Rare genetic coding variants associated with age-related episodic memory decline implicate distinct memory pathologies in the hippocampus.

Background: Approximately 40% of people aged 65 or older experience memory loss, particularly in episodic memory. Identifying the genetic basis of episodic memory decline is crucial for uncovering its underlying causes. Methods: We investigated common and rare genetic variants associated with episodic memory decline in 742 (632 for rare variants) Ashkenazi Jewish individuals (mean age 75) from the LonGenity study. All-atom MD simulations were performed to uncover mechanistic insights underlying rare variants associated with episodic memory decline. Results: In addition to the common polygenic risk of Alzheimer's Disease (AD), we identified and replicated rare variant association in ITSN1 and CRHR2 . Structural analyses revealed distinct memory pathologies mediated by interfacial rare coding variants such as impaired receptor activation of corticotropin releasing hormone and dysregulated L-serine synthesis. Discussion: Our study uncovers novel risk loci for episodic memory decline. The identified underlying mechanisms point toward heterogeneous memory pathologies mediated by rare coding variants.

Distinctive multicellular immunosuppressive hubs confer different intervention strategies for left- and right-sided colon cancers.

Primary colon cancers arising from the left and right sides exhibit distinct clinical and molecular characteristics. Sidedness-associated heterogeneity relies intricately on the oncogenic properties of cancer cells and multicellular interactions in tumor microenvironments. Here, combining transcriptomic profiling of 426,863 single cells from 105 colon cancer patients and validation with spatial transcriptomics and large-scale histological analysis, we capture common transcriptional heterogeneity patterns between left- and right-sided malignant epithelia through delineating two side-specific expression meta-programs. The proliferation stemness meta-program is notably enriched in left-sided malignant epithelia that colocalize with Mph-PLTP cells, activated regulatory T cells (Tregs), and exhausted CD8-LAYN cells, constituting the glucose metabolism reprogramming niche. The immune secretory (IS) meta-program exhibits specific enrichment in right-sided malignant epithelia, especially in smoking patients with right-sided colon cancer. The IShigh malignant epithelia spatially localize in hypoxic regions and facilitate immune evasion through attenuating Mph-SPP1 cell antigen presentation and recruiting innate-like cytotoxicity-reduced CD8-CD161 cells.

Genetic variants in C1GALT1 are associated with gastric cancer risk and immune infiltrations.

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-ß-galactosyltransferase 1 (C1GALT1) is known to play a critical role in the development of gastric cancer, but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer susceptibility. By using the genome-wide association study data from the database of Genotype and Phenotype (dbGAP), we evaluated these associations with a logistic regression model and identified that the rs35999583 in C1GALT1 was associated with gastric cancer risk (odd ratio, 0.83; 95% confidence interval [CI], 0.75-0.92; P = 3.95 × 10 -4]. C1GALT1 mRNA expression was significantly higher in gastric tumor tissues, and gastric cancer patients with higher C1GALT1 mRNA levels had the worse overall survival rates (hazards ratio, 1.33; 95% CI, 1.05-1.68; P log-rank = 1.90 × 10 -2). Furthermore, we found that C1GALT1 copy number variations differed in various immune cells and C1GALT1 mRNA expression was positively correlated with the infiltrating levels of CD4 + T cells and macrophages. These results highlight that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 to be a promising predictor of gastric cancer susceptibility and immune status.

Expression profiling and bioinformatics analysis of serum exosomal circular RNAs in lymph node metastasis of papillary thyroid carcinoma.

