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Lithium (Li) is one of the most important light elements that was primordially synthesized in the Big Bang Nucleosynthesis (BBN). It is also an element that confused astrophysicists for decades, as its observed abundance often contradicts with the theoretical prediction in many different types of celestial objects. Li-rich giant stars are such objects. Their atmospheres contain anomaly high Li abundance than that expected by the standard stellar evolution model. Although the first Li-rich giant star was discovered almost 40 years ago, their origin is still being debated. With the launch of massive spectroscopic survey program such as the Large Sky Area Multi-Object Fiber Spectroscopy Telescope (LAMOST) survey, the extending of available asteroseismology data from space satellites (such as Kepler), and the developments of data-driven techniques, breakthroughs have been archived in the field of Li-rich studies. In this paper, we review the progress that was made during the past four decades, and present our up-to-date understanding to Li-rich giant stars. [ABSTRACT FROM AUTHOR]

Fibroblast-like synoviocytes (FLS) with aberrant expression of microRNA (miRNA) are critical pathogenic regulators in rheumatoid arthritis (RA). Previous studies have found that overexpression or silencing of miRNA can contribute to the development of miRNA-based therapeutics in arthritis models. In this study, we explored the effects of miR-27a on cell migration and invasion in cultured FLS from RA patients. We found that miR-27a was markedly downregulated in the serum, synovial tissue, and FLS of RA patients. Meanwhile, the expression of follistatin-like protein 1 (FSTL1) was upregulated, which suggests that FSTL1 plays a key role in RA development. The results of a Transwell assay showed that miR-27a inhibited FLS migration and invasion. However, miR-27a inhibition promoted the migration and invasion of FLS. In addition, the downregulated expression of matrix metalloproteinases (MMP2, MMP9, and MMP13) and Rho family proteins (Rac1, Cdc42, and RhoA) was detected after treatment with miR-27a in RA-FLS by quantitative reverse transcription-PCR and western blot analysis. Then, a luciferase reporter assay validated that miR-27a targeted the 3-untranslated region (3'-UTR) of FSTL1. Moreover, miR-27a caused a significant decrease of FSTL1. In addition, the expression of TLR4 and NFκB was inhibited by miR-27a but increased by FSTL1 overexpression. In conclusion, we found that miR- 27a inhibited cell migration and invasion of RA-FLS by targeting FSTL1 and restraining the TLR4/NFκB pathway. [ABSTRACT FROM AUTHOR]

Topic Systematic review and meta-analysis of the genetic associations of primary angle-closure disease (PACD). Clinical Relevance To confirm the genetic biomarkers for PACD, including primary angle-closure glaucoma (PACG) and related phenotypes. Methods We searched in the MEDLINE and EMBASE databases for genetic studies of PACG or other PACD published from the start dates of the databases to May 11, 2015. We estimated the summary odds ratios (ORs) and 95% confidence intervals (CIs) for each polymorphism in PACG, primary angle-closure suspect (PACS), and primary angle-closure (PAC) using fixed- or random-effect models. We also performed sensitivity analysis to test the robustness of the results. Results Our literature search yielded 6463 reports. Among them, we identified 24 studies that fulfilled the eligibility criteria for meta-analysis, involving 28 polymorphisms in 11 genes/loci. We affirmed the association of PACG and combined PACS/PAC/PACG with 10 polymorphisms in 8 genes/loci, including COL11A1 (rs3753841-G, OR, 1.22; P = 0.00046), HGF (rs17427817-C, OR, 2.02; P = 6.9E-07; rs5745718-A, OR, 2.11; P = 9.9E-07), HSP70 (rs1043618, GG+GC, OR, 0.52; P = 0.0010), MFRP (rs2510143-C, OR, 0.66; P = 0.012; rs3814762-G, OR, 1.40; P = 0.0090), MMP9 (rs3918249-C, OR, 1.35; P = 0.034), NOS3 (rs7830-A, OR, 0.80; P = 0.036), PLEKHA7 (rs11024102-G, OR, 1.24; P = 8.3E-05), and PCMTD1-ST18 (rs1015213-A, OR, 1.59; P = 0.00013). Sensitivity analysis indicated that the results were robust. Conclusions In this study, we confirmed multiple polymorphisms in 8 genes/loci as genetic biomarkers for PACD, among which 3 were identified in a genome-wide association study ( COL11A1 , PLEKHA7, and PCMTD1-ST18 ), and 5 were identified in candidate gene studies ( HGF , HSP70 , MFRP , MMP9 , and NOS3 ). [ABSTRACT FROM AUTHOR]

