The structure of B-ARR reveals the molecular basis of transcriptional activation by cytokinin.

The phytohormone cytokinin has various roles in plant development, including meristem maintenance, vascular differentiation, leaf senescence, and regeneration. Prior investigations have revealed that cytokinin acts via a phosphorelay similar to the two-component system by which bacteria sense and respond to external stimuli. The eventual targets of this phosphorelay are type-B ARABIDOPSIS RESPONSE REGULATORS (B-ARRs), containing the conserved N-terminal receiver domain (RD), middle DNA binding domain (DBD), and C-terminal transactivation domain. While it has been established for two decades that the phosphoryl transfer from a specific histidyl residue in ARABIDOPSIS HIS PHOSPHOTRANSFER PROTEINS (AHPs) to an aspartyl residue in the RD of B-ARRs results in a rapid transcriptional response to cytokinin, the underlying molecular basis remains unclear. In this work, we determine the crystal structures of the RD-DBD of ARR1 (ARR1RD-DBD) as well as the ARR1DBD-DNA complex from Arabidopsis. Analyses of the ARR1DBD-DNA complex have revealed the structural basis for sequence-specific recognition of the GAT trinucleotide by ARR1. In particular, comparing the ARR1RD-DBD and ARR1DBD-DNA structures reveals that unphosphorylated ARR1RD-DBD exists in a closed conformation with extensive contacts between the RD and DBD. In vitro and vivo functional assays have further suggested that phosphorylation of the RD weakens its interaction with DBD, subsequently permits the DNA binding capacity of DBD, and promotes the transcriptional activity of ARR1. Our findings thus provide mechanistic insights into phosphorelay activation of gene transcription in response to cytokinin.

Anisotropic cell growth at the leaf base promotes age-related changes in leaf shape in Arabidopsis thaliana.

Plants undergo extended morphogenesis. The shoot apical meristem (SAM) allows for reiterative development and the formation of new structures throughout the life of the plant. Intriguingly, the SAM produces morphologically different leaves in an age-dependent manner, a phenomenon known as heteroblasty. In Arabidopsis thaliana, the SAM produces small orbicular leaves in the juvenile phase, but gives rise to large elliptical leaves in the adult phase. Previous studies have established that a developmental decline of microRNA156 (miR156) is necessary and sufficient to trigger this leaf shape switch, although the underlying mechanism is poorly understood. Here we show that the gradual increase in miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE transcription factors with age promotes cell growth anisotropy in the abaxial epidermis at the base of the leaf blade, evident by the formation of elongated giant cells. Time-lapse imaging and developmental genetics further revealed that the establishment of adult leaf shape is tightly associated with the longitudinal cell expansion of giant cells, accompanied by a prolonged cell proliferation phase in their vicinity. Our results thus provide a plausible cellular mechanism for heteroblasty in Arabidopsis, and contribute to our understanding of anisotropic growth in plants.

Redundant and specific roles of individual MIR172 genes in plant development.

Evolutionarily conserved microRNAs (miRNAs) usually have high copy numbers in the genome. The redundant and specific roles of each member of a multimember miRNA gene family are poorly understood. Previous studies have shown that the miR156-SPL-miR172 axis constitutes a signaling cascade in regulating plant developmental transitions. Here, we report the feasibility and utility of CRISPR-Cas9 technology to investigate the functions of all 5 MIR172 family members in Arabidopsis. We show that an Arabidopsis plant devoid of miR172 is viable, although it displays pleiotropic morphological defects. MIR172 family members exhibit distinct expression pattern and exert functional specificity in regulating meristem size, trichome initiation, stem elongation, shoot branching, and floral competence. In particular, we find that the miR156-SPL-miR172 cascade is bifurcated into specific flowering responses by matching pairs of coexpressed SPL and MIR172 genes in different tissues. Our results thus highlight the spatiotemporal changes in gene expression that underlie evolutionary novelties of a miRNA gene family in nature. The expansion of MIR172 genes in the Arabidopsis genome provides molecular substrates for the integration of diverse floral inductive cues, which ensures that plants flower at the optimal time to maximize seed yields.

Parallel-Forms Reliability and Minimal Detectable Change of the Four Telerehabilitation Version Mobility-Related Function Scales in Stroke Survivors.

