High-resolution quantification of hepatitis C virus genome-wide mutation load and its correlation with the outcome of peginterferon-alpha2a and ribavirin combination therapy

Hepatitis C virus (HCV) is a highly mutable RNA virus and circulates as a heterogeneous population in individual patients. The magnitude of such population heterogeneity has long been proposed to be linked with diverse clinical phenotypes, including antiviral therapy. Yet data accumulated thus far are fairly inconclusive. By the integration of long RT-PCR with 454 sequencing, we have built a pipeline optimized for the quantification of HCV genome-wide mutation load at 1% resolution of mutation frequency, followed by a retrospective study to examine the role of HCV mutation load in peginterferon-alpha2a and ribavirin combination antiviral therapy. Genome-wide HCV mutation load varied widely with a range from 92 to 1639 mutations and presented a Poisson distribution among 56 patients (Kolmogorov-Smirnov statistic  = 0.078, p = 0.25). Patients achieving sustained virological response (n = 26) had significantly lower mutation loads than that in null responders (n = 30) (mean and standard derivation: 524±279 vs. 805±271, p = 0.00035). All 36,818 mutations detected in 56 patients displayed a power-law distribution in terms of mutation frequency in viral population. The low-frequency mutation load, but not the high-frequency load, was proportional firmly to the total mutation load. In-depth analyses revealed that intra-patient HCV population structure was shaped by multiple factors, including immune pressure, strain difference and genetic drift. These findings explain previous conflicting reports using low-resolution methods and highlight a dominant role of natural selection in response to therapeutic intervention. By attaining its signatures from complex interaction between host and virus, the high-resolution quantification of HCV mutation load predicts outcomes from interferon-based antiviral therapy and could also be a potential biomarker in other clinical settings

Excessive Accumulation of Chinese Fir Litter Inhibits Its Own Seedling Emergence and Early Growth—A Greenhouse Perspective

Litter accumulation can strongly influence plants’ natural regeneration via both physical and chemical mechanisms, but the relative influence of each mechanism on seedling establishment remains to be elucidated. Chinese fir (Cunninghamia lanceolata) is one of the most important commercial plantations in southern China, but its natural regeneration is poor, possibly due to its thick leaf litter accumulation. We used natural and plastic litter to study the effects of Chinese fir litter on its own seedling emergence and early growth, as well as to assess whether the effect is physical or chemical in nature. Results showed that high litter amount (800 g·m−2) significantly reduced seedling emergence and the survival rate for both natural and plastic litter. Low litter amount (200 g·m−2) exerted a slightly positive effect on root mass, leaf mass, and total mass, while high litter amount significantly inhibited root mass, leaf mass, and total mass for both natural and plastic litter. Root-mass ratio was significantly lower, and leaf-mass ratio was significantly greater under high litter cover than under control for both natural and plastic litter. Although the root/shoot ratio decreased with increasing litter amount, such effect was only significant for high litter treatment for both natural and plastic litter. Seedling robustness (aboveground biomass divided by seedling height) decreased with increasing litter amount, with high litter treatment generating the least robust seedlings. Because plastic and natural litter did not differ in their effects on seedling emergence and growth, the litter layer’s short-term influence is primarily physical. These data indicated that as litter cover increased, the initial slightly positive effects on seedling emergence and early growth could shift to inhibitory effects. Furthermore, to penetrate the thick litter layer, Chinese fir seedlings allocated more resources towards stems and aboveground growth at the expense of their roots. This study provided experimental evidence of litter amount as a key ecological factor affecting seedling development and subsequent natural regeneration of Chinese fir

Locally informed Gravitational Search Algorithm

Gravitational search algorithm (GSA) has been successfully applied to many scientific and engineering applications in the past few years. In the original GSA and most of its variants, every agent learns from all the agents stored in the same elite group, namely Kbest. This type of learning strategy is in nature a fully-informed learning strategy, in which every agent has exactly the same global neighborhood topology structure. Obviously, the learning strategy overlooks the impact of environmental heterogeneity on individual behavior, which easily resulting in premature convergence and high runtime consuming. To tackle these problems, we take individual heterogeneity into account and propose a locally informed GSA (LIGSA) in this paper. To be specific, in LIGSA, each agent learns from its unique neighborhood formed by k local neighbors and the historically global best agent rather than from just the single Kbest elite group. Learning from the k local neighbors promotes LIGSA fully and quickly explores the search space as well as effectively prevents premature convergence while the guidance of global best agent can accelerate the convergence speed of LIGSA. The proposed LIGSA has been extensively evaluated on 30 CEC2014 benchmark functions with different dimensions. Experimental results reveal that LIGSA remarkably outperforms the compared algorithms in solution quality and convergence speed in general

