Comparison of liver resection and radiofrequency ablation in long-term survival among patients with early-stage hepatocellular carcinoma: a meta-analysis of randomized trials and high-quality propensity score-matched studies.

BACKGROUND: Whether radiofrequency ablation (RFA) and liver resection (LR) are comparable treatments for early-stage hepatocellular carcinoma (HCC) is controversial. We conducted this study to provide ample clinical evidence for the argument. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to identify randomized controlled trials (RCTs) and propensity score-matched (PSM) studies that compared long-term outcomes of both RFA and LR for patients with early-stage HCC. The hazard ratios (HRs) with 95% confidence intervals (95% CI) of overall survival (OS) and disease-free survival (DFS) were calculated. RESULTS: Thirty-six studies consisting of six RCTs and 30 PSM studies were included in this study, and a total of 7384 patients were involved, with 3694 patients being treated with LR and 3690 patients with RFA. Meta-analysis showed that LR provided better OS and DFS than RFA (HR: 1.22, 95% CI: 1.13-1.31; HR: 1.56, 95% CI: 1.39-1.74, respectively). A sensitivity analysis indicated that the results were stable. For the subgroup of patients with BCLC 0 stage, RFA and LR resulted in similar OS and DFS. For the subgroup of patients with single tumor sizes less than 3 cm, RFA reached similar OS (HR: 1.19, 95% CI: 0.90-1.58) but worse DFS compared with LR (HR: 1.45, 95% CI: 1.11-1.90). For the subgroup of ablation margin larger than 0.5 cm, LR still resulted in better OS than RFA (HR: 1.29, 95% CI: 1.09-1.53); while the ablation margin was larger than 1 cm, both RFA and LR resulted in similar OS. The modality of RFA was also a factor that affected results. Subgroup analysis showed that patients receiving ultrasound-guided RFA had worse OS and DFS than LR (HR: 1.24, 95% CI: 1.14-1.36; HR: 1.44, 95% CI: 1.25-1.66, respectively). CONCLUSIONS: Meta-analysis showed that LR provided better OS and DFS for patients with early-stage HCC. However, RFA and LR had similar effects on long-term survival in patients with BCLC 0 stage HCC. RFA and LR probably had similar effects on OS in patients with solitary HCC less than 3 cm or when the ablation margin was larger than 1 cm which need more studies to confirm. The effects of different modalities of RFA on long-term survival are needed for further assessment.

Efficacy of transarterial therapy combined with first-line tyrosine kinase inhibitors for unresectable hepatocellular carcinoma: a network meta-analysis.

BACKGROUND: Transarterial therapies, including transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and selective internal radiation therapy, combined with first-line tyrosine kinase inhibitors (TKIs) are considered the standard therapy for unresectable hepatocellular carcinoma. However, inconsistent results have been reported in various studies assessing different combinations of targeted agents. METHODS: A network meta-analysis (NMA) was performed by including 23 randomized controlled trials (RCTs) with 6175 patients to investigate the efficiency of transarterial therapies in combination with different TKIs. Outcomes of interest included overall survival (OS), progression-free survival (PFS), time to progression (TTP), and tumor objective response rate (ORR). A random-effects consistency model was used in this Bayesian NMA. Hazard ratio and odd risks with a 95% credible interval were calculated and agents were ranked based on ranking probability. RESULTS: HAIC showed maximal OS and TTP and TACE plus lenvatinib showed maximal PFS, ORR, and disease control rate (DCR). HAIC and TACE plus lenvatinib were ranked highest based on their respective parameters, which were OS for HAIC and PFS, ORR, and DCR for TACE plus lenvatinib. CONCLUSION: HAIC and TACE plus lenvatinib were relatively better choice for unresectable hepatocellular carcinoma. However, owing to the lack of statistically significant OS benefits among most agents, other agents should be considered as potential alternatives for unresectable hepatocellular carcinoma.

Effect of intermittent Pringle maneuver on perioperative outcomes and long-term survival following liver resection in patients with hepatocellular carcinoma: a meta-analysis and systemic review.

