Development of ensemble learning models for prognosis of hepatocellular carcinoma patients underwent postoperative adjuvant transarterial chemoembolization.

Background: Postoperative adjuvant transarterial chemoembolization (PA-TACE) has been increasing widely used to improve the prognosis of hepatocellular carcinoma (HCC) patients. However, clinical outcomes vary from patient to patient, which calls for individualized prognostic prediction and early management. Methods: A total of 274 HCC patients who underwent PA-TACE were enrolled in this study. The prediction performance of five machine learning models was compared and the prognostic variables of postoperative outcomes were identified. Results: Compared with other machine learning models, the risk prediction model based on ensemble learning strategies, including Boosting, Bagging, and Stacking algorithms, presented better prediction performance for overall mortality and HCC recurrence. Moreover, the results showed that the Stacking algorithm had relatively low time consumption, good discriminative ability, and the best prediction performance. In addition, according to time-dependent ROC analysis, the ensemble learning strategies were found to perform well in predicting both OS and RFS for the patients. Our study also found that BCLC Stage, hsCRP/ALB and frequency of PA-TACE were relatively important variables in both overall mortality and recurrence, while MVI contributed more to the recurrence of the patients. Conclusion: Among the five machine learning models, the ensemble learning strategies, especially the Stacking algorithm, could better predict the prognosis of HCC patients following PA-TACE. Machine learning models could also help clinicians identify the important prognostic factors that are clinically useful in individualized patient monitoring and management.

Whole-Exome Sequencing Reveals Novel NDP Variants in X-Linked Familial Exudative Vitreoretinopathy.

PURPOSE: To investigate causative variants in three Chinese families affected with familial exudative vitreoretinopathy (FEVR). METHODS: Three unrelated Chinese families were recruited in this study. The three probands and their family members experienced a comprehensive age-appropriate eye examination and genetic analysis. Luciferase assay was performed to evaluate impacts of variants on Norrin/ß-catenin signaling activity. RESULTS: Here we report two novel NDP variants associated with FEVR in three families, including c.17T>C (p.Leu6Pro) in family 1 and c.58G>A (p.Gly20Arg) in family 2 and 3. These two variants were co-segregated with the disease phenotypes within each family. In addition, both variants resulted in compromised Norrin/ß-catenin signaling activity. CONCLUSION: Our study identified two FEVR-associated pathogenic variants in NDP, which expanded the variant spectrum and provided information for the genetic diagnosis of FEVR.

Phosphorylation of ATG18a by BAK1 suppresses autophagy and attenuates plant resistance against necrotrophic pathogens.

Autophagy is critical for plant defense against necrotrophic pathogens, which causes serious yield loss on crops. However, the post-translational regulatory mechanisms of autophagy pathway in plant resistance against necrotrophs remain poorly understood. In this study, we report that phosphorylation modification on ATG18a, a key regulator of autophagosome formation in Arabidopsis thaliana, constitutes a post-translation regulation of autophagy, which attenuates plant resistance against necrotrophic pathogens. We found that phosphorylation of ATG18a suppresses autophagosome formation and its subsequent delivery into the vacuole, which results in reduced autophagy activity and compromised plant resistance against Botrytis cinerea. In contrast, overexpression of ATG18a dephosphorylation-mimic form increases the accumulation of autophagosomes and complements the plant resistance of atg18a mutant against B. cinerea. Moreover, BAK1, a key regulator in plant resistance, was identified to physically interact with and phosphorylate ATG18a. Mutation of BAK1 blocks ATG18a phosphorylation at four of the five detected phosphorylation sites after B. cinerea infection and strongly activates autophagy, leading to enhanced resistance against B. cinerea. Collectively, the identification of functional phosphorylation sites on ATG18a and the corresponding kinase BAK1 unveiled how plant regulates autophagy during resistance against necrotrophic pathogens.Abbreviations:35s: the cauliflower mosaic virus 35s promoter; A. thaliana: Arabidopsis thaliana; A. brassicicola: Alternaria brassicicola; ABA: abscisic acid; ATG: autophagy-related; ATG18a: autophagy-related protein 18a in A. thaliana; ATG8a: autophagy-related protein 8a in A. thaliana; ATG8-PE: ATG8 conjugated with PE; B. cinerea: Botrytis cinerea; BAK1: Brassinosteroid insensitive 1-associated receptor kinase1 in A. thaliana; BiFC: biomolecular fluorescence complementation; BIK1: Botrytis-insensitive kinase 1 in A. thaliana; BKK1: BAK1-like 1 in A. thaliana; BR: brassinosteroid; Co-IP: coimmunoprecipitation; dai: days after inoculation; DAMPs: damage-associated molecular patterns; E. coli: Escherochia coli; ER: endoplasmic reticulum; ETI: effector-triggered immunity; GFP: green fluorescent protein; HA: hemagglutinin; IP: immunoprecipitation; LC-MS/MS: liquid chromatography-tandem mass spectrometry; LCI: luciferase complementation imaging; MPK3: mitogen-activated protein kinase 3 in A. thaliana; MPK4: mitogen-activated protein kinase 4 in A. thaliana; MPK6: mitogen-activated protein kinase 6 in A. thaliana; N. benthamiana: Nicotiana benthamiana; NES: nuclear export sequence; PAMP: pathogen-associated molecular pattern; PCR: polymerase chain reaction; PE: phosphatidylethanolamine; PRR: pattern recognition receptor; PtdIns(3,5)P2: phosphatidylinositol (3,5)-biphosphate; PtdIns3P: phosphatidylinositol 3-biphosphate; PTI: PAMP-triggered immunity; qRT-PCR: quantitative reverse transcription PCR; SnRK2.6: SNF1-related protein kinase 2.6 in A. thaliana; TORC1: the rapamycin-sensitive Tor complex1; TRAF: tumor necrosis factor receptor-associated factor; WT: wild type plant; Yc: C-terminal fragment of YFP; YFP: yellow fluorescent protein; Yn: N-terminal fragment of YFP.