OBJECTIVE: To investigate the parallel-forms reliability, minimal detectable change with 95% confidence interval (MDC95), and feasibility of the 4 telerehabilitation version mobility-related function scales: Fugl-Meyer Assessment-lower extremity subscale (Tele-FMA-LE), Berg Balance Scale (Tele-BBS), Tinetti Performance Oriented Mobility Assessment-Gait subscale (Tele-POMA-G), and Rivermead Mobility Index (Tele-RMI). DESIGN: Reliability and agreement study and cross-sectional study. SETTING: Medical center. PARTICIPANTS: Stroke survivors' ability to independently walk 3 meters with assistive devices, age of ≥18 years for participants and their partners, stable physical condition, and absence of cognitive impairment (N=60). INTERVENTIONS: Not applicable. MAIN OUTCOMES MEASURES: Parallel-forms reliability and MDC95 of Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI. RESULTS: No significant differences (P>.05) were observed among the mean scores of the telerehabilitation version and face-to-face version mobility-related function scales. Intraclass correlation coefficients (ICCs) indicated good reliability for most scales, with Tele-FMA-LE, Tele-BBS, and Tele-RMI scores achieving values of 0.81, 0.78, and 0.84. Tele-POMA-G scores demonstrated moderate reliability (ICC=0.72). Weighted kappa (κw) showed good-to-excellent reliability for most individual items (κw>0.60). The MDCs of the Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI were 5.84, 8.10, 2.74, and 1.31, respectively. Bland-Altman analysis showed adequate agreement between tele-assessment and face-to-face assessment for all scales. The 5 dimensions affirm the robust feasibility of tele-assessment: assessment time, subjective fatigue perception, overall preference, participant satisfaction, and system usability. CONCLUSIONS: The study demonstrates good parallel-forms reliability, MDC, and promising feasibility of the 4 telerehabilitation version mobility-related function scales (Tele-FMA-LE, Tele-BBS, Tele-POMA-G, and Tele-RMI) in survivors of stroke.

A spatiotemporally regulated transcriptional complex underlies heteroblastic development of leaf hairs in Arabidopsis thaliana.

Heteroblasty refers to a phenomenon that a plant produces morphologically or functionally different lateral organs in an age-dependent manner. In the model plant Arabidopsis thaliana, the production of trichomes (epidermal leaf hairs) on the abaxial (lower) side of leaves is a heteroblastic mark for the juvenile-to-adult transition. Here, we show that the heteroblastic development of abaxial trichomes is regulated by a spatiotemporally regulated complex comprising the leaf abaxial fate determinant (KAN1) and the developmental timer (miR172-targeted AP2-like proteins). We provide evidence that a short-distance chromatin loop brings the downstream enhancer element into close association with the promoter elements of GL1, which encodes a MYB transcription factor essential for trichome initiation. During juvenile phase, the KAN1-AP2 repressive complex binds to the downstream sequence of GL1 and represses its expression through chromatin looping. As plants age, the gradual reduction in AP2-like protein levels leads to decreased amount of the KAN1-AP2 complex, thereby licensing GL1 expression and the abaxial trichome initiation. Our results thus reveal a novel molecular mechanism by which a heteroblastic trait is governed by integrating age and leaf polarity cue in plants.

[Mechanism of astragaloside â £ alleviating PC12 cell injury by activating PI3K/AKT signaling pathway: based on network pharmacology and in vitro experiments].