Telomere maintenance is essential for protecting chromosome ends. Aberrations in telomere length have been implicated in cancer and aging. Telomere elongation by human telomerase is inhibited in cis by the telomeric protein TRF1 and its associated proteins. However, the link between TRF1 and inhibition of telomerase elongation of telomeres remains elusive because TRF1 has no direct effect on telomerase activity. We have previously identified one Pin2/TRF1-interacting protein, PinXl, that has the unique property of directly binding and inhibiting telomerase catalytic activity (Zhou, X. Z., and Lu, K. P. (2001) Cell 107, 347-359). However, nothing is known about the role of the PinX1-TRF1 interaction in the regulation of telomere maintenance. By identifying functional domains and key amino acid residues in PinXl and TRF1 responsible for the PinX1-TRF1 interaction, we show that the TRF homology domain of TRF1 interacts with a minimal 20amino acid sequence of PinXl via hydrophilic and hydrophobic interactions. Significantly, either disrupting this interaction by mutating the critical Leu-291 residue in PinXl or knocking down endogenous TRF1 by RNAi abolishes the ability of PinXl to localize to telomeres and to inhibit telomere elongation in cells even though neither has any effect on telomerase activityperse. Thus, the telomerase inhibitor PinXl is recruited to telomeres by TRF1 and provides a critical link between TRF1 and telomerase inhibition to prevent telomere elongation and help maintain telomere homeostasis. [ABSTRACT FROM AUTHOR]

Human estrogenic 17β-hydroxysteroid dehydrogenase (17β-HSD1), a member of the short chain dehydrogenase/reductase (SDR) family, is responsible for the biosynthesis of all active estrogens. The crystal structures of two C19-steroid ternary complexes (17β-HSD1androstanedione-NADP and 17β-HSDl-androstenedione- NADP) reveal the critical role of Leu149 in regulating the substrate specificity and provide novel insight into the different fates of a conserved glutamate residue in the estrogen-specific proteins upon the binding of the keto and hydroxyl groups of steroids. The whole NADP molecule can be unambiguously defined in the NADP binary complex, whereas both ternary complexes show that the nicotinamide moiety of NADP cannot be located in the density maps. In both ternary complexes, the expected position of carboxamide oxygen of NADP is occupied by a water molecule, which makes a bifurcated hydrogen bond with the O3 of C19-steroid and the main chain nitrogen of Val188. These results demonstrate that the hydrogen bonding interaction between the main chain amide group and the carboxamide group of NAD(P)(H) plays an important role in anchoring the nicotinamide ring to the enzyme. This finding is substantiated by structural analyses of all 33 NAD(P)(H) complexes of different SDR proteins, because 29 structures of 33 show this interaction. This common feature reveals a general mechanism among the SDR family, providing a rational basis for inhibitor design against biologically relevant SDR targets. [ABSTRACT FROM AUTHOR]

The years-long high-precision photometric data observed by Kepler satellite combining with huge amount of spectra observed by LAMOST provide a great opportunity to study the relations between surface rotation and lithium abundance of li-rich giants. In this study, we cross match the Kepler data with li-rich giants catalog from LAMOST, and obtain 619 common sources. Then we measure 36 rotation periods from the full set of 295 li-rich giants with good data quality which consists of two sub-samples. The rotation periods of 14 stars was extracted from 205 stars with evolutionary stages determined using asteroseismology, including 11 core helium-burning stars (HeBs), 2 red giant branch stars (RGBs), and 1 unclassified star. All the super lithium-rich giant stars (A (Li) > 3.3 dex) are HeBs in our sample. The remaining 90 giants do not have evolutionary stages confirmed, and in this sub-sample, 22 giants have their rotation period measured. The rotation detection rate of the former sub-sample is 6.8%, which is significantly higher than the detection rate of a large giant sample in previous studies (2.08%). With the surface rotation period measured, we confirm the relation between stellar rotation and lithium enrichment of giants. Meanwhile, we find that the less Li-enriched stars have a relatively dispersed distribution of rotation periods, and the giants with a high Li enrichment is concentrated on the rapidly rotating area, which is consistent with earlier studies. The present work also shows a jump at A (Li) ≈ 3.3 dex in the relation between rotation period and Li abundance that coincidently is the boundary between Li-rich giants and super Li-rich giants which may indicate the different mechanisms. The rotation periods of super Li-rich giants become shorter as the lithium enrichment increases. This correlation provides an evidence for the rotational induced extra-mixing mechanism responsible for Li enrichment of giants. [ABSTRACT FROM AUTHOR]

