Risk of cardiovascular death in patients with hepatocellular carcinoma based on the Fine-Gray model.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common types of cancers worldwide, ranking fifth among men and seventh among women, resulting in more than 7 million deaths annually. With the development of medical technology, the 5-year survival rate of HCC patients can be increased to 70%. However, HCC patients are often at increased risk of cardiovascular disease (CVD) death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients. Moreover, CVD and cancer have become major disease burdens worldwide. Thus, further research is needed to lessen the risk of CVD death in HCC patient survivors. AIM: To determine the independent risk factors for CVD death in HCC patients and predict cardiovascular mortality (CVM) in HCC patients. METHODS: This study was conducted on the basis of the Surveillance, Epidemiology, and End Results database and included HCC patients with a diagnosis period from 2010 to 2015. The independent risk factors were identified using the Fine-Gray model. A nomograph was constructed to predict the CVM in HCC patients. The nomograph performance was measured using Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) value. Moreover, the net benefit was estimated via decision curve analysis (DCA). RESULTS: The study included 21545 HCC patients, of whom 619 died of CVD. Age (< 60) [1.981 (1.573-2.496), P < 0.001], marital status (married) [unmarried: 1.370 (1.076-1.745), P = 0.011], alpha fetoprotein (normal) [0.778 (0.640-0.946), P = 0.012], tumor size (≤ 2 cm) [(2, 5] cm: 1.420 (1.060-1.903), P = 0.019; > 5 cm: 2.090 (1.543-2.830), P < 0.001], surgery (no) [0.376 (0.297-0.476), P < 0.001], and chemotherapy(none/unknown) [0.578 (0.472-0.709), P < 0.001] were independent risk factors for CVD death in HCC patients. The discrimination and calibration of the nomograph were better. The C-index values for the training and validation sets were 0.736 and 0.665, respectively. The AUC values of the ROC curves at 2, 4, and 6 years were 0.702, 0.725, 0.740 in the training set and 0.697, 0.710, 0.744 in the validation set, respectively. The calibration curves showed that the predicted probabilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities. DCA demonstrated that the prediction model has a high net benefit. CONCLUSION: Risk factors for CVD death in HCC patients were investigated for the first time. The nomograph served as an important reference tool for relevant clinical management decisions.

GlanceSeg: Real-time microaneurysm lesion segmentation with gaze-map-guided foundation model for early detection of diabetic retinopathy.

Early-stage diabetic retinopathy (DR) presents challenges in clinical diagnosis due to inconspicuous and minute microaneurysms (MAs), resulting in limited research in this area. Additionally, the potential of emerging foundation models, such as the segment anything model (SAM), in medical scenarios remains rarely explored. In this work, we propose a human-in-the-loop, label-free early DR diagnosis framework called GlanceSeg, based on SAM. GlanceSeg enables real-time segmentation of MA lesions as ophthalmologists review fundus images. Our human-in-the-loop framework integrates the ophthalmologist's gaze maps, allowing for rough localization of minute lesions in fundus images. Subsequently, a saliency map is generated based on the located region of interest, which provides prompt points to assist the foundation model in efficiently segmenting MAs. Finally, a domain knowledge filtering (DKF) module refines the segmentation of minute lesions. We conducted experiments on two newly-built public datasets, i.e., IDRiD and Retinal-Lesions, and validated the feasibility and superiority of GlanceSeg through visualized illustrations and quantitative measures. Additionally, we demonstrated that GlanceSeg improves annotation efficiency for clinicians and further enhances segmentation performance through fine-tuning using annotations. The clinician-friendly GlanceSeg is able to segment small lesions in real-time, showing potential for clinical applications.

Aesthetic Cellulose Filaments with Water-Triggered Switchable Internal Stress and Customizable Polarized Iridescence Toward Green Fashion Innovation.

Healthy, convenient, and aesthetic hair dyeing and styling are essential to fashion trends and personal-social interactions. Herein, we fabricate green, scalable, and aesthetic regenerated cellulose filaments (ACFs) with customizable iridescent colors, outstanding mechanical properties, and water-triggered moldability for convenient and fashionable artificial hairdressing. The fabrication of ACFs involves cellulose dissolution, cross-linking, wet-spinning, and nanostructured orientation. Notably, the cross-linking strategy endows the ACFs with significantly weakened internal stress, confirmed by monitoring the offset of the C-O-C group in the cellulose molecular chain with Raman imaging, which ensures a tailorable orientation of the nanostructure during wet stretching and tunable iridescent polarization colors. Interestingly, ACFs can be tailored for three-dimensional shaping through a facile water-triggered adjustable internal stress: temporary shaping with low-level internal stress in the wet state and permanent shaping with high-level internal stress in the dry state. The health, convenience, and green aesthetic filaments show great potential in personal wearables.

Effects of thrombopoietin pre-treatment on peri-liver transplantation thrombocytopenia in a mouse model of cirrhosis with hypersplenism.

BACKGROUND: During cirrhosis, the liver is impaired and unable to synthesize and clear thrombopoietin properly. At the same time, the spleen assumes the function of hemofiltration and storage due to liver dysfunction, resulting in hypersplenism and excessive removal of platelets in the spleen, further reducing platelet count. When liver function is decompensated in cirrhotic patients, the decrease of thrombopoietin (TPO) synthesis is the main reason for the decrease of new platelet production. This change of TPO leads to thrombocytopenia and bleeding tendency in cirrhotic patients with hypersplenism. AIM: To investigate the clinical efficacy of recombinant human TPO (rhTPO) in the treatment of perioperative thrombocytopenia during liver transplantation in cirrhotic mice with hypersplenism. METHODS: C57BL/6J mice and TPO receptor-deficient mice were used to establish models of cirrhosis with hypersplenism. Subsequently, these mice underwent orthotopic liver transplantation (OLT). The mice in the experimental group were given rhTPO treatment for 3 consecutive days before surgery and 5 consecutive days after surgery, while the mice in the control group received the same dose of saline at the same frequency. Differences in liver function and platelet counts were determined between the experimental and control groups. Enzyme-linked immunosorbent assay was used to assess the expression of TPO and TPO receptor (c-Mpl) in the blood. RESULTS: Preoperative administration of rhTPO significantly improved peri-OLT thrombocytopenia in mice with cirrhosis and hypersplenism. Blocking the expression of TPO receptors exacerbated peri-OLT thrombocytopenia. The concentration of TPO decreased while the concentration of c-Mpl increased in compensation in the mouse model of cirrhosis with hypersplenism. TPO pre-treatment significantly increased the postoperative TPO concentration in mice, which in turn led to a decrease in the c-Mpl concentration. TPO pre-treatment also significantly enhanced the Janus kinase (Jak)/signal transducers and activators of transcription pathway protein expressions in bone marrow stem cells of the C57BL/6J mice. Moreover, the administration of TPO, both before and after surgery, regulated the levels of biochemical indicators, such as alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase in the C57BL/6J mice. CONCLUSION: Pre-treatment with TPO not only exhibited therapeutic effects on perioperative thrombocytopenia in the mice with cirrhosis and hypersplenism, who underwent liver transplantation but also significantly enhanced the perioperative liver function.

Retinal layers changes in patients with age-related macular degeneration treated with intravitreal anti-VEGF agents.

BACKGROUND: The purpose of this study was to investigate retinal layers changes in patients with age-related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (anti-VEGF) agents and to evaluate if these changes may affect treatment response. METHODS: This study included 496 patients with AMD or PCV who were treated with anti-VEGF agents and followed up for at least 6 months. A comprehensive analysis of retinal layers affecting visual acuity was conducted. To eliminate the fact that the average thickness calculated may lead to differences tending to converge towards the mean, we proposed that the retinal layer was divided into different regions and the thickness of the retinal layer was analyzed at the same time. The labeled data will be publicly available for further research. RESULTS: Compared to baseline, significant improvement in visual acuity was observed in patients at the 6-month follow-up. Statistically significant reduction in central retinal thickness and separate retinal layer thickness was also observed (p < 0.05). Among all retinal layers, the thickness of the external limiting membrane to retinal pigment epithelium/Bruch's membrane (ELM to RPE/BrM) showed the greatest reduction. Furthermore, the subregional assessment revealed that the ELM to RPE/BrM decreased greater than that of other layers in each region. CONCLUSION: Treatment with anti-VEGF agents effectively reduced retinal thickness in all separate retinal layers as well as the retina as a whole and anti-VEGF treatment may be more targeted at the edema site. These findings could have implications for the development of more precise and targeted therapies for AMD treatment.

Effects of the Long-Term Continuous Cropping of Yongfeng Yam on the Bacterial Community and Function in the Rhizospheric Soil.

Replant disease caused by continuous cropping commonly occurs in yam with consecutive monoculture. However, little is known about how the continuous cropping of yam affects the rhizospheric soil bacterial community structure. In this study, the effects of continuous cropping on rhizospheric soil characteristics, bacterial diversity, and community structure were investigated in the Yongfeng yam fields under monoculture for 1, 5, 10, 15, and 20 years. Long-term monoculture caused soil acidification and increased the concentration of available potassium (AK) and available phosphorus (AP), and soil bacterial richness, but decreased the soil bacterial diversity. An exception was for the field under monoculture for 20 years as it showed the highest bacterial diversity. The relative abundance of beneficial bacteria, such as Proteobacteria, Actinobacteria, and Chloroflexi decreased while the relative abundance of harmful bacteria, including Gemmatimonadetes and Acidobacteria, increased with an extended continuous cultivation time. The networks varied among yams with different cultivation years and became complex with the increase in cultivation years. However, after time in monoculture, the bacterial network decreased gradually and existed stably. These changes in bacterial community composition and co-occurrence of networks may increase the potential risk of soil-borne disease and reduce the yield and quality of Yongfeng yam.

Transport and retention of nano emulsified vegetable oil in porous media: Effect of pore straining, roughness wedging, and interfacial effects.

Emulsified vegetable oil (EVO), as one of the novel green substrates, has been widely used in subsurface remediation. In these applications, the retention behavior of EVO presents a challenge to remediation efficiency as mechanism insights into the retention of EVO is limited. Herein, Brinell funnels experiments with X-ray microtomography (XMT) were conducted to examine the drainage and retention of nanoscale EVO in porous media, with a specific focus on investigating the impact of pore straining, grain surface roughness, and interfacial effects on Nano-EVO (NEVO) retention. This study demonstrated that the retention of NEVO in porous media is the synergistic result of pore straining, roughness wedging, and interface attachment. With the action of these effects, three residual states of NEVO, incorporating retention at porous ganglia, grain-grain contacts, and grain surface, were identified by XMT in porous media. After multiple periods of drainage and imbibition, the NEVO arrived at stable retention proportions of 46.3%, 72.2%, and 85.9% in three independent systems with coarse, medium, and fine sand as porous media, respectively. The interfacial effects, including the attachment of solid-phase and air-liquid interface, are confirmed as the dominant factors for the retention of NEVO in porous media, which contributed 35.63-47.33% of total retention for the conditions employed. Correspondingly, the contributions of pore straining and roughness wedging only ranged 3.78-24.06% and 3.87-9.94%, respectively. The consistency of the contributions between the actual measurement of XMT and computational evaluation further confirmed the rationality and reliability of the results. In such the dominant factor, interfacial tension, contact angle, and capillary radius play an essential role in NEVO retention, which could be reflected by capillary rise height. These findings advance our understanding on NEVO retention caused by substrate-media interaction and also offer a promising direction for subsurface remediation.

Altered Brain Function and Causal Connectivity Induced by Repetitive Transcranial Magnetic Stimulation Treatment for Major Depressive Disorder.

Objective: Repetitive transcranial magnetic stimulation (rTMS) can effectively improve depression symptoms in patients with major depressive disorder (MDD); however, its mechanism of action remains obscure. This study explored the neuralimaging mechanisms of rTMS in improving depression symptoms in patients with MDD. Methods: In this study, MDD patients with first-episode, drug-naive (n = 29) and healthy controls (n = 33) were enrolled. Depression symptoms before and after rTMS treatment were assessed using the Hamilton Depression Rating Scale (HAMD-17). Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected both before and after the treatment. Changes in the brain function after the treatment were compared using the following two indices: the amplitude of the low-frequency fluctuation (ALFF) and regional homogeneity (ReHo), which are sensitive for evaluating spontaneous neuronal activity. The brain region with synchronous changes was selected as the seed point, and the differences in the causal connectivity between the seed point and whole brain before and after rTMS treatment were investigated via Granger causality analysis (GCA). Results: Before treatment, patients with MDD had significantly lower ALFF in the left superior frontal gyrus (p < 0.01), higher ALFF in the left middle frontal gyrus and left precuneus (p < 0.01), and lower ReHo in the left middle frontal and left middle occipital gyri (p < 0.01) than the values observed in healthy controls. After the rTMS treatment, the ALFF was significantly increased in the left superior frontal gyrus (p < 0.01) and decreased in the left middle frontal gyrus and left precuneus (p < 0.01). Furthermore, ReHo was significantly increased in the left middle frontal and left middle occipital gyri (p < 0.01) in patients with MDD. Before treatment, GCA using the left middle frontal gyrus (the brain region with synchronous changes) as the seed point revealed a weak bidirectional causal connectivity between the middle and superior frontal gyri as well as a weak causal connectivity from the inferior temporal to the middle frontal gyri. After treatment, these causal connectivities were strengthened. Moreover, the causal connectivity from the inferior temporal gyrus to the middle frontal gyri negatively correlated with the total HAMD-17 score (r = -0.443, p = 0.021). Conclusion: rTMS treatment not only improves the local neural activity in the middle frontal gyrus, superior frontal gyrus, and precuneus but also strengthens the bidirectional causal connectivity between the middle and superior frontal gyri and the causal connectivity from the inferior temporal to the middle frontal gyri. Changes in these neuroimaging indices may represent the neural mechanisms underlying rTMS treatment in MDD. Clinical Trial Registration: This study was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019761).

RPL15 promotes hepatocellular carcinoma progression via regulation of RPs-MDM2-p53 signaling pathway.

BACKROUND: RPL15 has been found to participate in human tumorigenesis. However, its function and regulatory mechanism in hepatocellular carcinoma (HCC) development are still unclear. Current study investigated the effects of RPL15 in HCC. METHODS: The expression of RPL15 in clinical tissues and cell lines of HCC was detected by RT-qPCR, Western blotting, and Immunohistochemistry (IHC). Colony formation, CCK-8, flow cytometry, Wound healing and Transwell invasion assays, were used to detect the carcinoma progression of HCC cells with RPL15 overexpression or knockdown in vitro. A xenograft model was constructed to assess the effect of RPL15 knockdown on HCC cells in vivo. The expression of CDK2 and Cyclin E1 related to cell cycles, Bax and Bcl-2 related to cell apoptosis, E-cadherin, N-cadherin and Vimentin related to epithelial-mesenchymal transition (EMT), p53 and p21 related to p53 signaling pathway, were detected by Western blotting. The connection between p53, MDM2 and RPL5/11 affected by RPL15 was analyzed using immunoprecipitation and Cycloheximide (CHX) chase assay. RESULTS: Elevated RPL15 was identified in HCC tissues, which was not only a prediction for the poor prognosis of HCC patients, but also associated with the malignant progression of HCC. RPL15 silencing arrested HCC cell cycle, suppressed HCC cell colony formation, proliferation, invasion, and migration, and induce cell apoptosis. On the contrary, RPL15 upregulation exerted opposite effects. Results also indicated that HCC cell invasion and migration were associated with EMT, and that the RPs-MDM2-p53 pathway was implicated in RPL15-mediated oncogenic transformation. In addition, RPL15 knockdown significantly suppressed HCC xenografts growth. CONCLUSIONS: RPL15 played crucial roles in HCC progression and metastasis, serving as a promising candidate for targeted therapies.

Application value of mixed reality in hepatectomy for hepatocellular carcinoma.

BACKGROUND: As a new digital holographic imaging technology, mixed reality (MR) technology has unique advantages in determining the liver anatomy and location of tumor lesions. With the popularization of 5G communication technology, MR shows great potential in preoperative planning and intraoperative navigation, making hepatectomy more accurate and safer. AIM: To evaluate the application value of MR technology in hepatectomy for hepatocellular carcinoma (HCC). METHODS: The clinical data of 95 patients who underwent open hepatectomy surgery for HCC between June 2018 and October 2020 at our hospital were analyzed retrospectively. We selected 95 patients with HCC according to the inclusion criteria and exclusion criteria. In 38 patients, hepatectomy was assisted by MR (Group A), and an additional 57 patients underwent traditional hepatectomy without MR (Group B). The perioperative outcomes of the two groups were collected and compared to evaluate the application value of MR in hepatectomy for patients with HCC. RESULTS: We summarized the technical process of MR-assisted hepatectomy in the treatment of HCC. Compared to traditional hepatectomy in Group B, MR-assisted hepatectomy in Group A yielded a shorter operation time (202.86 ± 46.02 min vs 229.52 ± 57.13 min, P = 0.003), less volume of bleeding (329.29 ± 97.31 mL vs 398.23 ± 159.61 mL, P = 0.028), and shorter obstructive time of the portal vein (17.71 ± 4.16 min vs 21.58 ± 5.24 min, P = 0.019). Group A had lower alanine aminotransferas and higher albumin values on the third day after the operation (119.74 ± 29.08 U/L vs 135.53 ± 36.68 U/L, P = 0.029 and 33.60 ± 3.21 g/L vs 31.80 ± 3.51 g/L, P = 0.014, respectively). The total postoperative complications and hospitalization days in Group A were significantly less than those in Group B [14 (37.84%) vs 35 (60.34%), P = 0.032 and 12.05 ± 4.04 d vs 13.78 ± 4.13 d, P = 0.049, respectively]. CONCLUSION: MR has some application value in three-dimensional visualization of the liver, surgical planning, and intraoperative navigation during hepatectomy, and it significantly improves the perioperative outcomes of hepatectomy for HCC.

Malignant rhabdoid tumor of the liver in a middle-aged woman: a case report and literature review.

BACKGROUND: Extrarenal malignant rhabdoid tumor (EMRT) is a rare and high-mortality malignant tumor, which is more common in infants and rarely seen in adults. We firstly report a case of liver malignant rhabdoid tumor (MRT) with a loss of SMARCB1 gene (alias INI1, SNF5, BAF47) expression in a middle-aged woman, and preliminarily summarize the clinical characteristics and discuss its potential treatment of liver MRT by reviewing 55 cases reported in the past. CASE PRESENTATION: We report a 40-year-old woman who was admitted to our hospital for right epigastric pain. Previously, the patient was treated with liver hematoma in another hospital until she came to our hospital for abdominal pain again. In our hospital, we performed surgical treatment on her and the pathology diagnosed EMRT with negative expression of SMARCB1. After surgery, the patient underwent genetic testing, but failed to screen for sensitive targeted or conventional chemotherapy drugs, and she did not receive further treatment. Due to lack of timely diagnosis and effective chemotherapy drugs, tumor recurrence and metastasis occurred one year after surgery. Then the patient chose traditional Chinese medicine for treatment. And the metastatic tumors had still progressed after one year of treatment, but the patient didn't have obvious discomfort symptoms. CONCLUSIONS: Liver MRT is a highly aggressive tumor with high metastatic potential and poor prognosis. It lacks specific symptoms and signs and is easy to be ignored and misdiagnosed. The mortality rate is extremely high as there is no effective treatment. But most tumors are accompanied by SMARCB1 deficiency, which may offer new research directions for cancer therapeutics. For the present, early detection, early diagnosis and early resection remain the key to improve the prognosis of patients.

Receptor Activator of Nuclear Factor (Nf)-kb Ligand Promotes T Helper 17 Cell Differentiation through Fas.

T helper 17 (Th17) cells play important role in the defense against pathogens and autoimmune diseases. Many cytokines can induce Th17 cell differentiation. However, the mechanism of Th17 cell differentiation is not well clarified. RankL, a member of the TNF superfamily, binds with Rank and then participates in the proliferation and differentiation of many kinds of cells. Recent studies showed that RankL-Rank signaling is closely related to Th17 differentiation and function. The detail of the Rank-RankL pathway in Th17 cell differentiation is still unclear. To illustrate the role of Rank-RankL in Th17 differentiation, naive CD4 + T cells were differentiated into Th17 cells with or without RankL stimulation. During Th17 differentiation, the expression of Rank obviously increased. The RankL stimulation significantly increased Th17 cell differentiation indicated by increased IL-17-positive cell number, highly expressed IL-17 and IL-22 and elevated IL-17 secretion. These effects were canceled by Rank-Fc addition. In further study, RankL treatment during Th17 differentiation up-regulated Fas expression. Fas knockdown inhibited the Th17 differentiation promoted by RankL. In this study, it was confirmed that Rank-RankL signaling could promote Th17 cell differentiation through Fas induction.

Long non-coding RNA BACE1-AS plays an oncogenic role in hepatocellular carcinoma cells through miR-214-3p/APLN axis.

BACE1 antisense RNA (BACE1-AS) is implicated in promoting cell proliferation in different types of tumors. However, the function and mechanism of BACE1-AS in hepatocellular carcinoma (HCC) are still unclear. In the present study, we found that the relative expression of BACE1-AS in HCC cell lines, HCC tissues, and serum samples of HCC patients was significantly increased, and its high expression was correlated with the poor prognosis of HCC patients. In addition, overexpression of BACE1 promoted HCC cell proliferation, cell cycle progression, migration, and invasion, but inhibited cell apoptosis, while knockdown of BACE1 exerted the opposite role. Furthermore, BACE1-AS sponged miR-214-3p and inhibited its expression, thus promoting Apelin (APLN) expression. Overexpression or knockdown of miR-214-3p could partially reverse the abnormal proliferation, cell cycle progression, migration, invasion, and apoptosis caused by overexpression or knockdown of BACE1. These findings suggest that the BACE1-AS/miR-214-3p/APLN axis is a novel signaling pathway that facilitates HCC.

lncRNA CYTOR promotes cell proliferation and tumor growth via miR-125b/SEMA4C axis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor worldwide with high morbidity and high mortality rates. Previous studies have demonstrated that cytoskeleton regulator RNA (CYTOR) plays critical roles in the tumorigenesis of various types of cancer. The present study aimed to investigate the clinical significance, biological function and molecular mechanism of CYTOR in the progression of HCC. The expression level of CYTOR was determined by reverse transcription quantitative PCR in HCC tissues and cell lines. The biological function of CYTOR was investigated using CCK-8 assay, EdU immunofluorescence, western blotting and TUNEL assay in vitro. A xenograft tumor model and immunohistochemistry were used to validate the role of CYTOR in vivo. The downstream targets of CYTOR and micro-RNA (miR)-125b were confirmed by RNA immunoprecipitation assay and luciferase reporter assays. The results demonstrated that CYTOR was significantly increased in HCC tissues compared with non-tumor tissues and that CYTOR expression was associated with the poor prognosis of patients with HCC. Furthermore, CYTOR silencing could inhibit the proliferation and promote the apoptosis of HCC cells. CYTOR overexpression had the opposite effects. The results from in vivo xenograft demonstrated that CYTOR knockdown suppressed tumor growth. In addition, CYTOR could directly interact with and negatively regulate miR-125b. Furthermore, semaphorin 4C (SEMA4C) was the target of miR-125b and CYTOR regulated SEMA4C expression by modulating miR-125b. Taken together, the findings from the present study demonstrated that CYTOR could promote cell proliferation and tumor growth by sponging miR-125b and upregulating SEMA4C, which suggested that CYTOR may act as a potential therapeutic target in HCC.

The antagonistic effect of bisphenol A and nonylphenol on liver and kidney injury in rats.

OBJECTIVE: Bisphenol A (BPA) and nonylphenol (NP) are widely distributed endocrine-disrupting compounds. We aimed to estimate the combined toxicity of BPA and NP at a clinically safe dose (100 µg/kg) in rats. MATERIALS AND METHODS: Liver and kidney functions were evaluated by detecting the relevant indicators. Hematoxylin and Eosin (HE) staining was performed to examine the injury in the tissue. TUNEL assay and Western blot were used to detect cell apoptosis and expressions of target factors, respectively. RESULTS: The body weight of rats in the BPA + NP group was lighter than that in the BPA or NP group. BPA or NP weakened liver function through increasing levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT), cholesterol (CHOL), triglyceride TG, globulin (GLOB), treponemiapallidum (TP), and total bilirubin (TBIL). BPA and NP could induce kidney damage by elevating the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). Moreover, the malondialdehyde (MDA) content was increased, whereas the activities of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-PX), glutathione sulfotransferase (GSH-ST), catalase (CAT), and peroxidase (POD) were reduced in those groups exposed to BPA or NP. HE staining exhibited injuries of the liver and kidney. Furthermore, the apoptosis of liver and kidney cells was enhanced by exposure to BPA or NP. Additionally, the expressions of CYP2D6, CYP1A1, and CYP2E1 were triggered by the treatment of BPA or NP. The combined effect of BPA and NP seemed to be antagonistic at a low dose. CONCLUSION: BPA and NP may have potential interactions.

Expression and prognostic impact of FZDs in pancreatic adenocarcinoma.

