Triple-negative breast cancer (TNBC) primarily relies on traditional adjuvant chemotherapy and radiotherapy, which have significant side effects and are prone to drug resistance. Poly ADP-ribose polymerase inhibitor (PARPi) has been approved for TNBC patients with BRCA mutation, but some BRCA wild-type patients with homologous recombination deficiencies are also sensitive to PARPi. Therefore, it is important to identify potential molecules that influence PARPi sensitivity in BRCA wild-type TNBC and to explore their specific mechanisms. Through CRISPR-cas9 loss-of-function screening, the lncRNA MTUS2-AS1 was identified to be significantly correlated with PARPi sensitivity in BRCA wild-type TNBC cells. In vitro and in vivo experiments were performed to investigate its function and underlying mechanism. We found that MTUS2-AS1 knockdown suppressed DNA damage repair and enhanced the anticancer effects of PARPi in BRCA-wild TNBC cells. Mechanistically, MTUS2-AS1 upregulates DDX5 protein expression by maintaining its stability, thereby promoting R-loop resolution, and suppressing DNA damage. Knocking down MTUS2-AS1 accelerated DDX5 protein degradation, reduced DDX5 protein expression, inhibitd R-loop resolution, promoted DNA damage, and ultimately enhanced the PARPi sensitivity in TNBC cells. Our study provided new insights into exploring the key molecules and mechanisms influencing the sensitivity of PARPi treatment and had great significance for screening benefit population and expanding the indications of PARPi treatment.

Studies have shown that abnormal mitochondrial function is closely associated with the development and progression of colorectal cancer (CRC); however, prognostic models based on mitochondria-related genes are still lacking. We systematically analyzed the expression of mitochondrial-related genes in CRC patients and constructed and validated a mitochondrial gene risk prognostic model using various bioinformatics methods across the TCGA and GEO databases. We also investigated the effects of tumor microenvironment, immune cell infiltration, tumor mutation load, and drug sensitivity on patient prognosis. In addition, we overexpressed the ABCD3 gene using CRISPR-dCas9 technology and further explored the role of ABCD3 in cell proliferation and apoptosis by protein blotting and flow cytometry. The mitochondrial gene risk model was effective in predicting the prognosis of CRC patients, which showed that the high-risk group was significantly different from the low-risk group in terms of immune cell infiltration. Further analyses revealed a strong association between risk scores and clinicopathological features, immune infiltration, and drug sensitivity. We constructed a prognostic prediction model based on mitochondria-related genes and found that ABCD3 provides a novel biomarker for the individualized treatment of CRC.

Acquired resistance to 5-fluorouracil (5-FU) curtails the survival benefit of chemotherapy in colorectal cancer (CRC). We asked whether a discrete subset of cancer-associated fibroblasts (CAFs) drives this phenotype. Multi-omic profiling of 24 CRC cohorts identified 10 collagen genes linked to poor outcome and 5-FU resistance; single-cell RNA-seq localized them to specific CAFs. Cellular communication modelling, in vitro proliferation, migration, apoptosis, and drug-sensitivity assays, together with CRISPR/Cas9 and siRNA perturbations, xenografts, and immunochemical analyses, examined the functional relevance of COL8A1-positive fibroblasts (COL8A1⁺Fibs) and their downstream signalling pathways. COL8A1⁺Fibs were enriched in advanced tumors and preferentially interacted with 5-FU-resistant malignant cells. Conditioned media from COL8A1⁺Fibs accelerated CRC cell growth, invasion, and 5-FU tolerance, and activated an epithelial–mesenchymal transition (EMT) programme. Secreted COL8A1 engaged integrin-β1 (ITGB1) on tumor cells; silencing ITGB1 or COL8A1 abrogated EMT induction, reduced proliferation, and restored 5-FU sensitivity in vitro and in vivo. COL8A1⁺Fibs orchestrate 5-FU resistance in CRC via a COL8A1/ITGB1-mediated EMT axis. Disrupting this stromal–tumor crosstalk represents a promising therapeutic strategy to overcome chemoresistance.

