Growth, immunity and transcriptome response to different stocking densities in Litopenaeus vannamei.

The effects of different stocking densities on Litopenaeus vannamei were investigated from the aspects of growth performance, immune response and transcriptome in this experiment. L. vannamei (initial body weight: 0.30 ± 0.02 g) were reared for 8 weeks at three stocking densities of 100 (LSD), 200 (MSD) and 300 (HSD) shrimp/m³, respectively. The results showed that the survival rate (SR), final body weight (FBW), weight gain rate (WGR), specific growth ratio (SGR) and protein efficiency ratio (PER) of L. vannamei significantly decreased, while the feed factor (FCR) significantly increased with the increase of stocking density. After Vibrio parahemolyticus infection, the SR of L. vannamei in the HSD group was significantly lower than that in the LSD and MSD groups. Increasing stocking density significantly increased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lysozyme (LYS) while significantly decreased the activities of catalase (CAT) and phenol oxidase (PO) in the serum of L. vannamei. Similar changes of the gene expression as the activities of immune enzymes were found in the hemocytes. Pairwise comparison between the LSD, MSD and HSD group in the transcriptome analysis identified that there were 304, 1376 and 2083 differentially expressed genes (DEGs) in LSD vs MSD, MSD vs HSD and LSD vs HSD, respectively. Among them, most of the immune-related DEGs were down-regulated and metabolism-related DEGs were up-regulated with the increasing stocking density. In addition, KEGG enrichment pathway analysis revealed that several immune and metabolic related pathways including PI3K-Akt signaling pathway and AMPK signaling pathway were significantly enriched. Of these, the PI3K-Akt signaling pathway had the most DEGs and was also the most significantly enriched pathway. Furthermore, 16 DEGs (such as FOXO, PCK2 and CTSC, etc.) and partial immune enzyme activity (such as AST, CAT and PO, etc.) changes were closely correlated with the increase of stocking density when partial immune-related DEGs and immune-related enzymes were analyzed jointly. All these results indicated that changes in stocking density had a significant effect on the growth performance, immunity and transcriptome of L. vannamei.

The enhancement effect of low-dose dietary lipopolysaccharide on the growth and immunity of Litopenaeus vannamei, and transcriptome analysis.

In this study, the effects of dietary lipopolysaccharide (LPS) on Litopenaeus vannamei were investigated to determine whether LPS could play a role as a potential immunostimulant in shrimp. L. vannamei with an initial body weight of 0.30 ± 0.02 g were fed a diet containing LPS at doses of 0, 0.2, 1, 5, 25 or 125 mg kg-1 for eight weeks (groups LPS0, LPS0.2, LPS1, LPS5, LPS25 and LPS125, respectively). After eight weeks of feeding, the growth performance, immunity and transcriptome response of L. vannamei were analysed. Only dietary LPS at 0.2 and 1 mg kg-1 resulted in a significant increase in the growth of L. vannamei (P < 0.05). According to the weight gain rate (WGR) and specific growth rate (SGR), the optimum dietary LPS level was 2.462 and 2.455 mg kg-1, respectively. When compared with the control group, the survival rate (SR) of L. vannamei in the LPS0.2 group was significantly increased after white spot syndrome virus (WSSV) infection and the SR of L. vannamei in the LPS1 group was significantly increased after Vibrio parahaemolyticus infection (both P < 0.05). Compared with the LPS0 group, immune enzyme activity in the serum of L. vannamei could be significantly increased and the content of maleic dialdehyde (MDA) significantly decreased by dietary LPS. Transcriptome analysis of the haemocytes of L. vannamei identified 399 up-regulated differentially expressed genes (DEGs) and 5000 down-regulated DEGs in the LPS0.2 compared to the control group. Most of the DEGs were significantly enriched in the following pathways: phosphatidylinositol signalling, Wnt signalling, Jak-STAT signalling and inositol phosphate metabolism. In conclusion, this study revealed that diets supplemented with low-dose LPS had positive effects on the growth and immunity of L. vannamei.

Catalytic and regulatory subunits of casein kinase 2 in Penaeus vannamei: Cloning, identification, expression profiles and functional analysis.

