Search

Background The aim of this meta-analysis was to explore associations between polymorphisms in CTLA-4/IL-18 and chronic liver diseases by combing the results of all relevant studies. Methods Eligible studies were searched from Pubmed, Embase, Web of Science and Cochrane library. We used Review Manager to combine the results of eligible studies. Results Sixty-seven studies were included in this meta-analysis. Combined results revealed that CTLA-4 rs231775 (dominant, recessive and allele comparisons), IL-18 rs1946518 (dominant, recessive and allele comparisons) and IL-18 rs187238 (dominant, over-dominant and allele comparisons) polymorphisms were all significantly associated with chronic liver diseases in the overall population. We also obtained similar positive results for rs231775, rs5742909, rs3087243, rs1946518 and rs187238 polymorphisms in subgroup analyses by ethnicity and type of disease. Conclusions This meta-analysis demonstrated that CTLA-4 rs231775, CTLA-4 rs5742909, CTLA-4 rs3087243, IL-18 rs1946518 and IL-18 rs187238 polymorphisms may confer susceptibility to certain types of chronic liver diseases.

Modified walnut shell (MWS) was obtained using diethylenetriamine through a grafting reaction and its adsorption capacity toward Cr(VI) was enhanced. The adsorbent was characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), and elemental analysis and the results showed that the modification was effective. To optimize experimental conditions, the effect of temperature, solution pH, salinity, contact time, and Cr(VI) concentration on adsorption quantity were performed in batch mode. It showed that the adsorption ability for Cr(VI) onto MWH can reach 50.1 mg·g−1 at 303 K with solution pH 3. Both the solution pH and salinity had a great impact on the adsorption capacity. The Langmuir model can predict the equilibrium process while the pseudo-second-order model can describe the kinetic process. The Yan model can be used to predict the column process. Additionally, there was also some regeneration ability for Cr-loaded MWH. Consequently, MWS is effective for removing Cr(VI) from solution.

The ship hull form optimization using the Computational Fluid Dynamics (CFD) method is increasingly employed in the early design of a ship, as an optimal ship hull form can obtain good hydrodynamics. However, it is time-consuming due to its many CFD simulations for the optimization. This paper presents a ship hull form optimization loop using the surrogate model, deep belief network (DBN), to reduce the wave-making resistance of the Wigley ship. The prediction performance of the wave-making resistance of the Wigley ship using the DBN method is discussed and compared with the traditional surrogate models found in this study. The results show that the resistance obtained using the deep belief network algorithm is superior to that obtained using the typical surrogate models. Then, a ship hull form optimization framework is built by integrating the Free From Deformation, non-linear programming by quadratic Lagrangian and deep belief network algorithms. The optimization results show that the deep belief network-based ship hull form optimization loop can be used to optimize the Wigley ship. The study presented in this paper could provide a deep learning algorithm for the ship design optimization.

Microreactors are good platforms to study polymerization, but the production of high molecular weight polymers in small reaction space is rather difficult. To obtain million grams/mole molecular weight product, we developed two microreactors to implement inverse suspension polymerization in separated droplets, working as mini-reactors. Protecting by the lubricant film around droplets, 3600 kg/mol polyacrylamide (PAM) was successfully prepared in 38 min residence time, without any clogging issues. Advanced to the batch reactors, the microreactors offered precise control over the whole polymerization process in terms of reaction time and properties of the products, which facilitated the understanding of the basic laws of reactions. Thermal-initiated and redox-initiated radical polymerizations were both investigated, and the thermal-initiated reaction was found to be suitable for preparing high molecular weight polyacrylamide (>1000 kg/mol). The redox-initiated polymerization was a mixing-controlled reaction, which finished quickly in the microreactor.

Mass spectrometry (MS)-based sequencing has advantages in direct sequencing of RNA, compared to cDNA-based RNA sequencing methods, as it is completely independent of enzymes and base complementarity errors in sample preparation. In addition, it allows for sequencing of different RNA modifications in a single study, rather than just one specific modification type per study. However, many technical challenges remain in de novo MS sequencing of RNA, making it difficult to MS sequence mixed RNAs or to differentiate isomeric modifications such as pseudouridine (Ψ) from uridine (U). Our recent study incorporates a two-dimensional hydrophobic end labeling strategy into MS-based sequencing (2D-HELS MS Seq) to systematically address the current challenges in MS sequencing of RNA, making it possible to directly and de novo sequence purified single RNA and mixed RNA containing both canonical and modified nucleotides. Here, we describe the method to sequence representative single-RNA and mixed-RNA oligonucleotides, each with a different sequence and/or containing modified nucleotides such as Ψ and 5-methylcytosine (m5C), using 2D-HELS MS Seq.

