All-Inorganic Perovskite NiTiO3/Cs3Sb2I9 Heterostructure for Photocatalytic CO2 Reduction to CH4 with High Selectivity.

Developing efficient and stable halide perovskite-based photocatalysts for highly selectivity reduction CO2 to valuable fuels remains a significant challenge due to their intrinsic instability. Herein, a novel heterostructure featuring 2D Cs3Sb2I9 nanosheets on a 3D flower-like mesoporous NiTiO3 framework using a top-down stepwise membrane fabrication technique is constructed. The unique bilayer heterostructure formed on the 3D mesoporous framework endowed NiTiO3/Cs3Sb2I9 with sufficient and close interface contact, minimizing charge transport distance, and effectively promoting the charge transfer at the interface, thus improving the reaction efficiency of the catalyst surface. As revealed by characterization and calculation, the coupling of Cs3Sb2I9 with NiTiO3 facilitates the hydrogenation process during catalytic, directing reaction intermediates toward highly selective CH4 production. Furthermore, the van der Waals forces inherent in the 3D/2D heterostructure with face-to-face contact provide superior stability, ensuring the efficient realization of photocatalytic CO2 reduction to CH4. Consequently, the optimized 3D/2D NiTiO3/Cs3Sb2I9 heterostructure demonstrates an impressive CH4 yield of 43.4 µmol g-1 h-1 with a selectivity of up to 88.6%, surpassing most reported perovskite-based photocatalysts to date. This investigation contributes to overcoming the challenges of commercializing perovskite-based photocatalysts and paves the way for the development of sustainable and efficient CO2 conversion technologies.

Effect of Solanum lyratum Polysaccharide on Malignant Behaviors of Lung Cancer Cells by Regulating the Circ_UHRF1/miR-513b-5p Axis.

This study aimed to investigate the effect of Solanum lyratum polysaccharide on the malignant behavior of lung cancer cells and its possible mechanism. For this purpose, lung cancer A549 cells were cultured in vitro and treated with different doses (0.4, 0.8, 1.2 mg/mL) of Solanum lyratum polysaccharide for 24 h. Then cell proliferation was detected by the CCK-8 method and clone formation test. Transwell test was used to detect cell migration and invasion, and flow cytometry was used to detect cell apoptosis. The protein expressions of Bax and Bcl-2 in cells were detected by Western blotting, and the protein expressions of circ_UHRF1 and miR-513b-5p were detected by the qRT-PCR method. Pearson correlation was used to analyze the correlation between circ_UHRF1 and miR-513b-5p expressions in lung cancer tissues. Results showed that compared with the control group, the proliferation inhibition rate and apoptosis rate of A549 cells that intervened with the Solanum lyratum polysaccharide and expression of Bax protein in the cells were all increased (P<0.05), but the number of clones, migration and invasion and the protein expression of Bcl-2 were all decreased (P<0.05), and were dose-dependent. The expression of circ_UHRF1 in A549 cells that intervened with the S. lyratum polysaccharide was decreased (P<0.05), but the expression of miR-513b-5p was increased (P<0.05). The expression of circ_UHRF1 in lung cancer tissues was higher than that of adjacent tissues (P<0.05), and the expression of miR-513b-5p was lower than that of adjacent tissues (P<0.05). The expressions of circ_UHRF1 and miR-513b-5p in lung cancer tissues were negatively correlated (r=-0.861, P<0.05). Circ_UHRF1 could target miR-513b-5p, and the expression of miR-513b-5p in A549 cells knocking down circ_UHRF1 was increased. After knocking down circ_UHRF1, the proliferation inhibition rate and apoptosis rate of A549 cells and protein expression of Bax in the cells were all increased (P<0.05), but the number of clones, migration and invasion and the protein expression of Bcl-2 were all decreased (P<0.05). Up-regulation of circ_UHRF1 reduced the effects of S. lyratum polysaccharide on the proliferation, migration, invasion and apoptosis of A549 cells. In general, S. lyratum polysaccharide could inhibit the proliferation, migration and invasion of lung cancer A549 cells, and induce cell apoptosis. Its mechanism may be related to the regulation of the circ_UHRF1/miR-513b-5p axis.