BACKGROUND: Intermittent Pringle maneuver (IPM) is commonly used to control bleeding during liver resection. IPM can cause ischemia-reperfusion injury, which may affect the prognosis of patients with hepatocellular carcinoma (HCC). The present meta-analysis was conducted to evaluate the effect of IPM use on perioperative outcomes and long-term survival in patients with HCC. METHODS: A systemic literature search was performed in the PubMed, Embase, Web of Science, and Cochrane Library databases to identify randomized controlled trials and retrospective studies that compared the effect of IPM with no Pringle maneuver during liver resection in patients with HCC. Hazard ratio (HR), risk ratio, standardized mean difference, and their 95% confidence interval (CI) values were calculated based on the type of variables. RESULTS: This meta-analysis included nine studies comprising one RCT and eight retrospective studies and involved a total of 3268 patients. Perioperative outcomes, including operation time, complications, and length of hospital stay, except for blood loss, were comparable between the two groups. After removing the studies that led to heterogeneity, the results showed that IPM was effective in reducing blood loss. Five studies reported overall survival (OS) and disease-free survival (DFS) data and eight studies reported perioperative outcomes. No significant difference in OS and DFS was observed between the two groups (OS: HR, 1.01; 95% CI, 0.85-1.20; p = 0.95; DFS: HR, 1.01; 95% CI, 0.88-1.17; p = 0.86). CONCLUSION: IPM is a useful technique to control blood loss during liver resection and does not affect the long-term survival of patients with HCC.

Does adjuvant hepatic artery infusion chemotherapy improve patient outcomes for hepatocellular carcinoma following liver resection? A meta-analysis.

BACKGROUND: Adjuvant hepatic artery infusion chemotherapy (HAIC) has been shown to be beneficial to the patient outcomes in hepatocellular carcinoma (HCC). METHODS: Randomized controlled trials (RCTs) and non-RCTs were identified from six databases up to January 26, 2023. Patient outcomes were assessed using overall survival (OS) and disease-free survival (DFS). Data were presented as hazard ratios (HR, 95% confidence intervals, or CIs). RESULTS: The present systematic review included 2 RCTs and 9 non-RCTs with a total of 1290 cases. Adjuvant HAIC improved OS (HR of 0.69; 95% CI of 0.56-0.84; p < 0.01) and DFS (HR of 0.64; 95% CI of 0.49-0.83; p < 0.01). Subgroup analysis showed that HCC patients with portal vein invasion (PVI) or microvascular invasion (MVI) benefit from adjuvant HAIC in terms of OS ((HR of 0.43; 95% CI of 0.19-0.95; p < 0.01) and (HR of 0.43; 95% CI of 0.19-0.95; p = 0.0373), respectively) and DFS ((HR of 0.38; 95% CI of 0.21-0.69; p < 0.01) and (HR of 0.73; 95% CI of 0.60-0.88; p = 0.0125), respectively). Adjuvant HAIC with the oxaliplatin-based approach significantly improved OS (HR of 0.60; 95% CI of 0.36-0.84; p = 0.02) and (HR of 0.59; 95% CI of 0.43-0.75; p < 0.01), respectively). CONCLUSION: This meta-analysis demonstrated that postoperative adjuvant HAIC was beneficial in HCC patients with PVI and MVI. It remains unclear whether HAIC can improve the survival outcome in all HCC patients after hepatic resection.

Efficacy analysis of hybrid operating room-based laparoscopic cholecystectomy combined with intraoperative endoscopic retrograde cholangiopancreatography in the treatment of cholelithiasis combined with choledocholithiasis - A case-control study.

