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At present, peptidoglycan (PGN) is commonly used as an immunostimulant in shrimp. However, little has been known about its mechanism. In this study, comparative transcriptome analysis was employed to investigate the impact of dietary PGN on the immune response in Litopenaeus vannamei. A total of 720 healthy juvenile L. vannamei (initial weight 0.31 ± 0.05 g) were randomly evenly allocated to 18 fibreglass buckets as 6 groups, fed with six isonitrogen (41.05%) and isolipid diets (8.16%) containing PGN at the doses of 0 (control), 0.2, 1, 5, 25, and 125 mg/kg, respectively. After 8 weeks feeding trail, the growth performance, immunity, and transcriptome response of L. vannamei were analyzed. The results showed that the growth performance of L. vannamei was not significantly influenced by dietary PGN (P > 0.05). According to the analysis of weight gain rate (WGR), the optimum dietary PGN level was 71.46 mg/kg. Compared with the control group, the survival rate (SR) after Vibrio parahaemolyticus infection of L. vannamei were significantly increased by dietary PGN at 5 mg/kg and the SR after white spot syndrome virus (WSSV) infection was improved by dietary PGN at 25 mg/kg (P

The type of protein source in diets has many effects on shrimp. In this study, Litopenaeus vannamei with an initial body weight of 3.68 ± 0.002 g were fed for 8 weeks on three experimental diets (isoproteic: 41.00%; isolipidic: 7.61%) that were formulated using fish meal (FM), Chlorella sorokiniana (CHL), and Clostridium autoethanogenum protein (CAP) as the primary protein sources, respectively. This study examined the growth, non-specific immunity, intestinal digestion, and microbiota of L. vannamei after the feeding experiment concluded. Compared to the FM group, the findings indicate that the weight gain rate (WGR), specific growth rate (SGR), and protein efficiency ratio (PER) of L. vannamei were notably enhanced via dietary CAP. The CHL group exhibited the highest levels of catalase (CAT), phenoloxidase (PO), and superoxide dismutase (SOD) activities in the gills of L. vannamei, whereas the FM group had the lowest levels. Conversely, the malondialdehyde (MDA) content showed the opposite trend. Both dietary CHL and CAP promoted the digestive enzyme activities of L. vannamei, with dietary CAP having a more pronounced promotional effect. An analysis of alpha diversity indicated that the consumption of dietary CHL substantially enhanced the abundance and diversity of microbiota in the intestinal tract of L. vannamei. Furthermore, the dietary CHL significantly increased the colonization of immune-associated beneficial bacteria and inhibited the colonization of pathogenic bacteria in the intestinal tract of L. vannamei, whereas dietary CAP mainly increased the colonization of growth-associated beneficial bacteria. Functional predictions showed that different dietary protein sources affect various metabolic activities and signaling pathways of L. vannamei, and some functions, including signal transduction, cell motility, and the immune system, were significantly enhanced in the CHL group. In summary, both dietary CHL and dietary CAP promoted growth and immunity in L. vannamei compared to dietary FM. The results of this study could be helpful for the sustainable development of shrimp farming.

The effects of dietary zymosan A on the growth performance and histological structure, digestive capacity, and microbiota were investigated in Litopenaeus vannamei, an important shrimp species used in aquaculture. L. vannamei (initial body weight = 0.41 ± 0.05 g) were fed diets supplemented with zymosan-A at doses of 0 mg/kg (Z0, control), 1 mg/kg (Z1), 5 mg/kg (Z5), 25 mg/kg (Z25), 125 mg/kg (Z125), or 625 mg/kg (Z625) for 8 weeks. The results showed that doses of 25 and 125 mg/kg significantly increased the final body weight, weight gain rate (WGR), and specific growth rate (SGR) and significantly decreased the feed conversion rate compared with the controls (p < 0.05). Analyses of the WGR and SGR revealed that the optimum dietary zymosan-A levels were 308.56 and 300.00 mg/kg, respectively. Compared with the controls, the intestinal villus height was significantly increased by the addition of zymosan-A at doses ≥25 mg/kg (p < 0.05). An obvious upregulation of the activities of trypsin and amylase was observed in all groups that received zymosan-A supplementation, while the activity of lipase was significantly increased in groups Z125 and Z625 (p < 0.05). Consistently, the gene expressions of trypsin and lipase were significantly higher in group Z125, while the gene expression of amylase was significantly increased in all zymosan-A-supplemented groups (p < 0.05). Analysis of the intestinal microbiota showed significant differences in the alpha diversity between group Z125 and controls. The supplemented groups showed altered intestinal bacterial community structures and compositions at the phylum, family, and genus levels, with statistical differences observed in the relative abundances of some dominant species. Tax4Fun predictions of the microbiota indicated that multiple intestinal functions were significantly altered in all zymosan-A-supplemented groups, except Z1. Among these groups, the functions related to transport and catabolism, substance dependence, cardiovascular disease, and signaling molecules and interactions were obviously increased by the addition of zymosan-A at different levels. In conclusion, dietary supplementation of the optimum amount of zymosan-A can improve growth and intestinal function in L. vannamei, which will be valuable in aquaculture.

