Decrease in GPSM2 mediated by the natural product luteolin contributes to colon adenocarcinoma treatment and increases the sensitivity to fluorouracil.

Luteolin, a monomeric substance, is a natural product of the Brucea javanica (BJ) plant. Brucea javanica oil emulsion injection (BJOEI) is a proprietary Chinese medicine purified from BJ that is widely used clinically as an anti-tumor treatment. Although a growing body of research suggests that luteolin and BJOEI have anti-tumor effects, the molecular mechanism of action has not been fully elucidated. In this study, through molecular docking technology, we found that luteolin can interact directly with GPSM2 and regulate the FoxO signaling pathway through GPSM2. In addition, the inhibitory effect of luteolin on colon adenocarcinoma (COAD) cells was found to be offset by knockdown of GPSM2. In contrast, the anti-proliferative effects of luteolin could be notably reversed by overexpression of GPSM2. The results reveal that GPSM2 is crucial in luteolin-mediated anti-proliferative effects. The mediation of anti-proliferative effects by GPSM2 has also been indirectly demonstrated in RKO and SW480 xenograft mice models. In addition, we verified that BJOEI inhibits the progression of COAD by mediating GPSM2 and regulating the FoxO signaling pathway. We also found that BJOEI achieved a better anti-tumor effect when combined with fluorouracil injection. Collectively, our data show that the anti-tumor effects of BJOEI and luteolin on COAD are GPSM2-dependent and downregulating the expression of GPSM2 to regulate the FoxO signaling pathway may be an effective way to treat COAD.

Assessment of arterial pulsatility of cerebral perforating arteries using 7T high-resolution dual-VENC phase-contrast MRI.

PURPOSE: Directly imaging the function of cerebral perforating arteries could provide valuable insight into the pathology of cerebral small vessel diseases (cSVD). Arterial pulsatility has been identified as a useful biomarker for assessing vascular dysfunction. In this study, we investigate the feasibility and reliability of using dual velocity encoding (VENC) phase-contrast MRI (PC-MRI) to measure the pulsatility of cerebral perforating arteries at 7 T. METHODS: Twenty participants, including 12 young volunteers and 8 elder adults, underwent high-resolution 2D PC-MRI scans with VENCs of 20 cm/s and 40 cm/s at 7T. The sensitivity of perforator detection and the reliability of pulsatility measurement of cerebral perforating arteries using dual-VENC PC-MRI were evaluated by comparison with the single-VENC data. The effects of temporal resolution in the PC-MRI acquisition and aging on the pulsatility measurements were investigated. RESULTS: Compared to the single VENCs, dual-VENC PC-MRI provided improved sensitivity of perforator detection and more reliable pulsatility measurements. Temporal resolution impacted the pulsatility measurements, as decreasing temporal resolution led to an underestimation of pulsatility. Elderly adults had elevated pulsatility in cerebral perforating arteries compared to young adults, but there was no difference in the number of detected perforators between the two age groups. CONCLUSION: Dual-VENC PC-MRI is a reliable imaging method for the assessment of pulsatility of cerebral perforating arteries, which could be useful as a potential imaging biomarker of aging and cSVD.

Assessment of Collateral Flow in Patients with Carotid Stenosis Using Random Vessel-Encoded Arterial Spin-Labeling: Comparison with Digital Subtraction Angiography.

BACKGROUND AND PURPOSE: Collateral circulation plays an important role in steno-occlusive internal carotid artery disease (ICAD) to reduce the risk of stroke. We aimed to investigate the utility of planning-free random vessel-encoded arterial spin-labeling (rVE-ASL) in assessing collateral flows in patients with ICAD. MATERIALS AND METHODS: Forty patients with ICAD were prospectively recruited. The presence and extent of collateral flow were assessed and compared between rVE-ASL and DSA by using Contingency (C) and Cramer V (V) coefficients. The differences in flow territory alterations stratified by stenosis ratio and symptoms, respectively, were compared between symptomatic (n = 19) and asymptomatic (n = 21) patients by using the Fisher exact test. RESULTS: Good agreement was observed between rVE-ASL and DSA in assessing collateral flow (C = 0.762, V = 0.833, both P < .001). Patients with ICA stenosis of ≥90% were more likely to have flow alterations (P < .001). Symptomatic patients showed a higher prevalence of flow alterations in the territory of the MCA on the same side of ICAD (63.2%), compared with asymptomatic patients (23.8%, P = .012), while the flow alterations in the territory of anterior cerebral artery did not differ (P = .442). The collateral flow to MCA territory was developed primarily from the contralateral internal carotid artery (70.6%) and vertebrobasilar artery to a lesser extent (47.1%). CONCLUSIONS: rVE-ASL provides comparable information with DSA on the assessment of collateral flow. The flow alterations in the MCA territory may be attributed to symptomatic ICAD.

