The homeostasis of a tissue such the gastrointestinal (GI) tract is of fundamental importance for human health, given its constant exposure to a wide variety of external substances. The Formyl peptide Receptor 1 (FPR1) is an innate immune receptor belonging to the FPR family, that can recognize various endogenous danger- and exogenous pathogen-associated molecules, triggering inflammation. Importantly, depending on the context and on the specific ligand, FPR1 can also stimulate inflammation resolution. Thus, FPR1 is a critical actor in GI physiopathology. Interestingly, not only FPR1 participates and is necessary for maintaining homeostasis, but it also exerts strong tumor suppressor properties in this tissue. The present review discusses the mechanisms responsible for this specific function of FPR1 in cancer of the GI tract, focusing in particular on FPR1-mediated signal transduction.

Circular RNAs (circRNAs), a class of non-coding RNAs characterized by covalently closed-loop structures, have emerged as key regulators in the tumor immune microenvironment (TIME) of lung cancer, owing to their high stability, tissue-specific expression, and multidimensional regulatory capabilities. This review systematically synthesizes the latest research progress and elucidates the processes by which circRNAs regulate the functional states of immune cells in the TIME through diverse molecular mechanisms, including acting as competing endogenous RNAs (ceRNAs) to sequester microRNAs (miRNAs), interacting with RNA-binding proteins (RBPs), and in some cases, encoding functional polypeptides. CircRNAs possess bidirectional regulatory capacities: they can promote tumor immune evasion by modulating the expression of immune checkpoint molecules, influencing the infiltration and activity of effector immune cells (e.g., CD8 + T cells), recruiting immunosuppressive cells (e.g., regulatory T cells and M2-type macrophages), and regulating immune signaling pathways; meanwhile, they can also activate antitumor immune responses. Furthermore, the review explores the potential of circRNAs as liquid biopsy biomarkers for lung cancer diagnosis and prognosis, as well as their translational prospects in therapeutic strategies including vaccines, circRNA-enhanced CAR-T therapy, and formulations encoding immunomodulatory factors. Despite challenges such as complex mechanisms, low delivery efficiency, and safety concerns, the development of multi-omics technologies, novel delivery systems, and gene-editing tools provides directions for the development of precision therapies targeting circRNAs, which aim to reshape the lung cancer immune microenvironment and overcome immunotherapy resistance.

Background Proliferative vitreoretinopathy (PVR) is a major complication of rhegmatogenous retinal detachment. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) plays a central role in PVR pathogenesis. This study aims to investigate the effect of ADP-ribosylation factor-like 13B (ARL13B) on RPE EMT in PVR. Methods The expression of ARL13B in PVR specimens was analyzed by immunofluorescence (IF) staining. The effect of ARL13B on RPE EMT was assessed by IF staining and Western blot. The proliferation and migration of RPE were measured with EdU and transwell and scratch assays, respectively. The EMT-related transcriptome was analyzed by bulk RNAseq. An intravitreal injection mouse model of PVR was used to investigate the role of ARL13B in PVR formation. Results Immunofluorescence revealed significantly reduced ARL13B levels in α-SMA-positive cells as compared with Pan-CK-positive cells in an epiretinal membrane derived from retinal tears. During EMT, TGFβ1 treatment remarkably reduced ARL13B expression and shortened the length of cilia in RPE cells. In line with this, ARL13B knockdown (KD) decreased the length of cilia and enhanced TGFβ1-induced EMT, evidenced by morphology change and a globally upregulated EMT-related gene expression in RPEs. Moreover, ARL13B KD enhanced TGFβ1-induced RPE proliferation and migration. Consistently, ARL13B KD promoted PVR formation in vivo . Mechanistically, ARL13B KD enhanced TGFβ1 signaling by increasing the phosphorylation and expression of Smad3. Conclusion This study demonstrated a crucial role of ARL13B on TGFβ1-induced RPE EMT, highlighting the importance of ARL13B in PVR formation.