Most papillary thyroid carcinoma (PTC) patients have a good prognosis, but lymph node metastasis (LNM) is the most common progressive manifestation and often leads to a poor-prognosis. However, few studies focused on the underlying mechanisms of LNM. This study aimed to identity the potential role of exosomal circRNAs that contribute to LNM in PTC. We found that 9000 aberrantly expressed exosomal circRNAs in PTC patients with LNM, including 684 observably upregulation and 2193 notably downregulation. Functional enrichment analyses indicated that these aberrantly expressed circRNAs were mainly enriched in a variety of molecules and signaling pathways related to the progression and LNM of PTC. Bioinformatics analysis screened 14 circRNA-miRNA-mRNA networks associated with LNM-related signaling pathways in PTC. Moreover, circTACC2-miR-7-EGFR and circBIRC6-miR-24-3p-BCL2L11 axes were verified for potential involvement in PTC with LNM. Additionally, 4 upregulated circRNAs-related hub genes and 8 hub genes associated with downregulated circRNAs were screened, some of which were involved in LNM of PTC through verification. Collectively, our data provided a novel framework for in-depth investigation of the function of dysregulated exosomal circRNAs and their potential biomarkers in PTC patients with LNM.

Biomimetic bone-periosteum scaffold for spatiotemporal regulated innervated bone regeneration and therapy of osteosarcoma.

The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.

Simultaneous Rapid Detection of Multiple Physicochemical Properties of Jet Fuel Using Near-Infrared Spectroscopy.

Jet fuel is the primary fuel used in the aviation industry, and its quality has a direct impact on the safety and operational efficiency of aircraft. The accurate quantitative detection and analysis of various physicochemical property indicators are important for improving and ensuring the quality of jet fuel in the domestic market. This study used near-infrared (NIR) spectroscopy to establish a suitable model for the simultaneous and rapid detection of multiple physicochemical properties in jet fuel. Using more than 40 different sources of jet fuel, a rapid detection model was established by optimizing the spectral processing methods. The measurement models were separately built using the partial least-squares (PLS) and orthogonal PLS algorithms, and the model parameters were optimized. The results show that after the Savitzky-Golay second derivative preprocessing, the PLS model built using the feature spectra selected by the uninformative variable elimination wavelength algorithm achieved the best measurement performance. Compared with the PLS model without preprocessing, the range of the resulting accuracy improvement was at least 15.01%. Under the optimal model parameters, the calibration set regression coefficient (Rc2) of the 11 jet fuel property index models ranged from 0.9102 to 0.9763, with the root-mean-square error of calibration values up to 0.8468 °C (for flash points). The regression coefficient (Rp2) of the validation set ranged from 0.8239 to 0.9557, with the root-mean-square error of prediction values up to 1.1354 °C (for flash points). The ratios of prediction to deviation (RPD) values were all in the range of 1.9-3.0, indicating high accuracy and reliability of the model. The rapid NIR analysis method established in this study enables the simultaneous and rapid detection of multiple physicochemical properties of jet fuel, thereby providing effective technical support for ensuring the quality of jet fuel in the market.

Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment.

The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a genome-wide survival association analysis to develop eight candidate PPSs. Further using an independent cohort with 470 patients, we identify the 287 variants-derived PPS (i.e., PPS287) achieving an optimal prediction performance [hazard ratio (HR) per SD = 1.99, P = 1.76 × 10-8], accompanied by additional tests in two external cohorts, with HRs per SD of 1.90 (P = 3.21 × 10-14; 543 patients) and 1.80 (P = 1.11 × 10-9; 713 patients). Notably, the detrimental impact of pathologic characteristics and genetic risk could be attenuated by a healthy lifestyle, yielding a 7.62% improvement in the 5-year overall survival rate. Therefore, our findings demonstrate the integrated contribution of pathologic characteristics, germline variants, and lifestyle exposure to the prognosis of colorectal cancer patients.

AKR1C2 genetic variants mediate tobacco carcinogens metabolism involving bladder cancer susceptibility.

