Machine learning-based method for tacrolimus dose predictions in Chinese kidney transplant perioperative patients.

WHAT IS KNOWN AND OBJECTIVES: Tacrolimus (TAC), a first-line immunosuppressant in solid-organ transplant, has a narrow therapeutic window and large inter-individual variability, which affects its use in clinical practice. Successful predictions using machine learning algorithms have been reported in several fields. However, a comparison of 10 machine learning model-based TAC pharmacogenetic and pharmacokinetic dosing algorithms for kidney transplant perioperative patients of Chinese descent has not been reported. The objective of this study was to screen and establish an appropriate machine learning method to predict the individualized dosages of TAC for perioperative kidney transplant patients. METHODS: The records of 2551 patients were collected from three transplant centres, 80% of which were randomly selected as a 'derivation cohort' to develop the dose prediction algorithm, while the remaining 20% constituted a 'validation cohort' to validate the final algorithm selected. Important features were screened according to our previously established population pharmacokinetic model of tacrolimus. The performances of the algorithms were evaluated and compared using R-squared and the mean percentage in the remaining 20% of patients. RESULTS AND DISCUSSION: This study identified several factors influencing TAC dosage, including CYP3A5 rs776746, CYP3A4 rs4646437, haematocrit, Wuzhi capsules, TAC daily dose, age, height, weight, post-operative time, nifedipine and the medication history of the patient. According to our results, among the 10 machine learning models, the extra trees regressor (ETR) algorithm showed the best performance in the training set (R-squared: 1, mean percentage within 20%: 100%) and test set (R-squared: 0.85, mean percentage within 20%: 92.77%) of the derivation cohort. The ETR model successfully predicted the ideal TAC dosage in 97.73% of patients, especially in the intermediate dosage range (>5 mg/day to <8 mg/day), whereby the ideal TAC dosage could be successfully predicted in 99% of the patients. WHAT IS NEW AND CONCLUSION: The results indicated that the ETR algorithm, which was chosen to establish the dose prediction model, performed better than the other nine machine learning models. This study is the first to establish ETR algorithms to predict TAC dosage. This study will further promote the individualized medication of TAC in kidney transplant patients in the future, which has great significance in ensuring the safety and effectiveness of drug use.

Chalcone-1-Deoxynojirimycin Heterozygote Reduced the Blood Glucose Concentration and Alleviated the Adverse Symptoms and Intestinal Flora Disorder of Diabetes Mellitus Rats.

Chalcone-1-deoxynojirimycin heterozygote (DC-5), a novel compound which was designed and synthesized in our laboratory for diabetes treatment, showed an extremely strong in vitro inhibitory activity on α-glucosidase in our previous studies. In the current research, its potential in vivo anti-diabetic effects were further investigated by integration detection and the analysis of blood glucose concentration, blood biochemical parameters, tissue section and gut microbiota of the diabetic rats. The results indicated that oral administration of DC-5 significantly reduced the fasting blood glucose and postprandial blood glucose, both in diabetic and normal rats; meanwhile, it alleviated the adverse symptoms of elevated blood lipid level and lipid metabolism disorder in diabetic rats. Furthermore, DC-5 effectively decreased the organ coefficient and alleviated the pathological changes of the liver, kidney and small intestine of the diabetic rats at the same time. Moreover, the results of 16S rDNA gene sequencing analysis suggested that DC-5 significantly increased the ratio of Firmicutes to Bacteroidetes and improved the disorder of gut microbiota in diabetic rats. In conclusion, DC-5 displayed a good therapeutic effect on the diabetic rats, and therefore had a good application prospect in hypoglycemic drugs and foods.

Effectiveness of a Mobile Device-Based Resilience Training Program in Reducing Depressive Symptoms and Enhancing Resilience and Quality of Life in Parents of Children With Cancer: Randomized Controlled Trial.