Objective: The objective is to compare the therapeutic effects of laparoscopic cholecystectomy (LC) combined with intraoperative endoscopic retrograde cholangiopancreatography (ERCP) in hybrid operating room and ERCP + LC under traditional conditions in the treatment of cholelithiasis and choledocholithiasis. Materials and Methods: Data of 82 patients with cholelithiasis complicated with choledocholithiasis treated by our centre from November 2018 to March 2021 were retrospectively analysed. Amongst them, 40 patients treated with LC combined with intraoperative ERCP in a hybrid operating room were placed into Group A, and 42 patients treated with ERCP first followed by LC under traditional conditions were placed into Group B. The differences in operative time, intraoperative blood loss, surgical success rate, stone clearance rate, pain score, exhaust time, ambulation time, post-operative complications, length of hospital stay, hospitalisation cost and other indicators between the two groups were compared. Results: There were no significant differences in operative time, intraoperative blood loss, surgical success rate and stone clearance rate between the two groups (P > 0.05), while there were significant differences in post-operative pain score, exhaust time, ambulation time, length of hospital stay, hospitalisation cost and complications (P < 0.05). Conclusion: LC combined with intraoperative ERCP in hybrid operating room for the treatment of cholelithiasis combined with choledocholithiasis has a better therapeutic effect than traditional ERCP followed by LC, which is worthy of further popularization. Notably, the reasonable selection should be made based on patients' own conditions and hospital facilities.

Me-Better Drug Design Based on Nevirapine and Mechanism of Molecular Interactions with Y188C Mutant HIV-1 Reverse Transcriptase.

In this paper, the Y188C mutant HIV-1 reverse transcriptase (Y188CM-RT) target protein was constructed by homology modeling, and new ligands based on nevirapine (NVP) skeleton were designed by means of fragment growth. The binding activity of new ligands to Y188CM-RT was evaluated by structural analysis, ADMET prediction, molecular docking, energy calculation and molecular dynamics. Results show that 10 new ligands had good absorbability, and their binding energies to Y188CM-RT were significantly higher than those of wild-type HIV-1 reverse transcriptase(wt). The binding mode explained that fragment growth contributed to larger ligands, leading to improved suitability at the docking pocket. In the way of fragment growth, the larger side chain with extensive contact at terminal is obviously better than substituted benzene ring. The enhancement of docking activity is mainly due to the new fragments such as alkyl chains and rings with amino groups at NVP terminal, resulting in a large increase in hydrophobic bonding and the new addition of hydrogen bonding or salt bonding. This study is expected to provide reference for the research on non-nucleoside reverse transcriptase inhibitors resistance and AIDS treatment.

A RNA-Targeted Two-Photon Bioprobe with High Selective Permeability into Nuclear Pore Complexes for Dynamically Tracking the Autophagy Process among Multi-Organelles.

Dynamic tracking of the spatiotemporal coordination among various organelles to in-depth understanding of the mechanism of autophagy have attracted considerable attention. However, the monitor of nucleoli participation in autophagy was somehow neglected. Herein, we report a RNA-targeted bioprobe (ADAP) with high selective permeability into nuclear pore complexes, which induced a two-photon (TP) fluorescence "off-on" response by groove combination with RNA, dynamically monitoring the autophagy process among multiorganelles (nucleoli, mitochondria, and mitochondria-containing lysosomes). This work provides a simple and convenient way to observe the dynamic behavior of multiorganelles during the autophagy process, which benefits the understanding of cellular metabolism.

A clinical study of choledochoscopic holmium laser lithotripsy for multiple intrahepatic calculi within ERAS programs.

OBJECTIVES: Multiple intrahepatic calculi, especially calculi in both sides of the liver, cannot be completely resolved by traditional surgery. In addition, morbidity after liver resection remains high. ERAS programs have been suggested that could relieve surgical stress and accelerate postoperative recovery. This study aimed to evaluate the safety and efficacy of choledocholithotomy combined with holmium laser lithotripsy in the treatment of multiple intrahepatic calculi within ERAS programs. METHODS: In all, 109 patients with multiple intrahepatic calculi were enrolled between January 2012 and September 2016, 42 of whom received choledocholithotomy combined with holmium laser lithotripsy. The remaining 67 patients underwent choledocholithotomy combined with choledochoscopic mechanical lithotripsy. Perioperative outcomes were compared and analyzed. RESULTS: Patient characteristics and preoperative details were similar between the groups (P > 0.05). The implementation of holmium laser lithotripsy could reduce the calculi residual rate (7.1% vs. 22.4%, P = 0.037), and even the liver resection rate (16.7% vs. 35.8%, P = 0.031). Additionally, holmium laser lithotripsy did not result in a higher morbidity (11.9% vs. 16.4%, P = 0.517), readmission rate (0% vs. 6%, P = 0.158), hospital stay (P = 0.189), hospital cost (P = 0.998), transfusion rate (P = 0.576), or operative time (P = 0.638). CONCLUSIONS: Holmium laser lithotripsy is feasible and efficient for treating multiple intrahepatic calculi within ERAS programs, which could reduce the liver resection rate and render refractory hepatic calculi easy to eliminate. In addition, holmium laser lithotripsy could be well coupled to the ERAS program to relieve surgical stress and accelerate postoperative recovery. Lasers Surg. Med. 51:161-166, 2019. © 2018 Wiley Periodicals, Inc.