There are various treatments for cystoid macular edema (CME) secondary to retinitis pigmentosa; however, the evidence for these treatments has not been previously systematically reviewed. Our review that includes 23 studies shows that oral carbonic anhydrase inhibitors (including acetazolamide and methazolamide) and topical carbonic anhydrase inhibitors (dorzolamide and brinzolamide) are effective first-line treatments. In patients unresponsive to carbonic anhydrase inhibitor treatment, intravitreal steroids (triamcinolone acetonide and sustained-release dexamethasone implants), oral corticosteroid (deflazacort), intravitreal antivascular endothelial growth factor agents (ranibizumab and bevacizumab), grid laser photocoagulation, pars plana vitrectomy, or ketorolac were also effective in improving CME secondary to retinitis pigmentosa. Oral acetazolamide has the strongest clinical basis for treatment and was superior to topical dorzolamide. Rebound of CME was commonly seen in the long term, regardless of the choice of treatment. Oral acetazolamide should be the first-line treatment in CME secondary to retinitis pigmentosa. Topical dorzolamide is an appropriate alternative in patients intolerant to adverse effects of oral acetazolamide. More studies are required to investigate the management of rebound CME. [ABSTRACT FROM AUTHOR]

Solar flares are a kind of violent solar eruptive activity phenomenon and an important warning device of space weather disturbance. In space weather forecasting, flare forecasting is an important forecast content. This paper proposes a flare prediction model based on long and short-term memory neural network, which uses the time sequence of magnetic field changes in the solar active region in the past 24 h to construct samples, and analyzes the time series evolution of magnetic field characteristics through the long and short-term memory neural network to predict whether ≥ M-level flares will occur in the next 48 h. This paper uses a data set for all active region samples from May 2010 to May 2017, and selects 10 magnetic field characteristic parameters of SDO/HMI SHARP. In the modeling process, six feature parameters with high weight, gain rate, and coverage rate were selected as input parameters through XGBoost method. Through test comparison, the false report rate and accuracy rate of the model are similar to the traditional machine learning model, and the accuracy rate and critical success index are better than the traditional machine learning model, which are 0.7483 and 0.7402, respectively. The overall effect of the model is better than that of the traditional machine learning model. [ABSTRACT FROM AUTHOR]

Purpose: To assess the efficacy and safety of topical cyclosporine versus placebo in the treatment of allergic conjunctivitis. Design: Systematic review and meta-analysis. Participants: Seven qualified studies incorporating 306 eyes of 153 patients were analyzed. Methods: Searches of randomized controlled trials were conducted in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. Main Outcome Measures: We assessed the methodologic quality of individual included trials and performed meta-analyses using the random effects model if P<0.1 in the test for heterogeneity, or otherwise used the fixed effects model. We assessed scores of composite signs and symptoms, reduction in steroid eye drop use in steroid-dependent patients, and safety outcomes (i.e., stinging or burning sensation). Results: At 2 weeks of follow-up or longer, evidence suggests a statistically significant improvement in the composite signs (standardized mean difference [SMD], −1.21; 95% confidence interval [CI], −1.80 to −0.62; I 2 = 71%) and symptoms (SMD, −0.84; 95% CI, −1.51 to −0.16; I 2 = 80%) after topical cyclosporine treatment for allergic conjunctivitis regardless of the dosage of treatment. There was a significant reduction (mean difference, −61.16; 95% CI, −101.61 to −20.72; I 2 = 58%) in the use of steroid eye drops in patients with steroid-dependent allergic conjunctivitis. Stinging or burning sensation (odds ratio, 2.56; 95% CI, 0.19–35.06; I 2 = 73%) was common in both the cyclosporine and placebo groups. Conclusions: This systematic review and meta-analysis suggests topical cyclosporine could be an effective and safe treatment method for allergic conjunctivitis. Further randomized controlled trials with larger sample sizes and standardized outcome measurements, follow-up periods, and cyclosporine concentrations are warranted to determine the short- and long-term efficacy and safety and the minimal effective dosage of topical cyclosporine for allergic conjunctivitis. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. [Copyright &y& Elsevier]