BACKGROUND: Caring for children with cancer can be a stressful experience for parents and may have negative effects on their physical and psychological well-being. Although evidence has shown that resilience is associated with positive psychological well-being, few interventions have been specifically designed to enhance the resilience of parents of children with cancer. OBJECTIVE: The aim of this study is to examine the effectiveness of a mobile device-based resilience training program in reducing depressive symptoms and enhancing resilience and quality of life (QoL) in parents of children with cancer. METHODS: Parents of children diagnosed with cancer were recruited from the pediatric oncology wards of 3 tertiary hospitals in China. The participants were randomly assigned to either the experimental group (52/103, 50.5%) to undergo an 8-week mobile device-based resilience training program or to the control group (51/103, 49.5%) to receive an 8-week program of placebo information. The study outcomes included resilience, depressive symptoms, and QoL, as measured by the Connor-Davidson Resilience Scale, the Self-Rating Depression Scale, and the Short Form of the 6-Dimension Health Survey, respectively. All data were collected at baseline and at 2 and 6 months of follow-up. The data analysis followed the intention-to-treat principle. A generalized estimating equation was used to examine the effects of the intervention. RESULTS: The participants were mostly female (72/103, 69.9%), and their mean age was 33.6 (SD 5.2) years. The participants in the experimental group showed significantly higher levels of resilience (mean 67.96, SD 15.8 vs mean 58.27, SD 19.0; P<.001) and lower levels of depressive symptoms (mean 40.17, SD 9.9 vs mean 46.04, SD 10.9; P<.001) than those in the control group at 6 months of follow-up. The intervention showed statistically significant effects in improving resilience (ß=6.082; P=.01) and decreasing depressive symptoms (ß=-2.772; P=.04) relative to the control group. The QoL score in the experimental group was higher than that in the control group at 6 months of follow-up (mean 0.79, SD 0.2 vs mean 0.76, SD 0.3; P=.07); however, no statistically significant intervention effect was detected (ß=.020; P=.38). CONCLUSIONS: The mobile device-based resilience training program effectively enhanced resilience and alleviated depressive symptoms in parents of children with cancer. It is highly recommended that health care professionals incorporate this resilience training program when providing psychological care to parents of children with cancer. TRIAL REGISTRATION: Clinical.Trials.gov NCT04038242; http://clinicaltrials.gov/ct2/show/NCT04038242.

Extracellular Histone Promotes Prostate Cancer Migration and Epithelial-Mesenchymal Transition through NF-κB-Mediated Inflammatory Responses.

INTRODUCTION: This study aims to explore the relationship betweenextracellular histone and prostate cancer and its mechanism. METHODS: Migration of prostate cancer cells was detected by Transwell. Inflammatory factor expression was investigated by ELISA. Epithelial-mesenchymal transition and expression of NF-κB pathway-related proteins were investigated using Western blotting. RESULTS: Under the induction of extracellular histones, the migration rate of prostate cancer cells and the levels of IL-1ß, TNF-α, and IL-6 were notably enhanced. Then, expression of E-cadherin was significantly down-regulated, while levels of N-cadherin, vimentin, ß-catenin, Snail, p-p65 and p-IκBα were significantly up-regulated, which was reversed by PDTC (pyrrolidine dithiocarbamate). CONCLUSION: Extracellular histone significantly promotes the progression of prostate cancer cells via NF-κB pathway-mediated inflammatory responses, which may serve as a novel target for treating prostate cancer.

Neutral-Eosin-Y-Photocatalyzed Silane Chlorination Using Dichloromethane.

Chlorosilanes are versatile reagents in organic synthesis and material science. A mild pathway is now reported for the quantitative conversion of hydrosilanes to silyl chlorides under visible-light irradiation using neutral eosin Y as a hydrogen-atom-transfer photocatalyst and dichloromethane as a chlorinating agent. Stepwise chlorination of di- and trihydrosilanes was achieved in a highly selective fashion assisted by continuous-flow micro-tubing reactors. The ability to access silyl radicals using photocatalytic Si-H activation promoted by eosin Y offers new perspectives for the synthesis of valuable silicon reagents in a convenient and green manner.

Mechanism of the Visible-Light-Mediated Copper-Catalyzed Coupling Reaction of Phenols and Alkynes.