Post-transcriptional modifications are intrinsic to RNA structure and function. However, methods to sequence RNA typically require a cDNA intermediate and are either not able to sequence these modifications or aretailored to sequence one specific nucleotide modification only. Interestingly, some of these modifications occur with Phe without cDNA by integrating atwo-dimensional hydrophobic RNA end-labeling strategy with an anchor-based algorithm in mass spectrometry-based sequencing (2D-HELS-AA MS Seq). The entire tRNAPhe was sequenced and the identity, location, and stoichiometry of all eleven different RNA modifications was determined, five of which were not 100% modified, including a 2'-O-methylated G (Gm) in the wobble anticodon position as well as an N2, N2-dimethylguanosine (m22G), a7-methylguanosine (m7G), a1-methyladenosine (m1A), and awybutosine (Y), suggesting numerous post-transcriptional regulations in tRNA. Two truncated isoforms at the 3'-CCA tail of the tRNAPhe (75 nt with a 3'-CC tail (80% abundance) and 74 nt with a 3'-C tail (3% abundance)) were identified in addition to the full-length 3'-CCA-tailed tRNAPhe (76 nt, 17% abundance). We discovered a new isoform with A-G transitions/editing at the 44 and 45 positions in the tRNAPhe variable loop, and discuss possible mechanisms related to the emergence and functions of the isoforms with these base transitions or editing. Our method revealed new isoforms, base modifications, and RNA editing as well as their stoichiometries in the tRNA that cannot be determined by current cDNA-based methods, opening new opportunities in the field of epitranscriptomics.

In order to reduce the resistance and improve the hydrodynamic performance of a ship, two hull form design methods are proposed based on the potential flow theory and viscous flow theory. The flow fields are meshed using body-fitted mesh and structured grids. The parameters of the hull modification function are the design variables. A three-dimensional modeling method is used to alter the geometry. The Non-Linear Programming (NLP) method is utilized to optimize a David Taylor Model Basin (DTMB) model 5415 ship under the constraints, including the displacement constraint. The optimization results show an effective reduction of the resistance. The two hull form design methods developed in this study can provide technical support and theoretical basis for designing green ships.

The seakeeping behavior of a ship in waves is different from its behavior in calm water. The resistance and seakeeping performance of a ship are of great importance and must be considered in the early-stage design of a ship’s hull form design. Therefore, this paper proposes a hull form optimization framework aiming to achieve the minimum total resistance in waves using a CFD technique. A sinusoidal wave is adopted to establish the numerical wave tank and the overset mesh technique is used to facilitate the motions of the ships in question. Considering the motions of pitching and heaving, the total resistance of the hull in waves is regarded as the objective function which is calculated using the Reynolds averaged Navier–Stokes (RANS) method. The arbitrary shape deformation (ASD) technique is used to change the geometry. Under displacement and design variables, a hybrid algorithm is developed to evaluate the objective function combining the optimal Latin hypercube design (Opt LHD) and the non-linear programming by quadratic Lagrangian (NLPQL) algorithm. Finally, two examples of hull form optimization are presented and discussed for David Taylor Model Basin (DTMB) model 5512 and WIGLEY III cases. The results show the effectiveness of the optimization framework developed in the present study, which can lay the foundation for further optimization of full-scale ships.

Different seasonal health effects of ambient ozone (O3) have been reported in previous studies. This might be due to inappropriate adjustment of temperature in different seasons. We used daily data on non-accidental mortality and ambient air pollution in Zhengzhou from January 19, 2013 to June 30, 2015. Season-stratified analyses using generalized additive models were conducted to evaluate the seasonal associations with adjustment of temperature with different lagged days (lag0-1 for warm season, lag0-14 for cold season). We recorded a total of 70,443 non-accidental deaths in Zhengzhou during the study period. Significant associations were observed between ambient O3 and mortality in cold season. Every 10-μg/m3 increment of 24-h O3 of 1-day lagged time was associated with a 1.38% (95% CI 0.60, 2.16%) increase in all cause mortality, 1.35% (95% CI 0.41, 2.30%) increase in cardiovascular mortality, and 1.78% (95% CI 0.43, 3.14%) increase in respiratory mortality. Similar associations were observed when using daily 1- and 8-h maximum concentrations of O3. No significant association was found during warm season. This study suggests a more pronounced ozone-mortality association in cold season in Zhengzhou, and we suggest that different lagged temperatures should be considered when examining the seasonal health effects of ambient ozone.