Tobacco carcinogens metabolism-related genes (TCMGs) could generate reactive metabolites of tobacco carcinogens, which subsequently contributed to multiple diseases. However, the association between genetic variants in TCMGs and bladder cancer susceptibility remains unclear. In this study, we derived TCMGs from metabolic pathways of polycyclic aromatic hydrocarbons and tobacco-specific nitrosamines, and then explored genetic associations between TCMGs and bladder cancer risk in two populations: a Chinese population of 580 cases and 1101 controls, and a European population of 5930 cases and 5468 controls, along with interaction and joint analyses. Expression patterns of TCMGs were sourced from Nanjing Bladder Cancer (NJBC) study and publicly available datasets. Among 43 TCMGs, we observed that rs7087341 T > A in AKR1C2 was associated with a reduced risk of bladder cancer in the Chinese population [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.72-0.97, P = 1.86 × 10-2]. Notably, AKR1C2 rs7087341 showed an interaction effect with cigarette smoking on bladder cancer risk (Pinteraction = 5.04 × 10-3), with smokers carrying the T allele increasing the risk up to an OR of 3.96 (Ptrend < 0.001). Genetically, rs7087341 showed an allele-specific transcriptional regulation as located at DNA-sensitive regions of AKR1C2 highlighted by histone markers. Mechanistically, rs7087341 A allele decreased AKR1C2 expression, which was highly expressed in bladder tumors that enhanced metabolism of tobacco carcinogens, and thereby increased DNA adducts and reactive oxygen species formation during bladder tumorigenesis. These findings provided new insights into the genetic mechanisms underlying bladder cancer.

Accurate identification of methanol and ethanol gasoline types and rapid detection of the alcohol content using effective chemical information.

Methanol and ethanol gasoline are two emerging clean energy sources with different characteristics. To achieve the qualitative identification and quantitative analysis of the alcohols present in methanol and ethanol gasoline, effective chemical information (ECI) models based on the characteristic spectral bands of the near-infrared (NIR) spectra of the methanol and ethanol molecules were developed using the partial least squares discriminant analysis (PLS-DA) and partial least squares (PLS) algorithms. The ECI model was further compared with models built from the full wavenumber (Full) spectra, variable importance in projection (VIP) spectra, and Monte Carlo uninformative variable elimination (MC-UVE) spectra to determine the predictive performance of ECI model. Among the various qualitative identification models, it was found that the ECI-PLS-DA model, which is built using the differences in molecular chemical information between methanol and ethanol, exhibited sensitivity, specificity and accuracy values of 100%. The ECI-PLS-DA model accurately identified methanol gasoline and ethanol gasoline with different contents. In the quantitative analysis model for methanol gasoline, the methanol gasoline and ethanol gasoline ECI-PLS models exhibited the smallest root mean squared error of predictions (RMSEP) of 0.18 and 0.21% (v/v), respectively, compared to the other models. Meanwhile, the F-test and T-test results revealed that the NIR method employing the ECI-PLS model showed no significant difference compared to the standard method. Compared with other spectral models examined herein, the ECI model demonstrated the highest recognition success and determination accuracy. This study therefore established a highly accurate and rapid determination model for the qualitative identification and quantitative analysis based on chemical structures. It is expected that this model could be extended to the NIR analysis of other physicochemical properties of fuel.

Single-cell and multi-omics analyses highlight cancer-associated fibroblasts-induced immune evasion and epithelial mesenchymal transition for smoking bladder cancer.

Tobacco carcinogens are recognized as critical hazard factors for bladder tumorigenesis, affecting the prognosis of patients through aromatic amines components. However, the specific function of tobacco carcinogens and systematic assessment models in the prognosis of bladder cancer remains poorly elucidated. We retrieved bladder cancer specific tobacco carcinogens-related genes from Comparative Toxicogenomic Database, our Nanjing Bladder Cancer cohort and TCGA database. Gene×Gene interaction method was utilized to establish a prognostic signature. Integrative assessment of immunogenomics, tumor microenvironments and single-cell RNA-sequencing were performed to illustrate the internal relations of key events from different levels. Finally, we comprehensively identified 33 essential tobacco carcinogens-related genes to construct a novel prognostic signature, and found that high-risk patients were characterized by significantly worse overall survival (HR=2.25; Plog-rank < 0.01). Single-cell RNA-sequencing and multi-omics analysis demonstrated that cancer-associated fibroblasts mediated the crosstalk between epithelial-mesenchymal transition progression and immune evasion. Moreover, an adverse outcome pathway framework was established to facilitate our understanding to the tobacco carcinogens-triggered bladder tumorigenesis. Our study systematically provided immune microenvironmental alternations for smoking-induced adverse survival outcomes in bladder cancer. These findings facilitated the integrative multi-omics insights into risk assessment and toxic mechanisms of tobacco carcinogens.

