Osmotic energy captured from a salinity gradient
via
an ion-selective membrane is regarded as one of the renewable clean energy resources to meet the increasing global energy demands. However, due to ...insufficient ion selectivity and high resistance, the output power achieved by most of the existing membranes is still below the commercial benchmark (5 W m
−2
), which restricts their practical applications. Herein, we report a simple drop-casting method for the fabrication of a polyelectrolyte (PE)-based heterogeneous ionic diode membrane consisting of a highly ordered alumina nanochannel membrane (ANM) and a space-charged Nafion layer. As demonstrated by experimental investigations and theoretical simulations, the incorporation of a space-charged PE layer into the heterogeneous membrane induces apparent ion rectification as well as shows enhanced ion transport and selectivity, which largely boost the osmotic energy conversion efficiency. When synthetic seawater and river water are mixed, the developed PE-based ionic diode membrane can achieve an osmotic power density as high as 5.13 W m
−2
. This output power can be further upgraded to 22.1 W m
−2
by mixing synthetic salt lake water and river water (5 M/0.01 M NaCl gradient), surpassing the performance of all the state-of-the-art ion-selective membranes. This work provides significant insights into the use of space-charged PE materials for the exploration of high osmotic energy harvesters.
The remarkable amplification of nanofluidic osmotic energy conversion performance has been demonstrated with a highly space-charged polyelectrolyte-incorporated ionic diode membrane.
Background & Aims
Transarterial chemoembolization (TACE) is a standard treatment for Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), but the outcome varied. This study ...aimed to develop a model to predict the outcome of TACE in HCC patients.
Methods
Consecutive 570 treatment‐naïve BCLC stage B HCC patients undergoing TACE as the initial treatment from 2007 to 2016 were retrospectively enrolled. Factors associated with survival were analysed. Patients undergoing TACE from 2007 to 2011 constituted the training cohort (n = 293), while patients undergoing TACE from 2012 to 2016 constituted the validation cohort (n = 277). Homogeneity and corrected Akaike information criterion (AICc) were compared between each prognostic model.
Results
A total of 1796 TACE sessions were performed for the 570 patients during the median follow‐up period of 18.3 months. By multivariate analysis, beyond up‐to‐11 criteria (hazard ratio HR = 1.694, P < .001), alpha‐foetoprotein >200 ng/mL (HR = 1.771, P < .001) and albumin‐bilirubin (ALBI) grade 2 or 3 (HR = 1.817, P < .001) were independent predictors of overall survival (OS) in the training cohort. An ALBI‐TAE model based on the three independent predictors of OS from the training cohort was developed to classify HCC patients into four subgroups. The performance of the ALBI‐TAE model was superior to other prognostic models with lowest AICc values and highest homogeneity in both the training and validation datasets as well as the overall cohort.
Conclusions
Albumin‐bilirubin grade is an important factor associated with survival in BCLC stage B HCC patients undergoing TACE. ALBI‐TAE model can be applied to select patients who can get most benefit from TACE.
The epithelial‐mesenchymal transition (EMT) is critical for induction of invasiveness and metastasis of human cancers. In this study we investigated the expression profiles of the EMT markers, the ...relationship between EMT markers and patient/tumor/viral factors, and the interplay between major EMT regulators in human hepatocellular carcinoma (HCC). Reduced E‐cadherin and nonmembranous β‐catenin expression, the hallmarks of EMT, were shown in 60.2% and 51.5% of primary HCC samples, respectively. Overexpression of Snail, Twist, or Slug, the major regulators of EMT, was identified in 56.9%, 43.1%, and 51.4% of primary HCCs, respectively. Statistical analysis determined that Snail and Twist, but not Slug, are major EMT inducers in HCC: overexpression of Snail and/or Twist correlated with down‐regulation of E‐cadherin, nonmembranous expression of β‐catenin, and a worse prognosis. In contrast, there were no such significant differences in samples that overexpressed Slug. Coexpression of Snail and Twist correlated with the worst prognosis of HCC. Hepatitis C‐associated HCC was significantly correlated with Twist overexpression. HCC cell lines with increased Snail and Twist expression (e.g., Mahlavu) exhibited a greater capacity for invasiveness/metastasis than cells with low endogenous Twist/Snail expression (e.g., Huh‐7). Overexpression of Snail or/and Twist in Huh‐7 induced EMT and invasiveness/metastasis, whereas knockdown of Twist or Snail in Mahlavu reversed EMT and inhibited invasiveness/metastasis. Twist and Snail were independently regulated, but exerted an additive inhibitory effect to suppress E‐cadherin transcription. Conclusion: Our study provides a comprehensive profile of EMT markers in HCC, and the independent and collaborative effects of Snail and Twist on HCC metastasis were confirmed through different assays. (HEPATOLOGY 2009.)