We report a direct method for sequencing tRNAPhe without cDNA by combining 2-dimensional hydrophobic RNA end-labeling with an anchor-based algorithm in mass spectrometry-based sequencing (2D-HELS-AA MS Seq). The entire tRNAPhe was sequenced and the identity, location and abundance of all 11 base modifications were determined. Changes in ratios of wybutosine and its depurinated form under different conditions were quantified, pointing to the ability of our technology to determine dynamic changes of nucleotide modifications. Two truncated isoforms at 3’CCA tail of the tRNAPhe (75 nt CC, 80% and 74 nt C, 3%) were identified in addition to the 76 nt tRNAPhe with a full-length 3’CCA tail (17%). We also discovered a new isoform with A-G transitions at both the 44 and 45 positions in the tRNAPhe variable loop.One Sentence SummaryDirect 2D-HELS-AA MS Seq of tRNA reveals different isoforms and base modifications

A complete understanding of the structural and functional potential of RNA requires understanding of chemical modifications and noncanonical bases; this in turn requires advances in current sequencing methods to be able to sequence not only canonical ribonucleotides, but at the same time directly sequence these nonstandard moieties. Here, we present the first direct and modification type-independent RNA sequencing method via integration of a hydrophobic end-labeling strategy with of 2-D mass-retention time LC/MS analysis to allow de novo sequencing of RNA mixtures and enhance sample usage efficiency. Our method can directly read out the complete sequence, while identifying, locating, and quantifying base modifications accurately in both single and mixed RNA samples containing multiple different modifications at single-base resolution. Our method can also quantify stoichiometry/percentage of modified RNA vs. its canonical counterpart RNA, simulating a real biological sample where modifications exist but may not be 100% at a particular site of the RNA. This method is a critical step towards fully sequencing real complex cellular RNA samples of any type and containing any modification types and can also be used in the quality control of modified therapeutic RNAs.

In order to reduce the total resistance of a hull, an optimization framework for the bulbous bow optimization was presented. The total resistance in calm water was selected as the objective function, and the overset mesh technique was used for mesh generation. RANS method was used to calculate the total resistance of the hull. In order to improve the efficiency and smoothness of the geometric reconstruction, the arbitrary shape deformation (ASD) technique was introduced to change the shape of the bulbous bow. To improve the global search ability of the particle swarm optimization (PSO) algorithm, an improved particle swarm optimization (IPSO) algorithm was proposed to set up the optimization model. After a series of optimization analyses, the optimal hull form was found. It can be concluded that the simulation based design framework built in this paper is a promising method for bulbous bow optimization.

With the rapid development of the computational technology, computational fluid dynamics (CFD) tools have been widely used to evaluate the ship hydrodynamic performances in the hull forms optimization. However, it is very time consuming since a great number of the CFD simulations need to be performed for one single optimization. It is of great importance to find a high-effective method to replace the calculation of the CFD tools. In this study, a CFD-based hull form optimization loop has been developed by integrating an approximate method to optimize hull form for reducing the total resistance in calm water. In order to improve the optimization accuracy of particle swarm optimization (PSO) algorithm, an improved PSO (IPSO) algorithm is presented where the inertia weight coefficient and search method are designed based on random inertia weight and convergence evaluation, respectively. To improve the prediction accuracy of total resistance, a data prediction method based on IPSO-Elman neural network (NN) is proposed. Herein, IPSO algorithm is used to train the weight coefficients and self-feedback gain coefficient of ElmanNN. In order to build IPSO-ElmanNN model, optimal Latin hypercube design (Opt LHD) is used to design the sampling hull forms, and the total resistance (objective function) of these hull forms are calculated by Reynolds averaged Navier–Stokes (RANS) method. For the purpose of this paper, this optimization framework has been employed to optimize two ships, namely, the DTMB5512 and WIGLEY III ships, and these hull forms are changed by arbitrary shape deformation (ASD) technique. The results show that the optimization framework developed in this study can be used to optimize hull forms with significantly reduced computational effort.

