Identification of Hsp20 gene family in Malus domestica and functional characterization of Hsp20 class I gene MdHsp18.2b.

Heat shock protein 20 (Hsp20) is a small molecule heat shock protein that plays an important role in plant growth, development, and stress resistance. Little is known about the function of Hsp20 family genes in apple (Malus domestica). Here, we performed a genome-wide analysis of the apple Hsp20 gene family, and a total of 49 Hsp20s genes were identified from the apple genome. Phylogenetic analysis revealed that the 49 genes were divided into 11 subfamilies, and MdHsp18.2b, a member located in the CI branch, was selected as a representative member for functional characterization. Treatment with NaCl and Botryosphaeria dothidea (B. dothidea), the causal agent of apple ring rot disease, significantly induced MdHsp18.2b transcription level. Further analysis revealed that overexpressing MdHsp18.2b reduced the resistance to salt stress but enhanced the resistance to B. dothidea infection in apple calli. Moreover, MdHsp18.2b positively regulated anthocyanin accumulation in apple calli. Physiology assays revealed that MdHsp18.2b promoted H2O2 production, even in the absence of stress factors, which might contribute to its functions in response to NaCl and B. dothidea infection. Hsps usually function as homo- or heterooligomers, and we found that MdHsp18.2b could form a heterodimer with MdHsp17.9a and MdHsp17.5, two members from the same branch with MdHsp18.2b in the phylogenetic tree. Therefore, we identified 49 Hsp20s genes from the apple genome and found that MdHsp18.2b was involved in regulating plant resistance to salt stress and B. dothidea infection, as well as in regulating anthocyanin accumulation in apple calli.

Functions of Phytochrome Interacting Factors (PIFs) in Adapting Plants to Biotic and Abiotic Stresses.

Plants possess the remarkable ability to sense detrimental environmental stimuli and launch sophisticated signal cascades that culminate in tailored responses to facilitate their survival, and transcription factors (TFs) are closely involved in these processes. Phytochrome interacting factors (PIFs) are among these TFs and belong to the basic helix-loop-helix family. PIFs are initially identified and have now been well established as core regulators of phytochrome-associated pathways in response to the light signal in plants. However, a growing body of evidence has unraveled that PIFs also play a crucial role in adapting plants to various biological and environmental pressures. In this review, we summarize and highlight that PIFs function as a signal hub that integrates multiple environmental cues, including abiotic (i.e., drought, temperature, and salinity) and biotic stresses to optimize plant growth and development. PIFs not only function as transcription factors to reprogram the expression of related genes, but also interact with various factors to adapt plants to harsh environments. This review will contribute to understanding the multifaceted functions of PIFs in response to different stress conditions, which will shed light on efforts to further dissect the novel functions of PIFs, especially in adaption to detrimental environments for a better survival of plants.

Plant disease resistance outputs regulated by AP2/ERF transcription factor family.

Plants have evolved a complex and elaborate signaling network to respond appropriately to the pathogen invasion by regulating expression of defensive genes through certain transcription factors. The APETALA2/ethylene response factor (AP2/ERF) family members have been determined as key regulators in growth, development, and stress responses in plants. Moreover, a growing body of evidence has demonstrated the critical roles of AP2/ERFs in plant disease resistance. In this review, we describe recent advances for the function of AP2/ERFs in defense responses against microbial pathogens. We summarize that AP2/ERFs are involved in plant disease resistance by acting downstream of mitogen activated protein kinase (MAPK) cascades, and regulating expression of genes associated with hormonal signaling pathways, biosynthesis of secondary metabolites, and formation of physical barriers in an MAPK-dependent or -independent manner. The present review provides a multidimensional perspective on the functions of AP2/ERFs in plant disease resistance, which will facilitate the understanding and future investigation on the roles of AP2/ERFs in plant immunity.

Inhibitory Effect of Tea Saponin on Major Apple-Disease-Inducing Fungi.