Clinical features and outcomes of 31 children with congenital hypothyroidism missed by neonatal screening.

OBJECTIVE: To investigate the clinical features and outcomes of children with congenital hypothyroidism (CH) missed by neonatal screening. METHODS: The clinical and laboratory date of 31 children with CH missed by neonatal screening from February 2015 to February 2022 in Guangzhou Women and Children's Medical Center were retrospectively analyzed. Whole-exome high-throughput sequencing analysis was performed in 17 patients. RESULTS: Among the 31 patients, 19 cases (61.3%) were preterm, 12 cases (38.7%) were term neonates. The median value of gestation age was 36 (26-40) weeks, birth weight was 2.35 (0.75-3.70) kg, diagnosed age was 20 d (7 d-4 years), dry blood spot thyrotropin was 4.18 (0.34-8.97) mU/L. Nine cases (29.0%) were same-sex twins and 4 cases (12.9%) had a family history of hypothyroidism. The initial clinical symptoms were growth retardation in 11 cases (35.5%), prolonged jaundice in 7 cases (22.6%), short stature, abdominal distension, fetal edema and goiter in 1 case (3.2%), respectively. Genetic analysis of the 17 children showed that DUOX2 gene mutations were detected in 10 cases (6 cases with biallelic mutations and 4 cases with monoallelic mutations), of whom 3 had a family history of hypothyroidism. A total of 22 patients were reevaluated at the age of 2-3 years, of whom 17 cases (77.3%) were transient CH and 5 cases (22.7%) were permanent CH. Among the 10 cases with DUOX2 gene mutations, 6 cases were transient CH, 1 case was permanent CH, and 3 cases (< 3 years old) were still under treatment with L-thyroxine. CONCLUSIONS: False negative results on neonatal screening for CH often occurs in preterm birth, low birth weight, same-sex twins, family history of hypothyroidism, and DUOX2 defects are the common molecular pathogenesis, most of whom are transient CH. Thyroid function should be evaluated in time for children with unexplained slow growth and delayed jaundice regression.

NLDock: a Fast Nucleic Acid-Ligand Docking Algorithm for Modeling RNA/DNA-Ligand Complexes.

Nucleic acid-ligand interactions play an important role in numerous cellular processes such as gene function expression and regulation. Therefore, nucleic acids such as RNAs have become more and more important drug targets, where the structural determination of nucleic acid-ligand complexes is pivotal for understanding their functions and thus developing therapeutic interventions. Molecular docking has been a useful computational tool in predicting the complex structure between molecules. However, although a number of docking algorithms have been developed for protein-ligand interactions, only a few docking programs were presented for nucleic acid-ligand interactions. Here, we have developed a fast nucleic acid-ligand docking algorithm, named NLDock, by implementing our intrinsic scoring function ITScoreNL for nucleic acid-ligand interactions into a modified version of the MDock program. NLDock was extensively evaluated on four test sets and compared with five other state-of-the-art docking algorithms including AutoDock, DOCK 6, rDock, GOLD, and Glide. It was shown that our NLDock algorithm obtained a significantly better performance than the other docking programs in binding mode predictions and achieved the success rates of 73%, 36%, and 32% on the largest test set of 77 complexes for local rigid-, local flexible-, and global flexible-ligand docking, respectively. In addition, our NLDock approach is also computationally efficient and consumed an average of as short as 0.97 and 2.08 min for a local flexible-ligand docking job and a global flexible-ligand docking job, respectively. These results suggest the good performance of our NLDock in both docking accuracy and computational efficiency.

Challenges and opportunities of automated protein-protein docking: HDOCK server vs human predictions in CAPRI Rounds 38-46.