2΄-5΄-linked RNAs play important roles in many biological systems. In addition, the mixture of 2΄-5΄ and 3΄-5΄ phosphodiester bonds have emerged as a plausible structural element in prebiotic RNAs. Toward our mechanistic studies of RNA folding and structures with heterogeneous backbones, we recently reported two crystal structures of a decamer RNA duplex containing two and six 2΄-5΄-linkages, showing how RNA duplexes adjust the structures to accommodate these non-canonical linkages (Proc. Natl. Acad. Sci. USA, 2014, 111, 3050–3055). Herein, we present two additional high-resolution crystal structures of the same RNA duplex containing four and eight 2΄-5΄-linkages at different positions, providing new insights into the effects of these modifications and a dynamic view of RNA structure changes with increased numbers of 2΄-5΄-linkages in the same duplex. Our results show that the local structural perturbations caused by 2΄-5΄ linkages can be distributed to nearly all the nucleotides with big ranges of changes in different geometry parameters. In addition, hydration pattern and solvation energy analysis indicate less favorable solvent interactions of 2΄-5΄-linkages comparing to the native 3΄-5΄-linkages. This study not only promotes our understanding of RNA backbone flexibility, but also provides a knowledge base for studying the biochemical and prebiotic significance of RNA 2΄-5΄-linkages.

A fast and accurate pathway for nonenzymatic RNA replication would simplify models for the emergence of the RNA world from the prebiotic chemistry of the early earth. However, numerous difficulties stand in the way of an experimental demonstration of effective nonenzymatic RNA replication. To gain insight into the necessary properties of potentially self-replicating informational polymers, we have studied several model systems based on amino-sugar nucleotides. Here we describe the synthesis of N3'-P5'-linked phosphoramidate DNA (3'-NP-DNA) by the template-directed polymerization of activated 3'-amino-2',3'-dideoxyribonucleotides. 3'-NP-DNA is an interesting model because of its very RNA-like A-type duplex conformation and because activated 3'-amino-2',3'-dideoxyribonucleotides are much more reactive than the corresponding activated ribonucleotides. In contrast to our previous studies with 2'-amino-2',3'-dideoxyribonucleotides (for which G and C but not A and T exhibit efficient template copying), we have found that all four canonical 3'-amino-2',3'-dideoxyribonucleotides (G, C, A, and T) polymerize efficiently on RNA templates. RNA templates are generally superior to DNA templates, and oligo-ribo-T templates are superior to oligo-ribo-U templates, which are the least efficient of the RNA homopolymer templates. We have also found that activation of 3'-aminonucleotides with 2-methylimidazole results in a ca. 10-fold higher polymerization rate relative to activation with imidazole, an observation that parallels earlier findings with ribonucleotides. We discuss the implications of our experiments for the possibility of self-replication in the 3'-NP-DNA and RNA systems.

A three-dimensional (3D) structural modeling of the Lower Cambrian–Upper Permian Yubei 3D area was performed to understand its structural evolution. This model reproduces the present-day structure of the basin and comprises 11 horizons within Lower Cambrian to Upper Permian rocks. The analysis is based on 3D depth views and faults. The results image salt movements due to tectonics and/or burial. From these observations, this paper deduces that salt structures are correlated to the main faults and tectonic events. From the model analysis, we interpret the timing and geometry of Tarim Basin tectonics. The fault geometry can be resolved based on the strike of the fault, the morphology of hanging wall strata, and the stratigraphic distribution. Emphasis is placed on gypsum rock detachment, considering its movements during the Middle Caledonian event and decoupling effects during tectonic evolution. Moreover, we point to the structural control of the Paleozoic basement and the crustal architecture (Yubei 3D Zone) on the geometry of the Tarim Basin.

Template-directed polymerization of chemically activated ribonucleotide monomers, such as nucleotide 5'-phosphorimidazolides, has been studied as a model for nonenzymatic RNA replication during the origin of life. Kinetic studies of the polymerization of various nucleotide monomers on oligonucleotide templates have suggested that the A-form (C3'-endo sugar pucker) conformation is optimal for both monomers and templates for efficient copying. However, RNA monomers are predominantly in the C2'-endo conformation when free in solution, except for cytidine, which is approximately equally distributed between the C2'-endo and C3'-endo conformations. We hypothesized that ribonucleotides undergo a switch in sugar pucker upon binding to an A-type template and that this conformational switch allows or enhances subsequent polymerization. We used transferred nuclear Overhauser effect spectroscopy (TrNOESY), which can be used for specific detection of the bound conformation of small-molecule ligands with relatively weak affinity to receptors, to study the interactions between nucleotide 5'-phosphorimidazolides and single-stranded oligonucleotide templates. We found that the sugar pucker of activated ribonucleotides switches from C2'-endo in the free state to C3'-endo upon binding to an RNA template. This switch occurs only on RNA and not on DNA templates. Furthermore, activated 2'-deoxyribonucleotides maintain a C2'-endo sugar pucker in both the free and template-bound states. Our results provide a structural explanation for the observations that activated ribonucleotides are superior to activated deoxyribonucleotides and that RNA templates are superior to DNA templates in template-directed nonenzymatic primer-extension reactions.