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Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

This article investigates the confidence interval (CI) construction of proportion difference for two independent partially validated series under the double-sampling scheme in which both classifiers are fallible. Several CIs based on the variance estimates recovery method of combining confidence limits from asymptotic, bootstrap, and Bayesian methods for two independent binomial proportions are developed under two models. Simulation results show that all CIs except for the bootstrap percentile-t CI and Bayesian credible interval with uniform prior under the independence model and all CIs under the dependence model generally perform well and are recommended. Two examples are used to illustrate the methodologies.

Considering the strong intermolecular interaction in all-polymer solar cells, 1-chloronaphthalene assisted layer-by-layer deposition was used to fabricate all-polymer solar cells with a P–i–N heterojunction and favorable crystallinity.

Background:. Nitinol-containing devices are widely used in clinical practice. However, there are concerns about nickel release after nitinol-containing device implantation. This study aimed to compare the efficacy and safety of a parylene-coated occluder vs. a traditional nitinol-containing device for atrial septal defect (ASD). Methods:. One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder (n = 54) or the control group to receive a traditional occluder (n = 54). The plugging success rate at 6 months after device implantation and the pre- and post-implantation serum nickel levels were compared between the two groups. A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device. The Cochran–Mantel–Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups. Results:. At 6 months after implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups (95% confidence interval (CI): [−4.90, 5.16]) based on per-protocol set analysis. The absolute value of the lower limit of the 95% CI was 4.90%, which was less than the specified non-inferiority margin of 8%. No deaths or severe complications occurred during 6 months of follow-up. The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group (P 0.05). Conclusions:. The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder. The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD, especially in patients with a nickel allergy.

The molecular clusters ((HO)3Si-O-Si(OH)3 and (HO)3Al-O-Si(OH)3) representative of aluminosilicate mineral surface were employed to study the dissolution of aluminosilicate in acidic condition via density functional theory (DFT) with the M06-2X+G(d,p) methodology. The surface termination sites (Si and Al) were both tetra-coordinated and the terminal oxygen was protonated in an acidic condition. In the dissolution reaction, the calculated barrier height of the six-membered ring transition state complex containing two water molecules was predicted to be 76.13 kJ/mol, lower than that of the four-membered ring transition state complex containing one water molecule. The barrier height of the reaction decreased to 6.17 kJ/mol and was 91.90% lower than that for the Siter-O-Si without protonation. In addition, the calculated barrier heights for Al-terminated sites were predicted to be 22.23 kJ/mol, lower than those for the Si-terminated sites, suggesting that breaking the Al-O bond is easier than the Si-O bond in the aluminosilicate mineral surface. With the fracture of Si-O and Al-O bonds, the Si and Al release from the aluminosilicate. The results indicate that the acidic condition facilitates the release of Si and Al from the aluminosilicate, and the concentration of Al leaching from the aluminosilicate is higher than the Si.

This study was aimed to analyze the role of hepatocyte nuclear factor -1α (HNF-1α) in regulating migrative and invasive potentials in cervical cancer via the involvement of pyruvate kinase L/R (PKLR). The expression of HNF-1α and PKLR in cervical cancer tissues classified by tumor size and FIGO (Federation International of Gynecology and Obstetrics) stage were detected by qRT-PCR. The expression correlation between HNF-1α and PKLR in cervical cancer tissues was analyzed by Pearson correlation test. After intervening HNF-1α and PKLR levels in SiHa and Hela cells, their migratory and invasive abilities were examined by the Transwell assay. HNF-1α was upregulated in cervical cancer tissues, particularly those with large tumor size or advanced FIGO stage. PKLR was highly expressed in cervical cancer tissues as well, presenting a positive correlation with the HNF-1α level. Knockdown of HNF-1α attenuated migratory and invasive abilities in SiHa cells, whereas overexpression of HNF-1α enhanced migratory and invasive abilities in SiHa cells. PKLR was able to abolish the regulatory effects of HNF-1α on cervical cancer metastasis. HNF-1α and PKLR synergistically promote cervical cancer to migrate and invade.