[The role of myeloid-derived suppressor cells in glioma microenvironment].

Glioma is one of the most common primary tumors in the human brain with poor prognosis. The local and systemic immunosuppressive environment created by glioma cells enables them to evade immunosurveillance. Myeloid-derived suppressor cells (MDSCs) are a critical component of the immunosuppression system. They are a heterogeneous cell population composed of early myeloid progenitor cells and precursor cells. Although the cells are diverse in phenotypes and functions, they all have strong immunosuppressive functions. MDSCs are extensively infiltrated into tumor tissues and play an important role in the glioma immunosuppressive microenvironment, which also hinders the immunotherapeutic effects of glioma. This article will review the phenotypic characteristics of MDSCs in the glioma microenvironment and their role in the progression of glioma. It is of positive significance to better understand the pathogenesis of glioma and explore effective comprehensive treatments.

Membrane-Penetrating Carbon Quantum Dots for Imaging Nucleic Acid Structures in Live Organisms.

The dynamics of DNA and RNA structures in live cells are important for understanding cell behaviors, such as transcription activity, protein expression, cell apoptosis, and hereditary disease, but are challenging to monitor in live organisms in real time. The difficulty is largely due to the lack of photostable imaging probes that can distinguish between DNA and RNA, and more importantly, are capable of crossing multiple membrane barriers ranging from the cell/organelle to the tissue/organ level. We report the discovery of a cationic carbon quantum dot (cQD) probe that emits spectrally distinguishable fluorescence upon binding with double-stranded DNA and single-stranded RNA in live cells, thereby enabling real-time monitoring of DNA and RNA localization and motion. A surprising finding is that the probe can penetrate through various types of biological barriers in vitro and in vivo. Combined with standard and super-resolution microscopy, photostable cQDs allow time-lapse imaging of chromatin and nucleoli during cell division and Caenorhabditis elegans (C. elegans) growth.

Establishment of malignantly transformed dendritic cell line SU3-ihDCTC induced by Glioma stem cells and study on its sensitivity to resveratrol.

BACKGROUND: As a factor contributing to the tumor cell drug resistance, tumor microenvironment (TME) is being paid increasingly attention. However, the drug resistance of malignantly transformed cells in TME has rarely been revealed. This paper is designed to investigate the sensitivity of malignantly transformed cell line (ihDCTC) induced by glioma stem cells (GSCs) in TME to chemotherapeutic drugs. METHODS: (1) Establishment of ihDCTC cell line,The bone marrow cells from enhanced green fluorescent protein (EGFP) transgenic nude mice were employed to culture the dendritic cells (DCs) in vitro, which were then co-cultured with red fluorescence protein (RFP) transgenic GSCs (SU3) to obtain ihDCTC (2) Res and Cis were used to intervene in the growth of abovemetioned cell lines in vitro and Res treated in bearing ihDCTC tumor mice, followed by evaluating their drug sensitivity and changes in key signaling proteins via half maximal inhibitory concentration (IC50), tumor mass and immunostaining method. RESULTS: (1) ihDCTC could express CD11c and CD80 as well as possessed immortalized potential, heteroploid chromosomes and high tumorigenicity in nude mice in vivo. (2) At 24 h, 48 h and 72 h, the IC50 value of ihDCTC treated with Cis was 3.62, 3.25 and 2.10 times higher than that of SU3, while the IC50 value of ihDCTC treated with Res was 0.03, 0.47 and 1.19 times as much as that of SU3; (3) The xenograft mass (g) in vivo in the control, Res, Cis and Res + Cis groups were 1.44 ± 0.19, 0.45 ± 0.12, 0.94 ± 0.80 and 0.68 ± 0.35(x ± s) respectively. The expression levels of IL-6, p-STAT3 and NF-κB proteins in the xenograft tissue were significantly reduced only in the Res treatment group. CONCLUSION: In vitro co-culture with GSC can induce the malignant transformation of bone marrow derived dendritic cells, on the one hand, ihDCTC shows higher drug resistance to the traditional chemotherapeutic drug Cis than GSCs, but, on the other hand, appears to be more sensitive to Res than GSCs. Therefore, our findings provide a broader vision not only for the further study on the correlation between TME and tumor drug resistance but also for the exploration of Res anti-cancer value.