A recent experimental study reported a visible-light-mediated aerobic oxidative coupling reaction of phenol with alkynes that produces hydroxyl-functionalized aryl ketones using inexpensive CuCl as catalyst under mild conditions. Here we apply the complete active space self-consistent field (CASSCF) method and multistate second-order perturbation (MS-CASPT2) theory in combination with density functional theory (DFT) to systematically explore the entire photocatalytic reaction between phenol and phenylacetylene in acetonitrile solution in the presence of molecular oxygen and CuCl. Our main findings are as follows: (1) The visible-light-driven conversion of phenylacetylene to PhCCCu(I) occurs thermally because of efficient excited-state deactivation to the S0 state. (2) The single electron transfer from PhCCCu(I) to molecular oxygen that leads to the PhCCCu(II) cation takes place in the T1 state after an efficient S1 → T1 intersystem crossing. (3) During the initial oxidation of phenol, molecular oxygen prefers to attack the para position of the phenol radical intermediate to produce 1,4-benzoquinone, which further reacts with PhCCCu(II) to generate para-hydroxyl-substituted aryl ketones; this is the origin of the experimentally observed regioselectivity. (4) The C≡C bond of the phenylacetylene moiety is not activated by the triplet-state single electron transfer from PhCCCu(I) to molecular oxygen but is cleaved at a later stage, in the [2+2] cycloaddition between PhCCCu(II) and 1,4-benzoquinone. (5) The substrate phenol plays an active role in several hydrogen transfer and decarboxylation reactions; the barriers to these phenol-assisted reactions are lower than those for the corresponding direct or water-assisted reactions, which explains the experimental finding that adding water does not enhance the photocatalytic reaction yield. In summary, while supporting the general features of the experimentally proposed mechanism, our computational study provides detailed mechanistic insights that should be useful for understanding and further improving visible-light-induced copper-catalyzed coupling reactions.

LIFR promotes tumor angiogenesis by up-regulating IL-8 levels in colorectal cancer.

Leukemia inhibitory factor receptor (LIFR) has been documented as a cancer promoter and to be present at high levels in various types of tumor tissues. In our search for molecules prognostic of colorectal cancer (CRC), we found high levels of LIFR in CRC tissue samples. Further analyses revealed that LIFR was indeed prognostic of CRC patient survival, and was associated with tumor size, lymphatic metastasis and stages. LIFR was found to promote tumor growth, metastasis and angiogenesis both in vitro and in vivo. High levels of LIFR in CRC facilitated proliferation and migration of endothelial cells, resulting in an increase in angiogenic activity. Moreover, interleukin 8 (IL-8) was found to play a role in the LIFR induced angiogenesis. IL-8 levels were correlated with LIFR levels in CRC tissues, whereas depletion of IL-8 led to a reduced angiogenic activity of LIFR in CRC cells. In addition, LIFR increased phosphorylation level of Erk, which regulates il-8 transcription. We conclude that LIFR is possibly a valuable prognostic marker for CRC. Our results also implicate a mechanism by which LIFR regulates tumor angiogenesis through Erk/IL-8 pathway, and that LIFR could be a potential therapeutic target for CRC.

QM/MM studies on ozonolysis of α-humulene and Criegee reactions with acids and water at air-water/acetonitrile interfaces.

Herein, we employed combined CASPT2 and B3LYP electronic structure methods in the framework of the quantum mechanics/molecular mechanics (QM/MM) approach to explore the ozonolysis of α-humulene and subsequent Criegee reactions with acids and water at the air-water/acetonitrile interface as a surrogate for atmospheric aqueous organic media. First, we found that the 1,3-cycloaddition reactions of ozone on α-humulene proceed concertedly and have small barriers (less than 2.5 kcal mol-1) at the QM(CASPT2)/MM level. Second, the five-membered ring cleavage reactions of the generated ozonides are rate-limiting steps and have considerable barriers (more than 10.0 kcal mol-1). These ring-opening reactions are also concerted and simultaneously lead to the cleavage of O-O and C-C bonds, producing sesquiterpene Criegee intermediates at the air-water/acetonitrile interface. Third, although these Criegee intermediates can react with water and acids near the air-water/acetonitrile boundary, the addition reactions with acids have smaller barriers, which range from 2.7 kcal mol-1 of R1-COOH to 5.6 kcal mol-1 of R7-COOH. In contrast, in water addition reactions, several different water-mediated reaction pathways have been disclosed. Their reaction barriers are found to decrease remarkably with an increase in the number of water molecules involved in the reactions. Finally, we found that in addition to low water concentration near the air-water/acetonitrile boundary, distinct reactivities of Criegee intermediates with acids and water play very important roles in the determination of the fates of the Criegee intermediates. Our present QM/MM study provides new mechanistic insights into ozonolysis and Criegee reactions at air-water/acetonitrile interfaces and gives important implications for new particle formation and secondary organic aerosol formation near the marine boundary.

The Origin of the Photoluminescence Enhancement of Gold-Doped Silver Nanoclusters: The Importance of Relativistic Effects and Heteronuclear Gold-Silver Bonds.