Protein-protein docking plays an important role in the computational prediction of the complex structure between two proteins. For years, a variety of docking algorithms have been developed, as witnessed by the critical assessment of prediction interactions (CAPRI) experiments. However, despite their successes, many docking algorithms often require a series of manual operations like modeling structures from sequences, incorporating biological information, and selecting final models. The difficulties in these manual steps have significantly limited the applications of protein-protein docking, as most of the users in the community are nonexperts in docking. Therefore, automated docking like a web server, which can give a comparable performance to human docking protocol, is pressingly needed. As such, we have participated in the blind CAPRI experiments for Rounds 38-45 and CASP13-CAPRI challenge for Round 46 with both our HDOCK automated docking web server and human docking protocol. It was shown that our HDOCK server achieved an "acceptable" or higher CAPRI-rated model in the top 10 submitted predictions for 65.5% and 59.1% of the targets in the docking experiments of CAPRI and CASP13-CAPRI, respectively, which are comparable to 66.7% and 54.5% for human docking protocol. Similar trends can also be observed in the scoring experiments. These results validated our HDOCK server as an efficient automated docking protocol for nonexpert users. Challenges and opportunities of automated docking are also discussed.

ITScore-NL: An Iterative Knowledge-Based Scoring Function for Nucleic Acid-Ligand Interactions.

Nucleic acid-ligand complexes underlie numerous cellular processes, such as gene function expression and regulation, in which their three-dimensional structures are important to understand their functions and thus to develop therapeutic interventions. Given the high cost and technical difficulties in experimental methods, computational methods such as molecular docking have been actively used to investigate nucleic acid-ligand interactions in which an accurate scoring function is crucial. However, because of the limited number of experimental nucleic acid-ligand binding data and structures, the scoring function development for nucleic acid-ligand interactions falls far behind that for protein-protein and protein-ligand interactions. Here, based on our statistical mechanics-based iterative approach, we have developed an iterative knowledge-based scoring function for nucleic acid-ligand interactions, named as ITScore-NL, by explicitly including stacking and electrostatic potentials. Our ITScore-NL scoring function was extensively evaluated for its ability in the binding mode and binding affinity predictions on three diverse test sets and compared with state-of-the-art scoring functions. Overall, ITScore-NL obtained significantly better performance than the other 12 scoring functions and predicted near-native poses with rmsd ≤ 1.5 Å for 71.43% of the cases when the top three binding modes were considered and a good correlation of R = 0.64 in binding affinity prediction on the large test set of 77 nucleic acid-ligand complexes. These results suggested the accuracy of ITScore-NL and the necessity of explicitly including stacking and electrostatic potentials.

Clinical and molecular characteristics of patients with Gaucher disease in Southern China.

Gaucher disease (GD) is a common lysosomal storage disorder caused by the deficiency of acid ß-glucosidase, due to mutations in the GBA gene. To explore the clinical and molecular characteristics of GD patients from Southern China, GBA gene were analyzed by nest PCR and direct Sanger-sequencing. Novel missense mutations were transiently transfected in COS-7 cells by plasmid system for functional verification. Among the 22 GD patients, 19 patients were classified as type 1 and three as type 2. Over 60% of the type 1 patient had the onset before two years of age and about 42% of them died before three years of age. Six type 1 patients with L444P homozygous genotype, presented with early onset and severe hepatosplenomegaly. Four novel mutations Y22C, F109L, L149F and c.983_990delCCCACTGG were identified. The GBA activities in vitro of novel mutants Y22C, F109L and L149F were 20.2%, 6.9% and 6.5% of the wild-type, respectively. L444P mutation accounted for 47.7% of the mutant alleles. Our results revealed that type 1 GD tends to present with a severe phenotype among southern Chinese. L444P was the most prevalent mutation and L444P homozygous genotype was associated with severe type 1 GD. Three novel missense mutations identified were pathogenic.

Clinical and molecular characteristics of 11 Chinese probands with GM1 gangliosidosis.