Hyperuricemia seriously jeopardizes human health by increasing the risk of several diseases, such as gout and stroke. Nuciferine is able to alleviate hyperuricemia significantly. However, the underlying metabolic regulation mechanism remains unknown. To understand the metabolic effects of nuciferine on hyperuricemia by establishing a rat model of rapid hyperuricemia, 1H NMR and liquid chromatography-mass spectrometry were used to conduct nontargeted metabolomics studies. A total of 21 metabolites were authenticated in plasma and urine to be closely related with hyperuricemia, which were mainly correlated to the six metabolic pathways. Moreover, 16S rRNA analysis indicated that diversified intestinal microorganisms are closely related to changes in differential metabolites, especially bacteria from Firmicutes and Bacteroidetes. We propose that indoxyl sulfate and N-acetylglutamate in urine may be the potential biomarkers besides uric acid for early diagnosis and prevention of hyperuricemia. Gut microbiological analysis found that changes in the gut microbiota are closely related to these metabolites.

To study the influence factors of low-temperature performance of semi-flexible pavement materials, a freezing test was conducted, and the cracking temperature was used as the evaluation index to study the influence of asphalt type (90 matrix asphalt, SBS-modified asphalt, TPS high-viscosity modified asphalt), cement-based grout material types (ordinary grout, rubber powder grout, emulsified asphalt grout), and skeleton void ratio (20%, 24%, 28%, 32%) on the low-temperature performance of semi-flexible pavement materials. Results indicate that the freezing test can effectively distinguish the low-temperature crack resistance improvement benefits of semi-flexible pavement materials with different asphalt, cement-based grouting materials, and skeleton void ratios. Cracking temperature can effectively evaluate the low-temperature performance of semi-flexible pavement materials. The substrate void ratio is in the range of 20%-32%, and the cracking temperature changes with the increase in the substrate void ratio, decreasing initially and then rising. When the void ratio is around 24%, the best low-temperature performance of semi-flexible materials is achieved. The improvement effect of the elasticity of grout on the low-temperature crack resistance of semi-flexible pavement materials is obvious; the improvement effect of emulsified asphalt grout on the low-temperature performance of semi-flexible pavement materials is better than that of rubber powder grout. After the modified asphalt is used in the substrate, the cracking temperature is reduced by 31.4%-38.3%, which is much greater than the effect of grouting. At the same time, the elasticity of the base asphalt is more effective than the viscosity increase in improving the low-temperature crack resistance of semi-flexible materials.

In this work, a theoretical formula based on equivalent circuit model is proposed to describe the influence of frequency on the droplet actuation behavior in reverse electrowetting. To verify the theory, changes of droplet profile are monitored by charge coupled device (CCD) camera and simulated by COMSOL. It shows that the threshold voltage required for the droplet to start contracting inward increases firstly and then decreases with the increasing frequency. When the frequency is 1 kHz, the threshold voltage reaches the maximum value. Once the droplet begins to move inward, its contact angle increases with the working voltage. As for 4 kHz, the contact angle increases linearly from 60° to 154° when voltage ranges from 16 V to 50 V, while the droplet remained stationary when U < 16 V. The relative experimental results well accord with the theoretical prediction.

Apoptotic resistance leads to persistent accumulation of senescent cells and sustained expression of a senescence-associated secretory phenotype, playing an essential role in the progression of tissue fibrosis. However, whether senescent renal tubular epithelial cells (RTECs) exhibit an apoptosis-resistant phenotype, and the role of this phenotype in diabetic nephropathy (DN) remain unclear. Our previous study was the first to demonstrate that decoy receptor 2 (DcR2) is associated with apoptotic resistance in senescent RTECs and renal fibrosis. In this study, we aimed to further explore the mechanism of DcR2 in apoptosis-resistant RTECs and renal fibrosis in DN. DcR2 was co-localized with fibrotic markers (α-SMA, collagen IV, fibronectin), senescent marker p16, and antiapoptotic proteins FLIP and Bcl2 but rarely co-localized with caspase 3 or TUNEL. DcR2 overexpression promoted renal fibrosis in mice with streptozotocin (STZ)-induced DN, as evidenced by augmented Masson staining and upregulated expression of fibrotic markers. DcR2 overexpression also enhanced FLIP expression while reducing the expression of pro-apoptotic proteins (caspases 8 and 3) in senescent RTECs, resulting in apoptotic resistance. In contrast, DcR2 knockdown produced the opposite effects in vitro and in vivo. Moreover, quantitative proteomics and co-immunoprecipitation experiments demonstrated that DcR2 interacted with glucose-related protein 78 kDa (GRP78), which has been shown to promote apoptotic resistance in cancer. GRP78 exhibited co-localization with senescent and antiapoptotic markers but was rarely co-expressed with caspase 3 or TUNEL. Additionally, GRP78 knockdown decreased the apoptosis resistance of HG-induced senescent RTECs with upregulated cleaved caspase 3 and increased the percentage of apoptotic RTECs. Mechanistically, DcR2 mediated apoptotic resistance in senescent RTECs by enhancing GRP78–caspase 7 interactions and promoting Akt phosphorylation. Thus, DcR2 mediated the apoptotic resistance of senescent RTECs and renal fibrosis by interacting with GRP78, indicating that targeting the DcR2–GRP78 axis represents a promising therapeutic strategy for DN.