In this study, the molecular mechanism of astragaloside Ⅳ(AS-Ⅳ) in the treatment of Parkinson's disease(PD) was explored based on network pharmacology, and the potential value of AS-Ⅳ in alleviating neuronal injury in PD by activating the PI3 K/AKT signaling pathway was verified through molecular docking and in vitro experiments. Such databases as SwissTargetPrediction, BTMAN-TAM, and GeneCards were used to predict the targets of AS-Ⅳ for the treatment of PD. The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) was employed to analyze protein-protein interaction(PPI) and construct a PPI network, and the Database for Annotation, Visualization and Integrated Discovery(DAVID) was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Based on the results of GO enrichment analysis and KEGG pathway analysis, the PI3 K/AKT signaling pathway was selected for further molecular docking and in vitro experiments in this study. The in vitro cell model of PD was established by MPP~+. The cell viability was measured by MTT assay and effect of AS-Ⅳ on the expression of the PI3 K/AKT signaling pathway-related genes and proteins by real-time polymerase chain reaction(RT-PCR) and Western blot. Network pharmacology revealed totally 122 targets of AS-Ⅳ for the treatment of PD, and GO enrichment analysis yielded 504 GO terms, most of which were biological processes and molecular functions. Totally 20 related signaling pathways were screened out by KEGG pathway analysis, including neuroactive ligand-receptor interaction, PI3 K/AKT signaling pathway, GABAergic synapse, and calcium signaling pathway. Molecular docking demonstrated high affinity of AS-Ⅳ to serine/threonine-protein kinases(AKT1, AKT2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3 CG), and phosphoinositide-3-kinase, catalytic, alpha polypeptide(PIK3 CA) on the PI3 K/AKT signaling pathway. In vitro experiments showed that AS-Ⅳ could effectively inhibit the decrease of the viability of PC12 induced by MPP~+ and up-regulate the mRNA expression levels of AKT1 and PI3 K as well as the phosphorylation levels of AKT and PI3 K. As an active component of Astragali Radix, AS-Ⅳ acts on PD through multiple targets and pathways. Furthermore, it inhibits neuronal apoptosis and protects neurons by activating the PI3 K/AKT signaling pathway, thereby providing reliable theoretical and experimental supports for the treatment of PD with AS-Ⅳ.

A Two-Step Model for de Novo Activation of WUSCHEL during Plant Shoot Regeneration.

Plant cells are totipotent and competent to regenerate from differentiated organs. It has been known for six decades that cytokinin-rich medium induces shoot regeneration from callus cells. However, the underlying molecular mechanism remains elusive. The homeodomain transcription factor WUSCHEL (WUS) is essential for de novo establishment of the shoot stem cell niche in Arabidopsis thaliana We found that WUS-positive (WUS+) cells mark the shoot progenitor region during regeneration. A cytokinin-rich environment initially promotes the removal of the repressive histone mark H3K27me3 at the WUS locus in a cell cycle-dependent manner. Subsequently, the B-type ARABIDOPSIS RESPONSE REGULATORs (ARRs) ARR1, ARR2, ARR10, and ARR12, which function as transcriptional activators in the cytokinin signaling pathway, spatially activate WUS expression through binding with microRNA165/6-targeted HD-ZIP III transcription factors. Thus, our results provide important insights into the molecular framework for cytokinin-directed shoot regeneration and reveal a two-step mechanism for de novo activation of WUS.

Cytokinin Signaling Activates WUSCHEL Expression during Axillary Meristem Initiation.

The homeodomain transcription factor WUSCHEL (WUS) defines the shoot stem cell niche, but the mechanisms underlying the establishment of WUS expression remain unclear. Here, we show that cytokinin signaling precedes WUS expression in leaf axils and activates WUS expression de novo in the leaf axil to promote axillary meristem initiation. Furthermore, type-B Arabidopsis response regulator proteins, which are transcriptional activators in the cytokinin signaling pathway, directly bind to the WUS promoter and activate its expression. Finally, we show that cytokinin activation of WUS in the leaf axil correlates with increased histone acetylation and methylation markers associated with transcriptional activation, supporting the fact that WUS expression requires a permissive epigenetic environment to restrict it to highly defined meristematic tissues. Taken together, these findings explain how cytokinin regulates axillary meristem initiation and establish a mechanistic framework for the postembryonic establishment of the shoot stem cell niche.