Abstract: Evidence indicates that concept mapping can reduce students’ cognitive load and facilitate meaningful learning. Using a concept map description approach, the ontology defines the relationship between concepts that is feasible for resource sharing and reusing. In this study, we implement a concept map learning system with ontology technology to help users search the concept map, determine relationships between nodes or predicates, and find the common concept or predicate among the concepts to help reduce the user’s cognitive load. [Copyright &y& Elsevier]

Mammalian acetylcholinesterase (AChE) is well-studied, being important in both cholinergic brain synapses and the peripheral nervous systems and also a key drug target for many diseases. In contrast, little is known about the structures and molecular mechanism of prokaryotic acetylcholinesterases. We report here the structural and biochemical characterization of ChoE, a putative bacterial acetylcholinesterase from Pseudomonas aeruginosa. Analysis of WT and mutant strains indicated that ChoE is indispensable for P. aeruginosa growth with acetylcholine as the sole carbon and nitrogen source. The crystal structure of ChoE at 1.35 Å resolution revealed that this enzyme adopts a typical fold of the SGNH hydrolase family. Although ChoE and eukaryotic AChEs catalyze the same reaction, their overall structures bear no similarities constituting an interesting example of convergent evolution. Among Ser-38, Asp-285, and His-288 of the catalytic triad residues, only Asp-285 was not essential for ChoE activity. Combined with kinetic analyses of WT and mutant proteins, multiple crystal structures of ChoE complexed with substrates, products, or reaction intermediate revealed the structural determinants for substrate recognition, snapshots of the various catalytic steps, and the molecular basis of substrate inhibition at high substrate concentrations. Our results indicate that substrate inhibition in ChoE is due to acetate release being blocked by the binding of a substrate molecule in a nonproductive mode. Because of the distinct overall folds and significant differences of the active site between ChoE and eukaryotic AChEs, these structures will serve as a prototype for other prokaryotic acetylcholinesterases. [ABSTRACT FROM AUTHOR]

Drug resistance is a big problem in cancer treatment and one of the most prominent mechanisms underlain is overexpression of ATP-binding cassette (ABC) transporters, particularly ABCB1, ABCC1 and ABCG2. Inhibition of ABC transporters is an important approach to overcome drug resistance. The inositol-requiring enzyme 1α (IRE1α), an arm of unfolded protein response (UPR), splices XBP1 mRNA to generate an active transcription factor XBP1s. UPR is implicated in drug resistance. However, the underlying mechanism is unclear. We found that the anticancer drugs such as 5-fluorouracil (5-FU) activated the IRE1α-XBP1 pathway to induce the expression of ABCB1, ABCC1 and ABCG2 in colon cancer cells. Inhibition of IRE1α RNase activity with small molecule 4μ8c suppressed the drug-induced expression of these ABC transporters and sensitized 5-FU-resistant colon cancer cells to drug treatment. In vivo xenograft assay indicates that administration of 4μ8C substantially enhanced the efficacy of 5-FU chemotherapy on 5-FU-resistant colon cancer cells. These results suggest that IRE1α-targeting might be a strategy to cope with drug resistance of colon cancer. [ABSTRACT FROM AUTHOR]