Plant secondary metabolites are well known for their biological functions in defending against pathogenic microorganisms. Tea saponin (TS), one type of secondary metabolite of the tea plant (Camellia sinensis), has been shown to be a valuable botanical pesticide. However, its antifungal activity in controlling the fungi Valsa mali, Botryosphaeria dothidea, and Alternaria alternata, which induce major diseases in apple (Malus domestica), has not been determined. In this study, we first determined that TS has higher inhibitory activity than catechins against the three types of fungi. We further utilized in vitro and in vivo assays to confirm that TS showed high antifungal activity against the three types of fungi, especially for V. mali and B. dothidea. In the in vivo assay, application of a 0.5% TS solution was able to restrain the fungus-induced necrotic area in detached apple leaves efficiently. Moreover, a greenhouse infection assay also confirmed that TS treatment significantly inhibited V. mali infection in leaves of apple seedlings. In addition, TS treatment activated plant immune responses by decreasing accumulation of reactive oxygen species and promoting the activity of pathogenesis-related proteins, including chitinase and ß-1,3-glucanase. This indicated that TS might serve as a plant defense inducer to activate innate immunity to fight against fungal pathogen invasion. Therefore, our data indicated that TS might restrain fungal infection in two ways, by directly inhibiting the growth of fungi and by activating plant innate defense responses as a plant defense inducer.

Irradiation stent with 125 I plus TACE versus sorafenib plus TACE for hepatocellular carcinoma with major portal vein tumor thrombosis: a multicenter randomized trial.

BACKGROUND AND AIM: Treatment strategy for hepatocellular carcinoma (HCC) and Vp4 [main trunk] portal vein tumor thrombosis (PVTT) remains limited due to posttreatment liver failure. We aimed to assess the efficacy of irradiation stent placement with 125 I plus transcatheter arterial chemoembolization (TACE) (ISP-TACE) compared to sorafenib plus TACE (Sora-TACE) in these patients. METHODS: In this multicenter randomized controlled trial, participants with HCC and Vp4 PVTT without extrahepatic metastases were enrolled from November 2018 to July 2021 at 16 medical centers. The primary endpoint was overall survival (OS). The secondary endpoints were hepatic function, time to symptomatic progression, patency of portal vein, disease control rate, and treatment safety. RESULTS: Of 105 randomized participants, 51 were assigned to the ISP-TACE group, and 54 were assigned to the Sora-TACE group. The median OS was 9.9 months versus 6.3 months (95% CI: 0.27-0.82; P =0.01). Incidence of acute hepatic decompensation was 16% (8 of 51) versus 33% (18 of 54) ( P =0.036). The time to symptomatic progression was 6.6 months versus 4.2 months (95% CI: 0.38-0.93; P =0.037). The median stent patency was 7.2 months (interquartile range, 4.7-9.3) in the ISP-TACE group. The disease control rate was 86% (44 of 51) versus 67% (36 of 54) ( P =0.018). Incidences of adverse events at least grade 3 were comparable between the safety populations of the two groups: 16 of 49 (33%) versus 18 of 50 (36%) ( P =0.73). CONCLUSION: Irradiation stent placement plus TACE showed superior results compared with sorafenib plus TACE in prolonging OS in patients with HCC and Vp4 PVTT.

Apple receptor-like kinase FERONIA regulates salt tolerance and ABA sensitivity in Malus domestica.

FERONIA (FER) is a membrane-localized receptor-like kinase that plays pivotal roles in male and female gametophyte recognition, hormone signaling crosstalk, and biotic and abiotic responses. Most reports focus on the functions of FER in model plant Arabidopsis thaliana. However, the functions of FER homologs have not been deeply investigated in apple (Malus domestica), an important economic fruit crop distributed worldwide, especially in China. In this study, we identified an apple homolog of Arabidopsis FER, named MdFER (MDP0000390677). The two proteins encoded by AtFER and MdFER share similar domains: an extracellular malectin-like domain, a transmembrane domain, and an intracellular kinase domain. MdFER was further proven to localize to the plasma membrane in the epidermal cells of Nicotiana benthamiana. MdFER was widely expressed in different apple tissues, but the highest expression was found in roots. In addition, expression of MdFER was significantly induced by treatment with abscisic acid (ABA) and salt (NaCl). Overexpressing MdFER dramatically improved the resistance to salt stress and reduced the sensitivity to ABA in apple callus, while suppressing MdFER expression showed contrary effects. Furthermore, ectopic expression of MdFER in Arabidopsis significantly increased the salt tolerance and reduced the sensitivity to ABA. In addition, under salt stress and ABA treatment, Arabidopsis with highly expressed MdFER accumulated less reactive oxygen species (ROS), and the enzymatic activity of two ROS scavengers, superoxide dismutase and catalase, was higher compared with that of wild type (WT). Our work proves that MdFER positively regulates salt tolerance and negatively regulates ABA sensitivity in apple, which enriched the functions of FER in different plant species.