In this work, we perform a combined analysis to the measured data of the cross section of open-strange processes ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{K}^{+}{K}^{\ensuremath{-}}$, ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}K{\overline{K}}^{*}+\mathrm{c}.\mathrm{c}.$, ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{K}^{*+}{K}^{*\ensuremath{-}}$, ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{K}_{1}(1270{)}^{+}{K}^{\ensuremath{-}}$, ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{K}_{1}(1400{)}^{+}{K}^{\ensuremath{-}}$, ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}{K}_{2}^{*}(1430)\overline{K}+\mathrm{c}.\mathrm{c}.$, and ${e}^{+}{e}^{\ensuremath{-}}\ensuremath{\rightarrow}K(1460{)}^{+}{K}^{\ensuremath{-}}$ with the support of study of hadron spectroscopy. We reveal the contribution of the possible light vector mesons around 2 GeV to reproduce the cross section data of the reported open-strange processes from ${e}^{+}{e}^{\ensuremath{-}}$ annihilation which may provide a new perspective to construct the light vector meson family and understand the $Y(2175)$.

PurposeTo explore the feasibility and safety of centrally located hepatocellular carcinoma (CL-HCC) treated by narrow-margin resection combined with intraoperative electron radiotherapy (IOERT).Methods and MaterialsFrom November 2009 to November 2016, 37 consecutive patients were treated with IOERT as adjuvant treatment during narrow-margin resection for CL-HCC. Long-term outcomes, adverse events for surgery, and acute and chronic toxicities were analyzed.ResultsThe median follow-up was 57.82 months (range, 3.75-111.41 months). A total dose of 15 Gy (range 12 to 17Gy) (prescribed at the 90% isodose) was delivered with a 0.9cm (range 0.8-1.2 cm) median treatment depth targeting the narrow-margin. The 1-year, 3-year and 5-year OS rates were 91.39%, 88.34% and 88.34%, respectively. The 1-year, 3-year and 5-year DFS rates were 80.81%, 68.59% and 54.17%, respectively. In the univariate analysis, none of the treatment characteristics were predictive of overall survival. Fifteen (40.5%) patients suffered from a recurrence event. No patient had marginal recurrence. The 1-year, 3-year and 5-year intrahepatic recurrence rates were 19.75%, 25.92% and 39.58%, respectively. The 1-year, 3-year and 5-year extrahepatic recurrence rates were 2.7%, 5.95% and 9.87%, respectively. There was no 30-day surgical-related death. Three patients had grade 4, and 28 patients had grade 3 alanine aminotransferase (ALT) levels, and seven patients had grade 4, and 30 patients had grade 3 aspartate transaminase (AST) levels. All of them returned to normal within four months. There was no acute radiation-induced liver injury during follow-up. There were no acute or chronic toxicities associated with IOERT.ConclusionIOERT for narrow-margin CL-HCC may achieve good long-term survival outcomes, without significantly increasing acute and chronic toxicities. An IOERT dose of 15Gy may be the safest and most feasible. IOERT might be considered as an adjuvant therapy for CL-HCC patients with a narrow-margin.