Predicting the Probability of Recurrence Based on Individualized Risk Factors After Primary Lateral Patellar Dislocation Treated Nonoperatively.

PURPOSE: To develop a comprehensive and effective personalized scoring system on the basis of demographic and clinical characteristics for predicting recurrence probability in patients with primary lateral patellar dislocation (LPD). METHODS: Participants included 261 primary patients with LPD with 2-year minimum follow-up from our hospital across 2013 to 2020. Demographic and clinical characteristics were collected retrospectively. The backward stepwise method was performed to identify independent predictors and construct a nomogram to predict the probability of recurrence. The predictive performance was assessed by receiver operating characteristic curves, calibration plots, and decision curve analysis. RESULTS: After variables selection, 6 independent predictors of recurrence (skeletal maturity, trochlear dysplasia, tibial tuberosity-trochlear groove distance, mechanical axis deviation, Insall-Salvati index, and patellar tilt) were enrolled in our model. Validation of this nomogram in both training and validation cohort revealed powerful predictive ability, with an area under the curve of 0.962 and 0.977, respectively. The nomogram also showed great calibration and good clinical practicability. CONCLUSIONS: Our study presented a nomogram that incorporates 6 independent risk factors (skeletal maturity, trochlear dysplasia, tibial tuberosity-trochlear groove distance, mechanical axis deviation, Insall-Salvati index, and patellar tilt), which can be conveniently used to accurately predicts the risk of recurrence after primary LPD in individual cases. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic study.

Three-dimensional echo-shifted EPI with simultaneous blip-up and blip-down acquisitions for correcting geometric distortion.

PURPOSE: EPI with blip-up/down acquisition (BUDA) can provide high-quality images with minimal distortions by using two readout trains with opposing phase-encoding gradients. Because of the need for two separate acquisitions, BUDA doubles the scan time and degrades the temporal resolution when compared to single-shot EPI, presenting a major challenge for many applications, particularly fMRI. This study aims at overcoming this challenge by developing an echo-shifted EPI BUDA (esEPI-BUDA) technique to acquire both blip-up and blip-down datasets in a single shot. METHODS: A 3D esEPI-BUDA pulse sequence was designed by using an echo-shifting strategy to produce two EPI readout trains. These readout trains produced a pair of k-space datasets whose k-space trajectories were interleaved with opposite phase-encoding gradient directions. The two k-space datasets were separately reconstructed using a 3D SENSE algorithm, from which time-resolved B0 -field maps were derived using TOPUP in FSL and then input into a forward model of joint parallel imaging reconstruction to correct for geometric distortion. In addition, Hankel structured low-rank constraint was incorporated into the reconstruction framework to improve image quality by mitigating the phase errors between the two interleaved k-space datasets. RESULTS: The 3D esEPI-BUDA technique was demonstrated in a phantom and an fMRI study on healthy human subjects. Geometric distortions were effectively corrected in both phantom and human brain images. In the fMRI study, the visual activation volumes and their BOLD responses were comparable to those from conventional 3D echo-planar images. CONCLUSION: The improved imaging efficiency and dynamic distortion correction capability afforded by 3D esEPI-BUDA are expected to benefit many EPI applications.

Hypoxia-induced ALDH3A1 promotes the proliferation of non-small-cell lung cancer by regulating energy metabolism reprogramming.

