Regulation of WOX11 Expression Represents the Difference Between Direct and Indirect Shoot Regeneration.

Somatic cells of higher plants possess the remarkable ability to regenerate new individuals via reestablishing apical meristems. Reconstitution of shoot meristem is the vital process and is required for application of plant biotechnology. Under in vitro culture condition, shoot meristem can be formed directly or indirectly, depending on the absence or presence of callus as the intermediate status. However, the difference of regulatory mechanisms between the two regeneration types remains unknown. In this study, we established a bi-directional system in which shoots regenerated directly from lateral root primordia (LRP) and indirectly from hypocotyl-derived callus simultaneously. The results based on this system revealed that regulation of WOX11 expression represents the difference between the two regeneration types in two aspects. Firstly, number of founder cells expressing WOX11 is tightly associated with regeneration types. Relatively more founder cells gave rise to callus and produce larger meristem, whereas less founder cells produce LRP that regenerate smaller meristem. Secondly, non-CG DNA methylation specifically regulated WOX11 transcription in LRP and promoted direct shoot regeneration, but had no influence on indirect regeneration. The results provide new insights for understanding the regulatory mechanisms of cell fate transition during de novo organogenesis.

[Start-up of CANON Process and Short-cut Nitrification in a Pilot-scale MBBR Reactor].

Using a 150 L moving bed biofilm reactor (MBBR), with the temperature controlled at 28℃ and high NH4+-N concentration (average concentration 350 mg·L-1), inorganic wastewater was used as an influent to start the completely autotrophic nitrogen removal over nitrite (CANON) process. Meanwhile, the flocculent sludge was taken into a 5 L sequencing batch reactor, and the influent NH4+-N concentration was maintained at 90-200 mg·L-1 for the recovery of short-cut nitrification. The results showed that in the MBBR reactor, when the average hydraulic retention time (HRT) was 12 h, short-cut nitrification and total nitrogen (TN) removal rate were mutually constrained, the average TN removal rate was 38.2%, and the average δNO3--N/TN value was 0.274; when the HRT dropped to 6 h, the δNO3--N/TN value decreased from 0.347 to 0.146. The sequencing batch reactor (SBR) maintained aeration and anoxic time for 30 min and 20 min, respectively, by intermittent aeration, while the dissolved oxygen concentration during the aerobic process was 0.5 mg·L-1 to 0.6 mg·L-1, the free nitrous acid concentration was higher than 0.18 mg·L-1 at the end of each cycle, NAR increased from 0 to 99.2% after 12 days, NUR decreased to 0 from an initial 24.8 mg·(g·h)-1, and the TN removal rate decreased from 13% to 3%; the system successfully converted to short-range nitrification. High-throughput sequencing results showed that the abundance of Candidatus Kuenenia in the flocculent sludge and biofilm in the MBBR reactor were 7.91% and 17.38% respectively, Nitrosomonas accounted for 27.43% and 2.55%, respectively, while Nitrospira accounted for 0.30% and 0.28%, respectively. After the recovery of short-cut nitrification in the SBR, the abundance of ammonia-oxidizing bacteria and anaerobic ammonia oxidation decreased to 1.18% and 0.01%, respectively, and the abundance of Nitrospira increased to 1.39%.

Perfusion Characteristics of Hepatocellular Carcinoma at Contrast-enhanced Ultrasound: Influence of the Cellular differentiation, the Tumor Size and the Underlying Hepatic Condition.

