Supplementary Material for: Development of a Genetic and Clinical Data-Based (GC) Risk Score for Predicting Survival of Hepatocellular Carcinoma Patients After Tumor Resection

<b><i>Background/Aims:</i></b> Carnitine palmitoyltransferase 1A (CPT1A) is a rate-limiting enzyme in the transport of long-chain fatty acids for β-oxidation. Increasing evidence has indicated that CPT1A plays an important role in carcinogenesis. However, the expression and prognostic value of CPT1A in hepatocellular carcinoma (HCC) have not been extensively studied. <b><i>Methods:</i></b> Here, we collected 66 post-operative liver cancer tissue samples. Gene profile expression was tested by RT-PCR. Receiver operating characteristic (ROC) analysis was performed and multivariate analysis with Cox’s Proportional Hazard Model was used for confirming the selected markers’ predictive efficiency for HCC patients’ survival. A simple risk scoring system was created based on Cox’s regression modeling and bootstrap internal validation. <b><i>Results:</i></b> Cox multivariate regression analysis demonstrated that CPT1A, tumor size, intrahepatic metastasis, TNM stage and histological grade were independent risk factors for the prognosis of HCC patients after surgery. Our genetic and clinical data-based (GC) risk scoring system revealed that HCC patients whose total score≥3 are more likely to relapse and die than patients whose total score < 3. Finally, the good discriminatory power of our risk scoring model was validated by bootstrap internal validation. <b><i>Conclusions:</i></b> The genetic and clinical data-based risk scoring model can be a promising predictive tool for liver cancer patients’ prognosis after operation

Supplementary Material for: Baicalein, a Natural Anti-Cancer Compound, Alters MicroRNA Expression Profiles in Bel-7402 Human Hepatocellular Carcinoma Cells

<i>Background/Aims:</i> Baicalein has been shown to possess significant anti-hepatoma activity by inhibiting cell proliferation. Whether the anti-proliferative effect of baicalein is related to its modulation of miRNA expression in hepatocellular carcinoma (HCC) is still unknown. <i>Methods:</i> The anti-proliferative effects of baicalein on HCC cell line Bel-7402 was assessed by detecting the proliferation activity, cell cycle distribution, expression changes of p21/CDKN1A, P27/CDKN1B, total Akt and phosphoryted AKT. Microarray analysis was conducted to determine the miRNA expression profiles in baicalein-treated or untreated Bel-7402 cells and then validated by qRT-PCR in two HCC cell lines (Bel-7402 and Hep3B). The gain-of-function of miR-3127-5p was performed by detecting anti-proliferative effects after transfecting miRNA mimics in cells. Finally, the expression level of miR-3127-5p in different HCC cell lines was determined by qRT-PCR. <i>Results:</i> Baicalein was able to inhibit the proliferation of Bel-7402 cells by inducing cell cycle arrest at the S and G2/M phase via up-regulating the expression of p21/CDKN1A and P27/CDKN1B and suppressing the PI3K/Akt pathway. Baicalein could alter the miRNA expression profiles in Bel-7402 cells. Putative target genes for differentially expressed miRNAs could be enriched in terms of cell proliferation regulation, cell cycle arrest and were mainly involved in MAPK, PI3K-Akt, Wnt, Hippo and mTOR signaling pathways. MiR- 3127-5p, one of up-regulated miRNAs, exhibits low expression level in several HCC cell lines and its overexpression could inhibit cell growth of Bel-7402 and Hep3B cell lines by inducing S phase arrest by up-regulating the expression of p21and P27 and repressing the PI3K/Akt pathway. <i>Conclusions:</i> Modulation of miRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein

Supplementary Material for: MicroRNA-9-1 Attenuates Influenza A Virus Replication via Targeting Tankyrase 1