Aldehyde dehydrogenase 3A1 (ALDH3A1) is an NAD+-dependent enzyme that is closely related to tumor development. However, its role in non-small-cell lung cancer (NSCLC) has not been elucidated. This study aimed to clarify the mechanism of ALDH3A1 and identify potential therapeutic targets for NSCLC. Here, for the first time, we found that ALDH3A1 expression could be induced by a hypoxic environment in NSCLC. ALDH3A1 was highly expressed in NSCLC tissue, especially in some late-stage patients, and was associated with a poor prognosis. In mechanistic terms, ALDH3A1 enhances glycolysis and suppresses oxidative phosphorylation (OXPHOS) to promote cell proliferation by activating the HIF-1α/LDHA pathway in NSCLC. In addition, the results showed that ALDH3A1 was a target of ß-elemene. ALDH3A1 can be downregulated by ß-elemene to inhibit glycolysis and enhance OXPHOS, thus suppressing NSCLC proliferation in vitro and in vivo. In conclusion, hypoxia-induced ALDH3A1 is related to the energy metabolic status of tumors and the efficacy of ß-elemene, providing a new theoretical basis for better clinical applications in NSCLC.

Clinical characteristics and risk factors of intracranial hemorrhage after spinal surgery.

BACKGROUND: Intracranial hemorrhage after spinal surgery is a rare and devastating complication. AIM: To investigate the economic burden, clinical characteristics, risk factors, and mechanisms of intracranial hemorrhage after spinal surgery. METHODS: A retrospective cohort study was conducted from January 1, 2015, to December 31, 2022. Patients aged ≥ 18 years, who had undergone spinal surgery were included. Intracranial hemorrhage patients were selected after spinal surgery during hospitalization. Based on the type of spinal surgery, patients with intracranial hemorrhage were randomly matched in a 1:5 ratio with control patients without intracranial hemorrhage. The patients' pre-, intra-, and post-operative data and clinical manifestations were recorded. RESULTS: A total of 24472 patients underwent spinal surgery. Six patients (3 males and 3 females, average age 71.3 years) developed intracranial hemorrhage after posterior spinal fusion procedures, with an incidence of 0.025% (6/24472). The prevailing type of intracranial hemorrhage was cerebellar hemorrhage. Two patients had a poor clinical outcome. Based on the type of surgery, 30 control patients were randomly matched in 1:5 ratio. The intracranial hemorrhage group showed significant differences compared with the control group with regard to age (71.33 ± 7.45 years vs 58.39 ± 8.07 years, P = 0.001), previous history of cerebrovascular disease (50% vs 6.7%, P = 0.024), spinal dura mater injury (50% vs 3.3%, P = 0.010), hospital expenses (RMB 242119.1 ± 87610.0 vs RMB 96290.7 ± 32029.9, P = 0.009), and discharge activity daily living score (40.00 ± 25.88 vs 75.40 ± 18.29, P = 0.019). CONCLUSION: The incidence of intracranial hemorrhage after spinal surgery was extremely low, with poor clinical outcomes. Patient age, previous stroke history, and dura mater damage were possible risk factors. It is suggested that spinal dura mater injury should be avoided during surgery in high-risk patients.

Bibliometric Analysis of Global Research on Tumor Dormancy.

Tumor dormancy continues to be a research hotspot with numerous pressing problems that need to be solved. The goal of this study is to perform a bibliometric analysis of pertinent articles published in the twenty-first century. We concentrate on significant keywords, nations, authors, affiliations, journals, and literature in the field of tumor dormancy, which will help researchers to review the results that have been achieved and better understand the directions of future research. We retrieved research articles on tumor dormancy from the Web of Science Core Collection. This study made use of the visualization tools VOSviewer, CiteSpace, and Scimago Graphica, as visualization helps us to uncover the intrinsic connections between information. Research on tumor dormancy has been growing in the 21st century, especially from 2015 to the present. The United States is a leader in many aspects of this research area, such as in the number of publications, the number of partners, the most productive institutions, and the authors working in this field. Harvard University is the institution with the highest number of publications, and Aguirre-Ghiso, Julio A. is the author with the highest number of publications and citations. The keywords that emerged after 2017 were "early dissemination", "inhibition", "mechanism", "bone metastasis", and "promotion". We believe that research on tumor dormancy mechanisms and therapy has been, and will continue to be, a major area of interest. The exploration of the tumor dormancy microenvironment and immunotherapeutic treatments for tumor dormancy is likely to represent the most popular future research topics.