This study aimed to analyze the influence of the cellular differentiation, the tumor size and the underlying hepatic condition on the enhancement pattern of hepatocellular carcinoma (HCC) on contrast-enhanced ultrasound (CEUS). 276 patients with single lesion ≤ 5 cm who underwent CEUS exam and were pathologically confirmed as HCC were retrospectively enrolled. Enhancement patterns, washout patterns, wash-in time and washout time were observed and recorded. During the arterial phase, more poorly differentiated HCCs (42.5%) and lesions > 3 cm (35.2%) performed inhomogeneous enhancement (p < 0.05). More well differentiated HCCs (63.4%) performed late washout or no washout while compared with moderately (37.8%) or poorly (24.1%) differentiated HCCs (p < 0.05). Poorly differentiated HCCs showed the shortest washout time (83.0 ± 39.8 s), moderately differentiated HCCs showed the moderate washout time (100.4 ± 52.1 s), and well differentiated HCCs showed the longest washout time (132.3 ± 54.2 s) (p < 0.05). Lesions > 3 cm (97.2 ± 51.3 s) washed out more rapidly than lesions ≤ 3 cm (113.9 ± 53.5 s) (p < 0.05). The dynamic enhancement procedure of HCC was influenced by the cellular differentiation and the tumor size. While, hepatic background showed no influence on the dynamic enhancement of HCC.

Primary hepatic neuroendocrine tumors: clinical characteristics and imaging features on contrast-enhanced ultrasound and computed tomography.

OBJECTIVE: Primary hepatic neuroendocrine tumor (PHNET) is an extremely rare liver neoplasm, and its clinical characteristics and imaging features are not well understood. The aim of this study was to analyze the clinical profiles and imaging features of PHNETs on contrast-enhanced ultrasound (CEUS) and computed tomography (CT) METHODS: Patients with PHNET between January 2008 and December 2015 were retrospectively identified, and their demographics, laboratory data, and imaging characteristics on CEUS and CT analyzed. RESULTS: Ten consecutive patients with PHNETs were included (including one G1, seven G2, and two G3 of tumor grades).The median age of patient was 45 years (range: 27-72 years), and 60.0% of patients were male. The most common symptom was abdominal pain (60.0%), and cirrhosis was found in 40.0% of patients. Tumors were confined within the liver in 60.0% of patients, while the remaining patients had extra-hepatic metastasis. The tumors revealed hyperechoic in 60% of patients and mixed echoic in 30% of patients on conventional US, displaying intense arterial enhancement followed by washout in the portal and/or the late phases in 80.0% of patients on CEUS and 60% at CT. CONCLUSIONS: Although PHNET is a very rare liver tumor, it should be considered as a possible differential diagnosis in the management of hepatic tumors. Most PHNETs were hyperechoic or mixed echoic on conventional US, showing similar enhancement patterns to that of hepatocellular carcinoma on CEUS.

Combined hepatocellular carcinoma and cholangiocarcinoma (biphenotypic) tumors: clinical characteristics, imaging features of contrast-enhanced ultrasound and computed tomography.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is an uncommon primary liver malignancy and little known about the clinical and imaging characteristics of cHCC-CC. We aim to define the demographics, imaging features of cHCC-CC on contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CT) in this study. METHODS: From January 2005 to December 2014, 45 patients with pathologically proven cHCC-CC who underwent preoperative CEUS and 43 patients who had additional CT scan in our institution were included. A retrospective review of the imaging studies and clinical data in these patients was conducted. RESULTS: In our series, cHCC-CC accounted for 1.6 % of all primary liver malignancy. Mean age of patient with cHCC-CC was 52.8 year (range: 28-74 year) and 88.9 % (40/45) of patients were male. Thirty of forty five patients (66.7 %) had cirrhosis and 20 % (9/45) of patients had chronic hepatitis B without cirrhosis. Alpha--fetoprotein (AFP) was elevated in 62.2 % (28/45) of patients and carbohydrate antigen 19-9 (CA19-9) elevated in 22.2 % (10/45) of patients). Both AFP and CA19-9 were simultaneously elevated in 15.6 % (7/45) of patients. Enhancement pattern resembling cholangiocarcinoma (CC) was noted in 53.3 % (24/45) of patients (on CEUS and in 30.2 % (13/43) of patients at CT. Enhancement pattern resembling hepatocellular carcinoma (HCC) was observed in 42.2 % (19/45) of patients on CEUS and in 58.1 % (25/43) of patients at CT. The percentage of tumors showing CC enhancement pattern (27.9 %, 12/43) was comparable with that of tumors showing HCC enhancement pattern (44.2 %, 19/43) on both CEUS and CT (p = 0.116). Simultaneous elevation of tumor markers (AFP and CA19-9) or tumor marker elevation (AFP or CA19-9) in discordance with enhancement pattern on CEUS was demonstrated in 51.1 % (23/45) of patients and on CT in 53.5 % (23/43) of patients, which was significantly more than simultaneous elevation of tumor markers (AFP and CA19-9) alone (p = 0.000). CONCLUSIONS: The clinical characteristics of cHCC-CC are similar to those of HCC. The cHCC-CC tumors display enhancement patterns resembling CC or HCC in comparable proportion on both CEUS and CT. Combination of simultaneous elevation of tumor makers (AFP and CA19-9) and tumor mark elevation (AFP or CA19-9) in discordance with presumptive imaging findings on CEUS or CT may lead significantly more patients to be suspicious of the diagnosis of cHCC-CC.