Wnt/β-catenin signalling plays an essential role in the immunity of Penaeus vannamei. In this study, the effects of dietary Wnt/β-catenin pathway activator TWS119 on the growth, immunity, and transcriptome response in P. vannamei were investigated. Penaeus vannamei were fed diets with added TWS119 at doses of 0 (T0), 0.25 (T0.25), 1 (T1), 4 (T4), 16 (T16), or 64 mg·kg−1 (T64), respectively. LvGSK3β activity was effectively inhibited in P. vannamei given TWS119. The growth of P. vannamei in the T16 group was significantly improved when compared with the control group. After Vibrio parahaemolyticus infection, the survival rates (SRs) of P. vannamei in all experimental groups except the T64 group were significantly higher than in the T0 group. Compared with the control group, the immune enzymes’ activities in the serum of P. vannamei increased in all the experimental groups, while the malondialdehyde (MDA) contents decreased. Transcriptome analysis identified 5,073 differentially expressed genes (DEGs) for P. vannamei in the T0 and T16 groups. Most of the DEGs are involved in the ribosome pathway, endocytosis, glycerophospholipid metabolism, Wnt signalling, and FoxO =signalling pathways. The majority of the DEGs were from the ribosome pathway, which is also the most significantly enriched pathway. The study confirmed that the growth and immunity status of P. vannamei could improve by increasing dietary TWS119, which probably regulates the activity of the Wnt/β-catenin pathway and may be closely related to ribosome function and energy metabolism.

Glycogen synthase kinase-3 (GSK3), a cytoplasmic serine/threonine-protein kinase involved in a large number of key cellular processes, is a little-known signaling molecule in virus study. In this study, a GSK3 protein which was highly similar to GSK3β homologs from other species in Litopenaeus vannamei (designated as LvGSK3β) was obtained. LvGSK3β was expressed constitutively in the healthy L. vannamei, at the highest level in the intestine and the lowest level in the eyestalk. White spot syndrome virus (WSSV) reduced LvGSK3β expression was in immune tissues including the hemocyte, intestine, gill and hepatopancreas. The inhibition of LvGSK3β resulted in significantly higher survival rates of L. vannamei during WSSV infection than the control group, and significantly lower WSSV viral loads in LvGSK3β-inhibited L. vannamei were observed. Knockdown of LvGSK3β by RNAi resulted in increases in the expression of LvDorsal and several NF-κB driven antimicrobial peptide (AMP) genes (including ALF, PEN and crustin), but a decrease in LvCactus expression. Accordingly, overexpression of LvGSK3β could reduce the promoter activity of LvDorsal and several AMPs, while the promoter activity of LvCactus was increased. Electrophoretic mobility shift assays (EMSA) showed that LvDorsal could bind to the promoter of LvGSK3β. The interaction between LvGSK3β and LvDorsal or LvCactus was confirmed using co-immunoprecipitation (Co-IP) assays. In addition, the expression of LvGSK3β was dramatically reduced by knockdown of LvDorsal. In summary, the results presented in this study indicated that LvGSK3β had a negative effect on L. vannamei by mediating a feedback regulation of the NF-κB pathway when it is infected by WSSV.