Expression characteristics and their functional role of IGFBP gene family in pan-cancer.

BACKGROUND: Insulin-like growth factor binding proteins (IGFBPs) are critical regulators of the biological activities of insulin-like growth factors. The IGFBP family plays diverse roles in different types of cancer, which we still lack comprehensive and pleiotropic understandings so far. METHODS: Multi-source and multi-dimensional data, extracted from The Cancer Genome Atlas (TCGA), Oncomine, Cancer Cell Line Encyclopedia (CCLE), and the Human Protein Atlas (HPA) was used for bioinformatics analysis by R language. Immunohistochemistry and qRT-PCR were performed to validate the results of the database analysis results. Bibliometrics and literature review were used for summarizing the research progress of IGFBPs in the field of tumor. RESULTS: The members of IGFBP gene family are differentially expressed in various cancer types. IGFBPs expression can affect prognosis of different cancers. The expression of IGFBPs expression is associated with multiple signal transduction pathways. The expression of IGFBPs is significantly correlated with tumor mutational burden, microsatellite instability, tumor stemness and tumor immune microenvironment. The qRT-PCR experiments verified the lower expression of IGFBP2 and IGFBP6 in gastric cancer and the lower expression of IGFBP6 in colorectal cancer. Immunohistochemistry validated a marked downregulation of IGFBP2 protein in gastric cancer tissues. The keywords co-occurrence analysis of IGFBP related publications in cancer showed relative research have been more concentrating on the potential of IGFBPs as tumor diagnostic and prognostic markers and developing cancer therapies. CONCLUSIONS: These findings provide frontier trend of IGFBPs related research and new clues for identifying novel therapeutic targets for various cancers.

Cardiometabolic index is associated with urinary albumin excretion and renal function in aged person over 60: Data from NHANES 2011-2018.

PURPOSE: Cardiometabolic index (CMI) is recently considered to have certain significance in the screening of diabetes, atherosclerosis, and renal dysfunction. Therefore, this study intends to explore the relationship between CMI and the risk of albuminuria. METHODS: This is a cross-sectional study involving 2732 elderly people (age ≥ 60). The research data are from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Calculate CMI index: Triglyceride (TG) (mmol/L)/ High density lipid-cholesterol (HDLC) (mmol/L) × WHtR. RESULTS: The CMI level in microalbuminuria group was significantly higher than that in normal albuminuria group (P < 0.05 or P < 0.01), whether in the general population or in diabetes and hypertensive population respectively. The proportion of abnormal microalbuminuria increased gradually with the increase of CMI tertile interval (P < 0.01). Correlation analysis showed that CMI was positively correlated with urinary albumin-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine (Scr), and negatively correlated with estimated glomerular filtration rate (eGFR). With the occurrence of albuminuria as the dependent variable, weighted logistic regression analysis showed that CMI was an independent risk factor for microalbuminuria. Weighted smooth curve fitting showed that CMI index was linearly related to the risk of microalbuminuria. Subgroup analysis and interaction test showed that they participated in this positive correlation. CONCLUSIONS: Obviously, CMI is independently associated with microalbuminuria, suggesting that CMI, a simple indicator, can be used for risk assessment of microalbuminuria, especially in diabetes patients.

Association of mitochondrial homeostasis and dynamic balance with malignant biological behaviors of gastrointestinal cancer.

Mitochondria determine the physiological status of most eukaryotes. Mitochondrial dynamics plays an important role in maintaining mitochondrial homeostasis, and the disorder in mitochondrial dynamics could affect cellular energy metabolism leading to tumorigenesis. In recent years, disrupted mitochondrial dynamics has been found to influence the biological behaviors of gastrointestinal cancer with the potential to be a novel target for its individualized therapy. This review systematically introduced the role of mitochondrial dynamics in maintaining mitochondrial homeostasis, and further elaborated the effects of disrupted mitochondrial dynamics on the cellular biological behaviors of gastrointestinal cancer as well as its association with cancer progression. We aim to provide clues for elucidating the etiology and pathogenesis of gastrointestinal cancer from the perspective of mitochondrial homeostasis and disorder.