As a highly conserved serine/threonine kinase with catalytic and regulatory subunits distributed ubiquitously in eukaryotic organisms, casein kinase 2 (CK2) is involved in multiple cellular functions, including immune regulation. In this study, two variants of the catalytic subunit (designated PvCK2α-1 and PvCK2α-2) and the regulatory subunit homologs (designated PvCK2ß-1 and PvCK2ß-2) in Penaeus vannamei were cloned and characterised. PvCK2α-1 and PvCK2α-2 shared the same genomic sequence consisting of six exons and five introns and encoded the same protein of 350 amino acids with an S_TKc domain, although there was a sequence deletion in 3'-UTR in PvCK2α-2 when compared with PvCK2α-1. Because of the sequence deletion in the ORF, PvCK2ß-1 and PvCK2ß-2 encoded different proteins with a CK_II_beta domain. The gene structures of PvCK2ß-1 and PvCK2ß-2 were identical and consisted of four exons and three introns. Semi-quantitative RT-PCR analyses revealed that PvCK2α and PvCK2ß were constitutively expressed in all P. vannamei tissues tested, with higher levels detected in the immune-related tissues including hemocytes, hepatopancreas, gills and intestine. In these four tissue types, all variants of PvCK2α and PvCK2ß were induced upon challenge with white spot syndrome virus (WSSV), Vibrio parahaemolyticus and Staphyloccocus aureus. The inhibition of PvCK2α, PvCK2ß-1 and PvCK2ßComb (the amount of PvCK2ß-1 and PvCK2ß-2) significantly reduced the survival rates of P. vannamei after WSSV infection and significantly increased the WSSV viral loads. Knockdown of PvCK2 by RNAi could distinctly decrease the expression of NF-κB related genes. All of these results suggest that PvCK2 plays an important role in the innate immune response to pathogen challenges in P. vannamei, with a positive role in anti-WSSV response which may be mediated through regulating the expression of NF-κB drived antimicrobial peptide genes.

A novel lamin A/C gene missense mutation (445 V > E) in immunoglobulin-like fold associated with left ventricular non-compaction.

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 ß2 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 ß 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 ß sheets and side chains may partially explain the aggregation of lamin A/C protein subjacent to the nuclear envelope.

Comparison of cardiovascular magnetic resonance characteristics and clinical consequences in children and adolescents with isolated left ventricular non-compaction with and without late gadolinium enhancement.

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.

A common NOS1AP genetic polymorphism, rs12567209 G>A, is associated with sudden cardiac death in patients with chronic heart failure in the Chinese Han population.

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 NOS1AP, 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 rs12567209 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 rs12567209 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.

Process Optimization and Mechanism Study for Sulfur Recovery from High-Silica Phosphogypsum via Carbothermal Reduction Smelting.

Phosphogypsum produced from wet-processed phosphoric acid mainly consists of calcium sulfate dihydrate, which is an important sulfur resource. The traditional sulfuric acid and cement process based on phosphogypsum suffers from unstable cement quality owing to impurities such as phosphorus and fluorine and kiln ringing caused by the low-melting phase. This study investigated sulfur recovery and value-added utilization of liquid slag from high-silica phosphogypsum via carbothermal reduction smelting. A phosphogypsum ingredient (PGI) system was constructed by adding appropriate amounts of silica, alumina, magnesium oxides, and iron oxides to meet the production requirements of slag wool. Carbothermal reduction smelting experiments suggested that the temperature and C/S molar ratio significantly affected the desulfurization rate and phase structure of the slag. More than 97.44 wt % of sulfur could be recovered with a C/S molar ratio of 0.5-0.8 at 1300 °C or above in the molten state, and the molten slag was an amorphous magnesium-calcium-aluminosilicate. The PGI desulfurization mechanism is discussed based on the phase transformation and slag microstructure evolution.

[Management of refractory ventricular tachycardia in patients with non-myxomas primary cardiac tumors].

OBJECTIVE: To summarize the clinical characteristics and treatment experience of patients with non-myxomas primary cardiac tumors accompanied with refractory ventricular tachycardia (VT). METHODS: Clinical and imaging data as well as therapy efficacy and outcome were analyzed in 10 patients with non-myxomas primary cardiac tumors accompanied with refractory VT. RESULTS: There were 5 male and 5 female patients in this cohort [mean age (37.6±18.2) years]. Palpitation was presented in all 10 patients, 7 patients experienced syncope, and 2 patients suffered from amaurosis. The diagnosis was made by combined use of transthoracic echocardiograms, MRI, and CT scan. The time from symptom to diagnosis was (33.2±36.7) months. Symptom-related VT was documented by ECG or Holter monitoring. MRI suggested lipoma in 7 patients, lymphoma in 1 patient and fibroma in another patient. Seven tumors were located in the left ventricle, 1 in right atria, 1 at peri-aortic root and 1 near right ventricular outflow tract. Nine out of 10 patients received anti-arrhythmic drug therapy. The ventricular tachyarrhythmia disappeared after surgical tumor resection in 4 patients. All other patients who were treated with antiarrhythmic drugs, radiofrequency ablation or subtotal excision showed only suboptimal efficacy during (39.4±25.1) months follow-up. CONCLUSION: Surgical tumor removal is the best treatment strategy for the treatment of refractory ventricular tachycardia in patients with primary cardiac benign tumors.

Biochemical Fulvic Acid Modification for Phosphate Crystal Inhibition in Water and Fertilizer Integration.

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.

[Clinical characteristics and outcome of 32 patients with long-QT syndrome accompanied with torsade de pointes].

