Colorectal cancer (CRC) is a highly heterogeneous malignancy that is divided into four consensus molecular subtypes (CMSs), with CMS4 considered to be the worst type of CRC. The CMS classification has not been translated into clinical practice through the transcriptomic data; thus, the identification of a novel biomarker that can identify CRC subpopulations is imperative. Using bioinformatic analysis and immunohistochemical verification, we found that PLXNC1 mRNA and protein expression were significantly up-regulated in CRC tissues. High PLXNC1 was found to be significantly associated with aggressiveness and poor prognosis and thus was confirmed as an independent prognostic factor for CRC. CMS4 CRC could be distinguished from other subtypes based on PLXNC1 expression. The tumor microenvironment was investigated by deconvolution algorithms through bulk and single-cell RNA-sequencing data. CRC with high PLXNC1 expression exhibited a distinct mesenchymal phenotype, accompanied by high infiltration of stromal components, angiogenesis, complement activation, and an immunosuppressive microenvironment. The functions of PLXNC1 were assessed by proliferation, migration, and invasion assays in CRC cells in vitro. A subcutaneous tumor model and liver metastasis model of CRC were generated to explore the effects of PLXNC1 in vivo. Combined with RNA-sequencing analysis, PLXNC1 promoted CRC growth and metastasis by regulating epithelial-mesenchymal transformation and immune escape. Knockdown of PLXNC1 reduced the CMS4-related phenotypes in CRC. In vitro co-culture and in vivo experiments revealed that PLXNC1 could impair the cytotoxicity of CD8+ T cells, thus facilitating immune evasion by CRC cells. We demonstrate that PLXNC1 may predict poor prognosis of CRC, exhibit pro-oncogenic effects, and accelerate tumor immune escape in CRC progression. Our study uncovers a novel biomarker for CMS4 CRC and suggests PLXNC1 as an indicator for prognosis and a potential drug target of high-risk CRC.

Advances in DNA technology are revolutionizing the landscape of illness prevention, providing new opportunities to combat hereditary abnormalities and chronic diseases before they manifest. CRISPR-Cas9 gene editing, epigenetic alterations, somatic cell genome editing, and RNA-based therapies are all significant advancements in this field. These techniques enable precise changes to DNA and gene expression, potentially preventing a wide range of illnesses at their genetic origins. The following discussion delves into the transformative potential of these technologies. CRISPR-Cas9 is notable for its precision in fixing defective genes, offering promise for avoiding diseases, such as cystic fibrosis and sickle cell anemia. Epigenetic modifications caused by environmental factors are also opening up new avenues for preventing chronic illnesses and malignancies. Furthermore, somatic cell genome editing is a potential, ethically viable strategy as it targets non-reproductive cells, preventing heritable genetic alterations. Along with these developments, RNA-based therapies are emerging as a new avenue for disease prevention. This paper will explore each of these advancements, their applications, and the ethical and technical challenges involved.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder accompanied by neuroinflammation. Many studies have demonstrated that interleukin-6 (IL-6) exhibits both anti-inflammatory and pro-inflammatory effects in the central nervous system, yet its role in PD remains controversial. In this study, Il6 -/- (knockout), Il6 +/-, and wild-type mice were utilized to investigate the impact of IL-6 on the pathology of MPTP- or α-SynucleinA53T-induced PD mice. Our findings revealed that Il6 deficiency exacerbated motor dysfunction in both female and male mice. MPTP intoxication resulted in earlier and more extensive injuries to the dopaminergic system and heightened glial reaction in the nigrostriatal pathway of female Il6 -/- mice compared with male Il6 -/- mice, which only displayed more severe dopaminergic neuronal loss at 7 days after MPTP administration. Toxic α-Synuclein overexpression in the substantia nigra region caused earlier motor dysfunction and aggravated dopaminergic neurodegeneration in female Il6 -/- mice. In Il6 +/- mice, MPTP-induced depletion of dopaminergic nerve fibers was unaffected, although astrocyte activation was attenuated. Moreover, intraperitoneal administration of recombinant IL-6 (rIL-6) partially ameliorated MPTP-induced motor dysfunction and striatal dopaminergic terminal depletion in both wild-type and knockout mice. Our findings underscore the crucial role of IL-6 in the inflammatory pathology of PD, highlighting sex-dependent differences, and suggest that rIL-6 holds potential promise for PD therapy.