GM1 gangliosidosis is an autosomal recessive lysosomal storage disease caused by the deficiency of ß-galactosidase activity, precisely due to mutations in the GLB1 gene. To explore the clinical and molecular characteristics of GM1 gangliosidosis patients from China, GLB1 gene were analyzed in 11 probands with GM1 gangliosidosis by exploiting direct Sanger-sequencing. Among them, five patients were classified as the infantile type and the remaining six as the late-infantile or juvenile type. In these probands, eight novel mutations p.Y50N, p.Y237C, p.S267F, p.G453R, p.K578 N, c.618delC, c.475_478delGACA and c.1979_1980insG have been identified. Among them, three novel missense mutations p.Y50N, p.S267F and p.G453R were transiently transfected in COS-7 cells by plasmid system for functional verification. In vitro GLB1 activities carrying the aforesaid missense mutants p.Y50N, p.S267F and p.G453R were 0.11%, 0 and 0.55% of wild-type, respectively. Mutation c.495_497delTCT and p.S149F accounted for 22.7 and 13.6% of the mutant alleles, respectively. Our results expand the spectrum of GLB1 gene, provide new insights into the clinical and molecular characteristics of GM1 gangliosidosis in China.

Network Pharmacology Based Elucidation of Molecular Mechanisms of Laoke Formula for Treatment of Advanced Non-Small Cell Lung Cancer.

OBJECTIVE: To explore the specific pharmacological molecular mechanisms of Laoke Formula (LK) on treating advanced non-small cell lung cancer (NSCLC) based on clinical application, network pharmacology and experimental validation. METHODS: Kaplan-Meier method and Cox regression analysis were used to evaluate the survival benefit of Chinese medicine (CM) treatment in 296 patients with NSCLC in Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2015. The compounds of LK were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the corresponding targets were performed from Swiss Target Prediction. NSCLC-related targets were obtained from Therapeutic Target Database and Comparative Toxicogenomics Database. Key compounds and targets were identified from the compound-target-disease network and protein-protein interaction (PPI) network analysis, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were used to predict the potential signaling pathways involved in the treatment of advanced NSCLC with LK. The binding affinities between key ingredients and targets were further verified using molecular docking. Finally, A549 cell proliferation and migration assay were used to evaluate the antitumor activity of LK. Western blot was used to further verify the expression of key target proteins related to the predicted pathways. RESULTS: Kaplan-Meier survival analysis showed that the overall survival of the CM group was longer than that of the non-CM group (36 months vs. 26 months), and COX regression analysis showed that LK treatment was an independent favorable prognostic factor (P=0.027). Next, 97 components and 86 potential targets were included in the network pharmacology, KEGG and GO analyses, and the results indicated that LK was associated with proliferation and apoptosis. Moreover, molecular docking revealed a good binding affinity between the key ingredients and targets. In vitro, A549 cell proliferation and migration assay showed that the biological inhibition effect was more obvious with the increase of LK concentration (P<0.05). And decreased expressions of nuclear factor κB1 (NF-κB1), epidermal growth factor receptor (EGFR) and AKT serine/threonine kinase 1 (AKT1) and increased expression of p53 (P<0.05) indicated the inhibitory effect of LK on NSCLC by Western blot. CONCLUSION: LK inhibits NSCLC by inhibiting EGFR/phosphoinositide 3-kinase (PI3K)/AKT signaling pathway, NFκB signaling pathway and inducing apoptosis, which provides evidence for the therapeutic mechanism of LK to increase overall survival in NSCLC patients.

Quantification of macromolecule crowding at single-molecule level.