BackgroundInflammatory bowel disease (IBD) is a systemic disease characterized by chronic inflammation of the gastrointestinal tract. Serological testing has the advantages of wide sources and easy detection.ObjectiveTo explore the correlation between the serological markers and endoscopic mucosal healing and histological healing. We also explored the predictive value of individual and combined detection on the disease activity of ulcerative colitis (UC) and Crohn’s disease (CD) and provide reference for clinical non-invasive evaluation.MethodsWe retrospectively analyzed 267 IBD patients treated at our hospital from May 2020 to June 2024. Patients were classified based on endoscopic, pathological, or imaging results into UC (141 patients) and CD (126 patients). UC patients were further divided into mucosal healing (32 cases, IMES ≤ 1), mild (41 cases, 3 ≤ IMES ≤ 5), moderate (49 cases, 6 ≤ IMES ≤ 10), and severe (19 cases, 11 ≤ IMES ≤ 12) phases by the Improved Mayo Endoscopic Score (IMES). CD patients were categorized by the Crohn’s Disease Activity Index (CDAI). According to the Geboes score, patients were divided into a histological healing group (n=63) and a histological activity group (n=204). Pearson analysis examined correlations and ROC analysis assessed their predictive value.ResultsIn severe cases, ALB and PA were lower, and CRP, ESR, NLR, and PLR were higher than in moderate cases (P<0.05). The serum ALB and PA levels in the histological activity group were lower, but CRP, ESR, NLR, and PLR were higher than the histological healing group (all P<0.05). Pearson analysis revealed negative correlations between IMES/CDAI scores and ALB/PA levels, and positive correlations with CRP, ESR, NLR, and PLR levels (P<0.05). The combined detection of serological indicators for predicting UC inflammatory activity had an AUC of 0.930, with 88.89% sensitivity and 89.47% specificity, outperforming individual indicators (Z-values all P<0.05). For CD, the combined AUC was 0.906, with 86.75% sensitivity and 85.71% specificity, again surpassing single indicators (Z-values all P<0.05).ConclusionDifferences in serum ALB, PA, CRP, ESR, NLR, PLR were correlated with mucosal healing and inflammation in IBD patients. Combined detection offers clinical value in predicting disease activity.

Background: Metabolic reprogramming is a hallmark of colorectal cancer (CRC), yet the molecular regulators that orchestrate this process remain incompletely understood. Although many long non-coding RNAs (lncRNAs) possess protein-coding potential, their translational products and metabolic functions have been largely overlooked. Here, we identify MUCP1, a microprotein encoded by the lncRNA MUC20-OT1, as a critical regulator of mitochondrial metabolism and epigenetic remodeling in CRC. Methods: Multi-omics data were integrated to identify MUC20-OT1 as a candidate lncRNA encoding a functional microprotein. Fusion reporter plasmids, mass spectrometry, and immunoblotting were used to validate MUCP1 translation and mitochondrial localization. Functional assays, metabolomic profiling, 13C5-glutamine isotope tracing, subcellular succinate quantification, CUT&Tag, and xenograft models were performed to investigate the role of MUCP1 in facilitating mitochondrial succinate export and maintaining glutamine metabolism homeostasis. Results: The microprotein MUCP1, encoded by the lncRNA MUC20-OT1, serves as an auxiliary regulator of SLC25A10-mediated mitochondrial succinate transport. MUCP1 is upregulated during CRC progression and localizes in the mitochondrial outer membrane, where it facilitates the balance of mitochondrial succinate metabolism. Elevated extramitochondrial succinate subsequently enhances H3K4me3 histone modifications, promoting the transcription of enzymes involved in glutamine metabolism and sustaining the high metabolic demands of CRC cells. Conclusions: This study identifies MUCP1 as a novel lncRNA-encoded microprotein that maintains metabolic homeostasis in CRC by coupling mitochondrial succinate transport to histone methylation. MUCP1 might be a promising metabolic vulnerability and therapeutic target in CRC.