Comparison of CT and contrast-enhanced ultrasound findings in hepatic angiomyolipoma with pathological correlations.

OBJECTIVE: To compare imaging findings of CT and contrast-enhanced US (CEUS) in hepatic angiomyolipoma (HAML) and investigate their pathological correlations. METHODS: Imaging findings and preoperative diagnosis of CT and CEUS were retrospectively compared head to head in 46 patients with 54 histologically proven HAMLs. Correlations between imaging features and preoperative diagnosis with pathological types of HAMLs were analyzed. RESULTS: Fat was detected in 100% of lipomatous type, 84.6% of mixed type, and 7.1% of myomatous type (p = 0.000) of HAML at unenhanced CT. Well-defined hyper-echogenicity was displayed in 100% of lipomatous type, 88.5% of mixed type, 50% of myomatous type, and 66.7% of angiomatous type of HAMLs at unenhanced US. More arterial hyper-enhancement was noted on CEUS (100%) than on CT (73.1%) in mixed type (p = 0.015) and in lipomatous type (90.9% vs. 9.1%, p = 0.000) of HAMLs. Washout was present in more HAMLs on CT than on CEUS (42.6% vs. 18.5%, p = 0.007). Correct preoperative diagnosis was suggested in more HAMLs of myomatous type on CEUS than on CT (42.9% vs. 0%, p = 0.016) but showed no difference in other types of HAMLs. CONCLUSION: There are considerable discrepancies between CT and CEUS findings of HAMLs, and the imaging appearance and preoperative diagnosis of HAMLs on CT and CEUS are significantly affected by pathological types of HAMLs.

Diagnosis of Hepatic Angiomyolipoma by Combination of Baseline and Contrast-Enhanced Ultrasound--A Prospective Study in Non-Cirrhotic Patients.

OBJECTIVES: Hepatic angiomyolipoma (HAML) is a rare, benign mesenchymal tumor of the liver and its diagnosis has been considered challenging. The aim of this study was to investigate prospectively the diagnostic efficacy of the incorporation of both baseline ultrasound (US) and contrast-enhanced ultrasound (CEUS) features of HAML in patients without cirrhosis. MATERIALS AND METHODS: Consecutive 1748 non-cirrhotic patients with focal liver lesions (FLLs) were prospectively enrolled. Baseline US and CEUS were performed before resection or biopsy. Ultrasound imaging diagnosis of FLLs was compared with the pathological results. RESULTS: Final diagnoses were established in 41 patients with HAML (2.3%) with normal alpha fetal protein (AFP) level and in 1707 patients with FLL other than HAML. Diagnostic criteria for HAML was based on the combination of baseline US and CEUS appearance of the nodule: (1) Well-defined, marked hyper-echoic nodule without surrounding hypo-echoic halo on baseline US; (2) hyper-enhancement in the arterial phase (exclude initial peripheral nodular enhancement and spoke-wheel arteries) and remains hyper-enhancement or iso-enhancement in the late phase. The diagnostic criteria were fulfilled in 31 HAMLs, 1 hepatocellular adenoma and 1 hemangioma. Ten HAMLs were misdiagnosed as other liver tumors because they did not meet the diagnostic criteria mentioned above and consequently yielded a sensitivity, specificity, positive predictive values, negative predictive values and Youden index of 75.61%, 99.88%, 93.94%, 99.42%, and 0.75 respectively. CONCLUSION: The combination of baseline US and CEUS may lead to the correct diagnosis noninvasively in the majority of HAMLs in non-cirrhotic patients with normal AFP level.