Nitrate-inducible MdBT2 acts as a restriction factor to limit apple necrotic mosaic virus genome replication in Malus domestica.

Apple necrotic mosaic virus (ApNMV) is highly associated with the occurrence of apple mosaic disease in China. However, ApNMV-host interactions and defence mechanisms of host plants against this virus are poorly studied. Here, we report that nitrate treatment restrains ApNMV genomic RNA accumulation by destabilizing viral replication protein 1a through the MdBT2-mediated ubiquitin-proteasome pathway. MdBT2, a nitrate-responsive BTB/TAZ domain-containing protein, was identified in a yeast two-hybrid screen of an apple cDNA library using viral protein 1a as bait, and 1a was further confirmed to interact with MdBT2 both in vivo and in vitro. It was further verified that MdBT2 promoted the ubiquitination and degradation of viral protein 1a through the ubiquitin-proteasome pathway in an MdCUL3A-independent manner. Viral genomic RNA accumulation was reduced in MdBT2-overexpressing transgenic apple leaves but enhanced in MdBT2-antisense leaves compared to the wild type. Moreover, MdBT2 was found to interfere with the interaction between viral replication proteins 1a and 2apol by competitively interacting with 1a. Taken together, our results demonstrate that nitrate-inducible MdBT2 functions as a limiting factor in ApNMV viral RNA accumulation by promoting the ubiquitination and degradation of viral protein 1a and interfering with interactions between viral replication proteins.

Effect of transjugular intrahepatic portosystemic shunt on transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: Hepatocellular carcinoma (HCC) usually occurs accompanied by portal hypertension. Transcatheter arterial chemoembolization (TACE) is recommended as an effective treatment in HCC. Recent studies had conflicting results regarding the effectiveness and safety of TACE for HCC in patients with transjugular intrahepatic portosystemic shunt (TIPS). This meta-analysis aimed to evaluate the influence of TIPS on the effectiveness and safety of TACE for patients with HCC. METHODS: A comprehensive search of studies among PubMed, Web of Science and Cochrane Library was conducted, from the earliest publishing date to January 27th, 2020. Statistical analyses were all performed using the Stata 13.0 software. I2 index statistic was used to assess heterogeneity. RESULTS: Six studies with a total of 536 patients with HCC were included in the analysis. The pooled response rate was 51% (95% CI: 25% to 77%) with a significant heterogeneity (I2=93.3%, p < 0.001). The TACE + TIPS group had an inferior response rate than the non-TIPS group, but the difference had no statistical significance (p = 0.171) and heterogeneity was low (I2=0.00%, p = 0.490). Pooled hepatic failure rate was 8.8% (95% CI: 5.2% to 12.4%) with low heterogeneity (I2=0.0%, p = 0.747). But the pooled hepatic failure rate increased to 12.7% (95% CI: 5.7% to 19.7%) with low heterogeneity (I2=11.5%, p = 0.323) if the patients who received TIPS after TACE were excluded. CONCLUSION: TIPS does not influence the effectiveness of TACE, but attention should be paid to the risk of hepatic failure.

Broadband photomultiplication organic photodetectors.

Broadband photomultiplication organic photodetectors (PMOPDs) can be achieved with a double-layered active layer prepared from IEICO-4F : PBDB-T blend solutions with different weight ratios (1 : 1 or 3 : 100, wt/wt). The response range of the double-layered PMOPDs covers from 310 nm to 930 nm, determined by the photon harvesting range of the IEICO-4F : PBDB-T (1 : 1, wt/wt) layer. The IEICO-4F : PBDB-T (3 : 100, wt/wt) layer was used as a PM layer in the double-layered PMOPDs, achieving external quantum efficiency (EQE) more than 100% based on the work mechanism of trap-assisted hole tunneling injection. The trapped electrons in PBDB-T/IEICO-4F/PBDB-T near the Al electrode will makeinterfacial-band-bending to narrow the injection barrier, resulting in hole-tunneling-injection from the external circuit. The polymer PBDB-T can provide an efficient charge transport channel for the injected hole from the external circuit. The specific detectivity (D*) and responsivity (R) of the double-layered PMOPDs are 1.05 ± 0.03 × 1012 Jones and 0.94 ± 0.03 A W-1 at 810 nm under a -10 V bias, respectively.