Macromolecule crowding has a prominent impact on a series of biochemical processes in the cell. It is also expected to promote macromolecular complexation induced by excluded volume effects, which conflicts with recent advances in the thermodynamic interaction between inert, synthetic polymers, and nucleic acids. Along this line, a method combining high-resolution magnetic tweezers and extended crowder-oxDNA model was applied to resolve these discrepancies by systematically studying the kinetics and thermodynamics of the folding-unfolding transition for an individual DNA hairpin in a crowded environment. More specifically, from the magnetic tweezers-based experiments, the linear dependence of the critical force of the DNA hairpin on the polyethylene glycol (PEG) concentration was demonstrated, which is consistent with the results based on the crowder-oxDNA model in which the Lennard-Jones potential was adopted to express the interaction between the crowders and the DNA hairpin. These consistencies highlight that the excluded volume effects are mainly responsible for the interaction between PEG and the DNA hairpin, which is different from the interaction between dextran and the DNA hairpin. In the meantime, the dependence of the folding rate on the molecule weight of PEG, which was different from fluorescence resonance energy transfer-based results, was identified. The proposed method opens a path to detect the interaction between an inert, synthetic molecule, and the DNA hairpin, which is important to accurately mimic the cytosolic environments using mixtures of different inert molecules.

Stability of DNA and RNA hairpins: a comparative study based on ox-DNA.

Advances in single-molecule experiments on macromolecular crowding urgently need an efficient simulation method to resolve their discrepancies quantitatively. Ox-DNA model has been since reworked to treat the thermodynamics and mechanical properties of DNA/RNA hairpin at a stretching force. In hopping experiments, the critical forces of RNA hairpins at different temperatures are greater than those of DNA hairpins, in addition, the Gibbs free energy at a fixed temperature required to convert an RNA hairpin into a single-stranded molecule at zero force is obviously greater than that of DNA hairpin and gradually decreases by increasing the temperature. As far as force-ramping experiments are concerned, the first-rupture forces of RNA/DNA hairpins corresponding to the maximum probability density linearly pertain to the force-loading rate, with those of RNA hairpins being greater. The extended ox-DNA model could potentially identify the interaction between biologically inert polymer and RNA/DNA hairpins in crowded environments.

Docking and scoring for nucleic acid-ligand interactions: Principles and current status.

Nucleic acid (NA)-ligand interactions have crucial roles in many cellular processes and, thus, are increasingly attracting therapeutic interest in drug discovery. Molecular docking is a valuable tool for studying molecular interactions. However, because NAs differ significantly from proteins in both their physical and chemical properties, traditional docking algorithms and scoring functions for protein-ligand interactions might not be applicable to NA-ligand docking. Therefore, various sampling strategies and scoring functions for NA-ligand interactions have been developed. Here, we review the basic principles and current status of docking algorithms and scoring functions for DNA/RNA-ligand interactions. We also discuss challenges and limitations of current docking and scoring approaches.

AAV9-coGLB1 Improves Lysosomal Storage and Rescues Central Nervous System Inflammation in a Mutant Mouse Model of GM1 Gangliosidosis.

BACKGROUND: GM1 gangliosidosis (GM1) is an autosomal recessive disorder characterized by the deficiency of beta-galactosidase (ß-gal), a ubiquitous lysosomal enzyme that catalyzes the hydrolysis of GM1 ganglioside. OBJECTIVE: The study aims to explore the application of the AAV9-coGLB1 for effective treatment in a GM1 gangliosidosis mutant mouse model. METHODS: We designed a novel adeno-associated virus 9 (AAV9) vector expressing ß-gal (AAV9- coGLB1) to treat GM1 gangliosidosis. The vector, injected via the caudal vein at 4 weeks of age, drove the widespread and sustained expression of ß-gal for up to 32 weeks in the Glb1G455R/G455R mutant mice (GM1 mice). RESULTS: The increased levels of ß-gal reduced the pathological damage occurring in GM1 mice. Histological analyses showed that myelin deficits and neuron-specific pathology were reduced in the cerebral cortex region of AAV9-coGLB1-treated mice. Immunohistochemical staining showed that the accumulation of GM1 ganglioside was also reduced after gene therapy. The reduction of the storage in these regions was accompanied by a decrease in activated microglia. In addition, AAV9 treatment reversed the blockade of autophagic flux in GM1 mice. CONCLUSION: These results show that AAV9-coGLB1 reduces the pathological signs of GM1 gangliosidosis in a mouse model.