The weak photoluminescence of silver nanoclusters prevents their broad application as luminescent nanomaterials. Recent experiments, however, have shown that gold doping can significantly enhance the photoluminescence intensity of Ag29 nanoclusters but the molecular and physical origins of this effect remain unknown. Therefore, we have computationally explored the geometric and electronic structures of Ag29 and gold-doped Ag29-x Aux (x=1-5) nanoclusters in the S0 and S1 states. We found that 1) relativistic effects that are mainly due to the Au atoms play an important role in enhancing the fluorescence intensity, especially for highly doped Ag26 Au3 , Ag25 Au4 , and Ag24 Au5 , and that 2) heteronuclear Au-Ag bonds can increase the stability and regulate the fluorescence intensity of isomers of these gold-doped nanoclusters. These novel findings could help design doped silver nanoclusters with excellent luminescence properties.

Theoretical studies of spin state-specific [2 + 2] and [5 + 2] photocycloaddition reactions of n-(1-penten-5-yl)maleimide.

N-alkenyl maleimides are found to exhibit spin state-specific chemoselectivities for [2 + 2] and [5 + 2] photocycloadditions; but, reaction mechanism is still unclear. In this work, we have used high-level electronic structure methods (DFT, CASSCF, and CASPT2) to explore [2 + 2] and [5 + 2] photocycloaddition reaction paths of an N-alkenyl maleimide in the S1 and T1 states as well as relevant photophysical processes. It is found that in the S1 state [5 + 2] photocycloaddition reaction is barrierless and thus overwhelmingly dominant; [2 + 2] photocycloaddition reaction is unimportant because of its large barrier. On the contrary, in the T1 state [2 + 2] photocycloaddition reaction is much more favorable than [5 + 2] photocyclo-addition reaction. Mechanistically, both S1 [5 + 2] and T1 [2 + 2] photocycloaddition reactions occur in a stepwise, nonadiabatic means. In the S1 [5 + 2] reaction, the secondary C atom of the ethenyl moiety first attacks the N atom of the maleimide moiety forming an S1 intermediate, which then decays to the S0 state as a result of an S1 → S0 internal conversion. In the T1 [2 + 2] reaction, the terminal C atom of the ethenyl moiety first attacks the C atom of the maleimide moiety, followed by a T1 → S0 intersystem crossing process to the S0 state. In the S0 state, the second CC bond is formed. Our present computational results not only rationalize available experiments but also provide new mechanistic insights. © 2017 Wiley Periodicals, Inc.

DFT studies on the mechanism of Ag2 CO3 -catalyzed hydroazidation of unactivated terminal alkynes with TMS-N3 : An insight into the silver(I) activation mode.

Silver-mediated hydroazidation of unactivated alkynes has been developed as a new method for the synthesis of vinyl azides. Density functional theory calculations toward this reaction reveal that terminal alkynes with TMS-N3 participated hydroazidation proceed through HN3 formation, deprotonation and silver acetylides formation, nucleophilic addition, and protonation of terminal carbon by AgHCO3 . It is also found that water molecules and activation modes of Ag (I) have a significant influence on the title reaction mechanism. Initially, catalyst Ag2 CO3 coordinates preferentially with internal N atom of TMS-N3 to assist water as hydrogen source and proton-shuttle in facilitating HN3 formation. Then, the regioselective anti-addition of HN3 to triple bond of active silver-acetylide or ethynyl carbinols affords product vinyl azide via Ag-C σ-bond activation or Ag…C π-coordination activation modes, and the former one is more favorable. The origin of the difference regioselectivity is ascribed to the electronic and orbital effects of the reactive sites. Moreover, Ag2 CO3 is the critical catalyst, acting as activator, base, and stabilizer to promote the HN3 and vinyl azide formation. Water molecule plays an important role as proton shuttle to promote HN3 and key active silver acetylides formation, thus improving the yield of product. © 2017 Wiley Periodicals, Inc.

Genetic variation in STAT4 predicts response to interferon-α therapy for hepatitis B e antigen-positive chronic hepatitis B.