Feature selection for the identification of antitumor compounds in the alcohol total extracts of Curcuma longa.

Antitumor activity has been reported for turmeric, the dried rhizome of Curcuma longa. This study proposes a new feature selection method for the identification of the antitumor compounds in turmeric total extracts. The chemical composition of turmeric total extracts was analyzed by gas chromatography-mass spectrometry (21 ingredients) and high-performance liquid chromatography-mass spectrometry (22 ingredients), and their cytotoxicity was detected through an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay against HeLa cells. A support vector machine for regression and a generalized regression neural network were used to research the composition-activity relationship and were later combined with the mean impact value to identify the antitumor compounds. The results showed that six volatile constituents (three terpenes and three ketones) and seven nonvolatile constituents (five curcuminoids and two unknown ingredients) with high absolute mean impact values exhibited a significant correlation with the cytotoxicity against HeLa cells. With the exception of the two unknown ingredients, the identified 11 constituents have been reported to exhibit cytotoxicity. This finding indicates that the feature selection method may be a supplementary tool for the identification of active compounds from herbs.

Detailed analysis of temporal features on contrast enhanced ultrasound may help differentiate intrahepatic cholangiocarcinoma from hepatocellular carcinoma in cirrhosis.

AIM: To verify if detailed analysis of temporal enhancement patterns on contrast enhanced ultrasound (CEUS) may help differentiate intrahepatic cholangiocarcinoma (ICC) from hepatocellular carcinoma (HCC) in cirrhosis. METHODS: Thirty three ICC and fifty HCC in cirrhosis were enrolled in this study. The contrast kinetics of ICC and HCC was analyzed and compared. RESULTS: Statistical analysis did not reveal significant difference between ICC and HCC in the time of contrast first appearance and arterial peak maximum time. ICC displayed much earlier washout than that of HCC (47.93±26.45 seconds vs 90.86±31.26 seconds) in the portal phase, and most ICC (87.9%) showed washout before 60 seconds than HCC (16.0%). Much more ICC (78.8%) revealed marked washout than HCC (12.0%) while most HCC (88.0%) showed mild washout or no washout in late part of the portal phase (90-120 seconds). Twenty six out of thirty three ICC (78.8%) demonstrated both early washout(<60 seconds) and marked washout in late part of the portal phase, whereas, only six of fifty HCC (12.0%)showed these temporal enhancement features (p = 0.000).When both early washout and marked washout in the portal phase are taken as diagnostic criterion for ICC, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 78.8%,88.0%,81.3%,86.3%,and 84.3% respectively by CEUS. CONCLUSIONS: Analysis of detailed temporal enhancement features on CEUS is helpful differentiate ICC from HCC in cirrhosis.If a nodule in cirrhotic liver displays hyper-enhancement in the arterial phase followed by early and marked washout in the portal phase, the nodule is highly suspicious of ICC rather than HCC.

A novel approach to active compounds identification based on support vector regression model and mean impact value.