Diagnosis, Treatment, and Associated Factors Among Patients with HCV Infection - Jiangsu Province, China, 2004-2020.

What is already known on this topic?: The global efforts to address the hepatitis C virus (HCV) are progressing, but there are still significant gaps in the diagnosis and treatment of HCV, leading to an increasing number of deaths related to HCV. What is added by this report?: An extensive investigation was conducted to assess HCV RNA diagnosis, treatment uptake, and associated factors among individuals infected with HCV within Jiangsu Province. The study encompassed a large geographical area and utilized a substantial sample size. What are the implications for public health practice?: Implementing focused interventions to improve the timely diagnosis of HCV RNA and increase the uptake of HCV treatment could effectively reduce the future burden of HCV-related health problems, deaths, and healthcare expenses. This is essential for achieving the global target of eliminating hepatitis C.

Ferroptosis: Mechanisms and role in diabetes mellitus and its complications.

Diabetes mellitus (DM) and its complications are major diseases that affect human health and pose a serious threat to global public health. Although the prevention and treatment of DM and its complications are constantly being revised, optimal treatment strategies remain unavailable. Further exploration of new anti-diabetic strategies is an arduous task. Revealing the pathological changes and molecular mechanisms of DM and its complications is the cornerstone for exploring new therapeutic strategies. Ferroptosis is a type of newly discovered iron-dependent regulated cell death. Notably, the role of ferroptosis in the occurrence, development, and pathogenesis of DM and its complications has gradually been revealed. Numerous studies have shown that ferroptosis plays an important role in the pathophysiology and pathogenesis of DM and its associated complications. The aim of this review is to discuss the known underlying mechanisms of ferroptosis, the relationship between ferroptosis and DM, and the relationship between ferroptosis as a mode of cell death and diabetic kidney disease, diabetic retinopathy, diabetic cardiomyopathy, diabetic osteoporosis, diabetes-associated cognitive dysfunction, DM-induced erectile dysfunction, and diabetic atherosclerosis.

Pyroptosis: Mechanisms and links with diabetic cardiomyopathy.

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycaemia that seriously affects human health. Diabetic cardiomyopathy (DCM) is a major cardiovascular complication and one of the main causes of death in patients with DM. Although DCM attracts great attention, and new therapeutic methods are continuously developed, there is a lack of effective treatment strategies. Therefore, exploring and targeting new signalling pathways related to the evolution of DCM becomes a hotspot and difficulty in the prevention and treatment of DCM. Pyroptosis is a newly discovered regulated cell death that is heavily dependent on the formation of plasma membrane pores by members of the gasdermin protein family and is reported to be involved in the occurrence, development, and pathogenesis of DCM. In this review, we focus on the molecular mechanisms of pyroptosis, its involvement in the relevant signalling pathways of DCM, and potential pyroptosis-targeting therapeutic strategies for the treatment of DCM. Our review provides new insights into the use of pyroptosis as a useful tool for the prevention and treatment of DCM and clarifies future research directions.

Cigarette smoking combined with genetic variation regulates the m6A methylation of CRNKL1 and is associated with bladder cancer risk.