A Series of Zn(II) Terpyridine-Based Nitrate Complexes as Two-Photon Fluorescent Probe for Identifying Apoptotic and Living Cells via Subcellular Immigration.

Two-photon active probe to label apoptotic cells plays a significant role in biological systems. However, discrimination of live/apoptotic cells at subcellular level under microscopy remains unachieved. Here, three novel Zn(II) terpyridine-based nitrate complexes (C1-C3) containing different pull/push units were designed. The structures of the ligands and their corresponding Zn(II) complexes were confirmed by single-crystal X-ray diffraction analysis. On the basis of the comprehensive comparison, C3 had a suitable two-photon absorption cross section in the near-infrared wavelength and good biocompatibility. Under two-photon confocal microscopy and transmission electron microscopy, it is found that C3 could target mitochondria in living cells but immigrate into the nucleolus during the apoptotic process. This dual-functional probe (C3) not only offers a valuable image tool but also acts as an indicator for cell mortality at subcellular level in a real-time manner.

Characterization and genetic mapping of the ß-diketone deficient eceriferum-b barley mutant.

KEY MESSAGE: The barley eceriferum-b.2 (cer-b.2) mutant produces glossy leaf sheaths and is deficient in the cuticular wax component 14,16-hentriacontanedione. The mutated gene maps to a 1.3-cM interval on chromosome 3HL flanked by the genes MLOC_10972 and MLOC_69561. The cuticular wax coating of leaves and stems in many grass species is responsible for the plants' glaucous appearance. A major component of the wax is a group of ß-diketone compounds. The barley eceriferum-b.2 (cer-b.2) mutant produces glossy leaf sheaths and is deficient for the compound 14,16-hentriacontanedione. A linkage analysis based on 708 gametes allowed the gene responsible for the mutant phenotype to be mapped to a 1.3-cM interval on chromosome 3HL flanked by the two genes MLOC_10972 and _69561. The product of the wild type allele may represent a step in the ß-diketone synthesis pathway.

NMR characterization of weak interactions between RhoGDI2 and fragment screening hits.

BACKGROUND: The delineation of intrinsically weak interactions between novel targets and fragment screening hits has long limited the pace of hit-to-lead evolution. Rho guanine-nucleotide dissociation inhibitor 2 (RhoGDI2) is a novel target that lacks any chemical probes for the treatment of tumor metastasis. METHODS: Protein-observed and ligand-observed NMR spectroscopy was used to characterize the weak interactions between RhoGDI2 and fragment screening hits. RESULTS: We identified three hits of RhoGDI2 using streamlined NMR fragment-based screening. The binding site residues were assigned using non-uniformly sampled Cα- and Hα-based three dimensional NMR spectra. The molecular docking to the proposed geranylgeranyl binding pocket of RhoGDI2 was guided by NMR restraints of chemical shift perturbations and ligand-observed transferred paramagnetic relaxation enhancement. We further validated the weak RhoGDI2-hit interactions using mutagenesis and structure-affinity analysis. CONCLUSIONS: Weak interactions between RhoGDI2 and fragment screening hits were delineated using an integrated NMR approach. GENERAL INTERESTS: Binders to RhoGDI2 as a potential anti-cancer target have been first reported, and their weak interactions were depicted using NMR spectroscopy. Our work highlights the powerfulness and the versatility of the integrative NMR techniques to provide valuable structural insight into the intrinsically weak interactions between RhoGDI2 and the fragment screening hits, which could hardly be conceived using other biochemical techniques.