Biochemical fulvic acid (BFA), produced by organic wastes composting, is the complex organic matter with various functional groups. A novel modified biochemical fulvic acid (MBFA) which possessed stronger chelating ability had been synthesized by the grafting copolymerization of BFA and acrylic acid (AA). Results showed that MBFA effectively inhibited the crystallization of calcium phosphate and increased the concentration of phosphate in water solution. The optimum reaction conditions optimized by Box–Behnken design and response surface methodology were reaction temperature 69.24 °C, the mass of monomer to fulvic acid ratio 0.713, the initiator dosage 19.78%, and phosphate crystal-inhibition extent was 96.89%. IR spectra demonstrated AA was grafted onto BFA. XRD data and SEM images appeared the formation and growth of calcium phosphate crystals was effectively inhibited by MBFA.

Stochastic Brownian dynamics is an extremely powerful way to simulate the polymer dynamics in solutions and melts. Mathematically, these models are described by stochastic differential equations. The most challenging problems are the Monte Carlo algorithm, which simulates the motion of a large number of model particles and hence requires an enormous amount of computer time. It is therefore necessary to develop an efficient numerical method in operational emergency response applications. In this paper, we give an improved multilevel Monte Carlo (improved-MLMC) method based on equilibrium control variables at each level to calculate the propagation of polymers. The improved-MLMC method can be shown to result in asymptotically optimal random errors and reduce total cost when compared to the standard Monte Carlo and MLMC methods. Finally, the effect of the Wi number (dimensionless parameter) on the total cost of the presented MLMC method is also discussed in detail.

Abstract Background Robust data regarding genotype–phenotype correlations in left ventricular noncompaction cardiomyopathy (LVNC) are lacking. Methods About 72 cardiomyopathy‐related genes were comprehensively screened in a cohort of LVNC patients using targeted sequencing. Baseline and follow‐up data were collected. The primary endpoint was a composite of death and heart transplantation. Results A total of 83 unrelated adult patients were included in analyses. Following stringent classification according to the American College of Medical Genetics and Genomics (ACMG) guidelines, 36 pathogenic variants of 14 genes were detected in 32 patients. Among them, 12 patients carried at least one nonsarcomere variant (NSV). At baseline, NSV carriers had a higher frequency of atrial fibrillation, but lower left ventricular ejection fraction, than did noncarriers. During a median follow‐up of 4.2 years, NSV carriers experienced a higher rate of the primary endpoint compared with noncarriers. There was no significant difference in the rate between carriers of sarcomere variant (SV) and noncarriers, as well as between carriers of SV and NSV. The presence of NSV was associated with an increased risk of the primary endpoint independent of age, sex, and cardiac function (hazard ratio: 3.61, 95% confidence interval: 1.42–9.19, p = .002). Conclusion NSV may act as a genetic modifier and worsen the clinical phenotype in patients with LVNC.

Yellow phosphorus slag (YPS) is a typical industrial solid waste, while it contains abundant silicon micronutrient required for the growth of rice. The key scientific problem to use the YPS as rice fertilizer is how to activate the slag efficiently during the phosphorite reduction smelting process. In this work, an alkaline rice fertilizer from the activated YPS was successfully prepared to use the micronutrients. Thermodynamic analyses of SiO2-CaO, SiO2-CaO-Al2O3, and SiO2-CaO-Al2O3-MgO systems were discussed to optimize the acidity for reduction smelting. Results showed that the reduction smelting followed by the water quenching process can realize the reduction of phosphorite and activation of YPS synchronously. Ternary acidity m(SiO2)/(m(CaO) + m(MgO)) of 0.92 is suitable for the reduction smelting and activation of the slag. After smelting, the molten YPS can be effectively activated by water quenching, and 78.28% P, 90.03% Ca, and 77.12% Si in the YPS are activated, which can be readily absorbed by the rice roots. Finally, high-strength granular rice fertilizers with a particle size of Φ2–4 mm were successfully prepared from the powdery nitrogen-phosphorus-potassium (NPK) and activated YPS mixture.