Objective The aim of this study was to conduct a systematic investigation into the effects of ocular rotation on postoperative residual astigmatism in patients undergoing small incision lenticule extraction (SMILE). Methods A prospective observational cohort study involved 79 patients (153 eyes) with myopia and astigmatism who underwent SMILE surgery. Ocular rotational magnitude was measured using manual corneal and scleral marking with a slit-lamp microscopy assessment. Preoperative and postoperative (1- and 3-month) assessments included uncorrected distance visual acuity (UDVA), best-corrected visual acuity (BCVA), refractive error, and other relevant ocular parameters. Results Residual astigmatism showed significant correlations with ocular rotation magnitude (r = 0.429, p < 0.001), preoperative intraocular pressure (r = −0.178, p = 0.032), and preoperative cylindrical lens power (r = 0.175, p = 0.035). A multiple linear regression analysis indicated that rotation magnitude significantly impacted postoperative residual astigmatism ( p < 0.001). However, preoperative intraocular pressure ( p = 0.349) and spherical equivalent ( p = 0.105) were not significantly related to residual astigmatism. Linear regression analysis further demonstrated significant positive correlations between rotation amplitude and various astigmatism parameters at both 1- and 3-month postoperative follow-ups (all p < 0.05). In particular, the relationships were quantified as follows: cylindrical lens (CYL [D]) (1 month: y = 7.058x + 17.480, p < 0.001; 3 months: y = 7.464x + 13.610, p < 0.001), target-induced astigmatism (TIA [D]) (1 month: y = 0.112x + 1.275, p = 0.012; 3 months: y = 0.097x + 1.217, p = 0.026), surgically induced astigmatism (SIA [D]) (1 month: y = 0.094x + 0.936, p < 0.001; 3 months: y = 0.059x + 0.911, p = 0.022), and difference vector (DV [D]) (1 month: y = 0.041x + 0.289, p = 0.005; 3 months: y = 0.037x + 0.866, p = 0.011). Notably, rotation amplitude exhibited the strongest association with postoperative CYL. Receiver operating characteristic (ROC) analysis determined the optimal thresholds for rotation magnitude in predicting residual astigmatism to be 1.5° at 1 month (AUC = 0.753; sensitivity 79.7%; specificity 58.2%) and 2.5° at 3 months (AUC = 0.929; sensitivity 92.9%; specificity 83.5%). Conclusion The magnitude of rotation shows a notably positive correlation with residual astigmatism during both the 1- and 3-month postoperative follow-ups. Thresholds of 1.5° (1 month) or 2.5° (3 months) prove predictive of residual astigmatism, with enhanced diagnostic precision at the later follow-up.

Bladder cancer (BC) remains a prevalent malignancy with high recurrence rates despite standard therapies. Bacille Calmette-Guérin (BCG) is the cornerstone of treatment for non-muscle-invasive bladder cancer (NMIBC); however, nearly half of patients experience relapse or develop resistance, highlighting the need for alternative strategies. Recent advances in immunotherapy have reshaped the therapeutic landscape. Immune checkpoint inhibitors (ICIs) restore T-cell function and show clinical activity in BCG-unresponsive disease. Viral vector–based approaches, including nadofaragene firadenovec and CG0070, provide localized immune activation, while cellular platforms such as CAR-T and CAR-NK therapies offer precision targeting of tumor antigens. Concurrently, nanotechnology-based delivery systems and antibody–drug conjugates (ADCs) enhance efficacy and safety by improving tumor-specific cytotoxicity. Collectively, these strategies signify a paradigm shift from traditional intravesical therapy toward personalized and durable immunotherapeutic interventions. Identification of predictive biomarkers and rational combination strategies will be critical to improving outcomes and guiding the future management of BC.

Stress granules (SGs) are transient, membraneless condensates that assemble dynamically within cells in response to diverse stressors. In recent years, SGs have been found to be closely associated with multiple pathological states and have attracted significant attention, particularly concerning their roles in hepatic pathophysiology. Functioning as critical hubs for post-transcriptional regulation, SGs maintain cellular homeostasis through the sequestration, transport, and translational suppression of mRNA, thereby potentially modulating the initiation and progression of various liver diseases. Our review summarizes the assembly mechanisms of SGs and recent research advances concerning their involvement in diseases including hepatocellular carcinoma, viral hepatitis, acute liver injury and fatty liver disease. It particularly focuses on SGs core RNA-binding proteins and associated regulatory networks. Although research into the impact of SGs on liver diseases remains in a nascent phase, with mechanistic details still elusive, SGs emerge as pivotal molecular nexuses connecting cellular stress responses to pathophysiological states, highlighting their therapeutic potential for liver disorders. This review aims to provide a theoretical foundation for a deeper understanding of the roles of SGs in liver pathologies and to promote their further development in both fundamental research and clinical translation.