The ankyrin repeat-containing protein MdANK2B regulates salt tolerance and ABA sensitivity in Malus domestica.

KEY MESSAGE: The ankyrin repeat-containing protein MdANK2B was identified to contribute to increasing resistance to salt stress and decreasing sensitivity to ABA in Malus domestica. Ankyrin (ANK) repeat-containing proteins occur widely in prokaryotes, eukaryotes, and even in some viruses and play a critical role in plant growth and development, as well as the response to biotic and abiotic stress. However, the function of ANK repeat-containing proteins in apple (Malus domestica) has not yet been investigated. Here, we identified apple MdANK2B based on homology analysis with the Arabidopsis ANK repeat-containing proteins AtAKR2A and AtAKR2B. MdANK2B was found to be localized in the cytoplasm, and its encoding gene was highly expressed in both apple leaves and fruits. In addition, MdANK2B gene expression was highly induced by salt stresses and abscisic acid (ABA). Overexpression of MdANK2B increased resistance to salt stress and decreased sensitivity to ABA in both transgenic apple calli and seedlings. In addition, overexpression of MdANK2B reduced the accumulation of reactive oxygen species (ROS) by enhancing the activity of antioxidant enzymes in response to salt stress. Our data revealed the role of MdANK2B in response to salt stress and ABA treatment in apple, which widens the known functions of ANK repeat-containing proteins in response to abiotic stress.

R2R3-MYB Transcription Factor MdMYB73 Confers Increased Resistance to the Fungal Pathogen Botryosphaeria dothidea in Apples via the Salicylic Acid Pathway.

MYB transcription factors (TFs) participate in many biological processes. However, the molecular mechanisms by which MYB TFs affect plant resistance to apple ring rot remain poorly understood. Here, the R2R3-MYB gene MdMYB73 was cloned from "Royal Gala" apples and functionally characterized as a positive regulator of the defense response to Botryosphaeria dothidea. qRT-PCR and GUS staining demonstrated that MdMYB73 was strongly induced in apple fruits and transgenic calli after inoculation with B. dothidea. MdMYB73 overexpression improved resistance to B. dothidea in apple calli and fruits, while MdMYB73 suppression weakened. Increased resistance to B. dothidea was also observed in MdMYB73-expressing Arabidopsis thaliana. Interestingly, salicylic acid (SA) contents and the expression levels of genes related with SA synthesis and signaling were greater in MdMYB73-overexpressing plant materials compared to wild-type controls after inoculation, suggesting that MdMYB73 might enhance resistance to B. dothidea via the SA pathway. Finally, we discovered that MdMYB73 interacts with MdWRKY31, a positive regulator of B. dothidea. Together, MdWRKY31 and MdMYB73 enhanced B. dothidea resistance in apples. Our results clarify the mechanisms by which MdMYB73 improves resistance to B. dothidea and suggest that resistance may be affected by regulating the SA pathway.

Determination of Protein Interactions among Replication Components of Apple Necrotic Mosaic Virus.

Apple mosaic disease is one of the most widely distributed and destructive diseases in apple cultivation worldwide, especially in China, whose apple yields account for more than 50% of the global total. Apple necrotic mosaic virus (ApNMV) is a newly identified ilarvirus that is closely associated with apple mosaic disease in China; however, basic viral protein interactions that play key roles in virus replication and the viral life cycle have not been determined in ApNMV. Here, we first identify an ApNMV-Lw isolate that belongs to subgroup 3 in the genus Ilarvirus. ApNMV-Lw was used to investigate interactions among viral components. ApNMV 1a and 2apol, encoded by RNA1 and RNA2, respectively, were co-localized in plant cell cytoplasm. ApNMV 1a interacted with itself at both the inter- and intramolecular levels, and its N-terminal portion played a key role in these interactions. 1a also interacted with 2apol, and 1a's C-terminal, together with 2apol's N-terminal, was required for this interaction. Moreover, the first 115 amino acids of 2apol were sufficient for permitting the 1a-2apol interaction. This study provides insight into the protein interactions among viral replication components of ApNMV, facilitating future investigations on its pathogenicity, as well as the development of strategies to control the virus and disease.