Macrophage migration inhibitory factor (MIF) promotes inflammation, regulates immune responses and chemotherapy resistance in the tumor microenvironment. However, its mechanism of action in colorectal cancer (CRC) metabolic reprogramming and targeted therapeutic potential remain unclear. This study aims to investigate the function, mechanism, and targeted therapeutic potential of MIF in CRC. Data were integrated from TCGA, GTEx, CPTAC, and HPA databases with clinical sample validation. Single-cell sequencing analysis (datasets GSE166555 and GSE144735) was performed, alongside functional assays and mechanistic studies. A novel high-potency MIF inhibitor was identified through virtual screening and validated in vitro and in vivo. MIF expression was found to be significantly elevated in CRC tissues and cell lines, correlating with poor overall survival (OS) and disease-specific survival (DSS). Single-cell sequencing confirmed malignant epithelial cells as the primary MIF source. Functional assays demonstrated that MIF knockout suppressed CRC cell proliferation, migration, and tumor growth in vivo, while MIF overexpression promoted these effects. Mechanistically, MIF binds CD74 to upregulate glycolytic enzymes (HK2, PKM2, LDHA), enhancing glucose uptake and lactate/pyruvate production, thereby driving the Warburg effect and CRC progression. Virtual screening identified a novel high-potency MIF inhibitor, F3277-0933 (IC50 = 8.284 μM). In vitro and in vivo, F3277-0933 surpassed the classical inhibitor ISO-1 in suppressing MIF-driven glycolytic reprogramming and proliferation. This study elucidates a novel mechanism by which the MIF-CD74 axis drives CRC progression through glycolytic reprogramming and provides robust preclinical evidence for developing MIF-targeted therapies.

The Golgi apparatus plays a key role in innate immune signaling, but its exact role in depression-related neuroinflammation remains unclear. The role of Dymeclin (DYM), a Golgi structural protein, in stress-related psychiatric disorders needs further clarification. This study aims to investigate whether DYM participates in the development of chronic stress-induced depression by regulating Golgi function. A mouse depression model was developed with chronic unpredictable mild stress (CUMS), followed by a rescue experiment using stereotactic injection of DYM-overexpressing lentiviruses into the hippocampus. Depression-associated behaviors, hippocampal metabolites, Golgi apparatus function, and inflammatory markers were examined using mass spectrometry, immunofluorescence, electron microscopy, and immunoprecipitation techniques. Overexpression of DYM mitigated depressive-like behaviors induced by CUMS in mice. Additionally, it enhanced the structural integrity of the Golgi apparatus, suppressed NLRP3 inflammasome activation, reduced levels of central and peripheral inflammatory factors, and partially ameliorated hippocampal metabolic disturbances. In vitro experiments further confirmed that DYM overexpression inhibited LPS-induced NLRP3 upregulation and inflammatory factor release in microglia. This study reveals that chronic stress causes depressive-like behaviors by reducing hippocampal DYM expression, leading to Golgi dysfunction and triggering NLRP3 inflammasome-related neuroinflammation and metabolic issues. This finding broadens the traditional framework of depression research, which has primarily focused on neurons and monoamine neurotransmitters, by underscoring the pivotal role of Golgi organelle homeostasis in mediating the interactions among stress, neuro-immune, and metabolic processes. Our research indicates that targeting the DYM/Golgi pathway could offer new treatment strategies and a theoretical foundation for reducing depression-related neuroinflammation and metabolic issues. Drugs targeting the structural stability of the Golgi apparatus may serve as potential candidates for novel antidepressants in the future.

Background and purposeInflammatory factors are pivotal in systemic and central nervous system inflammation post-stroke. This study examined if peripheral inflammatory factors were associated with outcomes after endovascular therapy for acute large vessel occlusion stroke by mediating infarct growth.MethodsWe conducted a retrospective analysis of the EVTRNA (Circulating Non-coding RNA in Acute Ischemic Stroke with Endovascular Treatment) trial. Patients who underwent pre-endovascular therapy multimodal MRI, postoperative day 1 inflammatory factor testing, and postoperative day 7 head CT for infarct volume evaluation were included in this study. Unfavorable outcome was defined as a modified Rankin Scale score of 3–5 at the 90-day follow-up. Regression analysis and mediation analysis were employed to assess the association between inflammatory factors and clinical outcomes.ResultsA total of 105 patients were included in this study, of whom 51 experienced unfavorable outcomes. Univariate analysis demonstrated that elevated interleukin-6 (IL-6) levels, higher baseline National Institutes of Health Stroke Scale scores at admission, increased fasting blood glucose levels, and infarct growth were all significantly associated with unfavorable outcomes. After adjustment by multivariate analysis, IL-6 (odds ratio 1.02, 95% confidence interval 1.01-1.03) and the other aforementioned factors remained independently associated with unfavorable outcomes. Further mediation analysis revealed that infarct volume growth partially accounts for the unfavorable prognosis observed in patients with elevated IL-6 levels.ConclusionsIL-6 was associated with unfavorable outcomes in patients undergoing endovascular therapy. Postoperative infarct volume growth partially mediated the effect of IL-6 on clinical outcomes.

