Antibiotics are a cornerstone of modern medicine, saving countless lives. However, their widespread use presents two major challenges. First, antibiotic-induced changes in the microbiome can disrupt immune function, increasing the susceptibility to diseases associated with these alterations. Second, prolonged antibiotic use fosters the proliferation of antibiotic resistance genes, leading to the emergence of resistant strains and threatening our ability to control infections. These challenges highlight an urgent global health crisis, necessitating in-depth investigation into the multifaceted effects of antibiotic exposure on microbiome dynamics and human health. In this review, we explore the potential effects of antibiotic exposure on the microbiome and its implications for overall health. Additionally, we examine the role of emerging technologies in addressing these challenges and in shaping future antibiotic development. Our goal is to provide insights that will inform more effective public health strategies and interventions aimed at mitigating the adverse consequences of antibiotic use, restoring microbial balance, and improving overall health outcomes.

Background: This study aimed to elucidate the consistency of differentially expressed hub mRNAs and proteins in lung adenocarcinoma (LUAD) across populations and to construct a comprehensive LUAD prognostic signature. Methods: The transcriptomic and proteomics data from different populations were standardized and analyzed using the same criteria to identify the consistently differential expressed mRNAs and proteins across genders and races. We then integrated prognosis-related mRNAs with clinical, pathological, and EGFR (epidermal growth factor receptor) mutation data to construct a survival model, subsequently validating it across populations. Through plasma proteomics, plasma proteins that consistently differential expressed with LUAD tissues were screened and validated, with their associations discerned by measuring expressions in tumor tissues and tumor vascular normalization. Results: The consistency rate of differentially expressed mRNAs and proteins was ~20–40%, with ethnic factors leading to about 40–60% consistency of differentially expressed mRNA or protein across populations. The survival model based on the identified eight hub mRNAs as well as stage, smoking status, and EGFR mutations, demonstrated good prognostic prediction capabilities in both Western and East Asian populations, with a higher number of unfavorable variables indicating poorer LUAD prognosis. Notably, GPI expression in tumor tissues was inversely correlated with vascular normalization and positively correlated with plasma GPI expression. Conclusion: Our study underscores the significance of integrating transcriptomics and proteomics data, emphasizing the need to account for genetic diversity among ethnic groups. The developed survival model may offer a holistic perspective on LUAD progression, enhancing prognosis and therapeutic strategies.

Ubiquitin modification and alternative polyadenylation play crucial roles in the onset and progression of cancer. Hence, this study aims to comprehensively and deeply understand gene regulation and associated biological processes in lung adenocarcinoma (LUAD) by integrating both mechanisms. Alternative polyadenylation (APA)-related E3 ubiquitin ligases in LUAD were identified through multiple databases, and the association between selected genetic loci influencing gene expression (apaQTL-SNPs) and LUAD risk were evaluated through the GWAS database of the Female Lung Cancer Consortium in Asia (FLCCA). Subsequently, the interaction between RNF213 and ZBTB20, as well as their functional mechanisms in LUAD, were investigated using bioinformatics analysis, Western blot, co-immunoprecipitation, and colony formation experiments. A total of five apaQTL-SNPs (rs41301932, rs4494603, rs9890400, rs56066320, and rs41301932), located on RNF213, were significantly associated with LUAD risk (p < 0.05), and they inhibit tumor growth through ubiquitin-mediated degradation of ZBTB20.