rather than genetic factors, with 100% of the correlations of systolic BP with cg19693031 (TXNIP) and cg00716257 (JDP2) determined by environmental effects acting on both systolic BP and methylation levels.

Exposure to multiple heavy metals associate with aberrant immune homeostasis and inflammatory activation in preschool children.

Heavy metals generate adverse health effects by interfering with immune homeostasis and promoting inflammation in individuals. Our objective was to explore the induction of immune and inflammatory responses by multiple heavy metals in children living in the e-waste contaminated area. A total of 147 preschool children were recruited, including 73 children from Guiyu, a typical e-waste recycling area, and 74 from a reference group. Blood levels of heavy metals, including lead (Pb), cadmium (Cd), mercury (Hg) and arsenic (As), were detected using an inductively coupled plasma mass spectrometry (ICP-MS). Immune cell counts (neutrophils, monocytes, lymphocytes) were determined by an automatic blood cell analyzer, pro-inflammatory cytokines (IL-1ß, IL-6, IL-8, TNF-α) and anti-inflammatory cytokines (IL-1RA, IL-4, IL-10, IL-13) were analyzed by a Luminex 200 multiplex immunoassay instrument. Multiple correspondences and linear regression analyses were applied to investigate the relationships between heavy metal exposure and relevant parameters. Results shows Guiyu children had higher levels of Pb, Cd, Hg, As, IL-1ß and IL-6, but decreased lymphocyte, IL-1RA and IL-13. Neutrophil count was positively correlated with Pb, Cd and Hg exposure. Anti-inflammatory IL-1RA concentration was negatively related with Pb, Cd, Hg and As, while pro-inflammatory IL-1ß and IL-6 were positively correlated with Pb. Guiyu children may have dysregulated immune response and high inflammation risk. Exposure to Pb, Cd, Hg and As could be harmful for immune response and inflammatory regulation. Our finding of decreased IL-RA production in children exposed to Pb, Cd, Hg, and As is novel and could be an opportunity for future research.

Elevated expression of AhR and NLRP3 link polycyclic aromatic hydrocarbon exposure to cytokine storm in preschool children.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs), as a group of persistent organic pollutants, are linked to impaired immune function and low-grade inflammation in adults and children. However, the potential of PAHs to lead to a cytokine storm associated with AhR (aryl hydrocarbon receptor) and NLRP3 (NLR family pyrin domain containing 3) in humans has been poorly studied. OBJECTIVES: We aimed to investigate the associations between PAH exposure, AhR and NLRP3 expression, and cytokines associated with a cytokine storm in healthy preschoolers. METHODS: Basic demographic surveys and physical examinations were conducted on 248 preschoolers from an electronic waste (e-waste) recycling area (Guiyu, n = 121) and a reference area (Haojiang, n = 127). Ten urinary PAH metabolite (OH-PAH) concentrations were measured. We also measured the expression levels of AhR and NLRP3 and seventeen serum cytokine levels. RESULTS: The concentrations of multiple OH-PAHs were significantly higher in the exposed group than those in the reference group, especially 1-hydroxynaphthalene (1-OH-Nap) and 2-hydroxynaphthalene (2-OH-Nap). PAH exposure was closely related to a child's living environment and hygiene habits. Expression levels of AhR and NLRP3 were significantly higher in the exposed group than in the reference group. Similarly, serum IL-1ß, IL-4, IL-5, IL-10, IL-12p70, IL-13, IL-17A, IL-18, IL-22, IL-23, and IFN-γ levels were notably higher in the e-waste-exposed children than in the reference children. After adjusting for age, gender, BMI, family income, parental education level, and second-hand smoke exposure, we found that increased PAH exposure was associated with higher AhR and NLRP3 expression and elevated IL-4, IL-10, IL-12p70, IL-18, IL-22, IL-23, TNF-α, and IFN-γ levels. The associations between PAH exposure and IL-1ß, IL-18, IFN-γ, and TNF-ß were mediated by NLRP3 expression, and the relationships between PAH exposure and IL-4, IL-10, IL-12p70, IL-22, IL-23, and TNF-α were mediated by AhR expression. CONCLUSIONS: Our findings suggest that the association between PAH exposure and a cytokine storm may be mediated by AhR and NLRP3 expression among preschoolers.