Purpose To construct a nomogram with the albumin-bilirubin (ALBI) grade to assess the long-term outcomes of patients with early-stage hepatocellular carcinoma (HCC) after radiofrequency ablation ...(RFA). Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. We studied 622 treatment-naïve patients with HCC according to the Milan criteria who subsequently underwent RFA from 2002 to 2013. Baseline characteristics were collected to identify the risk factors for determination of poor overall survival after RFA. The multivariate Cox proportional hazards model based on significant prognostic factors of overall survival was used to construct the nomogram. Results After a median follow-up time of 35.7 months, 190 patients had died. The cumulative 5- and 10-year overall survival rates were 63.1% and 48.7%, respectively. Stratified according to ALBI grade, the cumulative 5- and 10-year survival rates were 80.0% and 67.9% for patients with grade 1, respectively, and 48.6% and 35.1% for those with grades 2-3, respectively (P < .001). Multivariate analysis results showed that patient age older than 65 years, a prothrombin time international normalized ratio greater than 1.1, α-fetoprotein level greater than 20 ng/mL, multiple tumors, and ALBI grade 2 or 3 were associated with overall mortality. A nomogram was developed on the basis of these five variables. Internal validation with 200 bootstrapped sample sets had a good concordance index of 0.770 (95% confidence interval: 0.633, 0.876). Conclusion This simple nomogram based on the ALBI grade offers personalized long-term survival data for patients with early-stage HCC who undergo RFA.
RSNA, 2017 Online supplemental material is available for this article.
Abstract
Context
The association between circulating triglyceride (TG) and glycated hemoglobin A1c (HbA1c), a biomarker for type 2 diabetes, has been widely addressed, but the causal direction of the ...relationship is still ambiguous.
Objective
To confirm the causal relationship between TG and HbA1c by using bidirectional and 2-step Mendelian randomization (MR) approaches.
Methods
We carried out a bidirectional MR approach using the summarized results from the public database to examine any potential causal effects between serum TG and HbA1c in 16 000 individuals of the Taiwan Biobank cohort. We used the MR estimate and the MR inverse variance–weighted method to reveal that relationship between TG and HbA1c. To further determine whether the DNA methylation at specific sequences mediate the causal pathway between TG and HbA1c, using the 2-step MR approach.
Results
We identified that a single-unit increase in TG measured via log transformation of mg/dL data was associated with a significant increase of 10 units of HbA1c (95% CI = 1.05−18.95, P = 0.029). In contrast, the genetic determinants of HbA1c do not contribute to the amount of circulating TG (beta = 1.75, 95% CI = –11.50 to 14.90). Sensitivity analyses, included the weighted-median approach and MR-Egger regression, were performed to confirm no pleiotropic effect among these instrumental variables. Furthermore, we identified the genetic variant, rs1823200, is associated with both methylation of the CpG site adjacent to CADPS gene and HbA1c level.
Conclusion
Our study suggests that higher circulating TG can have an affect on genomic methylation status, ultimately causing elevated level of circulating HbA1c.
We investigated the outcomes of patients with ruptured hepatocellular carcinoma (HCC) and identified the optimal treatment modality for such patients. We retrospectively enrolled 91 patients with ...treatment-naive HCC and tumor rupture at diagnosis, including 38 patients who underwent surgical resection (SR) alone, 28 patients who were treated with transarterial chemoembolization (TACE) only, 20 patients who had a sequential combination therapy of TACE and SR, and 5 patients who received best supportive care. After a median follow-up of 13.1 months, 54 patients died. The cumulative 5 years overall survival (OS) rates were 55.1% and 0% in the SR group and non-SR group, respectively (p < 0.001). Non-SR therapy was associated with poorer OS according to a multivariate analysis with a hazard ratio of 6.649 (95% confidence interval 3.581-12.344, p < 0.001). Moreover, whether patients received TACE or not did not impact the OS in both the SR group and the non-SR group. In conclusion, for patients with HCC and tumor rupture at the time of diagnosis, SR could lead to better prognoses than non-surgery treatment modalities. Moreover, a sequential combination of TACE and SR had similar clinical outcomes when compared to SR alone.