Isolated medial patellofemoral ligament reconstruction is valid to stabilize patellofemoral joint but uncertain to reduce patellar height in setting of lateral patellar dislocation and patella alta.

INTRODUCTION: Medial patellofemoral ligament reconstruction (MPFLR) is the most commonly used surgical treatment for patients with lateral patellar dislocation (LPD). It is still poorly understood whether or not MPFLR has a contributory effect on decreasing patellar height. MATERIALS AND METHODS: Forty-five patients who underwent isolated MPFLR for LPD and patella alta were evaluated with a mean follow-up period of 24 months (22-25 months). Knee joint functions were evaluated by Banff patellofemoral instability instrument (BPII) 2.0 scores and Kujala scores. Patellofemoral engagement and stability were assessed by the patella tilt angle (PTA) and patellar congruence angle (PCA) measured by CT scans, and the patellar-glide test. Patellar height was calculated on lateral radiographs according to three methods: Caton-Deschamps ratios (CDR), Insall-Salvati ratios (ISR), and Blackburne-Peel ratios (BPR). A threshold value of p < 0.05 denoted a statistically significant difference. RESULTS: Significant improvements were found in both BPII 2.0 scores, which increased from 41.7 to 77.8 (p < 0.001) and Kujala scores, which increased from 49.2 to 85.5 (p < 0.001). Post-operative PTAs and PCA decreased from 19.6 ± 8.8 to - 3.4 ± 6.2, and from 24.6 ± 7.3 to 13.1 ± 3.8 degrees respectively (p < 0.001). No patients showed lateral translation more than grade II in the patellar-glide test. Regarding patellar height, a tiny reduction (Δ = 0.02, Δ max = 0.09) was discovered in using CDR (p = 0.027), rather than ISR or BPR. All measurements of radiographic indices had an excellent intra- and inter-rater reliability (ICC > 0.75). CONCLUSIONS: Isolated anatomic MPFLR is sufficient to achieve good clinical outcomes, as well as patellofemoral stability and high rates of return-to-sport. However, it is unclear if the reconstructed MPFL has a contributory effect on reducing patellar height.

Sclerostin antibody promotes bone formation through the Wnt/ß-catenin signaling pathway in femoral trochlear after patellar instability.

PURPOSE: The molecular mechanism of patellar instability (PI) remains unknown. The purpose of this study was to explore the function of SOST/sclerostin in PI and examine the effect of sclerostin antibody (Scl-Ab). MATERIALS AND METHODS: We randomly divided 60 male 3-week-old C57Bl/6 mice into four groups: sham, PI, Scl-Ab intraperitoneal injection (Scl-Ab IP), Scl-Ab intraarticular injection (Scl-Ab IA). PI was established in the latter three groups. The Scl-Ab IP/IA groups were administered with an intraperitoneal/intraarticular Scl-Ab injection (100 mg/kg, 20 µl), respectively, at 5-day intervals. Distal femurs were collected 30 days after the surgery. The SOST/sclerostin, ß-catenin, ALP, OPG and RANKL expression in distal femur were determined. Trochlear morphology and structural parameters of the trabecular and cortical bone compartments were determined by micro-CT. Further sub-regional analysis was performed. HE staining and Masson's trichrome staining were performed to evaluate cartilage changes. RESULTS: PI increased the expression of SOST/sclerostin and RANKL, and decreased ß-catenin, ALP and OPG levels, while Scl-Ab IP reversed these changes. Scl-Ab IP brought trochlear morphology closer to normality. Additionally, Scl-Ab IP significantly improved most of the bone parameters. Importantly, both PI and Scl-Ab IP acted mainly on trabecular bone. Histological analysis showed that Scl-Ab IP protected cartilage from degeneration. However, Scl-Ab IA did not protect against bone loss or cartilage degradation. CONCLUSIONS: SOST/sclerostin plays an important role in PI and systemic Scl-Ab use promotes bone formation through the Wnt/ß-catenin signaling pathway in the femoral trochlear after PI.