Transfer RNA-derived small RNAs (tsRNAs) are a novel class of small non-coding RNAs abundant in the bloodstream of cancer patients and involved in various physiological and pathological processes. However, the regulatory mechanisms and clinical significance of tsRNAs in colorectal cancer (CRC) remain unclear. In this study, PANDORA-seq was used as an exploratory screen of CRC tissues, paired adjacent tissues, and CRC plasma samples, followed by validation in larger independent cohorts. Quantitative real-time PCR quantified mt-5'-tiRNA-Tyr levels in tissues, plasma, and cells. Functional assays assessed the role of mt-5'-tiRNA-Tyr in CRC. Mechanistic studies utilized RNA pull-down, mass spectrometry, RNA immunoprecipitation, western blotting, and Co-immunoprecipitation. Results revealed that mt-5'-tiRNA-Tyr was significantly upregulated in CRC plasma and tissues. In vitro and in vivo studies demonstrated its oncogenic potential. Mechanistic assays showed that mt-5'-tiRNA-Tyr was enriched with HARS2 in RNA pull-down/RIP assays and associated with reduced HARS2-mt-tRNA-His association, increased HARS2 K91 succinylation, impaired mitochondrial protein translation, and mitochondrial damage. Moreover, succinate accumulation creates a positive feedback loop that enhances CRC proliferation. This study identifies a novel oncogenic tsRNA and uncovers a mechanism by which mt-5'-tiRNA-Tyr promotes CRC proliferation through HARS2 succinylation, supporting further evaluation of plasma mt-5'-tiRNA-Tyr as a candidate circulating biomarker for CRC.

Colorectal cancer (CRC) is one of the most common malignancies. Hypoxia can promote the occurrence and development of CRC. However, how hypoxia regulates the CRC immune microenvironment needs to be further explored. The bulk RNA sequencing data and clinicopathological information of CRC patients were enrolled from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The single-cell RNA sequencing (scRNA-seq) datasets of CRC were collected from and analyzed from the GEO database and the ArrayExpress database. The score of the hypoxia gene set was estimated using the "ssGSEA" algorithm in the "GSVA" R package. The functional characteristics of CAF subtypes were studied by bioinformatics analysis and in vitro experiments, and a prognostic model was constructed based on machine learning correlation. Hypoxia is associated with poor prognosis in CRC patients. Periostin (POSTN) + Fib is a cancer-associated fibroblast (CAF) closely associated with hypoxia, and high infiltration of POSTN + Fib is associated with adverse outcomes in overall survival (OS) and relapse-free survival (RFS) in CRC patients. Hypoxia can induce POSTN expression and secretion in CAFs. Hypoxia-induced increase of POSTN expression in CAFs can significantly promote the migration and proliferation of CRC cells. Hypoxia-induced increase of POSTN expression in CAFs can significantly promote the proliferation and migration of CRC cells. The POSTN+Fib Hypoxia-Related Risk Model (PFHRM) can predict the survival and immunotherapy response of CRC patients. Our study identified a POSTN+Fib cell subpopulation closely associated with hypoxia, which promotes the malignant progression of CRC. The development of PFHRM provides a theoretical basis for improving patient survival and prognosis.

Colorectal cancer (CRC) is a common gastrointestinal cancer with poor response to therapy and high metastatic risk. Cancer-associated fibroblasts (CAFs) support tumor progression, but their functional heterogeneity remains poorly understood. We integrated multi-omics data from 10,164 samples, including single-cell, bulk, spatial transcriptomics, and proteomics, to identify and characterize CAF subpopulations. Functional validation was performed using molecular assays, in vivo models, and drug screening. We identified a COL10A1-positive fibroblast subpopulation (COL10A1+Fib) associated with CRC progression and poor patient prognosis. COL10A1+Fib promotes tumor cell proliferation, immune suppression, and metastasis. Mechanistically, COL10A1+Fib facilitates epithelial–mesenchymal transition (EMT) in CRC cells via COL10A1 secretion and induces M2 macrophage polarization through the COL10A1/CD18/JAK1/STAT3 signaling axis. In turn, M2 macrophages enhance COL10A1 expression in fibroblasts via the TGF-β/RUNX2 pathway, forming a pro-tumorigenic feedback loop. The DNA-PKcs inhibitor NU7441 reduces COL10A1 expression, suppresses CAF activity, and reverses EMT and M2 polarization. Pan-cancer analysis suggests that COL10A1+Fib may have similar functional roles across multiple major solid tumors. Our study identifies a CAF subpopulation, COL10A1+Fib, associated with CRC progression and immune suppression, suggesting it as a potential therapeutic target in CRC and possibly other malignancies.

