BACKGROUND: A better understanding of the molecular mechanisms in liver regeneration holds promise for exploring the new potential therapy for liver failure. The present study was to investigate the ...role of zinc finger and BTB domain-containing protein 20(ZBTB20), a potential factor associated with liver regeneration, in a model of 70% hepatectomy in mice. METHODS: Parameters for liver proliferation such as liver/body ratio and BrdU positivity were obtained via direct measurement and immunohistochemistry. The levels of zinc fingers and homeoboxes 2(ZHX2), ZBTB20, alpha-fetoprotein(AFP) and glypican 3(GPC3) transcripts in the regenerating liver tissue of a 70% hepatectomy rodent model were monitored by real-time PCR analysis at different time points. Knockdown of ZBTB20 was performed to characterize its regulatory function. RESULTS: A negatively regulating relationship between ZHX2, ZBTB20 and AFP, GPC3 was revealed from 24 to 72 hours after 70% hepatectomy. ZBTB20 appears to negatively regulate AFP and GPC3 transcription since the knockdown of ZBTB20 promoted the proliferation of hepatocytes and the expression of AFP and GPC3. CONCLUSION: In addition to AFP, GPC3 and ZHX2, ZBTB20 is a new regulator in liver regeneration and the decrease of ZBTB20 expression following 70% hepatectomy promotes AFP and GPC3 expression.
Postoperative interferon-α(IFN-α) treatment delays hepatocellular carcinoma(HCC) recurrence and prolongs patient survival, and may thus be an effective form of adjuvant therapy. However, clinical ...observations found that HCC recurs in some patients within 8 months of IFN-α treatment being discontinued. We investigated whether HCC regrowth appears after IFN-α is discontinued, whether re-initiated IFN-α is effective, and the underlying mechanisms of IFN-α treatment.
The human HCC nude mouse model LCI-D20 was used to study the effects of IFN-α treatment, discontinued IFN-α treatment, and re-initiated IFN-α treatment on tumor growth. Tumor weight, microvessel density(MVD), serum vascular endothelial growth factor (VEGF), and tumor cell apoptosis were analyzed. Angiogenesis-related factors were studied using cDNA microarray in different tumor samples and confirmed using reverse transcription-polymerase chain reaction(RT-PCR) and Western blotting assays. Finally, imatinib was added with re-initiated IFN-α treatment to improve efficacy.
IFN-α (1.5 × 107 U/kg/day for 20 days) suppressed HCC growth by 60.3% and decreased MVD by 52.2% compared with the control. However, tumor regrowth occurred after IFN-α was discontinued, and re-initiated IFN-α treatment was not effective for inhibiting tumor growth or reducing MVD compared with a saline-treated group. cDNA microarray showed VEGF was down-regulated while platelet-derived growth factor-A (PDGF-A) was up-regulated when IFN-α treatment was re-initiated. These findings were further confirmed with RT-PCR and Western blotting assay. The combination of imatinib with re-initiated IFN-α reduced HCC weight by 30.7% and decreased MVD by 31.1% compared with IFN-α treatment only (P=0.003 and 0.015, respectively).
Tumor regrowth occurred after IFN-α treatment was discontinued. Re-initiated IFN-α treatment was not effective and was associated with up-regulation of PDGF-A, while the VEGF remained suppressed. The combination of a PDGF-receptor inhibitor with IFN-α improved the effect of the re-initiated treatment.
The additive strategy is widely used in optimizing the morphology of organic solar cells (OSCs). The majority of additives are liquid with high boiling points, which will be trapped within device and ...consequently deteriorate performance during operation. In this work, solid but volatile additives 2‐(4‐fluorobenzylidene)‐1H‐indene‐1,3(2H)‐dione (INB‐F) and 2‐(4‐chlorobenzylidene)‐1H‐indene‐1,3(2H)‐dione (INB‐Cl) are designed to replace the common 1,8‐diiodooctane (DIO) in nonfullerene OSCs. These additives present during solution casting but evaporate after moderate heating. Molecular dynamics simulations show that they can reduce the adsorption energy to improve π‐π stacking among nonfullerene acceptor (NFA) molecules, an effect that enhances light absorption and electron mobility. Both INB‐F and INB‐Cl enhance efficiency, with INB‐F achieving a maximum efficiency of 16.7% from 15.1% of the reference PBDB‐T‐2F (PM6):BTP‐BO‐4F (Y6‐BO) cell, and outperforming DIO. Remarkably, they can simultaneously enhance the operational stability, with the INB‐F‐treated OSC maintaining over 60% of the initial efficiency after 1000 h operation, demonstrating a T80 lifetime of 523 h, which is a significant improvement over T80 values of 66.2 h for the reference and 6.6 h for DIO‐treated OSC. The simultaneously enhanced efficiency and operational lifetime are also effective in PM6:BTP‐BO‐4Cl (Y7‐BO) OSCs, demonstrating a universal strategy to improve the performance of OSCs.