Shape-Aware 3D Small Vessel Segmentation with Local Contrast Guided Attention.

The automated segmentation and analysis of small vessels from in vivo imaging data is an important task for many clinical applications. While current filtering and learning methods have achieved good performance on the segmentation of large vessels, they are sub-optimal for small vessel detection due to their apparent geometric irregularity and weak contrast given the relatively limited resolution of existing imaging techniques. In addition, for supervised learning approaches, the acquisition of accurate pixel-wise annotations in these small vascular regions heavily relies on skilled experts. In this work, we propose a novel self-supervised network to tackle these challenges and improve the detection of small vessels from 3D imaging data. First, our network maximizes a novel shape-aware flux-based measure to enhance the estimation of small vasculature with non-circular and irregular appearances. Then, we develop novel local contrast guided attention(LCA) and enhancement(LCE) modules to boost the vesselness responses of vascular regions of low contrast. In our experiments, we compare with four filtering-based methods and a state-of-the-art self-supervised deep learning method in multiple 3D datasets to demonstrate that our method achieves significant improvement in all datasets. Further analysis and ablation studies have also been performed to assess the contributions of various modules to the improved performance in 3D small vessel segmentation. Our code is available at https://github.com/dengchihwei/LCNetVesselSeg.

Emergency Braking Evoked Brain Activities during Distracted Driving.

Electroencephalogram (EEG) was used to analyze the mechanisms and differences in brain neural activity of drivers in visual, auditory, and cognitive distracted vs. normal driving emergency braking conditions. A pedestrian intrusion emergency braking stimulus module and three distraction subtasks were designed in a simulated experiment, and 30 subjects participated in the study. The common activated brain regions during emergency braking in different distracted driving states included the inferior temporal gyrus, associated with visual information processing and attention; the left dorsolateral superior frontal gyrus, related to cognitive decision-making; and the postcentral gyrus, supplementary motor area, and paracentral lobule associated with motor control and coordination. When performing emergency braking under different driving distraction states, the brain regions were activated in accordance with the need to process the specific distraction task. Furthermore, the extent and degree of activation of cognitive function-related prefrontal regions increased accordingly with the increasing task complexity. All distractions caused a lag in emergency braking reaction time, with 107.22, 67.15, and 126.38 ms for visual, auditory, and cognitive distractions, respectively. Auditory distraction had the least effect and cognitive distraction the greatest effect on the lag.

Non-coding RNA and hepatitis B virus-related hepatocellular carcinoma: A bibliometric analysis and systematic review.

Objectives: A bibliometric analysis for non-coding RNA and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) was performed to describe international research status and visualize the research scope and emerging trends over the last two decades on this topic. Materials and methods: Research data of non-coding RNA and HBV-related HCC were retrieved and extracted from the Web of Science Core Collection (WoSCC) database from 1 January 2003 to 13 June 2022 and then analyzed by means of bibliometric methods. A total of 1,036 articles published in this field were assessed for specific characteristics, including the year of publication, journal, author, institution, country/region, references, and keywords. VOSviewer was employed to perform co-authorship, co-occurrence, and co-citation analyses accompanied by constructing a visual network. Results: Overall, 1,036 reports on non-coding RNA and HBV-related HCC from 2003 to 2022 were retrieved from WoSCC. The publication has gradually increased during the last two decades with 324 journals involved. Most research records (748 publications and 23,184 citations) were concentrated in China. A co-occurrence cluster analysis for the top 100 keywords was performed and four clusters were generated: (1) non-coding RNA as a molecular marker for the diagnosis and prognosis of HBV-related HCC; (2) dysregulation of non-coding RNA by hepatitis B virus X protein (HBx); (3) non-coding RNA affecting the biological behaviors of HBV-related HCC; and (4) epidemiological study for the effects of non-coding RNA on the risk of HBV-related HCC. Conclusion: The publications and citations involved in non-coding RNA and HBV-related HCC have increased over the last two decades associated with many countries, institutions, and authors. Our study revealed current development trends, global cooperation models, basic knowledge, research hotspots, and emerging frontiers in this field.

