Hao Wang

Environmental metal exposure is associated with adverse health outcomes, yet the relationship between long non-coding RNAs (lncRNAs) and metal exposure remains poorly understood. This study aimed to explore plasma lncRNA expression profiles in relation to multi-metal exposure, examine tissue enrichment patterns, and annotate pathway-level enrichment. We measured 23 plasma metals using inductively coupled plasma–mass spectrometry (ICP-MS) and profiled lncRNAs via high-throughput gene chip technology in 160 healthy Chinese adults. Associations were assessed using linear regression (FDR < 0.05), the two-way orthogonal partial least squares (O2PLS) model and quantile g-computation to evaluate mixture effects. Tissue enrichment patterns were explored using the tissue specificity index (TSI), and correlations between plasma and leukocyte lncRNA expression were examined using linear regression models. Functional pathways were analyzed through Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA). Linear regression identified nine metals associated with 1047 lncRNAs. Lead, nickel, and vanadium exhibited strong intercorrelations and were jointly associated with 300 lncRNAs. Both O2PLS and quantile g-computation revealed that a mixture of 11 metals was associated with decreased expression of three specific lncRNAs. Tissue-specific analysis indicated enrichment of Pb–Ni–V-related lncRNAs in the pituitary and brain. Seven of these lncRNAs were significantly correlated with leukocyte expression. GO enrichment classified the lncRNAs into two categories, one enriched in RNA processing and the other in vesicle transport. GSEA further showed enrichment of RNA processing-related lncRNAs in oxidative stress-related pathways and vesicle organization-related lncRNAs in secretory pathways. Our findings provided new insights into the health effects of environmental metal exposures and identified metal-associated lncRNA signals that may inform future hypothesis-driven research.

Background: The continuous evolution of SARS-CoV-2 necessitates the development of targeted strategies based on the immunological profiles of distinct age groups. Despite this imperative, comprehensive insights into the dynamics and broad-spectrum efficacy of neutralizing antibodies (NAbs) against emerging variants across different age groups, particularly in children, remain inadequate. Methods: Following the termination of China’s dynamic ‘zero-COVID-19’ policy in January 2023, which coincided with a widespread Omicron outbreak and numerous breakthrough infections, a longitudinal cohort study was established encompassing all age groups in Hubei, China. Follow-up assessments were conducted in March (Visit 1), June (Visit 2), and October (Visit 3) 2023. A total of 320 individuals were randomly selected and stratified into three age categories: children (<18 years, n = 80), adults (18–59 years, n = 167), and the elderly (≥60 years, n = 73). The NAbs against emerging SARS-CoV-2 variants BA.5, XBB.1.5, EG.5, and JN.1 were evaluated for each group. Trajectory modeling was employed to classify antibody trends into five categories: low-level stability, median-level stability, high-level stability, early increase, and late increase. Results: In March 2023, children exhibited significantly higher NAb levels against BA.5, XBB.1.5, EG.5, and JN.1 compared to adults and the elderly. However, these levels rapidly declined. From June to October 2023, no significant difference in NAb levels was observed between children and the other age groups. Regarding the broad-spectrum effectiveness of NAbs, the effectiveness in children was comparable to that of adults and the elderly in March 2023. However, from June to October 2023, children’s effectiveness became significantly lower than that of the other age groups. Trajectory analysis revealed that the highest proportions of high-level stability (31.3%) and median-level stability (42.5%) were observed among children. In contrast, adults and the elderly were most commonly categorized into the early increase (adult 46.7%, elderly 49.3%) and median-level stability (adult 22.1%, elderly 20.5%) categories. Conclusions: Although children initially demonstrate higher levels of NAbs, these levels decrease more rapidly than in adults and the elderly, eventually equalizing in later stages of recovery. Furthermore, the broad-spectrum effectiveness of NAbs in children is narrower than in other age groups. These findings suggest that children are at an elevated risk of infection with newly emerging variants, underscoring the urgent need to intensify focus on reinfections among children and develop tailored strategies to protect this vulnerable population.