Solid additives are demonstrated to enhance the initial device efficiency as well as the operational lifetime of nonfullerene organic solar cells, via solid‐additive‐mediated aggregation control.
The basic helix-loop-helix transcription factor E2A is an essential regulator of B lymphocyte lineage commitment and is required to activate the expression of numerous B lineage-specific genes. ...Studies involving ectopic expression of Id proteins, which inhibit E2A as well as other basic helix-loop-helix proteins such as HEB, suggest additional roles of E2A at later stages of B cell development. We use E2A-deficient and E2A and HEB double-deficient pre-B cell lines to directly assess the function of E2A and HEB in B cell development after lineage commitment. We show that, in contrast to the established role of E2A in lineage commitment, elimination of E2A and HEB in pre-B cell lines has only a modest negative impact on B lineage gene expression. However, E2A single and E2A and HEB double-deficient but not HEB single-deficient cell lines show dramatically enhanced apoptosis upon growth arrest. To address the possible role of E2A in the regulation of B cell survival in vivo, we crossed IFN-inducible Cre-transgenic mice to E2A conditional mice. Cre-mediated E2A deletion resulted in a block in bone marrow B cell development and a significant reduction in the proportion and total number of splenic B cells in these mice. We show that Cre-mediated deletion of E2A in adoptively transferred mature B cells results in the rapid depletion of the transferred population within 24 h of Cre induction. These results reveal that E2A is not required to maintain B cell fate but is essential in promoting pre-B and B cell survival.
The mixture formation process is vital for ethanol direct injection (EDI) plus gasoline port injection (GPI) engine, as the mixture preparation quality directly affects the combustion process and ...emission characteristics, especially for the dual-injection system. In this study, engine tests were first conducted to investigate the effects of ethanol injection timings (430 °CA, 570 °CA, 620 °CA and 670 °CA) and injection pressures (40 bar, 60 bar and 90 bar) on engine performance and combustion process. Then, the numerical simulations were performed with the focus on detailed mixture formation process, including in-cylinder flows, wall wetting and fuel evaporation. The experimental and numerical results indicated that the injection timing has a significant effect on the mixture formation in EDI + GPI engine. Due to the long evaporation time and strong in-cylinder TKE, early injection timing (430 °CA) can lead to a uniform mixture and complete combustion. The effect of ethanol injection pressure on mixture formation was not significant at this ethanol injection timing. As the injection timing was retarded, due to the reduced evaporation time, the formation of the homogeneous mixture became harder, and the effect of injection pressure on the mixture preparation became obvious. At injection timing of 620 °CA, high injection pressure generated high fuel spray momentum, which deformed the original in-cylinder vortex, and more ethanol fuel collided on the piston surface and the wall, resulting in uneven distribution of the mixture and poor combustion. When the injection timing was retarded to 670 °CA, the injection pressure of 60 bar could obtain a good balance among the fuel evaporate rate, the amount fuel impinging on the wall and the fuel evaporation time, resulting more complete combustion.
•The laminar burning velocities of iC8H18/H2/O2/H2O/N2 mixture are measured and simulated.•The effects of different concentrations of water and hydrogen on laminar burning velocities are analyzed.•A ...laminar burning velocity model, which use hydrogen and water contents as the control dimensions, is proposed.
The present study examines using water dilution and hydrogen as control measures to regulate the laminar burning velocity of iso-octane/air mixtures in a constant volume combustion bomb. Experimental results are obtained by processing schlieren photographs and simulation results are calculated by Chemkin software. The water dilution rates of the mixtures were between 0 and 5% and the hydrogen addition ratio was between 5 and 55%. The initial pressure was set at 101.3 kPa with the preheating temperature ranging from 400 K to 500 K. According to the results, laminar burning velocity varied almost linearly with the dilution of water and the addition of hydrogen, respectively. This study also distinguishes the thermal and kinetic effects of water on the combustion processes. The thermodynamic effect of water vapour on laminar burning velocity was higher than the kinetic effect. In kinetics, O, H, and OH were the most affected free radicals by the addition of water vapour. The main free radical change affected the rate of the elementary reaction. Besides, the kinetic effect of water vapour promoted combustion. However, this effect was offset by the thermodynamic effect. The introduced hydrogens of premixed mixtures did not lead to measurable improvements in laminar burning velocity. Additionally, the change in the reaction rate of the elementary reaction was not obvious, which was inconsistent with the change of laminar burning velocity. Lastly, a laminar burning velocity model using hydrogen and water vapor content as control parameters was proposed. Accordingly, the designated laminar burning velocity of the iso-octane/air mixture was achieved by altering hydrogen and water vapour ratios in the mixture. BP (Back-Propagation) neural network algorithm (a multi-layer feed forward neural network trained by error back propagation algorithm) and empirical data were used to verify the model, and the model’s maximum error was less than 5%.