[Efficacy of photodynamic therapy for peri-implantitis: A meta-analysis].

PURPOSE: This meta-analysis was undertaken to evaluate the efficacy of photodynamic therapy (PDT) in combination with non-surgical therapy compared to non-surgical therapy alone for patients with peri-implantitis. METHODS: Bibliographic databases including Cochrane Library, PubMed, EMbase, Web of Science, CNKI, VIP, Wanfang Data and CBM were searched from inception to April 1st 2018 , to collect randomized controlled trials (RCTs) of photodynamic therapy in combination with non-surgical therapy and non-surgical therapy alone for peri-implantitis. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the quality. Then after cross-checking, meta analyses was performed by using RevMan 5.3 software. Meta analysis of probing depth (PD), bleeding on probing(BOP) and clinical attachment level(CAL) was conducted using weighted mean differences (WMD) for continuous data with 95% confidence intervals(CI). RESULTS: Six studies met the inclusion criteria. Meta analysis results showed that compared to non-surgical therapy alone, PDT in combination with non-surgical therapy showed significant differences in PD(WMD=-0.81,95%CI -1.52 to -0.11, P=0.02), BOP(WMD=-5.15, 95%CI -6.29 to -4.01, P<0.00001), but no significant differences in CAL(WMD=-1.13, 95%CI -3.51 to 1.25, P=0.35). CONCLUSIONS: In the treatment of peri-implantitis, compared to non-surgical therapy alone, non-surgical therapy with PDT was more effective in reduction of probing depth and probing bleeding, but it did not significantly improve clinical attachment level. For the quantity and quality limitation of the included studies, the conclusion has to be further proved by performing more well-designed and high quality RCTs.

Evaluation of liver parenchyma stiffness in patients with liver tumours: optimal strategy for shear wave elastography.

OBJECTIVES: To determine the methodology of non-invasive test for evaluation of liver stiffness (LS) with tumours using two-dimensional (2D) shear wave elastography (SWE). METHODS: One hundred and twenty-seven patients with liver tumours underwent 2D-SWE before surgery to measure liver and spleen stiffness (SS). Two-dimensional SWE values were obtained in the liver at 0-1 cm, 1-2 cm and >2 cm from the tumour edge (PLS-1, PLS-2 and RLS, respectively). The influence of tumour-associated factors was evaluated. The area under the receiver operating characteristic curve (AUC) for each value was analysed to diagnose cirrhosis. RESULTS: PLS-1 was higher than PLS-2, which was even higher than RLS (p < 0.001). The AUCs of PLS-1, PLS-2, RLS and SS for diagnosing cirrhosis were 0.760, 0.833, 0.940 and 0.676, with the specificity of 75.7%, 67.6%, 90.3% and 77.4%, respectively. Tumour sizes, locations or types showed no apparent influence on 2D-SWE values except for RLS, which was higher in patients with primary hepatic carcinomas (p < 0.05). CONCLUSIONS: LS with tumours is best measured at >2 cm away from the tumour edge. SS measurement could be used as an alternative to LS measurement in the event of no available liver for detection. KEY POINTS: • Tumour-associated factors impact background liver stiffness assessment. • Background liver stiffness is best measured at >2 cm from tumour edge. • Spleen stiffness can be an alternative to assess background liver stiffness.

Different doses of sevoflurane facilitate and impair learning and memory function through activation of the ERK pathway and synthesis of ARC protein in the rat hippocampus.