Constructing Phylogenetic Networks Based on the Isomorphism of Datasets

Constructing rooted phylogenetic networks from rooted phylogenetic trees has become an important problem in molecular evolution. So far, many methods have been presented in this area, in which most efficient methods are based on the incompatible graph, such as the CASS, the LNETWORK, and the BIMLR. This paper will research the commonness of the methods based on the incompatible graph, the relationship between incompatible graph and the phylogenetic network, and the topologies of incompatible graphs. We can find out all the simplest datasets for a topology and construct a network for every dataset. For any one dataset C, we can compute a network from the network representing the simplest dataset which is isomorphic to C. This process will save more time for the algorithms when constructing networks

Cutting Force Predication Based on Integration of Symmetric Fuzzy Number and Finite Element Method

In the process of turning, pointing at the uncertain phenomenon of cutting which is caused by the disturbance of random factors, for determining the uncertain scope of cutting force, the integrated symmetric fuzzy number and the finite element method (FEM) are used in the prediction of cutting force. The method used symmetric fuzzy number to establish fuzzy function between cutting force and three factors and obtained the uncertain interval of cutting force by linear programming. At the same time, the change curve of cutting force with time was directly simulated by using thermal-mechanical coupling FEM; also the nonuniform stress field and temperature distribution of workpiece, tool, and chip under the action of thermal-mechanical coupling were simulated. The experimental result shows that the method is effective for the uncertain prediction of cutting force

Bobtraillite from Gejiu hyperagpaitic nepheline syenite, southwestern China: new occurrence and crystal structure

Abstract. A second occurrence of bobtraillite is described from the Gejiu nepheline syenite, southwestern China. The extremely rare and complex boron-bearing zirconium silicate is associated with albite, orthoclase, jadeite, fluorite, andradite, titanite, as well as other REE and zirconium-bearing minerals, catapleiite, moxuanxueite, låvenite, eudialyte, britholite-(Ce), and calcioancylite-(La). The EMP and LA-ICP-MS analyses of the studied material give an empirical formula: (Na9.70Li0.42K0.08□1.80)Σ12.00(Sr10.61Ca1.14Fe0.07□0.18)Σ12.00(Zr12.87Ti0.53Nb0.31REE0.08Y0.06U0.02Th0.01□0.12)Σ14.00(Si42.41B5.59Al0.02)Σ48.02O132(OH)12 ⚫ 12H2O. Bobtraillite is trigonal, with space group P3¯c1, a=19.6977(6), c=9.9770(3) Å, V=3352.4(2) Å3, Z=1. Single-crystal structure refinement revealed that all sodium occupies the Na(1) and Na(2) sites; the site occupancy of these two positions is 0.835(18) and 0.15(2), respectively, suggesting that Na(1) site is Na dominant, while Na(2) is a vacancy-dominant site. The [8]-coordinated site has been assigned to Sr and Ca, with free occupancy factors, 0.874(10) and 0.126(10), respectively. These new data indicate that the ideal formula of bobtraillite could be written as (Na,□)12(□,Na)12Sr12Zr14(Si3O9)10[Si2BO7(OH)2]6 ⚫ 12H2O

Vericiguat combined with “new quadruple” therapy enhances cardiac function and life quality in patients with heart failure: a single-center prospective study