Cigarette smoking was known to accelerate the occurrence and development of bladder cancer by regulating RNA modification. However, the association between the combination of cigarette smoking and RNA modification-related single nucleotide polymorphisms (RNAm-SNPs) and bladder cancer risk remains unclear. In this study, 1681 participants, including 580 cases and 1101 controls, were recruited for genetic association analysis. In total, 1 287 990 RNAm-SNPs involving nine RNA modifications (m6A, m1A, m6Am, 2'-O-Me, m5C, m7G, A-to-I, m5U, and pseudouridine modification) were obtained from the RMVar database. The interactive effect of cigarette smoking and RNAm-SNPs on bladder cancer risk was assessed through joint analysis. The susceptibility analysis revealed that 89 RNAm-SNPs involving m6A, m1A, and A-to-I modifications were associated with bladder cancer risk. Among them, m6A-related rs2273058 in CRNKL1 was associated with bladder cancer risk (odds ratios (OR) = 1.35, padj = 1.78 × 10-4), and CRNKL1 expression was increased in bladder cancer patients (p = 0.035). Cigarette smoking combined with the A allele of rs2273058 increased bladder cancer risk compared with nonsmokers with the G allele of rs2273058 (OR = 2.40, padj = 3.11 × 10-9). Mechanistically, the A allele of rs2273058 endowed CRNKL1 with an additional m6A motif, facilitating recognition by m6A reader IGF2BP1, thereby promoting CRNKL1 expression under cigarette smoking (r = 0.142, p = 0.017). Moreover, elevated CRNKL1 expression may accelerate cell cycle and proliferation, thereby increasing bladder cancer risk. In summary, our study demonstrated that cigarette smoking combined with RNAm-SNPs contributes to bladder cancer risk, which provides a potential target for bladder cancer prevention.

Assessment of human exposure to cadmium and its nephrotoxicity in the Chinese population.

BACKGROUND: Cadmium (Cd) is a toxic heavy metal that widely detected in environment and accumulated in kidney, posing a great threat to human health. However, there is a lack of systematic investigation of exposure profile and association of Cd exposure with renal function in the Chinese population. METHODS: Related articles were searched from PubMed, Web of Science, China National Knowledge Internet, and Wanfang to construct an aggregate exposure pathway (AEP) framework for Cd and to explore the correlation between Cd and renal function using random effects models. RESULTS: A total of 220 articles were included in this study, among which 215 investigated human exposure and 12 investigated the association of Cd with renal outcomes. The AEP framework showed that 96.5 % and 62.5 % of total Cd intake were attributed to dietary intake in nonsmokers and smokers, respectively. And 35.2 % originated from cigarette smoke inhalation in smokers. In human body, Cd was detected in blood, urine, placenta, etc. Although the concentrations of Cd in blood and urine from subjects living in polluted areas showed a sharp downward trend since the early 21st century, higher concentration of Cd in the environment and human body in polluted areas was found. Kidney was the target organ. The level of blood Cd was positively associated with urinary ß2-microglobulin [ß2-MG, r (95 % CI) = 0.12 (0.05, 0.19)], albumin [0.13 (0.06, 0.20)], and retinol-binding protein [RBP, 0.14 (0.03, 0.24)]. Elevated urinary Cd was correlated with increases in ß2-MG [0.22 (0.15, 0.29)], albumin [0.23 (0.16, 0.29)], N-acetyl-ß-d-glucosaminidase [NAG, 0.33 (0.22, 0.44)], and RBP [0.22 (0.14, 0.30)]. CONCLUSIONS: Foods and cigarette smoke were two major ways for Cd intake, and Cd induced renal injury in the Chinese population. This study enhanced the understanding of human exposure and nephrotoxicity of Cd, and emphasized the need for controlling Cd level in polluted areas.

A comparative study of laparoscopic choledocholithotomy with primary suture and T-tube drainage.

To investigate the clinical efficacy of laparoscopic choledocholithotomy with one-stage suture. The clinical data of 68 patients who underwent laparoscopic choledocholithotomy in our hospital from January 2015 to December 2021 were retrospectively analyzed. Among them, 29 patients underwent laparoscopic primary closure (PC group) and 39 underwent T-tube drainage (T-tube group). All patients were diagnosed with choledocholithiasis by B-ultrasound, CT or MRCP. The operation time, intraoperative blood loss, pain index, incidence of shoulder and back pain, postoperative satisfaction, postoperative bowel function recovery time, hospitalization time and expenses, and operation-related complications in the 2 groups were compared. 29 cases in PC group were successfully operated, and 39 cases in the T-tube drainage group (T-tube group) were successfully operated. The average operation time, postoperative bowel function recovery time, postoperative pain index, hospitalization time and expenses in PC group were significantly shorter or lower than those in T-tube group (P < .05) and the patient satisfaction in PC group was significantly higher than that in T-tube group (P < .05). In addition, the intraoperative blood loss and the incidence of surgical complications were similar between the 2 groups (P > .05). After laparoscopic common bile duct exploration, primary suture of common bile duct is a safe and effective treatment method, but the incidence of bile leakage is high, and clinical indications for surgery should be strictly controlled.