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. Tumor epithelial cells play a crucial role in shaping the tumor microenvironment (TME) and driving cancer progression. This study utilized a multi-omics approach, integrating data from 21 multi-center CRC cohorts (n = 2,767), including single-cell transcriptomics, bulk transcriptomics, spatial transcriptomics, and proteomics. Bioinformatic analyses were combined with in vitro and in vivo experiments for validation. A distinct epithelial subpopulation, ERO1A-positive epithelial cells (ERO1A + Epi), was identified and found to be significantly enriched in advanced-stage CRC, correlating with poor prognosis. ERO1A + Epi cells promoted proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, while in vivo models confirmed their role in tumor growth and liver metastasis. Spatial and intercellular interaction analyses revealed that ERO1A + Epi cells interact with CTHRC1 + cancer-associated fibroblasts (CTHRC1 + CAFs) and SPP1 + macrophages via MDK-LRP1, MIF-(CD74 + CD44), and APP-CD74 signaling pathways, fostering a pro-tumorigenic TME. Co-culture experiments demonstrated that ERO1A + Epi enhances the expression of CTHRC1 and SPP1. A risk prediction model (ETSRM) based on the ERO1A + Epi_TME_Score demonstrated superior prognostic accuracy over 111 existing CRC models. Integrating ETSRM with TNM staging further enhanced survival prediction. Our findings identify ERO1A + Epi as a significant driver of colorectal cancer progression. The ERO1A + Epi_TME_Score-based ETSRM provides a robust prognostic tool, offering new insights into CRC pathogenesis and highlighting potential therapeutic targets for improved patient outcomes. Summarizes ERO1A-positive tumor epithelial cells in colorectal cancer progression: a multi-omics perspective.

Background and purpose: Blood pressure (BP) management in the acute phage of stroke is associated with clinical outcomes among patients with after endovascular therapy (EVT). This study was to explore whether collateral circulation status modified the effect of BP course on clinical outcomes in patients with EVT. Methods: This study enrolled a total of 800 patients with ischemic stroke caused by large-vessel occlusion in the anterior circulation who underwent successful recanalization. Latent mixture modeling was used to determine systolic BP (SBP) trajectories according to 3 SBP measurements during the first 24 hours after EVT. Collateral status prior to EVT was assessed by digital subtracted angiography. Clinical outcomes including stroke disability (modified Rankin Scale 3-6), mortality, and symptomatic intracranial hemorrhage (sICH) were collected 90 days after stroke. Results:Three SBP trajectories were identified: high (7%), moderate 57.9%, and low (35.1%) SBP. SBP trajectories were independently associated with unfavorable 90-d outcome (P=0.012) after adjustment. Patients with high and moderate SBP trajectories had had an elevated risk of unfavorable outcome in the poor collateral (adjusted odds ratio, 6.19 [95%CI, 2.17-17.67], P<0.001 and adjusted odds ratio, 2.10 [95%CI, 1.23-3.57], P=0.007, respectively) rather than good collateral (P for interaction: 0.042). There was no significant difference regarding mortality and sICH across SBP trajectories. Conclusions: Patients with high or moderate SBP trajectory during the first 24 hours after successful recanalization had a higher risk of unfavorable outcome among patients with poor collateral. Registration: https://www.clinicaltrials.gov/ct2/show/NCT04775147; https://www.clinicaltrials.gov/ct2/show/NCT04230785 Unique identifier: NCT04775147 (registered on March 01, 2021) and NCT04230785 (registered on January18, 2020).