UNLABELLED: Interferon (IFN)-α is a first-line therapy for chronic hepatitis B (CHB) patients but only initiates a response in a minority of patients. A genetic variant, rs7574865 in STAT4, was recently reported to be associated with risk of developing CHB and hepatitis B virus-related hepatocellular carcinoma. We aimed to determine whether this variant is associated with the response to IFNα treatment for hepatitis B e antigen (HBeAg)-positive CHB patients. We studied 466 HBeAg-positive CHB patients who received either IFNα-2b (n = 224) or pegylated IFNα-2a (n = 242) therapy for 48 weeks and were followed for an additional 24 weeks. The rate of sustained virologic response (SVR), defined as HBeAg seroconversion along with hepatitis B virus DNA level <2000 copies/mL at week 72, was compared among patients with different genotypes of rs7574865. After 48 weeks of treatment and 24 weeks off treatment, the SVR rates in the IFNα-2b and pegylated IFNα-2a therapy groups were 30.4% and 28.9%, respectively. Compared to the rs7574865 GT/TT genotype, the GG genotype (a risk factor of CHB and hepatitis B virus-related hepatocellular carcinoma) was significantly associated with a reduced SVR rate in both patients who received IFNα-2b therapy (21.1% versus 37.2%, P = 0.01) and those who received pegylated IFNα-2a therapy (18.0% versus 41.2%, P = 9.74 × 10(-5) ). In joint analysis of the 466 patients, the GG genotype was associated with an approximately half SVR rate compared to the GT/TT genotype (19.3% versus 39.1%, P = 4.15 × 10(-6) ). A multivariate logistic regression model including rs7574865 and clinical variables showed that rs7574865 was the most significant factor for the prediction of SVR. CONCLUSION: STAT4 rs7574865 is a reliable predictor of response to IFNα therapy for HBeAg-positive CHB patients and may be used for optimizing the treatment of CHB.

Silver-mediated radical coupling reaction of isocyanides and alcohols/phenols in the presence of water: unprecedented hydration and radical coupling reaction sequence.

The radical coupling of isocyanides and alcohols/phenols promoted by silver in the presence of water is reported for the first time, which led to the formation of diverse carbamates. In contrast to the well-known 1,1-addition to form imidoyl radicals, a novel reaction mechanism, involving sequential hydration of isocyanides and coupling with alkoxyl/phenoxyl radicals, is disclosed by combining experimental and theoretical studies.

A theoretical study of the light-induced cross-linking reaction of 5-fluoro-4-thiouridine with thymine.

In contrast to photophysics of thio-substituted nucleobases, their photoinduced cross-linking reactions with canonical nucleobases remain scarcely investigated computationally. In this work, we have adopted combined CASPT2/PCM//CASSCF and B3LYP-D3/PCM electronic structure methods to study this kind of photochemical reaction of 5-fluoro-4-thiouridine (truncated 5-fluoro-1-methyl-4-thiouracil used in calculations) and 1-methylthymine (referred to as thymine for clarity hereinafter). On the basis of CASPT2/PCM computed results, we have proposed two efficient excited-state relaxation pathways to populate the lowest T1 state of the complex of 5-fluoro-1-methyl-4-thiouracil and thymine from its initially populated S2(1ππ*) state. In the first one, the S2 system first hops to the S1 state via an S2/S1 conical intersection, followed by a direct S1 → T1 intersystem crossing process enhanced by large S1/T1 spin-orbit coupling. In the second path, the resultant S1 system first jumps to the T2 state, from which an efficient T2 → T1 internal conversion occurs. The T1 cross-linking reaction is overall divided into two phases. The first phase is a stepwise and nonadiabatic photocyclization reaction, which starts from the T1 complex and ends up with an S0 thietane intermediate. The second phase is a thermal reaction. The system first rearranges its four- and six-membered rings to form three new rings; then, an S0 fluorine atom transfer occurs, followed by the formation of photoproducts. Finally, the present work paves the way for studying light-induced cross-linking reactions of thionucleobases with canonical bases in DNA and RNA.

Quantum Chemical Investigation on Photochemical Reactions of Nonanoic Acids at Air-Water Interface.