Comparative transcriptome profile of the leaf elongation zone of wild barley (Hordeum spontaneum) eibi1 mutant and its isogenic wild type.

The naturally occurring wild barley mutant eibi1/hvabcg31 suffers from severe water loss due to the permeable leaf cuticle. Eibi1/HvABCG31 encodes a full ATP-binding cassette (ABC) transporter, HvABCG31, playing a role in cutin deposition in the elongation zone of growing barley leaves. The eibi1 allele has pleiotropic effects on the appearance of leaves, plant stature, fertility, spike and grain size, and rate of germination. Comparative transcriptome profile of the leaf elongation zone of the eibi1 mutant as well as its isogenic wild type showed that various pathogenesis-related genes were up-regulated in the eibi1 mutant. The known cuticle-related genes that we analyzed did not show significant expression difference between the mutant and wild type. These results suggest that the pleiotropic effects may be a compensatory consequence of the activation of defense genes in the eibi1 mutation. Furthermore, we were able to find the mutation of the eibi1/hvabcg31 allele by comparing transcript sequences, which indicated that the RNA-Seq is useful not only for researches on general molecular mechanism but also for the identification of possible mutant genes.

[Metabolism of paeoniflorin by rat intestinal flora in vitro].

In order to clarify the effect of intestinal flora on the absorption and metabolism of paeoniflorin in vivo, the metabolism of paeoniflorin by rat intestinal flora was studied under the in vitro anaerobic condition. Paeoniflorin was incubated with rat anaerobic intestinal flora for 48 h, and UPLC was used to detect the changes of paeoniflorin at different incubation time points under the following chromatographic conditions：WelchromTM C18 chromatographic column (4.6 mm×100 mm, 5 µm), with 0.1% formic acid(A)-acetonitrile(B) as the mobile phase for gradient elution. The flow rate was 0.4 mL•min⁻¹, and column temperature was 30 ℃. UPLC-Q-TOF-MS with positive ion mode(ESI ion source) was applied to investigate the structural characterization of metabolic products. The structures of the metabolites were identified by accurate molecular weight, TOF-MS/MS fragmentation information, combined with retention time and literature data review, and the intestinal metabolic rules were then analyzed. After incubation for 24 h, the paeoniflorin was metabolized completely, and the resulting metabolites(albiflorin, albiflorinaglycone, deacylate albiflorin, deacylate albiflorin aglycone and paeonilactone-B) were detected in rat intestinal flora. The metabolic pathway analysis showed that the isolated rat intestinal flora first transformed peoniflorin into albiflorin, and then further metabolized by glucose removal, phenyl group removal, or four-membered ring pyrolysis and rearrangement. Paeoniflorin was gradually transformed into more hydrophobic metabolites with smaller molecular mass, which were better absorbed by the intestinal tract.

One-Step LC and ERCP Treatment of 40 Cases with Cholelithiasis Complicated with Common Bile Duct Stones.

BACKGROUND/AIMS: To discuss the clinical significance of combined application of laparoscopic cholecystectomy (LC) and endoscopic retrograde cholangiopancreatography (ERCP) for one-stage treatment of cholelithiasis complicated with common bile duct stones. METHODOLOGY: To retrospectively analyze 40 cases with cholelithiasis complicated with common bile duct stones treated with LC plus intraoperative ERCP between May 2005 and September 2012 and to evaluate the clinical efficacy in the treatment of cholelithiasis complicated with common bile duct stones. RESULTS: Among 40 cases, 36 successfully underwent LC plus intraoperative ERCP and 4 were transferred to open surgery. Eighteen patients with preoperative abnormal liver function showed declined indexes post-operatively. Compared with LC, more patients had abdominal distention and vomiting. Seven patients presented with transient increase in the levels of serum amylase with no incidence of acute pancreatitis. One had hematochezia and recovered after conservative treatment with no incidence of bile leakage and perforation and other severe complications. CONCLUSIONS: LC combined with intraoperative ERCP is safe and efficacious in the primary treatment of cholelithiasis complicated with common bile duct stones to avoid open surgery and double surgeries.

Characterization and genetic mapping of eceriferum-ym (cer-ym), a cutin deficient barley mutant with impaired leaf water retention capacity.