Deciphering the pivotal role of people with high-frequency occupational animal exposure in antibiotic resistance transmission between humans and animals.

BACKGROUND: The spread of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) among humans and food-producing animals has been widely reported. However, the transmission routes and associated risk factors remain incompletely understood. METHODS: Here, we used commensal Escherichia coli bacteria strains from faeces of pigs and local citizens [HEG: high exposure group (pig breeders, butchers or restaurant chefs) and LEG: low exposure group (other occupations)] to explore the dynamics of ARB and ARG transmission between animals and humans. RESULTS: Most ARGs (96%) present in pigs were shared with humans. Carriage rates of the shared ARGs suggest two transmission patterns among pigs, the HEG and LEG: one pattern was highest in pigs, gradually decreasing in the HEG and LEG (e.g. floR and cmlA1); the other pattern was increasing from pigs to the HEG but then decreasing in the LEG (e.g. mcr-1.1). Carriage rates of the HEG were higher than in the LEG in both patterns, implicating the HEG as a crucial medium in transmitting ARB and ARGs between food-producing animals and humans. Moreover, frequent inter/intragroup transmission via strains, plasmids and/or mobile elements was evident. Carriage of mcr-1.1 on human-gut-prevalent plasmids possibly promoted its enrichment in the HEG. CONCLUSIONS: The HEG is a crucial factor in transmitting ARB and ARGs between food-producing animals and humans. Rational measures to contain the risks of occupational exposure are urgently needed to keep dissemination of antibiotic resistance in check and safeguard public health.

PM2.5-derived exosomal long noncoding RNA PAET participates in childhood asthma by enhancing DNA damage via m6A-dependent OXPHOS regulation.

Fine particulate matter (PM2.5) is known to enhance DNA damage levels and is involved in respiratory diseases. Exosomes can carry noncoding RNAs, especially long noncoding RNAs (lncRNAs), as regulators of DNA damage, which participate in diseases. However, their role in PM2.5-induced childhood asthma remains unclear. We performed RNA-seq to profile aberrantly expressed exosomal lncRNAs derived from PM2.5-treated human bronchial epithelial (HBE) cell models. The role of exosomal lncRNAs in childhood asthma was determined in a case-control study. The intercellular communication mechanisms of exosomal lncRNA on DNA damage were determined in vitro. Exosomes secreted by PM2.5-treated HBE cells (PM2.5-Exos) could increase the DNA damage levels of recipient HBE cells and promote the expression levels of airway remodeling-related markers in sensitive human bronchial smooth muscle cells (HBSMCs). LncRNA PM2.5-associated exosomal transcript (PAET) was highly expressed in PM2.5-Exos and was associated with PM2.5 exposure in childhood asthma. Mechanistically, exosomal lncRNA PAET promoted methyltransferase-like 3 (METTL3) accumulation by increasing its stability, which stimulated N6-methyladenosine (m6A) modification of cytochrome c oxidase subunit 4I1 (COX4I1), and COX4I1 levels were decreased in a mechanism dependent on the m6A "reader" YTH domain family 3 (YTHDF3). COX4I1 deficiency subsequently disrupted oxidative phosphorylation (OXPHOS), resulting in attenuated adenosine triphosphate (ATP) production and accumulation of reactive oxygen species (ROS), which increased DNA damage levels. This comprehensive study extends the understanding of PM2.5-induced childhood asthma via DNA damage and identifies exosomal lncRNA PAET as a potential target for childhood asthma.