Incidence tendency, etiological classification and outcome of congenital hypothyroidism in Guangzhou, China: an 11-year retrospective population-based study.

OBJECTIVES: An increased incidence of congenital hypothyroidism (CH) has been described worldwide over the years. In this study, we aimed to investigate the epidemiologic characteristics of CH, the iodine status in Guangzhou, China and to investigate which factors might influence the CH incidence during the period 2010-2020. METHODS: We retrospectively reviewed all cases of CH detected by newborn screening during the period 2010-2020. CH was classified as either suspected thyroid dyshormonogenesis (SDH) or thyroid dysgenesis (TD) based on thyroid ultrasound at first diagnosis. Patients were re-evaluated after 4 weeks of L-thyroxine withdrawal at age of 2-3 years to confirm the diagnosis of permanent CH (PCH) or transient CH (TCH). RESULTS: From 2010 to 2020, 1,655 patients with CH were confirmed from 2,400,383 newborns (1:1,450). The CH incidence increased from 1:2,584 in period [2010-2014] to 1:1,086 in period [2015-2020]. Among the 1,337 patients with thyroid ultrasound, 84.29% were SDH whereas 15.71% had TD. Further analysis revealed that more SDH (78.32%) were TCH whereas more TD (87.12%) turned to be PCH. The proportion of blood spot thyrotropin values >5 mIU/L ranged from 8.03 to 20.46%, indicating iodine deficiency. The prevalence of preterm infants increased from 5.50% in period [2010-2014] to 7.06% in period [2015-2020] (p<0.001). CONCLUSIONS: In the past decade, the CH incidence has increased progressively. SDH was the majority of CH, most of which were TCH, while most patients with TD were PCH. The increased incidence might be mainly due to iodine deficiency and increased rates of preterm infants in our study.

A GM1 gangliosidosis mutant mouse model exhibits activated microglia and disturbed autophagy.

GM1 gangliosidosis is a rare lysosomal storage disease caused by a deficiency of ß-galactosidase due to mutations in the GLB1 gene. We established a C57BL/6 mouse model with Glb1G455R mutation using CRISPR/Cas9 genome editing. The ß-galactosidase enzyme activity of Glb1G455R mice measured by fluorometric assay was negligible throughout the whole body. Mutant mice displayed no marked phenotype at eight weeks. After 16 weeks, GM1 ganglioside accumulation in the brain of mutant mice was observed by immunohistochemical staining. Meanwhile, a declining performance in behavioral tests was observed among mutant mice from 16 to 32 weeks. As the disease progressed, the neurological symptoms of mutant mice worsened, and they then succumbed to the disease by 47 weeks of age. We also observed microglia activation and proliferation in the cerebral cortex of mutant mice at 16 and 32 weeks. In these activated microglia, the level of autophagy regulator LC3 was up-regulated but the mRNA level of LC3 was normal. In conclusion, we developed a novel murine model that mimicked the chronic phenotype of human GM1. This Glb1G455R murine model is a practical in vivo model for studying the pathogenesis of GM1 gangliosidosis and exploring potential therapies.

Rapid synthesis of thermoelectric SnSe thin films by MPCVD.

Microwave plasma chemical vapor deposition (MPCVD) has been traditionally used to synthesize carbon-based materials such as diamonds, carbon nanotubes and graphene. Here we report that a rapid and catalyst-free growth of SnSe thin films can be achieved by using single-mode MPCVD with appropriate source materials. The analysis combining microscope images, X-ray diffraction patterns and lattice vibration modes shows that the grown thin films were composed of orthorhombic structured SnSe polycrystals. Further thermoelectric (TE) characterization of the SnSe films reveals the high-performance power factor of 3.98 µW cm-1 K-2 at 600 K. Our results may open an avenue for rapid synthesis of new types of materials such as IV-VI compounds and be useful for TE application of these materials.