Background Left ventricular noncompaction cardiomyopathy (LVNC) is a genetically and phenotypically heterogeneous disease. This study aims to investigate the genetic basis and genotype‐phenotype correlations in a cohort of Chinese patients with LVNC. Methods and Results A total of 72 cardiomyopathy‐associated genes were comprehensively screened in 83 adults and 17 children with LVNC by targeted sequencing. Pathogenicity of the detected variants was determined according to their prevalence and American College of Medical Genetics and Genomics recommendations. Baseline and follow‐up clinical data were collected. The primary end point was a composite of death and heart transplantation. Overall, 42 pathogenic variants were identified in 38 patients (38%), with TTN, MYH7, MYBPC3, and DSP being the most commonly involved genes. At baseline, genotype‐positive adults had higher rates of atrial fibrillation and family history, and lower left ventricular ejection fraction, compared with genotype‐negative adults. During a median follow‐up of 4.2 years, more primary end points occurred in genotype‐positive adults than in genotype‐negative adults (50.0% versus 23.5%; P=0.013). Multivariable analysis demonstrated that genotype‐positive status was associated with higher risks of death and heart transplantation, independent of age, sex, and cardiac function at baseline in patients with LVNC (adjusted hazards ratio, 2.49; 95% confidence interval, 1.15–5.37; P=0.020). Conclusions Our study revealed a distinct genetic spectrum in Chinese patients with LVNC, with variants in TTN, MYH7, MYBPC3, and DSP being the most common. The presence of pathogenic variants is an independent risk factor for adverse outcomes and may aid in risk stratification in adult patients. Larger studies are needed to confirm these findings.

Aims: Two LMNA mutations (R644C and R190W) have been associated with familial and sporadic left ventricular non-compaction (LVNC). However, the mechanisms underlying these associations have not been elucidated.Methods and Results: Genomic DNA was isolated from peripheral blood leucocytes and analysed by direct sequencing. Human embryonic kidney 293 cells were transfected with either wild type or mutant LMNA and SCN5A for whole-cell patch-clamp experiment and fluorescence microscopy. Point mutation modeling for mutant LMNA was also performed. One novel LVNC-associated mutation (V445E) in β2 sheet of immunoglobulin (Ig)-like fold was found in the proband and his father. We also found that the peak current of sodium channel was markedly reduced in mutant LMNA compared with WT while the activation, inactivation, and recovery curves were not significantly altered. The mutant lamin A/C were aggregated into multiple highlighted particles. Three β sheets and multiple side chains in Ig-like fold were altered due to the replacement of a valine by glutamic acid.Conclusion: Our data associated a novel lamin A/C mutation (V445E) with a sudden death form of familial LVNC. The reduced sodium current in mutant LMNA may account for the advent of malignant ventricular arrhythmias. The altered structures of three β sheets and side chains may partially explain the aggregation of lamin A/C protein subjacent to the nuclear envelope. [ABSTRACT FROM AUTHOR]

Background: Although cardiovascular magnetic resonance (CMR) is showing increasingly diagnostic potential in left ventricular non-compaction (LVNC), relatively little research relevant to CMR is conducted in children with LVNC. This study was performed to characterize and compare CMR features and clinical outcomes in children with LVNC with and without late gadolinium enhancement (LGE). Methods: A cohort of 40 consecutive children (age, 13.7 ± 3.3 years; 29 boys and 11 girls) with isolated LVNC underwent a baseline CMR scan with subsequent clinical follow-up. Short-axis cine images were used to calculate left ventricular (LV) ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), myocardial mass, ratio of non-compacted-to- compacted myocardial thickness (NC/C ratio), and number of non-compacted segments. The LGE images were analyzed to assess visually presence and patterns of LGE. The primary end point was a composite of cardiac death and heart transplantation. Results: The LGE was present in 10 (25 %) children, and 46 (27 %) segments were involved, including 23 non-compacted segments and 23 normal segments. Compared with LGE- cohort, LGE+ cohort had significantly lower LVEF (23.8 ± 10.7 % vs. 42.9 ± 16.7 %, p < 0.001) and greater LVEDV (169.2 ± 65.1 vs. 118.2 ± 48.9 mL/m², p = 0.010), LVESV (131.3 ± 55.5 vs. 73.3 ± 46.7 mL/m², p = 0.002), and sphericity indices (0.75 ± 0.19 vs. 0.60 ± 0.20, p = 0.045). There were no differences in terms of number and distribution of non-compacted segments, NC/C ratio, and myocardial mass index between LGE+ and LGE- cohort. In the LGE+ cohort, adverse events occurred in 6 patients compared to 2 events in the LGE- cohort. Kaplan-Meier analysis showed a significant difference in outcome between LGE+ and LGE- cohort for cardiac death and heart transplantation (p = 0.011). Conclusions: The LGE was present in up to one-fourth of children with LVNC, and the LGE+ children exhibited a more maladaptive LV remodeling and a higher incidence of cardiovascular death and heart transplantation. [ABSTRACT FROM AUTHOR]