Traditionally, active compounds were discovered from natural product extracts by bioassay-guided fractionation, which was with high cost and low efficiency. A well-trained support vector regression model based on mean impact value was used to identify lead active compounds on inhibiting the proliferation of the HeLa cells in curcuminoids from Curcuma longa L. Eight constituents possessing the high absolute mean impact value were identified to have significant cytotoxicity, and the cytotoxic effect of these constituents was partly confirmed by subsequent MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays and previous reports. In the dosage range of 0.2-211.2, 0.1-140.2, 0.2-149.9 µm, 50% inhibiting concentrations (IC50 ) of curcumin, demethoxycurcumin, and bisdemethoxycurcumin were 26.99 ± 1.11, 19.90 ± 1.22, and 35.51 ± 7.29 µm, respectively. It was demonstrated that our method could successfully identify lead active compounds in curcuminoids from Curcuma longa L. prior to bioassay-guided separation. The use of a support vector regression model combined with mean impact value analysis could provide an efficient and economical approach for drug discovery from natural products.

Epidermal growth factor receptor mutations and their correlation with epidermal growth factor receptor-tyrosine kinase inhibitor therapy and association with the characteristics of patients with non-small-cell lung cancer: A meta-analysis.

BACKGROUND: Many studies have demonstrated that epidermal growth factor receptor (EGFR) mutation is associated with the response to therapy with single agent EGFR-tyrosine kinase inhibitors (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients, but the extent of the effect is varied. We carried out a meta-analysis to assess the association between EGFR mutation and the efficacy of EGFR-TKI therapy and the independent predictor of EGFR mutation in order to identify who would be likely to benefit from this kind of therapy. METHODS: All literature relating to EGFR mutation and EGFR-TKI therapy was researched and carefully selected. Related variables were abstracted and the pooled odds ratio calculated after a heterogeneity test with the software, State 10. Publication bias was evaluated at the same time. RESULTS: Seventeen studies were included according to the selection criteria. We found a statistically significant higher probability of response in patients with an EGFR mutation versus wild-type (19.33, 95% CI, 13.61-27.46, P < 0.0001). Furthermore, the pooled odds ration of susceptibility to EGFR mutation among female patients compared with male patients was 3.01 (95% confidence interval (CI), 2.34-3.88 P < 0.0001), adenocarcinoma patients compared with non-adenocarcinoma patients was 5.40 (95% CI, 2.55-11.40 P < 0.0001), and non-smoker patients compared smoker patients was 19.33 (95% CI:,13.61-27.46 P < 0.0001). The publication bias analysis had no statistically significant results. CONCLUSION: Female, adenocarcinoma and non-smoker are independent predictors for the EGFR mutation. Efficacy of EGFR-TKI therapy favors patients with an EGFR mutation. Without the gene mutational analysis, patients selected for EGFR-TKI therapy should be female non-smokers with adenocarcinoma.

Inhibition effects of high mechanical index ultrasound contrast on hepatic metastasis of cancer in a rat model.

RATIONAL AND OBJECTIVES: The liver is the most common organ for tumor metastasis. The development of new methods to depress hepatic metastasis is of great importance in improving survival. The aim of this study was to observe the effects of high-mechanical index ultrasound contrast on hepatic metastasis of colorectal cancer. MATERIALS AND METHODS: Hepatic metastasis models were established by injecting human colon carcinoma LoVo cells into the spleens of Sprague-Dawley rats. The rats were divided into a control group, a microbubble plus ultrasound group, a simple ultrasound group, and a simple microbubble group. The ultrasound contrast agent SonoVue (1 mL/kg) was injected via the tail vein, and high-mechanical index ultrasound contrast (frequency, 1.5 MHz; mechanical index, 1.7) was performed on the spleen intermittently for 2 minutes. The animals were sacrificed after 10 days, and the sizes and number of hepatic metastases were measured and compared. Histologic pathology and splenic ultrastructure were observed. RESULTS: The number and sizes of hepatic metastases patently decreased in rats in the microbubble plus ultrasound group (P < .01). There were no obvious differences among the control group, simple ultrasound group, and simple microbubble group in hepatic metastases (P > .05). Histologic pathology showed that the number of tumor cells in the spleens decreased considerably, and massive necroses, hemorrhages, and thrombi were observed in the tumor and spleen tissues of rats in the microbubble plus ultrasound group. Transmission electron microscopy showed that the mitochondria of tumor cells and endothelial cells were clearly swelled, and there were gaps among endothelial cells and platelets aggregated in capillary vessels. CONCLUSION: This research shows that intermittent high-mechanical index ultrasound contrast may inhibit the hepatic metastasis of cancer in a rat model.