MicroRNA-147b promotes lung adenocarcinoma cell aggressiveness through negatively regulating microfibril-associated glycoprotein 4 (MFAP4) and affects prognosis of lung adenocarcinoma patients.

BACKGROUND: Lung adenocarcinoma (LUAD) is widely known as the leading cause of death in patients with lung cancer. Extensive evidence has determined that microRNAs (miRNAs) exert critical effects on various biological processes in tumorigenesis. microRNA-147b (miR-147b) has been reported to serve as an oncogenic molecule in colorectal cancer and hepatocellular carcinoma, however, its prognostic value and biological effect in LUAD remain rare. MATERIALS AND METHODS: miR-147b and microfibril-associated glycoprotein 4 (MFAP4) data were collected from The Cancer Genome Atlas (TCGA) database to determine their expression levels in LUAD tissues. Kaplan-Meier method was used to plot the overall survival curves for the prognostic power of miR-147b and MFAP4 identification. Chi-square test was utilized to demonstrate the association between clinical characteristics and miR-147b or MFAP4 in LUAD. Luciferse reporter assay was implemented to identify the correlation between miR-147b and MFAP4. The mRNA and protein levels were detected by qRT-PCR and western blotting, respectively. To explore the effects of miR-147b and its potential mechanism in LUAD, cell counting kit 8 (CCK-8), colony formation and transwell assays were performed in LUAD cells with abnormal expression of miR-147b or/and MFAP4. RESULTS: Our results showed that miR-147b was up-regulated in LUAD tissues and cell lines, which induced poor outcome. Conversely, MFAP4, the putative target gene of miR-147b, was down-regulated in LUAD. The expression of MFAP4 in LUAD cells was negatively regulated by miR-147b. Results of experiments in vitro revealed that miR-147b could promote cell proliferation, colony formation, invasion and migration, while up-regulation of MFAP4 suppressed the impacts of miR-147b on cell malignant aggressiveness in A549 and Calu-3 cells. CONCLUSION: In conclusion, these findings determined that miR-147b contributed to the progression of LUAD via targeting MFAP4. Thus, understanding the potential mechanism of miR-147b/MFAP4 may improve the treatment of cancers, especially LUAD.

Plasma Choline as a Diagnostic Biomarker in Slow Coronary Flow.

AIM: The slow coronary flow (SCF) phenomenon was characterized by delayed perfusion of epicardial arteries, and no obvious coronary artery lesion in coronary angiography. The prognosis of patients with slow coronary flow was poor. However, there is lack of rapid, simple, and accurate method for SCF diagnosis. This study aimed to explore the utility of plasma choline as a diagnostic biomarker for SCF. METHODS: Patients with coronary artery stenosis <40% evaluated by the coronary angiogram method were recruited in this study and were grouped into normal coronary flow (NCF) and SCF by thrombolysis in myocardial infarction frame count (TFC). Plasma choline concentrations of patients with NCF and SCF were quantified by Ultra Performance Liquid Chromatography Tandem Mass Spectrometry. Correlation analysis was performed between plasma choline concentration and TFC. Receiver operating characteristic (ROC) curve analysis with or without confounding factor adjustment was applied to predict the diagnostic power of plasma choline in SCF. RESULTS: Forty-four patients with SCF and 21 patients with NCF were included in this study. TFC in LAD, LCX, and RCA and mean TFC were significantly higher in patients with SCF in comparison with patients with NCF (32.67 ± 8.37 vs. 20.66 ± 3.41, P < 0.01). Plasma choline level was obviously higher in patients with SCF when compared with patients with NCF (754.65 ± 238.18 vs. 635.79 ± 108.25, P=0.007). Plasma choline level had significantly positive correlation with Mean TFC (r = 0.364, P=0.002). Receiver operating characteristic (ROC) analysis showed that choline with or without confounding factor adjustment had an AUC score of 0.65 and 0.77, respectively. CONCLUSIONS: TFC were closely related with plasma choline level, and plasma choline can be a suitable and stable diagnostic biomarker for SCF.