Comprehensive Analysis and Validation of Solute Carrier Family 25 (SLC25) and Its Correlation with Immune Infiltration in Pan-Cancer.

As the largest gene family functioning in protein transport among human solute carriers, the SLC25 family (mitochondrial carrier family) can participate in development of cancer. However, a comprehensive exploration for the exactly roles of SLC family remains lacking. In the present study, a total of 15 functional SLC25 family genes were retrieved from all current publications. And multidimensional analyses were systematically performed based on the transcriptome and genome data of SLC25 family from a variety of online databases for their expression, immune cell infiltration, and cancer prognosis. Validation by qPCR and immunohistochemistry were further conducted for the expression of partial SLC25 family members in some tumor tissue. We found that the SLC25 family had strong correlation with immune cells, such as macrophages M2, CD8+ T cell, CD4+ T cell memory activated, and memory resting. Among them, SLC25A6 was most correlated with Macrophage M1 in uveal melanoma (r = -0.68, P = 1.9e - 0.5). Expression of mRNA level showed that SLC25A4 was downregulated in stomach adenocarcinoma and colon adenocarcinoma. SLC25A7 was highly expressed in stomach adenocarcinoma and colon adenocarcinoma. SLC25A23 was decreased in colon adenocarcinoma. qPCR and immunohistochemistry validation results were consistent with our bioinformatics prediction. SLC25A8 was associated with the prognosis of cancer. All these findings suggested that the SLC25 family might affects the immune microenvironment of the cancer and then had the potential to be predictive biomarkers for early diagnosis and prognosis as well as novel targets for individualized treatment of cancer.

RNA-sequencing reveals the expression profiles of tsRNAs and their potential carcinogenic role in cholangiocarcinoma.

BACKGROUND: Recently, the incidence of cholangiocarcinoma (CCA) has gradually increased. As CCA has a poor prognosis, the ideal survival rate is scarce for patients. The abnormal expressed tsRNAs may regulate the progression of a variety of tumors, and tsRNAs is expected to become a new diagnostic biomarker of cancer. However, the expression of tsRNAs is obscure and should be elucidated in CCA. METHODS: High-throughput RNA sequencing technology (RNA-seq) was utilized to determine the overall expression profiles of tsRNAs in three pairs CCA and adjacent normal tissues and to screen the tsRNAs that were differentially expressed. The target genes of dysregulated tsRNAs were predicted and the biological effects and potential signaling pathways of these target genes were explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate 11 differentially expressed tRFs with 12 pairs CCA and adjacent normal tissues. RESULTS: High-throughput RNA-seq totally demonstrated 535 dysregulated tsRNAs, of which 241 tsRNAs were upregulated, such as tRF-21-YLKZKWE5D，tRF-16-9NF5W8B，tRF-27-78YLKZKWE52，tRF-19-RLXN48KP，tRF-33-IK9NJ4S2I7L7DV，tRF-19-F8DHXYIV, and 294 tsRNAs were downregulated (tRF-20-739P8WQ0, tRF-34-JJ6RRNLIK898HR, tRF-17-VL8RPY5, tRF-23-YP9LON4VDP, tRF-39-EH623K76IR3DR2I2, tRF-17-18YKISM, tRF-19-Q1Q89PJZ, etc.) in CCA compared with adjacent normal tissues (|log2 [fold change] | ≥ 1 and p value <0.05). GO and KEGG enrichment analyses indicated that the target genes of dysregulated tRFs (tRF-34-JJ6RRNLIK898HR, tRF-38-0668K87SERM492V, and tRF-39-0668K87SERM492E2) were mainly enriched in the Notch signaling pathway, Hippo signaling pathway, cAMP signaling pathway and in growth hormone synthesis, secretion and action, etc. qRT-PCR result showed that tRF-34-JJ6RRNLIK898HR/tRF-38-0668K87SERM492V/tRF-39-0668K87SERM492E2 was downregulated (p = 0.021), and tRF-20-LE2WMK81 was upregulated in CCA (p = 0.033). CONCLUSION: Differentially expressed tRFs in CCA are enriched in many pathways associated with neoplasms, which may impact the tumor progression and have potential to be diagnostic biomarkers and therapeutic targets of CCA.