Unusual sonographic appearance of a huge angiomyolipoma of the liver.

Hepatic angiomyolipoma is a rare, benign, hepatic mesenchymal neoplasm. We report a case of an extremely large hepatic angiomyolipoma in a 58-year-old woman with unusual sonographic features. The tumor was well demarcated from the surrounding liver and showed a heterogeneous cystic appearance with a thick echogenic rim. Color Doppler showed blood flow in the echogenic rim and around the lesion. Contrast sonography demonstrated strong enhancement in the solid rim from early arterial phase to the late phase and no enhancement in the central cystic part of the lesion. Spiral CT showed a well-defined huge heterogeneous cystic mass with fatty density. At surgery the tumor was soft and encapsulated with a thin, smooth membrane. The cut surface of the tumor revealed a cystic appearance with necrotic tissue. The diagnosis of hepatic angiomyolipoma was confirmed by immunohistochemistry.

Methylazacalix[4]pyridine: en route to Zn2+-specific fluoresence sensors.

[structure: see text] Owing to the electronic nature of the bridging nitrogen atoms which can adopt different hybridizations and form various conjugations with the adjacent pyridine(s), methylazacalix[4]pyridine underwent conformation and cavity preorganization to highly selectively bind the Zn(2+) ion. Rigidification and coplanarity of the macrocyclic ring led to a great enhancement of fluorescence of the intrinsic fluorescent host molecule.

Methylazacalixpyridines: remarkable bridging nitrogen-tuned conformations and cavities with unique recognition properties.

Methylazacalix[n]pyridines (n = 4, 8) and methylazacalix[m]arene[n]pyridines (m = n = 2, 4) have been synthesized by a convenient fragment coupling approach starting from 2,6-dibromopyridine, 2,6-diaminopyridine, and benzene-1,3-diamine. Thanks to the intrinsic electronic nature of nitrogen, which can adopt mainly sp(2) hybridization, allowing it variously to conjugate, partially conjugate, or not conjugate with the adjacent one or two pyridine rings, the resulting nitrogen-bridged calixpyridine derivatives act as a unique class of macrocyclic host molecules with intriguing conformational structures offering fine-tunable cavities and versatile recognition properties. Whilst in solution it is fluxional, in the solid state methylazacalix[4]pyridine adopts a 1,3-alternate conformation with a C(2v) symmetry in which every two bridging nitrogen atoms conjugate with one pyridine ring. After protonation, the methylazacalix[4]pyridinium species has a different conjugation system of its four bridging nitrogen atoms, yielding the similar twisted 1,3-alternate conformations with an approximate S(4) symmetry. The cavity of each protonated methylazacalix[4]pyridine, however, varies finely to accommodate guest species of different size and geometry, such as planar DMF or HO(2)CCO(2) (-) ion, a twisted HO(2)CCO(2) (-) ion, and a tetrahedral ClO(4) (-) ion. As giant macrocyclic hosts, both methylazacalix[8]pyridine and methylazacalix[4]arene[4]pyridine interact efficiently with fullerenes C(60) and C(70) through van der Waals forces. Their ease of preparation, versatile conformational structures, and recognition properties make these multinitrogen-containing calixarenes or cyclophanes unique and powerful macrocyclic hosts in supramolecular chemistry.