Group A flavin-dependent monooxygenases catalyze the cleavage of the oxygen-oxygen bond of dioxygen, followed by the incorporation of one oxygen atom into the substrate molecule with the aid of NADPH and FAD. These flavoenzymes play an important role in many biological processes, and their most distinct structural feature is the choreographed motions of flavin, which typically adopts two distinct conformations (OUT and IN) to fulfill its function. Notably, these enzymes seem to have evolved a delicate control system to avoid the futile cycle of NADPH oxidation and FAD reduction in the absence of substrate, but the molecular basis of this system remains elusive. Using protein crystallography, size-exclusion chromatography coupled to multi-angle light scattering (SEC-MALS), and smallangle X-ray scattering (SEC-SAXS) and activity assay, we report here a structural and biochemical characterization of PieE, a member of the Group A flavin-dependent monooxygenases involved in the biosynthesis of the antibiotic piericidin A1. This analysis revealed that PieE forms a unique hexamer. Moreover, we found, to the best of our knowledge for the first time, that in addition to the classical OUT and IN conformations, FAD possesses a "sliding" conformation that exists in between the OUT and IN conformations. This observation sheds light on the underlying mechanism of how the signal of substrate binding is transmitted to the FAD-binding site to efficiently initiate NADPH binding and FAD reduction. Our findings bridge a gap currently missing in the orchestrated order of chemical events catalyzed by this important class of enzymes. [ABSTRACT FROM AUTHOR]

Topic A systematic review and meta-analysis of the genetic association with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD). Clinical Relevance To identify genetic biomarkers that are potentially useful for genetic diagnosis of PCV and for differentiating PCV from nAMD. Methods We performed a literature search in EMBASE, PubMed, Web of Science, and the Chinese Biomedical Database for PCV genetic studies published before February 6, 2015. We then conducted a meta-analysis of all polymorphisms that had sufficient genotype/allele data reported in ≥2 studies and estimated the summary odds ratio (OR) and 95% confidence intervals (CIs) for PCV. We also compared the association profiles between PCV and nAMD, and performed a sensitivity analysis. Results A total of 66 studies were included in the meta-analysis, involving 56 polymorphisms in 19 genes/loci. In total, 31 polymorphisms in 10 genes/loci ( age-related maculopathy susceptibility 2 [ ARMS2 ], high-temperature requirement factor A1 [ HTRA1 ], complement factor H [ CFH ], complement component 2 [ C2 ], CFB , RDBP , SKIV2L , CETP , 8p21, and 4q12) were significantly associated with PCV. Another 25 polymorphisms in 13 genes ( ARMS2 , HTRA1 , C2 , CFB , ELN , LIPC , LPL , ABCA1 , VEGF-A , TLR3 , LOXL1 , SERPING1, and PEDF ) had no significant association. Twelve polymorphisms at the ARMS2-HTRA1 locus showed significant differences between PCV and nAMD. The sensitivity analysis validated the significance of our analysis. Conclusions This study revealed 31 polymorphisms in 10 genes/loci that contribute to PCV susceptibility. Among them, ARMS2-HTRA1 also showed allelic diversity between PCV and nAMD. Our results confirm the gene variants that could affect the phenotypic expressions of PCV and nAMD. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate prostate cancer spatial distribution patterns with transperineal ultrasound navigated 11-region prostate biopsy template in a Chinese screening population. Methods: From May 2004 to December 2007, 215 patients with a median prostate-specific antigen (PSA) level of 21.0 ng/ml were diagnosed with prostate cancer through transperineal ultrasound guided 11-region template prostate biopsy at Peking Union Medical College Hospital. The characteristics of our sample cancer spatial distribution were assessed in relation with different PSA levels. Results: The mean positives for the cancer of regions 1–10 and region 11 (the apical region) were 61.2% vs. 66.4% in patients whose PSA > 20 ng/ml (P = 0.29), and 35.7% vs. 47.6% in patients with PSA ≤ 20 ng/ml (P = 0.001). The positives for cancer contained within the anterior and posterior parts were 96.5% vs. 90.9% (P = 0.10) in patients with PSA > 20 ng/ml and 75.2% vs. 75.2% in patients with PSA ≤ 20 ng/ml (P = 1.00). Conclusions: The current study suggests that prostate carcinoma foci are more frequently localized in the apical region in patients with normal to moderately increased PSA. Special attention should be paid to the apical region during the selection process of biopsy regions for this group of patients. [Copyright &y& Elsevier]