Colorectal cancer (CRC) is one of the most serious gastrointestinal tumors. The survival rate of patients with advanced stages is meager, so it is urgent to identify new diagnostic biomarkers with high sensitivity and specificity. tRNA-derived small RNAs (tsRNAs) are an emerging class of small non-coding RNAs that are highly abundant in the blood of cancer patients and are associated with various physiological and pathological processes. Therefore, the clinical value of tsRNAs in diagnosing CRC requires further investigation. In this study, we identified the differential expression profiles of tsRNAs in CRC tissues via Pandora sequencing. We selected 5'-tiRNA-His that were significantly highly expressed in CRC plasma and tissues for further investigation. Interestingly, the expression level of 5'-tiRNA-His was increased dramatically in the plasma of CRC patients and correlated with various clinicopathologic parameters. ROC analysis revealed that 5'-tiRNA-His had good diagnostic value in diagnosing CRC patients, superior to that of CEA, CA199, and CA724, and could significantly differentiate patients with CRC from healthy donors and patients with intestinal polyps. Moreover, 5'-tiRNA-His still had good diagnostic efficacy in the diagnosis of patients with early-stage CRC, and the diagnostic efficacy was further elevated when combined with clinically used tumor markers. In conclusion, our study identified plasma 5'-tiRNA-His as a promising biomarker for diagnosing and screening CRC.

Colorectal cancer (CRC) is a prevalent malignancy, yet the role of lactylation in its progression remains unclear. This study investigates High Mobility Group Box 2 positive tumor epithelial cells (HMGB2+Epi), a lactylation-associated subpopulation. By integrating multi-omics data, including proteomics, single-cell, spatial, and bulk transcriptomics, we explored the function of HMGB2+Epi in CRC. Elevated lactylation levels in CRC tissues were correlated with poor prognosis. Single-cell analysis identified HMGB2+Epi as a central lactylation-enriched subpopulation. Functionally, HMGB2 enhanced the Warburg effect, promoting CRC cell proliferation, migration, and invasion. HMGB2 knockout reduced lactylation levels and inhibited tumor progression. Mechanistically, NFYB directly bound to the HMGB2 promoter, forming the NFYB-HMGB2 axis that drives lactylation and metabolic reprogramming. Cell-cell communication analysis revealed enhanced interactions between HMGB2+Epi and fibroblasts, endothelial cells, and T/NK cells. Molecular dynamics and in-vitro assays suggest that BI-2536 downregulates HMGB2 and lactylation in CRC cells. A risk model based on HMGB2+Epi outperformed 125 previously published models in independent cohorts. In summary, HMGB2+Epi represents a key lactylation-enriched subgroup, with the NFYB-HMGB2 axis driving CRC progression via lactylation. BI-2536 as a tool compound implicating the HMGB2-lactylation axis, and the HMGB2+Epi-based risk model provides a novel target for precision CRC therapy.

The recombinant oncolytic adenovirus is a novel anticancer agent to replicate selectively in colon cancer cell lines. Loss of imprinting (LOI) of insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality phenomenon. We utilized the IGF2 LOI in gene therapy for the malignant tumor cell lines. We investigated the tumoricidal effects of IGF2 LOI on four cell lines by oncolytic adenovirus, and constructed novel adenovirus vectors Ad312-E1A and Ad312-EGFP. The expression of E1A was monitored by real-time PCR and western blot analysis. The viability and apoptosis of colorectal cells infected with Ad312-E1A were tested by CCK-8 and flow cytometry. In addition, we established a colorectal cancer model in nude mice. The results showed that HCT-8 and HT-29 with IGF2 LOI were infected with Ad312-EGFP and then produced the EGFP. Nevertheless, SW480 and GES-1, which were IGF2 MOI, did not produce the EGFP. The Ad312-E1A obviously reduced the cell viability and induced apoptosis in HCT-8 and HT-29 in vitro, and successfully suppressed tumor growth in HT-29 xenografts in nude mice. In summary, the conditionally replicative adenovirus with loss of IGF2 imprinting system has a positive effect on gene therapy.