This study characterized the dry deposition flux and dry deposition velocity (Vd) of metallic elements attached on particulate matter. Specifically, large particles (>10 μm), coarse particles ...(10 μm∼2.5 μm), and fine particles (<2.5 μm) were studied at the Gong Ming Junior High School (Taichung Airport) and Taichung Harbor sampling sites in central Taiwan. Ambient air samples were collected to determine total suspended particulate matter (TSP), dry deposition plate (DDP), Vd, coarse particulate matter (PM
2.5-10
) and fine particulate matter (PM
2.5
), and metallic elements concentrations at the Airport and Taichung Harbor sites between June 17, 2013, and November 14, 2013. The results revealed that the average TSP, DDP, Vd, PM
2.5-10
, and PM
2.5
particulate at the Airport were 54.55 (μg/m
3
), 902.25 (μg/m
2
-min), 17.11 (m/sec), 0.003 (μg/m
3
), and 0.010 (μg/m
3
), respectively; while these values at Taichung Harbor were 63.66 (μg/m
3
), 539.69 (μg/m
2
-min), 9.94 (m/sec), 0.003 (μg/m
3
), and 0.014 (μg/m
3
), respectively. In addition, the results showed that the average Cu and Pb concentrations were higher than Cr, Ni, and Cd for both the airport and harbor sampling sites. Furthermore, Cr, N, Cu, Cd, and Pb had the highest average concentrations versus those reported for other study areas, with one exception: The results obtained in Kacanik, Kosovo, during 2005. The average metallic elements concentrations order was Cu > Pb > Cr > Ni > Cd.
The low utilization efficiency in the visible region of the sunlight spectrum and the rapid recombination of photogenerated charge carriers are two crucial drawbacks that suppress the practical usage ...of metal oxide semiconductors as photocatalysts. In this article, we report a rational design of In2O3-In2S3 heterojunctions encapsulated by N-doped carbon with a hollow dodecahedral structure (In2O3-In2S3/N-C HDS), which can effectively handle the two drawbacks of metal oxide semiconductors and behave active for organic transformation under the irradiation of visible light even with long wavelengths. As exemplified by the selective oxidative coupling reaction of amine to imine, the obtained In2O3-In2S3/N-C HDS as the photocatalyst has exhibited excellent activity and stability. Experimental and density functional theory studies have verified that the excellent performance of In2O3-In2S3/N-C HDS can be attributed to the synergistic effect of In2O3-In2S3 heterojunctions, the coating of N-doped carbon, and the hollow porous structure with nanosheets as subunits.
Adult granulosa cell tumors (aGCTs) are rare ovarian neoplasms with a relatively favorable prognosis. They follow an indolent course, characterized by a prolonged natural history and a tendency to ...late recurrences, Around a quarter of patients develop recurrence and More than 70% of women with recurrence die from their disease, The percentage of patients received chemotherapy increases over time, whether adjuvant chemotherapy improve the prognosis of aGCTs is equivocal? The purpose of this review is to summarize the previously published evidence to evaluate whether adjuvant chemotherapy improve the prognosis of aGCTs to provide guidance for clinical practice. EMBASE, PubMed, Web of Science, WanFang Data and Chinese National Knowledge Infrastructure are searched up to December 2020, used the search strategy of ovar* and granulosa cell* and (tumor* or tumour* or malignan* or cancer* or carcinom* or neoplasm*) and chemotherapy. The screening process was conducted strictly based on inclusion and exclusion criteria. Clinical studies based on human including randomized controlled trial, quasi-randomised controlled trials, nonrandomised trials cohort study and case control study were included without restriction of time. The percentage of patients received chemotherapy increases over time, but the benefit of adjuvant chemotherapy is lack of high-grade evidence of prospective study, based on the current retrospective studies, we still do not have the evidence to confirm the survival benefit of adjuvant chemotherapy in early stage, advanced stage or recurrent aGCT with no residual tumor, but for inoperable disseminated disease or disease with suboptimal cytoreduction, adjuvant chemotherapy maybe an Optable options. Multinational prospective randomised controlled trials are urgently needed to validate the role of adjuvant chemotherapy. Further research on molecular mechanisms and developing novel targeted medicines may improve the survival of aGCTs.
Various genome editing tools have been developed for programmable genome manipulation at specified genomic loci. However, it is crucial to comprehensively interrogate the off-target effect induced by ...these genome editing tools, especially when apply them onto the therapeutic applications. Here, we outlined the off-target effect that has been observed for various genome editing tools. We also reviewed detection methods to determine or evaluate the off-target editing, and we have discussed their advantages and limitations. Additionally, we have summarized current RNA editing tools for RNA therapy and medicine that may serve as alternative approaches for genome editing tools in both research and clinical applications.
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