ObjectiveTo investigate the therapeutic effect of Vericiguat combined with “new quadruple” drugs on patients with heart failure (HF).MethodsFrom December 1, 2022 to February 1, 2024, 103 patients with heart failure were consecutively enrolled from the cardiology clinic or ward of the First Affiliated Hospital of Nanjing Medical University. Before enrollment, the patients’ left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), liver and kidney function electrolytes, and Minnesota Living with Heart Failure Questionnaire (MLHFQ) and other indicators were measured. Patients diagnosed with reduced ejection fraction (HFrEF) and with heart failure with mildly reduced ejection fraction (HFmrEF) were treated with Vericiguat combined with “ARNI, BB, MRA, SGLT2i” therapy. Patients diagnosed with preserved ejection fraction (HFpEF) were treated with Vericiguat combined with “ARNI, BB, SGLT2i” therapy. The above indicators were rechecked after 1 month of treatment.ResultsFor all patients, comparison after treatment: LVEF (38.1 ± 8.5% vs. 43.1 ± 8.5%, P < 0.01), LVEDD (60.5 ± 8.1 vs. 58.2 ± 7.3 mm, P < 0.01), NT-proBNP (4,567.8 ± 5,163.9 vs. 1,895.6 ± 2,702.1 ng/L, P < 0.01), MLHFQ (45.72 ± 11.09 vs. 32.29 ± 9.41, P < 0.01). Further subgroup analysis showed that Vericiguat combined with “ARNI, BB, SGLT2i or MRA” improved the LVEF and reduced NT-proBNP levels in patients with HFrEF, HFmrEF or HFpEF. and improved patients’ quality of life scores. The intergroup comparison showed the therapeutic effect of the combination was equivalent in HF caused by myocardial Infarction (MI), dilated cardiomyopathy (DCM) or Valvular Heart Disease (VHD).ConclusionVericiguat combined with the “new quadruple” therapy has a significant therapeutic effect on patients with heart failure caused by MI, DCM or VHD

Causal associations of birth body size and adult body size with systemic lupus erythematosus: a bidirectional mendelian randomization study

ObjectiveBody size is associated with the onset of systemic lupus erythematosus (SLE). However, the evidence for this association is inconclusive. In this study, we aimed to investigate the causal relationship between body size and SLE.MethodWe performed a bidirectional Mendelian randomization (MR) analysis that utilized summary statistics sourced from genome-wide association study (GWAS) data obtained from the IEU Open GWAS project website. The inverse variance weighting (IVW) method was used to evaluate the causality, and four additional MR methods were used to supplement the IVW results. Sensitivity analyses were performed using the Cochran’s Q test, MR-Egger regression, leave-one-out analysis, and the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global test.ResultsIn the forward direction analysis, the IVW model demonstrated that birth weight (odds ratio (OR), 1.811; 95% confidence interval (CI), 1.174–2.793; p < 0.05) and adult height (OR, 1.225; 95% CI, 1.046–1.434; p < 0.05) were positively associated with SLE. Four additional MR scans were performed parallel to the IVW results. Conversely, SLE was a weak causal factor for increased height (OR, 1.010; 95% CI, 1.002–1.018; p < 0.05) using the IVW method. Heterogeneity, MR-Egger intercept, and leave-one-out analyses indicated that the results were robust. The MR-PRESSO suggested the presence of pleiotropy. Following the exclusion of instrumental variables (IVs) inducing pleiotropy, subsequent MR analysis yielded consistent results, thereby reinforcing the robustness of our findings.ConclusionPositive causal associations were observed between birth weight, adult height, and SLE incidence. In the reverse analysis, SLE was a weak causal factor for adult height

Visit-to-visit variability in triglyceride-glucose index and diabetes:A 9-year prospective study in the Kailuan Study

Instruction/Aims: It is unknown whether variability in the triglyceride-glucose index (TyG-index) is associated with the risk of diabetes. Here, we sought to characterize the relationship between TyG-index variability and incident diabetes. Methods: We performed a prospective study of 48,013 participants in the Kailuan Study who did not have diabetes. The TyG-index was calculated as ln [triglyceride (TG, mg/dL) concentration × fasting blood glucose concentration (FBG, mg/dL)/2]. The TyG-index variability was assessed using the standard deviation (SD) of three TyG-index values that were calculated during 2006/07, 2008/09, and 2010/11. We used the Cox proportional hazard models to analyze the effect of TyG-index variability on incident diabetes. Results: A total of 4,055 participants were newly diagnosed with diabetes during the study period of 8.95 years (95% confidence interval (CI) 8.48–9.29 years). After adjustment for confounding factors, participants in the highest and second-highest quartiles had significantly higher risks of new-onset diabetes versus the lowest quartile, with hazard ratios (95% CIs) of 1.18 (1.08–1.29) and 1.13 (1.03–1.24), respectively (P trend< 0.05). These higher risks remained after further adjustment for the baseline TyG-index. Conclusions: A substantial fluctuation in TyG-index is associated with a higher risk of diabetes in the Chinese population, implying that it is important to maintain a normal and consistent TyG-index