Predicting Prognosis of Hepatocellular Carcinoma Patients Based on the Expression Signatures of Mitophagy Genes.

Background: The unbalance of mitophagy was closely related to hepatocellular carcinoma (HCC) progression. At present, it has not been uncovered about the influence of mitophagy genes on HCC prognosis and their potential pathogenesis. Materials and Methods: The expression and clinical information of HCC in TCGA cohort were used to identify mitophagy differentially expressed genes (MDEGs) with prognostic value. The prognostic model of mitophagy genes was built and externally validated by LASSO regression in TCGA cohort and ICGC cohort, respectively. The function of the prognostic signature and its association with immune cell infiltration were explored. The profile of MDEGs was validated with 39 pairs HCC and paracarcinoma tissues by quantitative reverse transcription-PCR (qRT-PCR). Results: A total of 18 mitophagy genes that were upregulated and contributed to poor prognosis in HCC were identified. These genes could interact with each other. The correlation analysis showed that there was positively correlation among mitophagy genes. According to optimal λ value, 8 mitophagy gene signatures were involved in prognostic model. Based on median risk scores, HCC patients were divided into high-risk group and low-risk group. Compared with the low-risk group, the high-risk group has worse overall survival in TCGA cohort and ICGC cohort. The univariate and multivariate Cox regression analysis suggested that risk score was an independent prognostic factor of HCC patients. Time-dependent ROC curve was used to identify and validate good predicting performance of the prognostic model. Enrichment analysis showed that risk differentially expressed genes were enriched in various metabolism and cell division processes. The immune cell infiltration score and immune function were significantly different in two groups. qRT-PCR validation result showed that QSTM1, CSNK2B, PGAM5, and ATG5 were upregulated. Conclusion: Mitophagy genes could influence HCC progression through regulating the metabolism and immune functions and could be used to predict prognosis and considered as potential prognostic biomarker and precise therapeutic target of HCC.

Pan-cancer analysis of forkhead box Q1 as a potential prognostic and immunological biomarker.

Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family involved in the occurrence and development of different tumors. However, the specific expression patterns and functions of FOXQ1 in pan-cancer remain unclear. Therefore, we collected the expression, mutation, and clinical information data of 33 tumors from The Cancer Genome Atlas database. Via public pan-cancer transcriptome data analysis, we found that FOXQ1 is differentially expressed in various tumors at tissue and cell levels, such as liver hepatocellular carcinoma, colon adenocarcinoma, lung adenocarcinoma, lung squamous cell carcinoma, thyroid carcinoma, and kidney renal clear cell carcinoma. Kaplan-Meier and Cox analyses suggested that FOXQ1 expression was associated with poor overall survival of cutaneous melanoma and thymoma. Its expression was also associated with good disease-specific survival (DSS) in prostate adenocarcinoma but poor DSS in liver hepatocellular carcinoma. In addition, FOXQ1 expression was associated with poor disease-free survival of pancreatic adenocarcinoma. Moreover, FOXQ1 expression was closely related to the tumor mutational burden in 14 tumor types and microsatellite instability (MSI) in 8 tumor types. With an increase in stromal and immune cells, FOXQ1 expression was increased in breast invasive carcinoma, pancreatic adenocarcinoma, thyroid carcinoma, lung adenocarcinoma, and ovarian serous cystadenocarcinoma, while its expression was decreased in pancreatic adenocarcinoma, bladder urothelial carcinoma, and stomach adenocarcinoma. We also found that FOXQ1 expression was related to the infiltration of 22 immune cell types in different tumors (p < 0.05), such as resting mast cells and resting memory CD4 T cells. Last, FOXQ1 was coexpressed with 47 immune-related genes in pan-cancer (p < 0.05). In conclusion, FOXQ1 expression is closely related to prognosis, clinicopathological parameters, cancer-related pathway activity, the tumor mutational burden, MSI, the tumor microenvironment, immune cell infiltration, and immune-related genes and has the potential to be a diagnostic and prognostic biomarker as well as an immunotherapy target for tumors. Our findings provide important clues for further mechanistic research into FOXQ1.