Characterization of the complete chloroplast genome of Chlorophytum comosum (Liliaceae).

Chlorophytum comosum is a perennial ornamental plant in the family Liliaceae, it is also a valuable medicinal plant. To enrich the genetic resources of C. comosum, its chloroplast genome was determined by Illumina sequencing data. The chloroplast genome is a typical quadripartite structure with a size of 153,983 bp, of which the LSC region is 83,471 bp, the SSC region is 18,010 bp, and the pair of IR regions is 26,251 bp. The overall GC content is 37%. It contains 131 genes, including 85 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Phylogenetic analyses showed that C. comosum is closely related to Chlorophytum rhizopendulum. However, it can be distinguished from other plants. This study enriches the sequence resources of C. comosum and provides important data for the development of molecular identification markers.

MicroRNA-621 inhibits the growth of gastric cancer cells by targeting SYF2.

Increasing evidence indicates that aberrantly expressed microRNAs play a role in tumorigenesis and progression of gastric cancer. Recently, a novel cancer-related microRNA, miR-621, was found to be involved in cancer pathogenesis. However, the precise molecular mechanisms underlying the oncogenic activity of miR-621 remain unclear and require further investigation. In the current study, we demonstrate that miR-621 expression is downregulated in gastric cancer tissues and cell lines, and its reduction is associated with malignant clinical features including tumor size, lymph node metastasis, tumor-node-metastasis stage and poor prognosis. Functional studies involving gain- and loss-of-function experiments revealed that miR-621 represses cell viability, colony formation, cell cycle progression and proliferation in vitro, and miR-621 overexpression inhibited tumor growth in a gastric cancer xenograft model. SYF2 was identified as a direct target gene of miR-621 in gastric cancer. MiR-621 directly interacts with the SYF2 3'-UTR and post-transcriptionally repressed SYF2 expression in gastric cancer cells. SYF2 was significantly overexpressed in gastric cancer tissues and negatively correlated with miR-621 expression. Moreover, inhibition of SYF2 expression reversed the effects of miR-621 loss in gastric cancer cells. SYF2 overexpression was similar to that induced by miR-621 loss in gastric cancer. Taken together, these studies suggest that miR-621 may be a viable therapeutic target in gastric cancer.

Copper Ions are Required for Cochliobolus heterostrophus in Appressorium Formation and Virulence on Maize.

Cochliobolus heterostrophus is the causal agent of southern corn leaf blight, a destructive disease on maize worldwide. However, how it regulates virulence on maize is still largely unknown. Here, we report that two copper transporter genes, ChCTR1 and ChCTR4, are required for its virulence. chctr1 and chctr4 mutants showed attenuated virulence on maize compared with the wild-type strain TM17 but development phenotypes of those mutants on media with or without infection-related stress agents were the same as the wild-type strain. Moreover, ChCTR1 and ChCTR4 play critical roles in appressorium formation and mutation of ChCTR1 or ChCTR4 suppresses the appressorium formation. Furthermore, copper-chelating agent ammonium tetrathiomolybdate suppressed the appressorium formation and virulence of C. heterostrophus on maize, whereas copper ions enhanced the appressorium formation and virulence on maize. The results indicate that copper ions are required for appressorium formation and virulence of C. heterostrophus on maize and are acquired from the environment by two copper transporters: ChCTR1 and ChCTR4.