Photoinduced chemical reactions of organic compounds at the marine boundary layer have recently attracted significant experimental attention because this kind of photoreactions has been proposed to have substantial impact on local new particle formation and their photoproducts could be a source of secondary organic aerosols. In this work, we have employed first-principles density functional theory method combined with cluster models to systematically explore photochemical reaction pathways of nonanoic acids (NAs) to form volatile saturated and unsaturated C9 and C8 aldehydes at air-water interfaces. On the basis of the results, we have found that the formation of C9 aldehydes is not initiated by intermolecular Norrish type II reaction between two NAs but by intramolecular T1 C-O bond fission of NA generating acyl and hydroxyl radicals. Subsequently, saturated C9 aldehydes are formed through hydrogenation reaction of acyl radical by another intact NA. Following two dehydrogenation reactions, unsaturated C9 aldehydes are generated. In parallel, the pathway to C8 aldehydes is initiated by T1 C-C bond fission of NA, which generates octyl and carboxyl radicals; then, an octanol is formed through recombination reaction of octyl with hydroxyl radical. In the following, two dehydrogenation reactions result into an enol intermediate from which saturated C8 aldehydes are produced via NA-assisted intermolecular hydrogen transfer. Finally, two dehydrogenation reactions generate unsaturated C8 aldehydes. In these reactions, water and NA molecules are found to play important roles. They significantly reduce relevant reaction barriers. Our work has also explored oxygenation reactions of NA with molecular oxygen and radical-radical dimerization reactions.

Genetic variants in five novel loci including CFB and CD40 predispose to chronic hepatitis B.

UNLABELLED: Hepatitis B virus affects more than 2 billion people worldwide, 350 million of which have developed chronic hepatitis B (CHB). The genetic factors that confer CHB risk are still largely unknown. We sought to identify genetic variants for CHB susceptibility in the Chinese population. We undertook a genome-wide association study (GWAS) in 2,514 CHB cases and 1,130 normal controls from eastern China. We replicated 33 of the most promising signals and eight previously reported CHB risk loci through a two-stage validation totaling 6,600 CHB cases and 8,127 controls in four independent populations, of which two populations were recruited from eastern China, one from northern China and one from southern China. The joint analyses of 9,114 CHB cases and 9,257 controls revealed significant association of CHB risk with five novel loci. Four loci are located in the human leukocyte antigen (HLA) region at 6p21.3, including two nonsynonymous variants (rs12614 [R32W] in complement factor B [CFB], Pmeta =1.28 × 10(-34) ; and rs422951 [T320A] in NOTCH4, Pmeta = 5.33 × 10(-16) ); one synonymous variant (rs378352 in HLA-DOA corresponding to HLA-DOA*010101, Pmeta = 1.04 × 10(-23) ); and one noncoding variant (rs2853953 near HLA-C, Pmeta = 5.06 × 10(-20) ). Another locus is located at 20q13.1 (rs1883832 in the Kozak sequence of CD40, Pmeta = 2.95 × 10(-15) ). Additionally, we validated seven of eight previously reported CHB susceptibility loci (rs3130542 at HLA-C, rs1419881 at TCF19, rs652888 at EHMT2, rs2856718 at HLA-DQB1, rs7453920 at HLA-DQB2, rs3077 at HLA-DPA1, and rs9277535 at HLA-DPA2, which are all located in the HLA region, 9.84 × 10(-71) ≤ Pmeta ≤ 9.92 × 10(-7) ). CONCLUSION: Our GWAS identified five novel susceptibility loci for CHB. These findings improve the understanding of CHB etiology and may provide new targets for prevention and treatment of this disease.

MiR-608 rs4919510 is associated with prognosis of hepatocellular carcinoma.

Single nucleotide polymorphisms (SNPs) within microRNAs (miRNAs) are considered potential markers for risk and prognosis of various cancers. In the current study, we aimed to determine whether miR-608 rs4919510 affected hepatocellular carcinoma (HCC) prognosis. We genotyped rs4919510 using DNA from blood samples of 362 HCC patients receiving surgical resection of HCC tumor. Associations between rs4919510 and overall survival (OS) and demographic characteristics and clinical features were estimated using the Cox proportional hazards model. Results showed that HCC patients who carried the rs4919510 CC genotype had a significantly longer OS compared to those who carried the GG genotype (P = 0.013, hazard ratio [HR] = 0.600, 95 % confidence interval [CI] 0.402-0.897) and the CG + GG genotype (P = 0.033, HR = 0.681, 95 % CI 0.479-0.970) in univariate analysis. Similar results were obtained in multivariate analysis. Further stratification analysis indicated that rs4919510 was significantly associated with OS in patients who were satisfied with one of the following criteria: male gender, HbsAg-positive, α-fetoprotein (AFP)-positive, tumor size >5 cm, cirrhosis, solitary tumor, I + II pTNM stage, or no tumor capsule. Finally, a significantly higher frequency of rs4919510 CC genotype was observed in patients with cirrhosis (22.9 %, 55/240) than those without cirrhosis (14.0 %, 17/121) (P = 0.047). In conclusion, our results illustrated the potential role of miR-608 rs4919510 as a prognostic marker for HCC patients undergoing surgical resection of the tumor.

miR-492G>C polymorphism (rs2289030) is associated with overall survival of hepatocellular carcinoma patients.