Lung cancer is the leading cause of cancer-related death and has the second-highest incidence worldwide. For patients with advanced EGFR-mutated non-small cell lung cancer, EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the preferred treatment option; however, acquired resistance to TKIs is inevitable. Gefitinib and osimertinib, the first-generation and third-generation EGFR-TKI, have shown promising results in patients with EGFR-mutated lung cancer in clinical treatment. Here, we identified that pyruvate dehydrogenase kinase 1 (PDK1) was up-regulated in gefitinib- and osimertinib-resistant cell lines, and PDK1 knockdown rendered cells more sensitive to TKI treatment. PDK1 expression levels were significantly increased in lung, colon, liver, and breast cancer tissues compared with those in normal tissues. Histone demethylase KDM3A was also induced in TKI-resistant cell lines, and demethylated histone H3 lysine 9 to facilitate PDK1 expression to regulate TKI resistance. Further study demonstrated that METTL16 promoted the m6A modification of PDK1 mRNA, and the m6A reader IGF2BP1 directly recognized and enhanced PDK1 mRNA stability. Interestingly, KDM3A also induced METTL16 expression. Moreover, PDK1 inhibitor JX06 rendered cancer cells more sensitive to gefitinib treatment in vivo, and JX06 and gefitinib combination treatments have a synergic effect to inhibit tumor growth. In conclusion, the KDM3A/METTL16/PDK1 axis plays an important role in cancer development and TKI resistance, which may offer new prognostic biomarkers and therapeutic targets for TKI resistance in the future.

The KCNE single-span transmembrane subunits modulate the function of voltage-gated potassium (Kv) channels, which are critical for maintaining electrical excitability and signal transduction across various tissues, by interacting with different Kv channel α-subunits to form diverse channel complexes with unique biophysical properties and regulatory mechanisms. These interactions profoundly impact physiological processes. Mutations or altered expression of KCNE genes have been implicated in a range of pathophysiological conditions. Emerging research has provided significant insights into the dynamic interactions between the KCNE gene and Kv channels, highlighting their critical roles in channel function modulation. This increasing understanding paves the way for designing novel therapeutic strategies to address ion channel-related disorders. To deepen the understanding of research advancements, this review seeks to elucidate the roles of KCNE across various organs and to provide constructive recommendations for future research.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a significant global health threat because of its rapid evolution and high mutation rate, which limits the performance of existing molecular diagnostics. This study presents a dual-mode, aptamer-based detection platform that combines high sensitivity with mutation resilience. Using a computer-assisted X-aptamer Systematic Evolution of Ligands by EXponential enrichment (SELEX) approach, we identified NP14, a high-affinity, dual-target DNA aptamer that specifically binds to the SARS-CoV-2 nucleocapsid (N) protein at its N-terminal domain. Analyses via molecular docking, aptamer truncation, and targeted mutagenesis revealed that NP14 interacted with both SARS-CoV-2 and SARS-CoV N proteins and identified key nucleotides C24 and G27 of the P1 region and structural determinants critical for its high-affinity binding. Building on this discovery, we engineered a dual-mode biosensing system by integrating NP14 into a multicolor dynamic light scattering-enhanced enzyme-linked aptamer-antibody assay (MD ELAAA). MD ELAAA synergistically combines two complementary detection strategies: i) non-aggregative plasmonic colorimetry for visual signal detection and ii) dynamic light scattering for ultrasensitive quantitative analysis, in which Au/Ag nanomaterials are used to amplify optical and scattering signals. This system achieves a sensitivity of 0.43 TCID50/mL, representing a 47-fold improvement over standard methods. By integrating high sensitivity, specificity, variant recognition, and dual-mode signal output, the MD ELAAA platform enables reliable detection of low-abundance SARS-CoV-2 antigens. Its robust performance supports early-stage diagnostics and high-throughput variant monitoring, establishing MD ELAAA as a robust platform for next-generation viral detection and surveillance.