A nomogram to predict survival of patients with intermediate-stage hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

OBJECTIVES: To develop a prognostic nomogram based on the albumin-bilirubin (ALBI) grade for prediction of the long-term survival of patients with intermediate-stage hepatocellular carcinoma (HCC) after transarterial chemoembolization combined with microwave ablation (TACE-MWA). METHODS: We retrospectively studied 546 consecutive patients with intermediate-stage HCC according to the Barcelona Clinic Liver Cancer guidelines who underwent TACE-MWA between January 2000 and December 2016. Overall survival (OS) and progression-free survival (PFS) were analyzed. The predictive value of the ALBI grade was investigated. The prognostic nomogram was constructed using the independent predictors assessed by the multivariate Cox proportional hazards model. RESULTS: After a median follow-up of 35.0 months (range, 4.0-221.0 months), 380 patients had died. The median OS was 35.0 months (95% confidence interval (CI), 30.84-39.16 months), and the median PFS was 6.5 months (95% CI, 6.13-6.87 months). The ALBI grade was validated as an independent predictor of OS (p < 0.001). Multivariate analyses showed that Eastern Cooperative Oncology Group performance status score more than 0, presence of liver cirrhosis, a-fetoprotein level above 400 ng/mL, tumor size greater than 5 cm, tumor number more than 3, advanced ALBI grade, and treatment sessions of TACE or MWA fewer than 3 were independently associated with overall mortality. The prognostic nomogram incorporating these eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770 (95% CI, 0.746-0.795). CONCLUSIONS: The prognostic nomogram based on the ALBI grade resulted in reliable efficacy for prediction of individualized OS in patients with intermediate-stage HCC after TACE-MWA. KEY POINTS: • TACE-MWA was associated with a median overall survival of 35.0 months for patients with intermediate-stage HCC. • A prognostic nomogram was built to predict individualized survival of patients with intermediate-stage HCC after TACE-MWA. • The prognostic nomogram incorporating eight predictors achieved good calibration and discriminatory abilities with a concordance index of 0.770.

Optimization of perioperative approaches for advanced and late stages of gastric cancer: clinical proposal based on literature evidence, personal experience, and ongoing trials and research.

BACKGROUND: The high incidence of gastric cancer (GC) and paradoxical high prevalence of advanced stage GC, amounting to around 2/3 at time of diagnosis, have urged doctors and researchers around the world not only to ameliorate the detection rate of GC at early stages but also to optimize the clinical management of GC at advanced stages. CONTENT: We hereby recommend a more goal-oriented multimodality approach with objectives to increase survival rate and improve survival status. Based on precision and accurate clinical staging at diagnosis, we suggest that advanced stage GC (AGC) patients should be channeled into different treatment plans according to their disease status where they can be subjected to comprehensive measures involving chemo, radio, immunological, or target therapies depending on the pathophysiological behavior of their tumor. Patients assessed as potentially resectable cT4N + M0 can undergo neoadjuvant chemotherapy with intent of tumor downsizing and downgrading followed by surgery with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) to decrease the incidence of peritoneal dissemination due to surgical trauma and adjuvant chemotherapy and radiation in cases of bulky nodal metastasis. In cases with distal metastasis, conversion therapy is recommended with the possibility of surgery of curative intent in case of favorable response. The options of alternate treatment options such as trans-catheter arterial chemoembolization (TACE) for limited liver lesions or neoadjuvant intraperitoneal plus systemic chemotherapy (NIPS) for peritoneal carcinomatosis have to be negotiated. With surgery as the cornerstone for cancer treatment, there is acknowledgment of the significance of perioperative comprehensive approaches but there has not been some consensus guiding clinical application. Henceforth, in this review, based on past literature, current guidelines and ongoing clinical trials, we have shared a proposal of the current treatment modalities in practice for the advanced stages of gastric cancer. CONCLUSION: Even though surgery is the golden standard of radical cancer treatment, clinical reality shows that without proper perioperative management, patients undergoing radical resections manifest high rates of recurrence and metastasis. Hence, in this review, we have outlined a clinical agenda to optimize the management of advanced stage GC with objective to improve survival outcome and quality of life of patients.

Chemical Deprenylation of N6 -Isopentenyladenosine (i6 A) RNA.

N6 -isopentenyladenosine (i6 A) is an RNA modification found in cytokinins, which regulate plant growth/differentiation, and a subset of tRNAs, where it improves the efficiency and accuracy of translation. The installation and removal of this modification is mediated by prenyltransferases and cytokinin oxidases, and a chemical approach to selective deprenylation of i6 A has not been developed. We show that a selected group of oxoammonium cations function as artificial deprenylases to promote highly selective deprenylation of i6 A in nucleosides, oligonucleotides, and live cells. Importantly, other epigenetic modifications, amino acid residues, and natural products were not affected. Moreover, a significant phenotype difference in the Arabidopsis thaliana shoot and root development was observed with incubation of the cation. These results establish these small organic molecules as direct chemical regulators/artificial deprenylases of i6 A.