An unstable influenza genome leads to the virus resistance to antiviral drugs that target viral proteins. Thus, identification of host factors essential for virus replication may pave the way to develop novel antiviral therapies. In this study, we investigated the roles of the poly(ADP-ribose) polymerase enzyme, tankyrase1 (TNKS1) and the endogenous small noncoding RNA, miR-9-1 in influenza A virus (IAV) infection. Increased expression of TNKS1 was observed in IAV-infected human lung epithelial cells and mouse lungs. TNKS1 knock-down by RNA interference repressed influenza viral replication. A screen using TNKS1 3’-untranslation region (3’-UTR) reporter assays and predicted microRNAs identified that miR-9-1 targeted TNKS1. Overexpression of miR-9-1 reduced influenza viral replication in lung epithelial cells as measured by viral mRNA and protein levels as well as virus production. miR-9-1 induced type I interferon production and enhanced the phosphorylation of STAT1 in cell culture. The ectopic expression of miR-9-1 in the lungs of mice by using an adenoviral viral vector enhanced type I interferon response, inhibited viral replication and reduced susceptibility to IAV infection. Our results indicate that miR-9-1 is an antiinfluenza microRNA that targeting TNKS1 and enhanced cellular antiviral state

Supplementary Material for: Distinguishing intracranial diabetes-related atherosclerotic plaques : A high-resolution MRI-based radiomics study

Introduction: Diabetes markedly affects the formation and development of intracranial atherosclerosis. The study was aimed at evaluating whether radiomics features can help distinguish plaques primarily associated with diabetes. Materials and Methods: We retrospectively analyzed patients who were admitted to our center because of acute ischemic stroke due to intracranial atherosclerosis between 2016 and 2022. Clinical data, blood biomarkers, conventional plaque features and plaque radiomics features were collected for all patients. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined from logistic regression models. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to describe diagnostic performance. The DeLong test was used to compare differences between models. Results: Overall, 157 patients (115 men; mean age, 58.7 ± 10.7 years) were enrolled. Multivariate logistic regression analysis showed that plaque length (OR: 1.17; 95% CI: 1.07–1.28) and area (OR: 1.13; 95% CI: 1.02–1.24) were independently associated with diabetes. On combining plaque length and area as a conventional model, the AUCs of the training and validation cohorts for identifying diabetes patients were 0.789 and 0.720, respectively. On combining radiomics features on T1WI and contrast-enhanced T1WI sequences, a better diagnostic value was obtained in the training and validation cohorts (AUC: 0.889 and 0.861). The DeLong test showed the model combining radiomics and conventional plaque features performed better than the conventional model in both cohorts (p < 0.05). Conclusions: The use of radiomics features of intracranial plaques on hrMRI can effectively distinguish culprit plaques with diabetes as the primary pathological cause, which will provide new avenues of research into plaque formation and precise treatment

Supplementary Material for: Association between Triglyceride-Glucose Index and 1-year Recurrent Stroke after Acute Ischemic Stroke: Results from the Xi’an Stroke Registry Study of China

Introduction: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. Methods: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. Results: Among 2,288 participants, the mean TyG index was 8.8 0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98–2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a non-linear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR =2.95; 95% CI, 1.09–7.94; p = 0.032); the risk increased when the TyG index was > 8.73. However, no significant correlation was observed in males. Conclusion: A non-linear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients

Supplementary Material for: Association between Triglyceride-Glucose Index and 1-year Recurrent Stroke after Acute Ischemic Stroke: Results from the Xi’an Stroke Registry Study of China

Introduction: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. Methods: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. Results: Among 2,288 participants, the mean TyG index was 8.8 0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98–2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a non-linear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR =2.95; 95% CI, 1.09–7.94; p = 0.032); the risk increased when the TyG index was > 8.73. However, no significant correlation was observed in males. Conclusion: A non-linear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients

Supplementary Material for: Association between Triglyceride-Glucose Index and 1-year Recurrent Stroke after Acute Ischemic Stroke: Results from the Xi’an Stroke Registry Study of China

Introduction: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. Methods: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. Results: Among 2,288 participants, the mean TyG index was 8.8 0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98–2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a non-linear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR =2.95; 95% CI, 1.09–7.94; p = 0.032); the risk increased when the TyG index was > 8.73. However, no significant correlation was observed in males. Conclusion: A non-linear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients