Small Transjugular Intrahepatic Portosystemic Shunt Plus Variceal Embolization for Gastric Varices: A Multicenter Cohort Study.

BACKGROUND & AIMS: The effect of transjugular intrahepatic portosystemic shunt (TIPS) plus variceal embolization for treating gastric varices (GVs) remains controversial. This nationwide multicenter cohort study aimed to evaluate whether adding variceal embolization to a small diameter (8-mm) TIPS could reduce the rebleeding incidence in patients with different types of GVs. METHODS: This retrospective cohort study involved 629 patients who underwent 8-mm TIPS for gastric varices at 7 medical centers. The primary endpoint was all-cause rebleeding, and the secondary endpoints included overt hepatic encephalopathy (OHE) and all-cause mortality. RESULTS: A total of 629 patients were included. Among them, 429 (68.2%) had gastroesophageal varices type 1 (GOV1), 145 (23.1%) had gastroesophageal varices type 2 (GOV2), and 55 (8.7%) had isolated gastric varices type 1 (IGV1). In the entire cohort, adjunctive embolization reduced rebleeding (6.2% vs 13.6%; P = .005) and OHE (31.0% vs 39.4%; P = .02) compared with TIPS alone. However, no significant differences were found in mortality (12.0% vs 9.7%; P = .42). In patients with GOV2 and IGV1, TIPS plus variceal embolization reduced both rebleeding (GOV2: 7.8% vs 25.1%; P = .01; IGV1: 5.6% vs 30.8%; P = .03) and OHE (GOV2: 31.8% vs 51.5%; P = .008; IGV1: 11.6% vs 38.5%; P = .04). However, in patients with GOV1, adjunctive embolization did not reduce rebleeding (5.9% vs 8.7%; P = .37) or OHE (33.1% vs 35.3%; P = .60). CONCLUSIONS: Compared with TIPS alone, 8-mm TIPS plus variceal embolization reduced rebleeding and OHE in patients with GOV2 and IGV1. These findings suggest that patients with GOV2 and IGV1, rather than GOV1, could benefit from embolization with TIPS.

Efficacy of TIPS plus extrahepatic collateral embolisation in real-world data: a validation study.

OBJECTIVES: The efficacy of transjugular intrahepatic portosystemic shunt (TIPS) plus extrahepatic collateral embolisation (TIPS+E) in reducing rebleeding and hepatic encephalopathy (HE) post-TIPS was recently reported in a meta-analysis, but further validation is essential. This study aims to confirm the effectiveness of TIPS+E using real-world data. METHODS: The multicentre retrospective cohort included 2077 patients with cirrhosis who underwent TIPS±E (TIPS: 631, TIPS+E: 1446) between January 2010 and December 2022. Regression and propensity score matching (PSM) were used to adjust for baseline characteristic differences. After PSM, clinical outcomes, including rebleeding, HE, survival and further decompensation (FDC), were analysed. Baseline data from all patients contributed to the construction of prognostic models. RESULTS: After PSM, 1136 matched patients (TIPS+E: TIPS=568:568) were included. TIPS+E demonstrated a significant reduction in rebleeding (HR 0.77; 95% CI 0.59 to 0.99; p=0.04), HE (HR 0.82; 95% CI 0.68 to 0.99; p=0.04) and FDC (HR 0.85; 95% CI 0.73 to 0.99; p=0.04), comparing to TIPS. Significantly, TIPS+E also reduced rebleeding, HE and FDC in subgroup of using 8 mm diameter stents and embolising of gastric varices+spontaneous portosystemic shunts (GV+SPSS). However, there were no differences in overall or subgroup survival analysis. Additionally, the random forest models showed higher accuracy and AUROC comparing to other models. Controlling post-TIPS portal pressure gradient (pPPG) within 7 mm Hg

Protective effect of naringin against radiation-induced heart disease in rats via Sirt1/NF-κB signaling pathway and endoplasmic reticulum stress.

This study was designed to explore the protective effect and mechanism of naringin (NG) on radiation-induced heart disease (RIHD) in rats. Rats were divided into four x-ray (XR) irradiation groups with different absorbed doses (0/10/15/20 Gy), or into three groups (control, XR, and XR + NG groups). Subsequently, the ultrasonic diagnostic apparatus was adopted to assess and compare the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular internal diameter at end diastole (LVIDd), and left ventricular internal diameter at end systole (LVIDs) in rats. Hematoxylin-eosin (H&E) staining and Masson staining were applied to detect the pathological damage and fibrosis of heart tissue. Western blot was used to measure the expression levels of myocardial fibrosis-related proteins, endoplasmic reticulum stress-related proteins, and Sirt1 (silent information regulator 1)/NF-κB (nuclear factor kappa-B) signaling pathway-related proteins in cardiac tissues. Additionally, enzyme-linked immunosorbent assay was utilized to detect the activities of pro-inflammatory cytokines, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in cardiac tissue. The results showed that NG treatment significantly attenuated the 20 Gy XR-induced decline of LVEF and LVFS and the elevation of LVIDs. Cardiac tissue damage and fibrosis caused by 20 Gy XR were significant improved after NG treatment. Meanwhile, in rats irradiated by XR, marked downregulation was identified in the expressions of fibrosis-related proteins (Col I, collagen type I; α-SMA, α-smooth muscle actin; and TGF-ß1, transforming growth factor-beta 1) and endoplasmic reticulum stress-related proteins (GRP78, glucose regulatory protein 78; CHOP, C/EBP homologous protein; ATF6, activating transcription factor 6; and caspase 12) after NG treatment. Moreover, NG treatment also inhibited the production of pro-inflammatory cytokines [interleukin-6, interleukin-1ß, and monocyte chemoattractant protein-1 (MCP-1)], reduced the expression of MDA, and promoted the activities of SOD and CAT. Also, NG treatment promoted Sirt1 expression and inhibited p65 phosphorylation. Collectively, XR irradiation induced cardiac injury in rats in a dose-dependent manner. NG could improve the cardiac injury induced by XR irradiation by inhibiting endoplasmic reticulum stress and activating Sirt1/NF-κB signaling pathway.

Phenolic acids from Prunella vulgaris alleviate cardiac remodeling following myocardial infarction partially by suppressing NLRP3 activation.

Acute myocardial infarction (MI) is one of the leading causes of mortality around the world. Prunella vulgaris (Xia-Ku-Cao in Chinese) is used in traditional Chinese medicine practice for the treatment of cardiovascular diseases. However, its active ingredients and mechanisms of action on cardiac remodeling following MI remain unknown. In this study, we investigated the cardioprotective effect of P. vulgaris on MI rat models. MI rats were treated with aqueous extract of P. vulgaris or phenolic acids from P. vulgaris, including caffeic acid, ursolic acid or rosmarinic acid, 1 day after surgery and continued for the following 28 days. Then the cardioprotective effect, such as cardiac function, inflammatory status, and fibrosis areas were evaluated. RNA-sequencing (RNA-seq) analysis, real-time polymerase chain reaction (PCR), western blotting, and ELISA were used to explore the underlying mechanism. In addition, ultra-high performance liquid chromatography/mass spectrometer analysis was used to identify the chemicals from P. vulgaris. THP-1NLRP3-GFP cells were used to confirm the inhibitory effect of P. vulgaris and phenolic acids on the expression and activity of NLRP3. We found that P. vulgaris significantly improved cardiac function and reduced infarct size. Meanwhile, P. vulgaris protected cardiomyocyte against apoptosis, evidenced by increasing the expression of anti-apoptosis protein Bcl-2 in the heart and decreasing lactate dehydrogenase (LDH) levels in serum. Results from RNA-seq revealed that the therapeutic effect of P. vulgaris might relate to NLRP3-mediated inflammatory response. Results from real-time PCR and western blotting confirmed that P. vulgaris suppressed NLRP3 expression in MI heart. We also found that P. vulgaris suppressed NLRP3 expression and the secretion of HMGB1, IL-1ß, and IL-18 in THP-1NLRP3-GFP cells. Further studies indicated that the active components of P. vulgaris were three phenolic acids, those were caffeic acid, ursolic acid, and rosmarinic acid. These phenolic acids inhibited LPS-induced NLRP3 expression and activity in THP-1 cells, and improved cardiac function, suppressed inflammatory aggregation and fibrosis in MI rat models. In conclusion, our study demonstrated that P. vulgaris and phenolic acids from P. vulgaris, including caffeic acid, ursolic acid, and rosmarinic acid, could improve cardiac function and protect cardiomyocytes from ischemia injury during MI. The mechanism was partially related to inhibiting NLRP3 activation.

FOXP2 suppresses the proliferation, invasion, and aerobic glycolysis of hepatocellular carcinoma cells by regulating the KDM5A/FBP1 axis.

The Warburg effect is the preference of cancer cells to use glycolysis rather than oxidative phosphorylation to generate energy. Accumulating evidence suggests that aerobic glycolysis is widespread in hepatocellular carcinoma (HCC) and closely related to tumorigenesis. The purpose of this study was to investigate the role and mechanism of forkhead box P2 (FOXP2) in aerobic glycolysis and tumorigenesis in HCC. Here, we found that FOXP2 was lower expressed in HCC tissues and cells than in nontumor tissues and normal hepatocytes. Overexpression of FOXP2 suppressed cell proliferation and invasion of HCC cells and promoted cell apoptosis in vitro, and hindered the growth of mouse xenograft tumors in vivo. Further researches showed that FOXP2 inhibited the Warburg effect in HCC cells. Moreover, we demonstrated that FOXP2 up-regulated the expression of fructose-1, 6-diphosphatase (FBP1), and the inhibitory effect of FOXP2 on glycolysis was dependent on FBP1. Mechanistically, as a transcription factor, FOXP2 negatively regulated the transcription of lysine-specific demethylase 5A (KDM5A), and then blocked KDM5A-induced H3K4me3 demethylation in FBP1 promoter region, thereby promoting the expression of FBP1. Consistently, overexpressing KDM5A or silencing FBP1 effectively reversed the inhibitory effect of FOXP2 on HCC progression. Together, our findings revealed the mechanistic role of the FOXP2/KDM5A/FBP1 axis in glycolysis and malignant progression of HCC cells, providing a potential molecular target for the therapy of HCC.

Discovery of Salidroside as a Novel Non-Coding RNA Modulator to Delay Cellular Senescence and Promote BK-Dependent Apoptosis in Cerebrovascular Smooth Muscle Cells of Simulated Microgravity Rats.

Cardiovascular aging has been reported to accelerate in spaceflights, which is a great potential risk to astronauts' health and performance. However, current exercise routines are not sufficient to reverse the adverse effects of microgravity exposure. Recently, salidroside (SAL), a valuable medicinal herb, has been demonstrated to display an important role for prevention and treatment in cardiovascular and other diseases. In the present work, Sprague-Dawley rats with four-week tail-suspension hindlimb-unloading were used to simulate microgravity effects on the cardiovascular system. We found that intragastrical administration of SAL not only significantly decreased the expressions of senescence biomarkers, such as P65 and P16, but also obviously increased the expressions of BK-dependent apoptotic genes, including the large-conductance calcium-activated K+ channel (BK), Bax, Bcl-2, and cleaved caspase-3, in vascular smooth muscle cells (VSMCs) in vivo and in vitro. In addition, relative non-coding RNAs were screened, and a luciferase assay identified that SAL increased apoptosis by activating LncRNA-FLORPAR, inhibiting miR-193, and then triggering the activity of the BK-α subunit. Our work indicated that SAL is a novel non-coding RNA modulator for regulating the LncRNA-FLORPAR sponging miR-193 pathway, which significantly promoted BK-dependent apoptosis and delayed cerebrovascular aging-like remodeling during simulated microgravity exposure. Our findings may provide a new approach to prevent cardiovascular aging in future spaceflights.

Activation of peroxymonosulfate with biochar-supported CuO (CuO@BC) for natural organic matter removal and membrane fouling control.

To achieve excellent activation efficiency of peroxymonosulfate (PMS), this work prepared a biochar-supported CuO (CuO@BC) catalyst, and the CuO@BC/PMS system was proposed to remove the organic matter in natural surface water and reduce the fouling of ultrafiltration membrane. The successful synthesis of CuO@BC was demonstrated through characterization of its microscopic morphology and chemical composition by various techniques. The prepared heterogeneous catalyst showed a strong catalytic effect on PMS, which significantly removed natural organic matter through the production of active substances (•OH, SO4•-, O2•- and 1O2) from water. With respective degradation rates of 39.4% and 59.4%, the concentrations of DOC and UV254 dropped to 1.702 mg/L and 0.026 cm-1, respectively. Additionally, the CuO@BC/PMS oxidation displayed potent oxidation capabilities for contaminants and fluorescent organics with various molecular weights. The system effectively decreased the amount of organic matter that caused reversible and irreversible fouling of polyethersulfone membranes in natural water by 85.8% and 56.3%, respectively. The main fouling mechanisms changed as well, with standard and complete blocking dominating the entire filtration process. The results demonstrated the capacity of the CuO@BC/PMS system to remove contaminants in natural water and mitigate membrane fouling.

Association of Subjective Sleep Pattern with Self-reported Diabetes in China.

There is limited research investigating the relationship between self-reported diabetes mellitus and subjective sleep patterns. Our study aims to explore this association by analyzing trends in a cohort study conducted in China using data from the China Health and Nutrition Survey longitudinal research (CHNS). We used multilevel logistic regression models to analyze the relationship. Our findings indicate that the prevalence of self- reported diabetes in China increased from 1.10% in 2004 to 3.36% in 2015, with an increase in the prevalence of short-term sleep from 7.03-10.24%. The prevalence of self-reported diabetes increased with increasing BMI levels (Normal and below: 0.67-2.16%, Overweight: 1.58-4.35%, Obesity: 2.68-6.57%, p < 0.01). The short-term sleep subgroup had the highest prevalence (2.14-5.64%). Additionally, we found significant associations between age, education level, ethnicity, coffee, smoking, drinking and the self-reported diabetes. Interestingly, the risk ratios for self-reported diabetes differed between sleep durations. With 6-8hours as the reference group, the risk ratios for self-reported diabetes in the short-term, and long-term sleep subgroups were 1.80 (95% CI: 1.23-2.63), and 1.41 (95%CI: 1.01-1.96), respectively. Raising awareness about the impact of irregular sleep duration on diabetes risk is essential, and these initiatives may serve as effective policies for diabetes control.

Conversion of primary liver cancer after targeted therapy for liver cancer combined with AFP-targeted CAR T-cell therapy: a case report.

Primary liver cancer (PLC) that originates in the liver is a malignant tumor with the worst prognosis. Hepatocellular carcinoma (HCC) is the most common type of PLC. Most PLC cases are diagnosed at advanced stages mainly due to their insidious onset and rapid progression. Patients with PLC undergo surgical intervention or localized treatment, but their survival is often affected by its high relapse rate. Medical treatment is the primary option for patients with liver cancer, especially with advanced extrahepatic metastases. Molecular targeted therapy exerts an anti-tumor effect by acting on various signaling pathways involved in molecular pathogenesis; however, high drug resistance and low therapeutic responsiveness of PLC to molecular targets challenge the treatment option. In recent years, after surgical intervention, radiotherapy, chemotherapy, and/or molecular targeted therapy, autologous cell immunotherapy has been adopted for PLC. As a typical autologous cell immunotherapy, CAR T-cell therapy uses genetically modified T cells to express tumor-specific chimeric antigen receptors (CARs). Its targeting ability, persistent nature, and tumor-killing function result in a significant impact on the treatment of hematological tumors. However, no breakthrough has happened in the research specific to the curation of lung cancer, liver cancer, breast cancer, and other common solid tumors. In this context, a combination of molecular targeted therapy and CAR T-cell therapy was used to treat a patient with advanced HCC to achieve a partial remission(PR) and facilitate further liver transplantation.

Liver Injury in Patients with COVID-19: A Retrospective Study.

Objectives: The objective of this study is to explore the incidence, characteristics, risk factors, and prognosis of liver injury in patients with COVID-19. Methods: We collected clinical data of 384 cases of COVID-19 and retrospectively analyzed the incidence, characteristics, and risk factors of liver injury of the patients. In addition, we followed the patient two months after discharge. Results: A total of 23.7% of the patients with COVID-19 had liver injury, with higher serum AST (P < 0.001), ALT (P < 0.001), ALP (P = 0.004), GGT (P < 0.001), total bilirubin (P = 0.002), indirect bilirubin (P = 0.025) and direct bilirubin (P < 0.001) than the control group. The median serum AST and ALT of COVID-19 patients with liver injury were mildly elevated. Risk factors of liver injury in COVID-19 patients were age (P = 0.001), history of liver diseases (P = 0.002), alcoholic abuse (P = 0.036), body mass index (P = 0.037), severity of COVID-19 (P < 0.001), C-reactive protein (P < 0.001), erythrocyte sedimentation rate (P < 0.001), Qing-Fei-Pai-Du-Tang treatment (P = 0.032), mechanical ventilation (P < 0.001), and ICU admission (P < 0.001). Most of the patients (92.3%) with liver injury were treated with hepatoprotective drugs. 95.6% of the patients returned to normal liver function tests at 2 months after discharge. Conclusions: Liver injury was commen in COVID-19 patients with risk factors, most of them have mild elevations in transaminases, and conservative treatment has a good short-term prognosis.

Individualized portal pressure gradient threshold based on liver function categories in preventing rebleeding after TIPS.

BACKGROUND: The evidence in Portal pressure gradient (PPG) < 12 mmHg after transjugular intrahepatic portosystemic shunt (TIPS) for preventing rebleeding mostly comes from observations in uncovered stents era. Moreover, association between Child-Pugh classes and post-TIPS hepatic encephalopathy (HE) has indicated that tolerance of PPG reduction depends on liver function. This study aimed to investigate the optimal PPG for covered TIPS and explore the optimal threshold tailored to the Child-Pugh classes to find individualized PPG to balance rebleeding and overt HE. METHODS: This multicenter retrospective study analyzed rebleeding, OHE, and mortality of patients associated with post-TIPS PPGs (8, 10, 12, and 14 mmHg) in the entire cohort and among different Child-Pugh classes. Propensity score matching (PSM) and competing risk analyses were performed for sensitivity analyses. RESULTS: We included 2100 consecutively screened patients undergoing TIPS. In all patients, PPG < 12 mmHg reduced rebleeding after TIPS (p = 0.022). In Child-Pugh class A, none of the PPG thresholds were discriminative of clinical outcomes. In Child-Pugh class B, 12 mmHg (p = 0.022) and 14 mmHg (p = 0.037) discriminated rebleeding, but 12 mmHg showed a higher net benefit. In Child-Pugh class C, PPG < 14 mmHg had a lower rebleeding incidence (p = 0.017), and exhibited more net benefit than 12 mmHg. CONCLUSION: Different PPG standards may be required for patients with different liver function categories. A PPG threshold < 12 mmHg might be suitable for patients in Child-Pugh class B, while < 14 mmHg might be optimal for patients in Child-Pugh class C.

A passive-active combined strategy for ultrafiltration membrane fouling control in continuous oily wastewater purification.

Membrane-based technology has been confirmed as an effective way to treat emulsified oily wastewater, however, membrane fouling is still one of practical challenges in long-term operation. Herein, a novel passive-active combined strategy was proposed to control membrane fouling in continuous oily wastewater purification, where the δ-MnO2 decoration layer helped to reduce the total fouling ratio (passive strategy for fouling mitigation) and the catalytic cleaning effectively removed the irreversible oil fouling (active strategy for fouling removal). The functional membrane was prepared via in-situ modification, referred to as δ-MnO2@TA-PES. The morphology, crystalline phase, chemical structure and surface properties of the membranes were systematically characterized. Compared with PES, the δ-MnO2@TA-PES possessed superhydrophilicity, enhanced electronegativity and narrowed pore size. The δ-MnO2@TA-PES achieved high water permeation flux of 723.9 L·m - 2·h - 1·bar-1, excellent oil rejection with separation efficiency above 98.5% for various emulsions, and durable anti-oil-fouling performance with FRRb of 98.0%. Notably, the oil cake layer fouling on δ-MnO2@TA-PES was greatly alleviated owing to its enhanced surface properties. In addition, δ-MnO2@TA-PES showed high cleaning efficiency in the peroxymonosulfate (PMS) cleaning process, where the radical and nonradical pathways occurred simultaneously. And the active substances generated in the nonradical process (especially 1O2) were considered as the main contributor to the reduction of irreversible fouling. Overall, the novel strategy of fouling control ensured the efficient operation of ultrafiltration membranes for the continuous oily wastewater purification.

miR-200a-3p- and miR-181-5p-Mediated HOXB5 Upregulation Promotes HCC Progression by Transcriptional Activation of EGFR.

Background: Hepatocellular carcinoma (HCC) remains a worldwide burden. However, the mechanisms behind the malignant biological behavior of HCC remain unclear. The homeobox (HOX) family could act as either promoters or suppressors in different kinds of malignancies. Our study discovered the role of HOXB5 in regulating HCC progression. Methods: The HOXB5 expression was assessed by RT-PCR analysis in human HCC samples and cell lines. HOXB5 transcriptional regulation of the EGFR was verified by the luciferase reporter assay and chromatin immunoprecipitation experiment. The oncogenic role of HOXB5 in HCC progression was analyzed by CCK8, colony-forming, and transwell assays. Results: Upregulation of HOXB5 was found in human HCC, and was strongly correlated with HCC tumor size, tumor-nodule metastasis, TNM stage, and relatively unfavorable OS and DFS. Ectopic expression of HOXB5 promoted the capacity of cell growth and clonogenicity, while the inhibition of HOXB5 decreased the proliferation and clonogenicity potential in vitro by CCK8 and colony-forming assays. In addition, HOXB5 also promoted cell migration by transwell experiment. Mechanism studies elucidated that HOXB5 triggers HCC progression via direct transcriptional activation of EGFR. The upregulation of HOXB5 is regulated by miR-200a-3p and miR-181-5p. Transfection of miR-200a-3p and miR-181-5p mimics blocked the cell proliferation and migration regulated by HOXB5, while overexpression of the 3'-UTR mutant HOXB5 abolished the suppressive effect of miR-200a-3p and miR-181-5p, but not the wild-type HOXB5. Conclusion: HOXB5 is a promising prognostic factor in human HCC. Targeting miR-200a-3p and the miR-181-5p/HOXB5/EGFR signaling pathway may provide new options for the treatment strategies of HCC.

Effect of peroxydisulfate oxidation catalyzed with ordered mesoporous carbons on controlling ultrafiltration membrane fouling by algal organic matter.

As typical ordered mesoporous carbons (OMCs) materials, CMK-3 and CMK-8 were proposed for catalyzing peroxydisulfate (PDS), and the OMCs/PDS process was combined with membrane filtration to remove algal extracellular organic matter and mitigate membrane fouling. The CMK-3/PDS process achieved substantial reduction of dissolved organic carbon and UV254, followed by CMK-8/PDS. The degradation behavior of fluorescent organics demonstrated the superior performance of OMCs/PDS, while the decomposition of high molecular weight (MW) compounds and generation of lower MW organics were observed. Generally, CMK-3 possessed higher catalytic activity on PDS compared with CMK-8 and powdered activated carbon. The CMK-3/PDS process distinctly decreased the fouling resistances for polyether sulfone and polyvinylidene fluoride membranes, with the reversible resistance reduced by 59.5-83.2% and irreversible resistance declined by 71.7-73.0%. In the meanwhile, CMK-3/PDS prolonged the volumes to the transition period, and postponed the cake layer's generation. The characterization of the membrane morphologies and chemical compositions also showed effective alleviation of fouling. The generated SO4-, OH, O2- and 1O2 as major active oxidation species provided radical as well as non-radical reaction ways for pollutants removal. Overall, our study provides some new ideas for membrane-based combined water purification processes.

MicroRNA-455-3p functions as a tumor suppressor by targeting HDAC2 to regulate cell cycle in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers. MicroRNA has been studied more and more deeply and may become a new target for the treatment of HCC. Here, we investigated the role of miR-455-3p in HCC progression. Compared with non-tumor tissues and normal human hepatic cells, miR-455-3p expression was significantly downregulated in HCC tissues and cell lines. And overexpression of miR-455-3p inhibited cell proliferation and migration but promoted cell apoptosis in HCC cell lines HepG2 and Huh7. Mechanism studies displayed that miR-455-3p targeted HDAC2 and negatively regulated HDAC2 expression. Moreover, HDAC2 was highly expressed in HCC tissues and cell lines. Overexpression of HDAC2 reversed the inhibitory effects of miR-455-3p on cell proliferation, migration and cell cycle protein (CDK6 and cyclin D1) expression, and neutralized the promotion effects of miR-455-3p on cell apoptosis and the activation of p53 pathway. Furthermore, a p53 inhibitor Pifithrin-α (PFT-α) effectively abolished the effects of miR-455-3p on HCC cell behaviors. Additionally, the role of miR-455-3p in tumorigenesis was evaluated by using a mouse xenograft model, and the data showed that miR-455-3p suppressed tumor growth in vivo. In summary, our results suggested that miR-455-3p targeted HDAC2 to inhibit cell proliferation, migration and promote cell apoptosis via the activation of p53 pathway.

Synergistic process using calcium peroxide and ferrous iron for enhanced ultrafiltration of Microcystis aeruginosa-laden water.

Algal blooms and eutrophication in natural surface water not only pose a threat to human health, but also adversely affect the water purification process. Ultrafiltration (UF) has been proved to be effective for the retention of algal cells, but its further application is still restricted by the relatively limited removal of algal organics and membrane fouling. To enhance the UF performance, a synergistic process using calcium peroxide and ferrous sulfate (CaO2/FeSO4) was proposed for the treatment of Microcystis aeruginosa-laden water. The results suggested that the removal of algal cells and organics, fluorescent components were effectively increased with the synergism of CaO2 and FeSO4. The particle size distribution and morphology revealed that the size of algal pollutants apparently increased due to the formation of algal flocs. With CaO2/FeSO4 pretreatment, the terminal specific flux of polyethersulfone and polyvinylidene fluoride membranes were increased by 75.0% and 56.5%, individually. The fouling resistances were significantly reduced, and the fouling mechanism transition to cake filtration was delayed. The membrane interface properties including morphologies and functional groups were characterized, further verifying the effectiveness. The in-situ formed Fe3+ integrated with Ca(OH)2 showed excellent coagulation effect, thus promoting the agglomeration of algal foulants. Simultaneously, the generated hydroxyl radical could improve the oxidative degradation of algal organics. In conclusion, the CaO2/FeSO4 strategy has great advantages and application prospects in enhancing UF performance for Microcystis aeruginosa-laden water treatment.

The role of PAC adsorption-catalytic oxidation in the ultrafiltration performance for treating natural water: Efficiency improvement, fouling mitigation and mechanisms.

Powdered activated carbon (PAC) has turned out to be an efficient adsorbent in drinking water treatment, whereas its application integrated with membrane filtration is still controversial because of the combined fouling effect between organic pollutants and PAC. To this end, an integrated process of combining PAC adsorption-catalytic oxidation and membrane filtration was proposed for natural surface water treatment. The synergistic effect of PAC and peroxymonosulfate (PMS) was confirmed through the generation of reactive oxidation species, and both radical oxidative pathways (•OH, SO4•- and O2•-) and nonradical (1O2 and PMS) pathways involved in the process. The removal efficiency of DOC and UV254 was significantly strengthened by PAC/PMS, with removal rates of 56.1% and 64.9%, respectively. The integration of PAC and PMS could significantly enhance the reduction of fluorescent organics, and pollutants with varying molecular weights. The fouling condition of membrane was dramatically alleviated, with the flux increased by 38.9%, and the reversible and irreversible resistances declined by 79.7% and 48.3%, respectively. The major fouling mechanism was significantly changed, and complete pore blocking always played a dominant role, rather than cake filtration. The effectiveness of PAC/PMS was further verified by the characterization of membrane surface morphologies and functional groups. Moreover, the attractive interactions between foulants and membrane were converted to repulsive interactions with the pretreatment of PAC/PMS. The proposed synergistic process was efficient and convenient, which could significantly improve the purification efficiency of conventional PAC-UF system in drinking water treatment.

HIPK3 Circular RNA Promotes Metastases of HCC Through Sponging miR-338-3p to Induce ZEB2 Expression.

BACKGROUND: Upregulation of circHIPK3 has been observed in several kinds of malignancies. However, the mechanisms of circHIPK3 in HCC metastases remains unclear. We investigated the role and the mechanisms of circHIPK3 in the development of HCC. METHODS: HCC tissues and paired adjacent non-tumor tissues of surgical patients were used to evaluate circHIPK3 expression. A series of biological experiments had been taken to evaluate the pro-metastatic ability of circHIPK3 during HCC development in vitro and in vivo. The potential mechanisms of circHIPK3 in HCC development were identified by RT-qPCR, Western blot, RIP, and luciferase reporter assays. RESULTS: CircHIPK3 expression is significantly upregulated during HCC development. Overexpression of circHIPK3 promotes cell migration, invasion, and metastases in vitro and in vivo. CircHIPK3 promoted HCC metastases by sponging miR-338-3p to regulate EMT-associated proteins E-cadherin, vimentin, and ZEB2 expression. CONCLUSION: CircHIPK3 plays a regulatory role in metastatic HCC by sponging miR-338-3p to induce ZEB2 expression, thus promoting EMT procession.

Ferrous-activated sodium percarbonate pre-oxidation for membrane fouling control during ultrafiltration of algae-laden water.

Membrane technology has been shown to be promising for the treatment of algae-laden water, but membrane fouling is still an obstacle influencing the purification efficiency and effluent quality. To mitigate ultrafiltration membrane fouling during Microcystis aeruginosa-laden water treatment, a strategy of sodium percarbonate pre-oxidation activated with ferrous ion (Fe2+/SPC) was put forward in this study. Due to the synergistic effect of Fe2+ and SPC, this process was significantly more efficient with the terminal specific flux increased from 0.097 to 0.397, and the reversible fouling resistance reduced by approximately 80%. It was also found that subsequent sedimentation followed by Fe2+/SPC could further improve the fouling control efficiency. The model fitting results indicated that Fe2+/SPC pre-oxidation delayed the transition from standard blocking to cake filtration. Extracellular organic matter and algal cells were extracted from algal foulants to explore the contribution of each component, and the fouling control efficiencies were systematically studied. The characteristics of the algal foulants were determined with fluorescence excitation-emission matrix spectrum, and the results suggested that macromolecular proteinaceous substances were more efficiently removed by Fe2+/SPC, in comparison with humic-like matters. The alleviation of membrane fouling was also verified by the characterization methods of scanning electron microscopy and attenuated total reflection-Fourier infrared spectroscopy. Overall, the proposed strategy of Fe2+/SPC has an application prospect for membrane fouling control in algal-laden water treatment.