Predictive value of the albumin-bilirubin grade on long-term outcomes of CT-guided percutaneous microwave ablation in intrahepatic cholangiocarcinoma.

PURPOSE: To assess the efficacy of the albumin-bilirubin (ALBI) grade on assessing long-term outcomes of computed tomography (CT)-guided percutaneous microwave ablation (CT-PMWA) in the treatment of patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Between April 2011 and March 2018, 78 patients who underwent CT-PMWA were enrolled in this study. Overall survival (OS) and recurrence-free survival (RFS) were compared in the groups stratified by the ALBI grade and Child-Pugh score. Cox proportional hazard regression analyses were performed to determine independent predictors of OS and RFS. RESULTS: After a median follow-up of 22.7 months (range 1-86.7 months), 67 patients had died. The cumulative 1-, 3-, and 5-year OS rates were 89.5%, 52.2%, and 35.0%, respectively. Stratified by the ALBI grade, the cumulative 1-, 3-, and 5-year OS rates were 100%, 69.2%, and 25.6% for patients with the grade 1, respectively. For patients with the ALBI grade 2, the cumulative 1-, 3-, and 5-year OS rates were 41.0%, 10.3%, and 10.3%, respectively. Patients with a hepatic function of the ALBI grade 1 had significantly higher OS rates than patients with the ALBI grade 2 (p < .001). The multivariate analysis showed tumor size (Hazard Ratio[HR] 95% Confidence Interval[CI]:9.03[1.01-80.52], p = .049) and the ALBI grade (HR[95%CI]:9.56[1.58-58.00], p = .014) were associated with OS, and tumor size (HR: 2.03[0.69-8.04], p = .049) was associated with RFS. CONCLUSIONS: The preliminary data of this study showed the ALBI grade was effective to predict long-term outcomes of CT-PMWA in ICCs. Further study is necessary to validate our results by a large, multi-center patient cohort.

Comparison of albumin-bilirubin grade, platelet-albumin-bilirubin grade and Child-Turcotte-Pugh class for prediction of survival in patients with large hepatocellular carcinoma after transarterial chemoembolization combined with microwave ablation.

Purpose: To compare the predictive value of albumin-bilirubin (ALBI) grade, platelet-ALBI (PALBI) grade and Child-Turcotte-Pugh (CTP) class in patients with large hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) combined with microwave ablation (TACE-MWA). Methods: A total of 349 consecutive HCC patients (89.1% male; mean [± SD] age 53.4 ± 12.27 years) from three medical centers, who underwent TACE-MWA for up to 3 HCCs with maximum diameters of 5.1-8.0 cm between January 2000 and June 2018, were investigated. Overall survival (OS) and progression-free survival (PFS) were analyzed. The prognostic performances of ALBI grade, PALBI grade and CTP class were compared. Results: TACE procedures were performed using lobaplatin (20-50 mg), epirubicin (30-60 mg), lipiodol (5-25 mL) and gelatin sponge particles (350-560 µm). The end point of the TACE procedure was stasis of blood flow in the feeder artery. The median follow-up duration was 28.0 months, the median OS was 28.0 months (95% confidence interval [CI] 23.55-32.45 months), and the median PFS was 4.8 months (95% CI 4.26-5.34 months). Patients with a ablation margin size of 11-15 mm experienced better PFS than those with a margin size of 6-10 or 0-5 mm (median, 6.5 versus [vs] 4.0 vs 2.3 months; p < .001). PALBI grade demonstrated significantly greater area under the curve values than ALBI grade or CTP class in predicting 1-, 3- and 5-year OS. Conclusions: PALBI grade provided better predictive value than ALBI grade or CTP class in patients with large HCCs after TACE-MWA.

An intrinsic microRNA timer regulates progressive decline in shoot regenerative capacity in plants.