Graphene oxide quantum dots (GOQDs) with different oxygenation levels were successfully prepared using a facile, rapid, and cost-effective microwave-assisted hydrothermal method under neutral ...conditions using hydrogen peroxide (MGOH) or potassium permanganate (MGOK) as an oxidizing agent. GOQDs with an average diameter of 7–12 nm for both MGOH and MGOK samples were observed using transmission electron microscopy (TEM). X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) analyses revealed that MGOH exhibited a high quantity of C–O and C=O groups in its structure, whereas MGOK consisted of highly ordered sp2/sp3 bonds in its aromatic unit and had less oxygenated functional groups. The photoluminescence measurements showed that MGOH and MGOK QDs emitted yellowish-green and blue light with quantum yields of 15.1% and 8.4%, respectively. The luminescence mechanisms of MOGK and MGOH were attributed to π–π* and n–π* electron transitions in C–C/C=C bonds and in π* states to non-bonding oxygen states, respectively. Density functional theory calculations were employed to determine the optical absorption of GOQDs in terms of surface functional groups and oxygenation degrees. Theoretical calculations demonstrate that the high oxygenation degree of GOQDs resulted in band gap reduction and light absorption due to electron transitions. Our theoretical and experimental results suggested that GOQDs with high quantum yields can serve as promising materials in applications including biosensing, imaging, and labeling.
Hepatitis B virus (HBV) hijacks autophagy for its replication. Nucleos(t)ide analogs (NUCs) treatment suppressed HBV replication and reduced hepatocellular carcinoma (HCC) incidence. However, the use ...of NUCs in chronic hepatitis B (CHB) patients with normal or minimally elevated serum alanine aminotransferase (ALT) levels is still debated. Animal models are crucial for studying the unanswered issue and evaluating new therapies. MicroRNA‐122 (miR‐122), which regulates fatty acid and cholesterol metabolism, is downregulated during hepatitis and HCC progression. The reciprocal inhibition of miR‐122 with HBV highlights its role in HCC development as a tumor suppressor. By crossbreeding HBV‐transgenic mice with miR‐122 knockout mice, we generated a hybrid mouse model with a high incidence of HCC up to 89% and normal ALT levels before HCC. The model exhibited early‐onset hepatic steatosis, progressive liver fibrosis, and impaired late‐phase autophagy. Metabolomics and microarray analysis identified metabolic signatures, including dysregulation of lipid metabolism, inflammation, genomic instability, the Warburg effect, reduced TCA cycle flux, energy deficiency, and impaired free radical scavenging. Antiviral treatment reduced HCC incidence in hybrid mice by approximately 30–35% compared to untreated mice. This effect was linked to the activation of ER stress‐responsive transcription factor ATF4, clearance of autophagosome cargo p62, and suppression of the CHOP‐mediated apoptosis pathway. In summary, this study suggests that despite minimal ALT elevation, HBV replication can lead to liver injury. Endoplasmic reticulum stress, reduced miR‐122 levels, mitochondrial and metabolic dysfunctions, blocking protective autophagy resulting in p62 accumulation, apoptosis, fibrosis, and HCC. Antiviral may improve the above‐mentioned pathogenesis through HBV suppression.
Background and Aims
PreS mutants of HBV have been reported to be associated with HCC. We conducted a longitudinal study of the role of HBV preS mutations in the development of HCC, particularly in ...patients with chronic hepatitis B (CHB) having low HBV DNA or alanine aminotransferase (ALT) levels, and investigated the effects of secretion‐defective preS2 deletion mutant (preS2ΔMT) on hepatocyte damage in vitro and liver fibrosis in vivo.
Approach and Results
Association of preS mutations with HCC in 343 patients with CHB was evaluated by a retrospective case–control follow‐up study. Effects of preS2ΔMT on HBsAg retention, endoplasmic reticulum (ER) stress, calcium accumulation, mitochondrial dysfunction, and liver fibrosis were examined. Multivariate analysis revealed a significant association of preS mutations with HCC (HR, 3.210; 95% CI, 1.072‐9.613; P = 0.037) including cases with low HBV DNA or ALT levels (HR, 2.790; 95% CI, 1.133‐6.873; P = 0.026). Antiviral therapy reduced HCC risk, including cases with preS mutations. PreS2ΔMT expression promoted HBsAg retention in the ER and unfolded protein response (UPR). Transmission electron microscopic examination, MitoTracker staining, real‐time ATP assay, and calcium staining of preS2ΔMT‐expressing cells revealed aberrant ER and mitochondrial ultrastructure, reduction of mitochondrial membrane potential and ATP production, and calcium overload. Serum HBV secretion levels were ~100‐fold lower in preS2ΔMT‐infected humanized Fah–/–/ Rag2–/–/Il2rg–/– triple knockout mice than in wild‐type HBV‐infected mice. PreS2ΔMT‐infected mice displayed up‐regulation of UPR and caspase‐3 and enhanced liver fibrosis.
Conclusions
PreS mutations were significantly associated with HCC development in patients with CHB, including those with low HBV DNA or ALT levels. Antiviral therapy reduced HCC occurrence in patients with CHB, including those with preS mutations. Intracellular accumulation of mutated HBsAg induced or promoted ER stress, calcium overload, mitochondrial dysfunction, impaired energy metabolism, liver fibrosis, and HCC.
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