Background: The dietary inflammatory index (DII) is a literature-derived index to assess the inflammatory potential of diet. While numerous studies have linked a higher DII score to an increased risk of mortality, there are limited studies among individuals with diabetes. Objective: To investigate the association of the DII with all-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality among individuals with diabetes, and to explore whether diabetes duration could modify these associations. Methods: A total of 9942 participants with diabetes from the UK Biobank were included. The DII scores were calculated based on 24-h dietary data. Outcomes were ascertained from linked records. The hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality according to DII quartiles were estimated using Cox proportional hazards models. Results: During the median follow-up period of 12.1 years, 1225 (12.3%) participants with diabetes died. The multivariable HRs (95% CIs) in the highest quartile compared with the lowest DII quartiles were 1.30 (1.06, 1.58) for mortality, 1.67 (1.13, 2.48) for CVD mortality, and 1.00 (0.73, 1.38) for cancer mortality. Spline regression analysis indicated significant nonlinear associations between DII and mortality, while the relationship with CVD mortality was linear. Moreover, diabetes duration significantly modified the association between DII and all-cause mortality (P-interaction = 0.002). In participants with diabetes duration of less than 5 years, the HR (95% CIs) for all-cause mortality in the highest versus lowest DII quartile was 1.73 (1.25, 2.39), while for those with diabetes duration of 5 years or more, the HR (95% CIs) was 1.08 (0.83, 1.39). Conclusion: A higher DII, indicating a pro-inflammation dietary pattern, is associated with an elevated risk of all-cause mortality and CVD mortality in individuals with diabetes. Notably, the association with mortality is more pronounced in those with diabetes duration less than 5 years.

Objectives: Identifying immune-protective biomarkers is crucial for the effective management and mitigation of current and future COVID-19 outbreaks, particularly in preventing or counteracting the immune evasion exhibited by the Omicron variants. The emergence of SARS-CoV-2 variants, especially those within the Omicron lineage, has highlighted their capacity to evade neutralizing antibodies, emphasizing the need to understand the role of antibody-dependent cell-mediated cytotoxicity (ADCC) in combating these infections. Methods: This study, conducted in Qichun City, Hubei province, from December 2021 to March 2023, involved 50 healthy Chinese adults who had received two doses of inactivated vaccines and had subsequently experienced mild infections with the Omicron BA.5 variant. Blood samples from these 50 healthy Chinese adults were collected at six distinct time points: at baseline and at the 1st, 3rd, 6th, and 9th months following the third dose of the inactivated vaccine, as well as 3 months post-breakthrough infection. Their sera were analyzed to assess ADCC and neutralization effects. Results: The results indicated that the antibodies elicited by the inactivated SARS-CoV-2 vaccine targeted the spike protein, exhibiting both pre-existing neutralizing and ADCC activities against Omicron variants BA.5 and XBB.1.5. Notably, the ADCC activity demonstrated greater stability compared to that of the neutralizing effects, persisting for at least 15 months post-vaccination, and could be augmented by additional vaccine doses and breakthrough infections. The ADCC effect associated with hybrid immunity effectively targets a spectrum of prospective Omicron variants, including BA.2.86, CH.1.1, EG.5.1, and JN.1. Conclusions: In light of its stability and broad-spectrum efficacy, we recommend the use of the ADCC effect as a biomarker for assessing protective immunity and guiding the development of vaccines and monoclonal antibodies.

Summary: System-wide molecular characteristics of COVID-19, especially in those patients without comorbidities, have not been fully investigated. We compared extensive molecular profiles of blood samples from 231 COVID-19 patients, ranging from asymptomatic to critically ill, importantly excluding those with any comorbidities. Amongst the major findings, asymptomatic patients were characterized by highly activated anti-virus interferon, T/natural killer (NK) cell activation, and transcriptional upregulation of inflammatory cytokine mRNAs. However, given very abundant RNA binding proteins (RBPs), these cytokine mRNAs could be effectively destabilized hence preserving normal cytokine levels. In contrast, in critically ill patients, cytokine storm due to RBPs inhibition and tryptophan metabolites accumulation contributed to T/NK cell dysfunction. A machine-learning model was constructed which accurately stratified the COVID-19 severities based on their multi-omics features. Overall, our analysis provides insights into COVID-19 pathogenesis and identifies targets for intervening in treatment.