The cuticle covers the aerial parts of land plants, where it serves many important functions, including water retention. Here, a recessive cuticle mutant, eceriferum-ym (cer-ym), of Hordeum vulgare L. (barley) showed abnormally glossy spikes, sheaths, and leaves. The cer-ym mutant plant detached from its root system was hypersensitive to desiccation treatment compared with wild type plants, and detached leaves of mutant lost 41.8% of their initial weight after 1 h of dehydration under laboratory conditions, while that of the wild type plants lost only 7.1%. Stomata function was not affected by the mutation, but the mutant leaves showed increased cuticular permeability to water, suggesting a defective leaf cuticle, which was confirmed by toluidine blue staining. The mutant leaves showed a substantial reduction in the amounts of the major cutin monomers and a slight increase in the main wax component, suggesting that the enhanced cuticle permeability was a consequence of cutin deficiency. cer-ym was mapped within a 0.8 cM interval between EST marker AK370363 and AK251484, a pericentromeric region on chromosome 4H. The results indicate that the desiccation sensitivity of cer-ym is caused by a defect in leaf cutin, and that cer-ym is located in a chromosome 4H pericentromeric region.

Molecular Mechanisms Underlying Hull-Caryopsis Adhesion/Separation Revealed by Comparative Transcriptomic Analysis of Covered/Naked Barley (Hordeum vulgare L.).

The covered/naked caryopsis trait of barley is an important agronomic trait because it is directly linked to dietary use. The formation of covered/naked caryopsis is controlled by an NUD transcription factor, which is involved in pericarp cuticle development. However, the molecular mechanism underlying this trait remains so far largely unknown. In this study, comparative transcriptomes of grains three weeks after anthesis of Tibetan Hulless barley landrace Dulihuang and covered barley Morex were analyzed using RNA-seq technique. A total of 4031 differentially expressed genes (DEGs) were identified. The Nud gene was overexpressed in Morex, with trace expression in Dulihuang. Among seventeen cuticle related DEGs, sixteen were down regulated and one up regulated in Morex. These results suggest that the Nud gene in covered caryopsis might down regulate cuticle related genes, which may cause a permeable cuticle over pericarp, leading to a hull-caryopsis organ fusion. A functional cuticle covering the pericarp of naked caryopsis might be the result of deletion or low expression level of the Nud gene. The functional cuticle defines a perfect boundary to separate the caryopsis from the hull in naked barley.

[Tumor angiogenesis promoted by fusion of glioma stem/progenitor cells with bone marrow mesenchymal stem cells].

OBJECTIVE: The aim of this study was to clarify whether the fusion of bone marrow mesenchymal stem cells (MSCs) with tumor cells can promote tumor angiogensis. METHODS: Human glioma stem/progenitor cells (GSPCs) (SU3 cells) were transfected with red fluorescent protein (RFP) gene. Bone marrow mesenchymal stem cells (MSCs) were harvested from nude mice with whole-body green fluorescent protein (GFP) gene expression. Then the two kinds of cells were co-cultured in vitro. At the same time SU3-RFP was transplanted into the brain of GFP-expressing nude mice to establish xenograft tumors. The co-cultured cells, GFP/RFP double positive (yellow) cells and blood vessels obtained from the xenograft tumors were observed under fluorescent microscope and laser scanning confocal microscope. RESULTS: After five passages in vitro, MSCs maintained the proliferative activity and highly expressed CD105. CD105 was also expressed in the femurs of GFP-expressing nude mice, tumor cells, blood vessels of SU3 xenograft tumors, and clinical malignant gliomas. When MSCs were co-cultured with SU3-RFP, the ratio of yellow cells co-expressing RFP and GFP was significantly increased after extended time and continuous passages. According to the flow cytometry, yellow cells co-expressing RFP and GFP were 83.7% of the cultured cells. In tissue slices of the xenograft tumors, bundles of yellow vessel-like structure and cross-sectioned yellow vascular wall structures including vascular wall stroma cells were observed with RFP and GFP expression, and were identified as de novo formed vessels derived from fusion of MSCs with SU3-RFP cells. CONCLUSION: Cell fusion occurs between tumor cells and host MSCs and it promotes tumor angiogenesis.