BACKGROUND: Sevoflurane has been shown to stimulate or depress memory in adult rats; however, the cellular mechanism of this bidirectional effect has not been fully investigated. METHODS: We used an intra-hippocampal microinfusion of U0126 to suppress ERK activation. Male SD rats were randomly assigned to four groups: Sham, 0.11%SEV, 0.3%SEV and 0.3%+U0126. They received bilateral injections of U0126 or saline. Rats were anesthetized, and Inhibitory Avoidance (IA) training was performed immediately after anesthesia. The memory retention latency was observed 24 h later. In another experiment, the hippocampus was removed 45 min after IA training to assess ARC expression, the synapsin 1 protein levels and the phosphorylation level of ERK. RESULTS: Treatment with 0.11%SEV led to rapid phosphorylation of ERK, while 0.3%SEV inhibited phosphorylation; the latter change was reversed by the microinfusion of U0126 in the hippocampus. The memory latency result had similar tendencies. The local infusion of U0126 abolished the 0.3%SEV-induced memory impairment and ERK inhibition. Selective upregulations of ARC and synapsin 1 proteins were observed in the 0.3%SEV group compared with the 0.11%SEV group. CONCLUSIONS: The results indicate that different doses of sevoflurane trigger synaptic plasticity-related cytoskeleton proteins through the ERK signaling pathway. This novel modulation by inhalational agents may help to reduce their side-effects on memory function.

Significance of oral cancer-associated fibroblasts in angiogenesis, lymphangiogenesis, and tumor invasion in oral squamous cell carcinoma.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are recognized as a pivotal promoter in cancer initiation and development. However, the role of CAFs in the progression and metastasis of oral squamous cell carcinoma (OSCC) has not been fully elucidated. MATERIALS AND METHODS: Lymphatic vessel density (LVD) and microvessel density (MVD) and the expression of α-smooth muscle actin (α-SMA) and matrix metalloproteinase-9 (MMP-9) were evaluated by immunohistochemistry in 86 cases of OSCC. The correlations between α-SMA expression and MMP-9 expression, LVD, MVD, and other clinicopathological parameters were analyzed. In vitro invasion assay was performed to assess the effect of CAFs on the invasion of OSCC cells. We also investigated the effect of CAFs on the angiogenesis and lymphangiogenesis by inoculating CAFs with OSCC cells into nude mice subcutaneously. RESULTS: Positive expression of α-SMA protein was detected in 69.8% of the tumors. Increased α-SMA expression was correlated strongly with enhanced tumor invasion, higher tumor grade, increased risk of recurrence, lymph node involvement, and higher peritumoral lymphatic vessel density and microvessel density (P < 0.05). CAFs induced more cancer cells to invade relative to normal fibroblasts (NFs) (P < 0.05). Compared with co-injection of OSCC cells and NFs or injection of tumor cells alone, co-injection of OSCC cells and CAFs resulted in earlier tumor formation and bigger tumor volume accompanied with increased angiogenesis and lymphangiogenesis (P < 0.05). CONCLUSION: CAFs may play critical roles in OSCC progression as an inducer of tumor invasion, angiogenesis, and lymphangiogenesis. Therapeutic strategies targeting CAFs against OSCC is promising and need further exploration.

A preoperative mathematic model for computed tomographic guided microwave ablation treatment of hepatic dome tumors.

PURPOSE: This study sought to prospectively evaluate the feasibility and safety of a preoperative mathematic model for computed tomographic(CT) guided microwave(MW) ablation treatment of hepatic dome tumors. METHODS: This mathematic model was a regular cylinder quantifying appropriate puncture routes from the bottom up. A total of 103 patients with hepatic dome tumors were enrolled and randomly divided into 2 groups based on whether this model was used or not: Group A (using the model; n = 43) versus Group B (not using the model; n = 60). All tumors were treated by CT-guided MW ablation and follow-up contrast CT were reviewed. RESULTS: The average number of times for successful puncture, average ablation time, and incidence of right shoulder pain were less in Group A than Group B (1.4 vs. 2.5, P = 0.001; 8.8 vs. 11.1 minutes, P = 0.003; and 4.7% vs. 20%, P = 0.039). The technical success rate was higher in Group A than Group B (97.7% vs. 85.0%, P = 0.032). There were no significant differences between the two groups in primary and secondary technique efficacy rates (97.7% vs. 88.3%, P = 0.081; 90.0% vs. 72.7%, P = 0.314). No major complications occurred in both groups. CONCLUSION: The mathematic model of regular cylinder is feasible and safe for CT-guided MW ablation in treating hepatic dome tumors.