Klebsiella Phage KP34 RNA Polymerase and Its Use in RNA Synthesis.

We have characterized the single subunit RNA polymerase from Klebsiella phage KP34. The enzyme is unique among known bacteriophage RNA polymerases in that it recognizes two unrelated promoter sequences, which provided clues for the evolution of phage single-subunit RNA polymerases. As the first representative enzyme from the "phiKMV-like viruses" cluster, its use in run-off RNA synthesis was investigated. RNA-Seq analysis revealed that the KP34 RNA polymerase does not possess the undesired self-templated RNA terminus extension known for T7 RNA polymerase and is suitable to synthesize RNAs with structured 3' termini such as sgRNAs. A KP34 RNA polymerase Y603F mutant is engineered to incorporate deoxy- and 2'-fluoro ribonucleotide into RNA.

The association of PM2.5 with airway innate antimicrobial activities of salivary agglutinin and surfactant protein D.

Fine particulate matter ≤2.5 µm (PM2.5) is a prominent global public health risk factor that can cause respiratory infection by downregulating the amounts of antimicrobial proteins and peptides (AMPs). Both salivary agglutinin (SAG) and surfactant protein D (SPD) are important AMPs in respiratory mucosal fluid, providing protection against airway pathogen invasion and infection by inducing microbial aggregation and enhancing pathogen clearance. However, the relationship between PM2.5 and these AMPs is unclear. To better understand the relationship between PM2.5 and airway innate immune defenses, we review the respiratory antimicrobial activities of SAG and SPD, as well as the adverse effects of PM2.5 on airway innate antimicrobial defense. We speculate there exists a dual effect between PM2.5 and respiratory antimicrobial activity, which means that PM2.5 suppresses respiratory antimicrobial activity through downregulating airway AMPs, while airway AMPs accelerate PM2.5 clearance by inducing PM2.5 microbial aggregation. We propose further research on the relationship between PM2.5 and these AMPs.

Elevated lead levels from e-waste exposure are linked to sensory integration difficulties in preschool children.

Exposure to lead is associated with adverse effects on neurodevelopment. However, studies of the effects of lead on sensory integration are few. The purpose of this research is to investigate the effect of lead exposure on child sensory integration by correlating the blood lead levels of children with sensory processing measures. A total of 574 children, from 3 to 6 years of age, 358 from an electronic waste (e-waste) recycling town named Guiyu, and 216 from Haojiang, a nearby town with no e-waste recycling activity, were recruited in this study. The median blood lead level in Guiyu children was 4.88 µg/dL, higher than the 3.47 µg/dL blood lead level in Haojiang children (P < 0.001). 47.2% of Guiyu children had blood lead levels exceeding 5 µg/dL. The median concentration of serum cortisol, an HPA-axis biomarker, in Guiyu children was significantly lower than in Haojiang, and was negatively correlated with blood lead levels. All subscale scores and the total score of the Sensory Processing Measure (Hong Kong Chinese version, SPM-HKC) in Guiyu children were higher than Haojiang children, indicating greater difficulties, especially for touch, body awareness, balance and motion, and total sensory systems. Sensory processing scores were positively correlated with blood lead, except for touch, which was negatively correlated with serum cortisol levels. Simultaneously, all subscale scores and the total SPM-HKC scores for children with high blood lead levels (blood lead > 5 µg/dL) were higher than those in the low blood lead level group (blood lead < 5 µg/dL), especially for hearing, touch, body awareness, balance and motion, and total sensory systems. Our findings suggest that lead exposure in e-waste recycling areas may result in a decrease in serum cortisol levels and an increase in child sensory integration difficulties. Cortisol may be involved in touch-related sensory integration difficulties.