A label-free aptasensor for ultrasensitive Pb2+ detection based on electrochemiluminescence resonance energy transfer between carbon nitride nanofibers and Ru(phen)32.

A label-free aptasensor was developed for ultrasensitive detection of Pb2+ based on electrochemiluminescence resonance energy transfer (ECL-RET) from graphitic carbon nitride nanofibers (CNNFs) to Ru(phen)32+. The CNNFs synthesized via a facile two-step hydrolysis-electrolysis strategy showed intense and stable ECL signal by taking advantages of amplifying and stabilizing effect of carbon nanotubes and Au nanoparticles. After the specific hybridation between capture DNA and Pb2+ specific aptamer, Ru(phen)32+ could be captured onto CNNFs modified electrode by effectively intercalating into the grooves of double-strand DNA, thus triggering the ECL-RET and leading to highly enhanced ECL intensity. The presence of Pb2+ would result in the detachment of Ru(phen)32+ and then the inhibition of ECL-RET. Then Pb2+ concentration could be quantified based on ECL change before and after introduction of Pb2+. The target recycling based on exonuclease I (Exo I) mediated digestion of Pb2+-aptamer complex was implemented to further improve the sensitivity. These synergistic amplification strategies enabled the aptasensor to be ultrasensitive for Pb2+ determination with a detection limit of 0.04 pM. The proposed probe was utilized to analyze environmental samples with satisfactory results.

Light-Driven Nano-oscillators for Label-Free Single-Molecule Monitoring of MicroRNA.

Here, we present a mapping tool based on individual light-driven nano-oscillators for label-free single-molecule monitoring of microRNA. This design uses microRNA as a single-molecule damper for nano-oscillators by forming a rigid dual-strand structure in the gap between nano-oscillators and the immobilized surface. The ultrasensitive detection is attributed to comparable dimensions of the gap and microRNA. A developed surface plasmon-coupled scattering imaging technology enables us to directly measure the real-time gap distance vibration of multiple nano-oscillators with high accuracy and fast dynamics. High-level and low-level states of the oscillation amplitude indicate melting and hybridization statuses of microRNA. Lifetimes of two states reveal that the hybridization rate of microRNA is determined by the three-dimensional diffusion. This imaging technique contributes application potentials in a single-molecule detection and nanomechanics study.

A Spectral Shift-Based Electrochemiluminescence Sensor for Hydrogen Sulfide.

Classic electrochemiluminescence (ECL) assays relying on the change in luminescence intensity face a challenge in the quantitative analysis of complex samples. Here, we report the design and implementation of a new sensing strategy, using the maximum luminescence wavelength (λmax) shift as the readout to achieve quantitative detection. This approach includes an ECL luminophore (RuSiO2@GO) and a H2S-sensitive inner filter absorber (CouMC). The absorbance of CouMC illustrates a dependence on the H2S concentration, which induces a change in the maximum luminescence wavelength (Δλmax) of the ECL luminophore. Both experimental and simulated results suggest that the spectral shift of ECL effectively avoids the interference of the total luminescence intensity fluctuations, enabling a highly reliable quantitative analysis. This spectral shift-based ECL assay strategy offers a wide application potential by extending types of ECL luminophores and absorptive chemodosimeters, based on an inner filter effect.

The optimization of isoamylase processing conditions for the preparation of high-amylose ginkgo starch.

A high-amylose starch was prepared from ginkgo by hydrolysis using isoamylase and its structures (morphology and crystallinity) and physicochemical properties (swelling factor, water solubility and gelatinization) were determined. The experiments used response surface methodology to determine the optimum parameters for enzymatic hydrolysis: pH 5.0 at 52 °C for 170 min, using an enzyme dose greater than 100 IU/ml. The experimentally observed maximum yield of ginkgo amylose under these conditions was 74.74% and the blue value was 0.756. The high-amylose ginkgo starch showed an irregular surface and porous inner structure while the native starch granules were oval with a smooth surface. X-ray showed that the high-amylose starch displayed a V-type structure. Because of its high amylose content and different structural characteristics, high-amylose starch exhibited a higher gelatinization peak temperature (109.25 °C) and water solubility, and a lower crystallinity (19.13%), gelatinization enthalpy (63.83 J/g), and swelling power. The present study has indicated that high-amylose starch prepared using isoamylase has unique functional properties, which lays the foundation for the wider application of ginkgo starch.

[Pharmacognostical study on four origin plants of folk medicine Sikuaiwa].

In order to develop characteristic folk medicine resources in Jiangxi, a pharmacognostical study was systematically performed for four different origin plants of Sikuaiwa, the result of study provides the microscopic features of powder and tissue of the crude drug. The research provided reference for the identification of Sikuaiwa, as well as a theoretical basis for the further development and the formulation of quality standards.