Plant cells are totipotent and competent to regenerate from differentiated organs. It has been shown that two phytohormones, auxin and cytokinin, play critical roles within this process. As in animals, the regenerative capacity declines with age in plants, but the molecular basis for this phenomenon remains elusive. Here, we demonstrate that an age-regulated microRNA, miR156, regulates shoot regenerative capacity. As a plant ages, the gradual increase in miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors leads to the progressive decline in shoot regenerative capacity. In old plants, SPL reduces shoot regenerative capacity by attenuating the cytokinin response through binding with the B-type ARABIDOPSIS RESPONSE REGULATORs, which encode the transcriptional activators in the cytokinin signaling pathway. Consistently, the increased amount of exogenous cytokinin complements the reduced shoot regenerative capacity in old plants. Therefore, the recruitment of age cues in response to cytokinin contributes to shoot regenerative competence.

Safety and effect on ablation size of hydrochloric acid-perfused radiofrequency ablation in animal livers.

PURPOSE: Our objective was to determine the safety and ablation size of hydrochloric acid-perfused radiofrequency ablation (HCl-RFA) in liver tissues, prospectively using in vivo rabbit and ex vivo porcine liver models. MATERIALS AND METHODS: The livers in 30 rabbits were treated in vivo with perfusions of normal saline (controls) and HCl concentrations of 5%, 10%, 15%, and 20%, during RFA at 103 °C and 30 W for 3 min. For each experimental setting, six ablations were created. Safety was assessed by comparing baseline weight and selected laboratory values with those at 2, 7, and 14 days' post-ablation, and by histopathological analysis. The livers in 25 pigs were treated ex vivo with the same five perfusions during RFA at 103 °C, at both 30 W and 60 W, for 30 min. Ablation diameters and volumes were measured by two examiners. RESULTS: Rabbit weights and selected laboratory values did not differ significantly from baseline to 7 and 14 days' post-ablation, liver tissues outside the ablation zones were normal histologically, and adjacent organs showed no macroscopic damage. The mean ablation volumes in the porcine livers treated with HCl-RFA were all larger than those treated with normal saline perfusion during RFA (NS-RFA), at both 30 W and 60 W (p < 0.001). The largest ablation volume and transverse diameter were observed in the porcine livers during 10% HCl-RFA at 60 W, measuring 179.22 (SD = 24.79) cm3 and 6.84 (SD = 0.36) cm, respectively. CONCLUSIONS: Based on our experiments, HCl-RFA in the liver appears to be as safe as NS-RFA while also resulting in larger ablation zones.

Increasing radiofrequency ablation volumes with the use of internally cooled electrodes and injected hydrochloric acid in ex vivo bovine livers.

PURPOSE: We used an impedance-controlled generator with an internally cooled electrode to perform radiofrequency ablation (RFA) in ex vivo bovine livers, with a single injection of either 38.5% sodium chloride (NaCl) or 10% hydrochloric acid (HCl), to determine the relative effects of these two solutions on tissue impedance, temperature and ablation volume. MATERIALS AND METHODS: We performed 10 ablations each with injections of NaCl (NaCl-RFA), HCl (HCl-RFA) or nothing (RFA-alone), with a power setting of 200 W for 15 minutes. We recorded tissue impedance before and after injection. We logged temperatures obtained from thermocouple probes positioned 5, 10, 15 and 20 mm from the internally cooled RF electrode. After ablation, we measured ablation zone longitudinal and transverse diameters, and we calculated a spherical ratio (SR) for each ablation. RESULTS: Mean post-injection impedance of 30.3 (standard deviation [SD] 2.5) ohms for HCl was significantly lower than that of 55.4 (SD 3.5) ohms for NaCl (p < .001). Mean maximum temperatures recorded at each respective distance from the RFA electrode were all highest for HCl-RFA and lowest for RFA-alone (p < .001). Mean longitudinal and transverse diameters after HCl-RFA (5.50 [SD 0.25] cm and 5.28 [SD 0.22] cm, respectively) were significantly larger than those after NaCl-RFA (4.24 [SD 0.35] cm and 3.55 [SD 0.43] cm, respectively) and after RFA-alone (3.60 [SD 0.10] cm and 2.70 [SD 0.13] cm, respectively) (p < .001). Mean SR after HCl-RFA (0.93, SD 0.02) was significantly higher than mean SR after NaCl-RFA (0.76, SD 0.06) and RFA-alone (0.72, SD 0.04) (p < .001). CONCLUSION: Monopolar, impedance-controlled RFA, with an internally cooled electrode and a single 10% HCl injection may allow larger tumors to be treated, potentially resulting in improved patient outcomes.