Colorectal cancer (CRC) ranks among the most aggressive malignancies globally, with advanced-stage patients exhibiting notably low survival rates. Consequently, there is an urgent imperative to identify novel biomarkers characterized by high sensitivity and specificity. Ribosomal RNA-derived small RNAs (rsRNAs), which originate from ribosomal RNAs, represent the most prevalent small noncoding RNAs (sncRNAs) in CRC tissues and plasma. Thus, the development of a diagnostic panel comprising multiple rsRNAs holds considerable significance for CRC diagnosis. Utilizing PANDORA-seq, we have, for the first time, delineated a novel sncRNA expression profile in CRC tissues and plasma, identifying rsRNAs as the predominant sncRNAs within these contexts. We identified six rsRNAs that were significantly upregulated in CRC plasma and subsequently constructed a co-diagnostic panel. This panel demonstrated an area under the curve (AUC) value of 0.898, which increased to 0.942 when combined with clinically utilized tumor markers, indicating robust diagnostic efficacy. Our study is the first to establish that rsRNAs are the most abundantly expressed sncRNAs in CRC tissues and plasma. We have developed an rsRNA panel with substantial diagnostic efficacy in CRC plasma, presenting promising potential as diagnostic biomarkers.

BACKGROUND AND PURPOSE:Symptomatic intracranial artery stenosis (sICAS) is strongly associated with an elevated risk of recurrent ischemic stroke, yet the underlying risk factors remain elusive. In this present study, we aimed to investigate the risk factors and predictive value of imaging features for recurrent ischemic stroke in patients with watershed infarction caused by ICAS. METHODS:We prospectively collected clinical information and imaging data from patients with watershed infarction caused by ICAS. The primary outcome was recurrent ischemic cerebrovascular events in the same territory within 1 year. The original magnetic resonance images (MRI) were post-processed by the Fast-processing of ischemic stroke (F-Stroke) software to compute the perfusion parameters. The assessment of white matter hyperintensity (WMH) was performed in accordance with the Fazekas scale. Binary logistic regression analysis was performed to explore the association of imaging characteristics and recurrent ischemic stroke. Subsequently, we performed ROC curve analyses to determine their discriminatory capacity for ischemic stroke recurrence. RESULTS:A total of 139 patients were successfully enrolled in the present study. The recurrence rate in the total population was 18.71 %. Compared with patients without recurrent ischemic stroke, those who experienced recurrence had a higher proportion of prior ischemic stroke history (25.66 % vs. 53.85 %) and severe WMH (30.77 % vs. 7.97 %), as well as higher baseline NIHSS scores and volume of Tmax > 4 s. Logistic regression analysis revealed that both the volume of Tmax > 4 s and severe WMH significantly influenced the risk of recurrent ischemic stroke occurrence. Furthermore, ROC curve analyses demonstrated that the discriminatory capacity of the volume of Tmax > 4 s (AUC = 0.64, 95 %CI = 0.51-0.77, P = 0.029) was marginally superior to WMH scores (AUC = 0.62, 95 %CI = 0.49-0.75, P = 0.066). Whereas, the combination of the volume of Tmax > 4 s and the WMH scores showed better discriminatory capacity (AUC = 0.73, 95 %CI = 0.61-0.85, P < 0.001). CONCLUSION:MR-guiding cerebral hypoperfusion and severe WMH is susceptible to recurrence of ischemic stroke, thereby serving as valuable predictors for recurrence in patients with watershed infarction caused by ICAS.

The treatment of acute ischemic stroke (AIS) aims to achieve early vascular recanalization and reperfusion of the penumbra. However, the effect of early penumbral imaging within 6 h on clinical outcomes remains unclear. The objective of this study was to determine the effect of magnetic resonance-guided (MR-guided) perfusion imaging within 6 h after symptom onset on endovascular thrombectomy outcomes in AIS patients. We prospectively collected the clinical information of consecutive AIS patients undergoing endovascular thrombectomy based on MR-guided perfusion imaging within 6 h after symptom onset from AISRNA and EVTRNA studies. The primary outcome was defined as the poor outcome (mRS > 2 within 90 days). The perfusion-weighted imaging/diffusion-weighted imaging (PWI/DWI) mismatch was assessed by an automated software. We enrolled 84 patients (25 in the mismatch ≤ 1.8 group and 59 in the mismatch > 1.8 group). Significant difference was found between the mismatch > 1.8 group and the mismatch ≤ 1.8 group for the incidence of disabling stroke (mRS > 2) within 90 days (40.7