BACKGROUND: Despite the high number of researches on pancreatic adenocarcinoma (PAAD) over past decades, little progress had been made due to lack of effective treatment regimens. We aimed to investigate the expression level, mutation, and clinical significance of the Frizzled (FZD) family in PAAD so as to establish a sufficient scientific evidence for clinical decisions and risk management. METHODS: PAAD samples were extracted from The Cancer Genome Atlas (TCGA). Oncomine, Gene expression profiling interactive analysis (GEPIA), human protein atlas (HPA), Kaplan-Meier Plotter, cBioPortal, LinkedOmics, DAVID database, and R software (× 64 3.6.2) were used to comprehensively analyze the roles of FZDs. p value below to 0.05 was considered as significant difference. RESULTS: In total, 179 PAAD tissues and 171 paracancerous tissues were included. The expression levels of FZD1, 2, 6, 7, and 8 were higher in PAAD tissues than those in normal pancreatic tissue. The higher the expression levels of FZD2 and FZD7, the higher the clinical stage. The overall survival (OS) time was significantly different between low FZD3, 4, 5, 6, and 9 expression group and high expression group. Multivariable analysis showed that FZD3 and FZD6 were independent prognostic factors. The recurrence free survival (RFS) time was significantly different between low FZD4 and FZD8 expression group and high expression group. The RFS difference between low FZD6 expression group and high expression group had not reached statistical significance (p = 0.067), which might be due to the small sample size. However, multivariable analysis showed that FZD6 was the only independent factor for RFS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that FZDs played a critical role in the Wnt signaling pathway, which was further confirmation that FZDs were transmembrane receptors of Wnt signaling pathway. CONCLUSIONS: Our results strongly indicated a crucial role of the FZD family in PAAD. FZD3 and FZD6 could be potential prognostic and predictive markers, and FZD6 might also function as a potential therapeutic target in PAAD by blocking Wnt/ß-catenin pathway.

Knockdown of CYP301B1 and CYP6AX1v2 increases the susceptibility of the brown planthopper to beta-asarone, a potential plant-derived insecticide.

The cytochrome P450 monooxygenases of insects play crucial roles in the metabolic detoxification of insecticides. Our previous finding showed that two cytochrome P450 genes, both CYP301B1 and CYP6AX1v2, in the BPH underwent overexpression due to ß-asarone. In this study, we investigated the molecular characteristics, expression patterns and functions of these two cytochrome P450 genes. The results showed that CYP301B1 had the highest expression level in the eggs, while CYP6AX1v2 was expressed in macropterous female adults. Moreover, the expression level of CYP301B1 in the head was higher than that in the integument, fat body and gut. The expression level of CYP6AX1v2 in the fat body and gut was higher than that in head and integument. Importantly, silencing CYP301B1 and CYP6AX1v2 separately could increase the sensitivity, resulting in significant higher mortality of BPH following treatment with ß-asarone. Our findings indicated that CYP301B1 and CYP6AX1v2 could contribute to the resistance of BPH to ß-asarone, and these two genes may be involved in the detoxification metabolism of ß-asarone in BPH.

Enhancer RNA LINC00242-Induced Expression of PHF10 Drives a Better Prognosis in Pancreatic Adenocarcinoma.

Enhancer RNA is a kind of non-coding RNA, which is transcribed from the enhancer region of gene and plays an important role in gene transcription regulation. However, the role of eRNA in pancreatic adenocarcinoma (PAAD) is still unclear. In this study, we identified the key eRNA and its target gene in PAAD. The transcriptome data and clinical information of pancreatic cancer were downloaded from the UCSC Xena platform. A total of 2,695 eRNAs and its target gene predicted by the PreSTIGE method were selected as candidate eRNA-target pairs. After survival analysis, we found that LINC00242 was the eRNA most related to patients' survival, and correlation analysis further indicated that LINC00242 and its target gene PHF10 had a significant co-expression relationship. Downregulation of LINC00242 was significantly associated with unfavorable clinicopathological features. Based on pan-cancer analysis, we found that LINC00242 was associated with the survival of multiple cancers, and LINC00242 was co-expressed with its target genes in multiple cancer types. External experiments further demonstrated that PHF10 was the downstream target gene of LINC00242. After ssGSEA analysis, PAAD patients were classified as high, medium, and low immune cell infiltration clusters. Compared with the low and medium immune infiltration clusters, the expression level of PHF10 was significantly upregulated in the high immune infiltration clusters. After performing the CIBERSORT algorithm, we found that there was a significant difference in the abundance of immune infiltrating cells between the PHF10 high- and low-expression groups. Additionally, the web tool TIMER was used to detect the distribution and expression of PHF10 in pan-cancer.