Single-nucleotide polymorphisms (SNPs) of microRNAs (miRNAs) are considered potential markers of cancer risk and prognosis in various cancers. In the current study, the primary aim is to determine whether the miR-492G>C polymorphism (rs2289030) altered hepatocellular carcinoma (HCC) prognosis. The SNP rs2289030 of miR-492 was genotyped using DNA from blood samples of 362 HCC patients that had undergone surgical resection of a HCC tumor. The associations between overall survival and demographic characteristics, clinical features, and the SNP rs2289030 were estimated using the Cox proportional hazards model. Results showed that patients who carried the CG genotype (P = 0.015, hazard ratio [HR] = 0.704, 95 % confidence interval [CI] 0.530-0.934) and CG+GG genotype (P = 0.011, HR = 0.703, 95 % CI 0.536-0.924) had significantly decreased risk of death compared to those with the CC genotype. Similar results were found in the multivariate analysis adjusted by tumor size and venous invasion. Further stratification analysis indicated that the effect of rs2289030 had more prominence in patients ≤50 years old and that reported ever using alcohol, male gender, a family history of HCC, being HbsAg or alpha fetoprotein (AFP) positive, differentiation I + II, presence of venous invasion or cirrhosis, multiple tumors, and pTNM stage I + II. Results from this study illustrate the potential use of miR-492 rs2289030 as a prognostic marker for HCC patients that have undergone a surgical resection of the tumor.

[Study on action mechanism of Danhong injection based on computational system biology approach].

Danhong injection is a compound preparation of traditional Chinese medicine Salvia miltiorrhiza and Carthamus tinctorius, and has been widely applied in treating coronary heart diseases and ischemic encephalopathy in clinic. Despite the complexity of its chemical compounds and the diversity of targets, especially in system biology, there have not a report for its action mechanism as a whole regulatory biological network. In this study, protein data of S. miltiorrhiza and C. tinctorius were searched in TCMGeneDIT database and agilent literature search (ALS) system to establish the multi-component protein network of S. miltiorrhiza, C. tinctorius and Danhong injection. Besides, the protein interaction network was built based on the protein-protein interaction in Genecards, BIND, BioGRID, IntAct, MINT and other databases. According to the findings, 10 compounds of S. miltiorrhiza and 14 compounds of C. tinctorius were correlated with proteins. The 24 common compounds had interactions with 81 proteins, and formed a protein interaction network with 60 none-isolated nodes. The Cluster ONE module was applied to make an enrichment analysis on the protein interaction network and extract one sub-network with significant difference P <0.05. The sub-network contains 23 key proteins, which involved five signaling pathways, namely Nod-like receptor signaling pathway, epithelial cell signaling in helicobacter pylori infection, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway and neurotrophin signaling pathway through KEGG signaling pathway mapping. In this study, the computational system biology approach was adopted to preliminarily explain the molecular mechanism of main compounds of Danhong injection in preventing and treating diseases and provide reference for systematic studies on traditional Chinese medicine compounds.

Band gap engineering of FeS2 under biaxial strain: a first principles study.

The promising photovoltaic activity of pyrite (FeS2) is attributed to its excellent optical absorptivity and earth abundance, but its band gap, 0.95 eV, is slightly lower than the optimum value of 1.3 eV. Here we report the first investigation of strained FeS2, whose band gap can be increased by ∼0.3 eV. The influence of uniaxial and biaxial strains on the atomic structure as well as the electronic and optical properties of bulk FeS2 is systematically examined by the first principles calculations. We found that the biaxial strain can effectively increase the band gap with respect to uniaxial strain. Our results indicate that the band gap increases with increasing tensile strain to its maximum value at 6% strain, but under the increasing compressive strain, the band gap decreases almost linearly. Moreover, the low intensity states at the bottom of the conduction band disappear and a sharp increase in the intensity appears at the lower energy level under the tensile strain, which causes the red shift of the absorption edge and enhances the overall optical absorption. With the increase of the band gap and enhanced optical absorption, FeS2 will make a better photovoltaic material.