The E3 ligase APC/C-Cdh1 regulates MEF2A-dependent transcription by targeting SUMO-specific protease 2 for ubiquitination and degradation.

Activity-dependent stimuli induced a calcineurin-mediated dephosphorylation of the transcriptional factor MEF2A at serine408 and promoted a switch from SUMOylation to acetylation at lysine403 which led to MEF2A transcriptional activation. We previously identified SENP2 is the de-SUMOylation enzyme for MEF2A and promotes MEF2A-dependent transcription. We report here a requirement for APC(Cdh1)-SENP2-MEF2A axis in the regulation of MEF2A transcriptional activation. APC(Cdh1) interacts with and targets SENP2 for ubiquitination and destruction in the cytoplasm by recognizing a conserved canonical D-box motif in SENP2. Moreover, Cdh1 regulates the transcriptional activity of MEF2A in a SENP2 dependent manner. Activity-dependent stimuli prevented APC(Cdh1)-induced SENP2 ubiquitination, promoted SENP2 nuclear accumulations, and caused MEF2A de-SUMOylation and MEF2A acetylation, leading to MEF2A transcriptional activation. Thus, our findings defined a post-transcriptional mechanism underlying activity-dependent stimuli-induced MEF2A transcriptional activation.

Lobaplatin-TACE combined with radioactive 125I seed implantation for treatment of primary hepatocellular carcinoma.

AIM: To investigate the efficacy and safety of lobaplatin-transcatheter arterial chemoembolization (TACE) combined with radioactive 125I seed implantation in treatment of primary hepatocellular carcinoma (HCC). METHODS: 75 patients with primary HCC were enrolled in the study, among them 43 receiving lobaplatin- TACE (TACE group) and 32 lobaplatin-TACE combined with 125I seed implantation (TACE+125I group). After treatment, the local remission rates and postoperative complications of two groups were compared using the Pearson Chi-square test. Overall survival in the two groups was calculated using Kaplan-Meier survival curves and the differences were tested using Log-rank test. RESULTS: There were 7 cases of complete response (CR), 13 of partial response (PR), 6 of stable disease (SD) and 17 of progressive disease (PD) in the TACE group, with 13 cases of CR, 9 of PR, 5 of SD and 5 of PD in the TACE+125I group. The disease control rates of TACE and TACE+125I group were 60.5% (26/43) and 84.4% (27/32), respectively, with a significant difference between them (P < 0.05). The survival rates at 6, 12 and 18 months in the TACE group were 100.0%, 81.8% and 50.0%, respectively, and those in TACE+125I group were 100.0%, 93.8% and 65.6%. The mean survival times in the TACE and TACE+125I groups were 19.5 and 22.9 months, respectively. There was a significant difference in the overall survival rate between two groups (P < 0.05). No serious complications were encountered in either group. CONCLUSION: Lobaplatin-TACE combined with 125I seed implantation is favorable and safe for treatment of primary HCC.

[Clinical value of CT-guided (125)I brachytherapy for retroperitoneal metastatic lymph node from PHC].

OBJECTIVE: To discuss the clinical value of CT-guided (125)I brachytherapy with retroperitoneal metastatic lymph nodes from primary hepatic carcinoma(PHC). METHODS: Twenty patients with retroperitoneal metastatic lymph node recurrence from PHC were percutaneously treated by (125)I brachytherapy with computed tomographic (CT) guidance. The number, radioactive dose, placed position of radioactive seeds and puncture path were determined by computerized treatment planning system (TPS). The radioactive seeds were implanted when the needles were in right position by CT scan. Radiotherapy verification and quality assessment were performed after treatment by CT scan. Follow-up contrast material-enhanced CT were reviewed. RESULTS: The local control rate of 3, 6, 10, 15 months was 70.0%, 56.3%, 44.4%, 25.0% respectively. There were no severe complications such as massive bleeding and radiation injury of normal tissues. CONCLUSION: CT-guided (125)I brachytherapy are effective and may be safely applied to retroperitoneal metastatic lymph nodes from PHC.