Microbial-Phosphorus-Enabled Synthesis of Phosphide Nanocomposites for Efficient Electrocatalysts.

Transition-metal phosphides have recently been identified as low-cost and efficient electrocatalysts that are highly active for the hydrogen evolution reaction. Unfortunately, to achieve a controlled phosphidation of nonprecious metals toward a desired nanostructure of metal phosphides, the synthetic processes usually turned complicated, high-cost, and even dangerous due to the reaction chemistry related to different phosphorus sources. It becomes even more challenging when considering the integration of those active metal phosphides with the structural engineering of their conductive matrix toward a favorable architecture for optimized catalytic performance. Herein, we identified that the biomass itself could act as an effective synthetic platform for the construction of supported metal phosphides by recovering its inner phosphorus upon reacting with transition-metals ions, forming well-dispersed, highly active nanoparticles of metal phosphides incorporated in the nanoporous carbon matrix, which promised high catalytic activity in the hydrogen evolution reaction. Our synthetic protocol not only provides a simple and effective strategy for the construction of a large variety of highly active nanoparticles of metal phosphides but also envisions new perspectives on an integrated utilization of the essential ingredients, particularly phosphorus, together with the innate architecture of the existing biomass for the creation of functional nanomaterials toward sustainable energy development.

Primary tumor location as a predictor of the benefit of palliative resection for colorectal cancer with unresectable metastasis.

BACKGROUND: It is still under debate that whether stage IV colorectal cancer patients with unresectable metastasis can benefit from primary tumor resection, especially for asymptomatic colorectal cancer patients. Retrospective studies have shown controversial results concerning the benefit from surgery. This retrospective study aims to evaluate whether the site of primary tumor is a predictor of palliative resection in asymptomatic stage IV colorectal cancer patients. METHODS: One hundred ninety-four patients with unresectable metastatic colorectal cancer were selected from Sun Yat-sen University Cancer Center Database in the period between January 2007 and December 2013. All information was carefully reviewed and collected, including the treatment, age, sex, carcinoembryonic antigen, site of tumor, histology, cancer antigen 199, number of liver metastases, and largest diameter of liver metastasis. The univariate and multivariate analyses were used to detect the relationship between primary tumor resection and overall survival of unresectable stage IV colorectal cancer patients. RESULTS: One hundred twenty-five received palliative resection, and 69 received only chemotherapy. Multivariate analysis indicated that primary tumor site was one of the independent factors (RR 0.569, P = 0.007) that influenced overall survival. For left-side colon cancer patients, primary tumor resection prolonged the median overall survival time for 8 months (palliative resection vs. no palliative resection: 22 vs. 14 months, P = 0.009); however, for right-side colon cancer patients, palliative resection showed no benefit (12 vs. 10 months, P = 0.910). CONCLUSIONS: This study showed that left-side colon cancer patients might benefit from the primary tumor resection in terms of overall survival. This result should be further explored in a prospective study.

Gibberellin regulates the Arabidopsis floral transition through miR156-targeted SQUAMOSA promoter binding-like transcription factors.

Gibberellin (GA), a diterpene hormone, plays diverse roles in plant growth and development, including seed germination, stem elongation, and flowering time. Although it is known that GA accelerates flowering through degradation of transcription repressors, DELLAs, the underlying mechanism is poorly understood. We show here that DELLA directly binds to microRNA156 (miR156)-targeted SQUAMOSA PROMOTER BINDING-LIKE (SPL) transcription factors, which promote flowering by activating miR172 and MADS box genes. The interaction between DELLA and SPL interferes with SPL transcriptional activity and consequently delays floral transition through inactivating miR172 in leaves and MADS box genes at shoot apex under long-day conditions or through repressing MADS box genes at the shoot apex under short-day conditions. Our results elucidate the molecular mechanism by which GA controls flowering and provide the missing link between DELLA and MADS box genes.