Background: Variants in NOS1AP associated with cardiac repolarization and sudden cardiac death (SCD) in coronary artery disease have been reported. Whether they are related to mortality and QTc interval in chronic heart failure (CHF) has not been investigated. Methods and Results: A total of 1,428 patients with CHF and 480 control subjects were genotyped for 6 SNPs of NOS1 AP, and the genetic associations with mortality as well as QTc interval were analyzed. During a median follow-up period of 52 months, 467 patients (32.70%) died, of which deaths 169 (36.19%) were SCD. The A allele of rsl2567209 was associated with greater risk of all-cause death and SCD (hazard ratio [HR] 1.381, 95% confidence interval [CI] 1.124-1.698 [P = .002], and HR 1.645, 95% CI 1.184-2.287 [P = .003], respectively). After adjusting for other risk factors, significant differences remained (HR 1.309, 95% CI 1.054-1.624 [P = .015]. and HR 1.601, 95% CI 1.129-2.271 [P = .008]). The A allele was also associated with prolongation of QTc interval by 4.04 ms in the entire population (P = .026). Conclusions: The A allele of rs 12567209 in NOS1AP may serve as an independent predictor of all-cause death and SCD in patients with CHF, it is also associated with prolonged QTc interval in the Chinese Han population. [ABSTRACT FROM AUTHOR]

The densities and viscosities of clopidogrel hydrogen sulfate +methanol and clopidogrel hydrogen sulfate +ethanol have been measured at the temperatures (278.15, 283.15, 288.15, 293.15, 298.15, 303.15, 308.15, and 313.15) K. The experimental data of densities were calculated with the Vogel−Tamman−Fulcher equation, and viscosities were analyzed with linear fit to temperature. [ABSTRACT FROM AUTHOR]

Although N-terminal pro-brain natriuretic peptide (NT-proBNP) is a useful screening test of impaired right ventricular (RV) function in conditions affecting the right-sided cardiac muscle, the role of NT-proBNP remains unclear in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study was designed to clarify the relation between the plasma NT-proBNP level and the RV function evaluated by cardiovascular magnetic resonance (CMR) imaging. We selected 56 patients with confirmed ARVC only when their blood specimens for NT-proBNP measurements were collected within 48 hours of a CMR scan. The NT-proBNP level was significantly higher in patients with RV dysfunction than in patients without RV dysfunction (median of 655.3 [interquartile range 556.4 to 870.0] vs 347.0 [interquartile range 308.0 to 456.2] pmol/L, p <0.001). The NT-proBNP levels were positively correlated with RV end-diastolic and end-systolic volume indices (r = 0.49 and 0.70, respectively) and negatively correlated with RV ejection fraction (r = –0.76, all p <0.001), which remained significant after adjustment for age, gender, and body mass index. The area under the receiver-operating characteristic curve for NT-proBNP was 0.91 (95% confidence interval 0.80 to 0.97, p <0.001). The cut-off value of NT-proBNP (458 pmol/L) was associated with sensitivity, specificity, and positive and negative predictive values of 91%, 89%, 67%, and 98%, respectively. In conclusion, NT-proBNP is a useful marker for the detection of RV dysfunction and associated with extent of RV dilatation and dysfunction determined by CMR in patients with ARVC. [ABSTRACT FROM AUTHOR]