Background and objectives A comparative evaluation of large language models (LLMs) is crucial for their application in specialized fields, such as ophthalmology. This study systematically assesses five prominent LLMs (ChatGPT 4, Claude 3 Opus, Gemini 1.5 Flash, ERNIE 3.5, and iFLY Healthcare) to quantify their performance across key clinical domains and provide evidence-based guidance for their integration. Methods We evaluated the LLMs across three simulated ophthalmic scenarios. For clinical assistance, the models responded to 50 questions, which were assessed for accuracy, completeness, and readability. For diagnosis and treatment, models answered 375 qualification exam questions to assess clinical reasoning. For doctor-patient communication, models responded to 20 SPIKES-based scenarios, which were analyzed for emotional and social engagement. Results In clinical assistance, Gemini 1.5 Flash demonstrated superior accuracy and completeness, while Claude 3 Opus produced the most readable text. For diagnosis and treatment, all models surpassed the passing threshold for the qualification exam, with Claude 3 Opus achieving the highest overall accuracy (81.07%). In doctor-patient communication, Gemini 1.5 Flash showed the strongest performance in positive emotional expression and social engagement. Conclusion This study innovatively evaluates LLMs in ophthalmic practice. Gemini 1.5 Flash excels in generating accurate clinical content and engaging with patients, whereas Claude 3 Opus demonstrates exceptional clinical reasoning and readability of text. Findings validate LLMs’ clinical potential while providing evidence-based selection criteria for ophthalmic AI applications. The results establish practical foundations for optimizing ophthalmic AI model development and systematically constructing intelligent ophthalmic hospital systems.

The Microprocessor is an essential protein complex that is responsible for the first processing step in the biogenesis of canonical microRNAs. The core of this complex is composed of two proteins, the ribonuclease III enzyme DROSHA and its double-stranded RNA-binding cofactor DGCR8. Dysregulation of the expression of the Microprocessor contributes to many disorders, including pluripotency defects, immune dysfunction, cancers, and neurological diseases. Multiple post-translational modifications (PTMs) have been reported for DROSHA and DGCR8, and these are thought to play roles in regulating Microprocessor levels and its functions; however, most of these PTMs remain functionally uncharacterized. In this review, we discuss these PTMs of the Microprocessor, focusing on phosphorylation, acetylation, ubiquitination, and SUMOylation, and how these modifications are thought to regulate protein stability, microRNA production, and other non-canonical Microprocessor activities.

Pancreatic ductal adenocarcinoma (PDAC) exhibits early systemic dissemination that precedes clinical detection, challenging the classical model of metastasis as a late evolutionary event. Mounting evidence indicates that molecular and cellular programs enabling invasion and distant colonization emerge at preinvasive or early carcinoma stages. This mini-review synthesizes recent advances defining how tumor-intrinsic mechanisms, such as KRAS-driven basal extrusion, epithelial–mesenchymal plasticity and chromosomal instability, cooperate with microenvironmental cues to promote early metastatic competence. The desmoplastic stroma, rich in fibroblasts, inflammatory mediators and aligned extracellular matrix, provides both structural and biochemical support for tumor-cell escape. Additionally, neural and immune interactions, including chemokine and cytokine signaling, facilitate perineural invasion and systemic pre-metastatic niche (PMN) conditioning via extracellular vesicles and cytokine networks. Recognizing PDAC as a systemic disease from inception reframes therapeutic priorities: early systemic therapy and biomarker-guided patient stratification may intercept occult dissemination. We propose that integrating mechanistic insights on tumor–microenvironment crosstalk with perioperative and liquid-biopsy-driven clinical strategies could redefine early intervention in PDAC.