OBJECTIVE: To summarize the clinical characteristics and outcome of patients with long-QT syndrome (LQTs) accompanied with torsade de pointes. METHODS: Thirty-two eligible patients were included in this study. Clinical and electrocardiographic data were analyzed and telephone or out-patient follow-up were made in all patients. RESULTS: There were 15 patients with inherited LQTs (h-LQTs) and 17 patients with acquired LQTs (a-LQTs). There are more women (n = 24) than men (n = 8). ß blockers, potassium and magnesium supplement were the basic therapy for h-LQTs patients, bivent pacemaker was implanted in 2 patients and implantable cardioverter defibrillator was implanted in 5 patients. Ventricular tachyarrhythmias and syncope occurred in 4 patients during (39.4 ± 25.1) months follow-up. In 17 a-LQTs patients, one patient with dilated cardiomyopathy died suddenly and another patient with implanted cardioverter defibrillator experienced one ventricular tachycardia during (30.9 ± 13.3) months follow-up. CONCLUSIONS: The prognosis in h-LQTs and a-LQTs patients with structure heart disease is poor. ICD or CRT-D therapy is suggestive for a-LQTs patients with structure heart disease.

Identification and function of an Arasin-like peptide from Litopenaeus vannamei.

Antimicrobial peptides (AMPs) play an important role in the host defense system of shrimps. In this study, an Arasin-like peptide, named as LvArasin-like, was identified from the hemocytes of the pacific white shrimp, Litopenaeus vannamei. The complete open reading frame (ORF) of LvArasin-like was 213 bp, encoding 70 amino acid residues with a predicted molecular mass of 5.68 kDa and a theoretical isoelectric point (pI) of 6.73. The predicted peptide consisted of a signal peptide, an N-terminal Pro/Arg-rich domain, and a C-terminal cysteine-rich domain. LvArasin-like expression was most abundant in the gills and was up-regulated in hemocytes after LPS or Poly I:C injection as well as challenges by Vibrio parahaemolyticus or Staphylococcus aureus infection. In the heterologous expression system, LvArasin-like protein (rLvArasin-like) was recombinantly expressed in the forms of a dimer or both a monomer and dimer. The rLvArasin-like could directly bind to gram-positive and gram-negative bacteria and exhibited broad-spectrum antimicrobial activity towards them, with 50 % of minimal inhibitory concentrations (MIC50) of 6.25-50 µM. Moreover, dsRNA-mediated knockdown of LvArasin-like enhanced the susceptibility of shrimp to V. parahaemolyticus. In addition, the transcriptional level of LvArasin-like was downregulated when silencing of the transcription factors LvDorsal and LvRelish using RNAi in vivo. All of these results suggest that LvArasin-like is involved in host defense against bacterial infection. Therefore, it is a potential therapeutic agent for disease control in shrimp aquaculture.

Sustainable and Clean Utilization of Yellow Phosphorus Slag (YPS): Activation and Preparation of Granular Rice Fertilizer.

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.

Patient reported outcomes and quality of life in Chinese patients with implantable cardioverter defibrillators✰.

OBJECTIVES: Patient reported outcomes in Implantable Cardioverter Defibrillator (ICD) patients can describe the experience of living with heart disease and with an ICD. However, very little is known about patient outcomes among Chinese patients which may limit effective patient discussions and interventions for these patients. The purposes of this study were to examine device related experiences (e.g., device acceptance, shock anxiety) in Chinese ICD patients and identify potential variables that influence health related quality of life (HRQOL) and to compare HRQOL outcomes to healthy and heart failure populations. METHODS: This study used a cross-sectional research design with serially recruited ICD patients (N = 100) from clinics in China. Participants completed surveys including: the 12-Item Short-Form Health Survey Questionnaire (SF-12), Florida Patient Acceptance Survey (FPAS), Florida Shock Anxiety Scale (FSAS), Type D Scale (DS-14), and general information questionnaire. RESULTS: Participants were 100 ICD patients in China with a mean age of 53.32(SD = 13.70). The mean scores of the SF-12 physical component summary (PCS) and mental component summary (MCS)of ICD patients (43.55 and 47.07, respectively) were lower than the Chinese general population (P<0.001) and general health, social functioning, and role emotional scores were lower than chronic heart failure patients (P<0.001). Multiple linear regression analysis indicated that LVEF, positive shock history, age and shock anxiety were significant predictors of physical function and accounted for 24.5% of the adjusted variance. Type D personality, shock history, and shock anxiety were predictors of the mental health component and accounted for 25.9% of the variance. Shock history, age, type D personality, and shock anxiety significantly predicted device acceptance (FPAS-Total) and accounted for 32% of variance. CONCLUSIONS: ICD patients reported health outcomes were generally lower than the Chinese general population and patients with heart failure in relation to general health, social functioning, and role emotional. Both generic and disease specific HRQOL were influenced by both medical and psychosocial predictors. This suggests that current Western society based comprehensive models of patient HRQOL and patient care needs may extend to Chinese patients with ICDs.

The T cell factor, pangolin, from Litopenaeus vannamei play a positive role in the immune responses against white spot syndrome virus infection.

As a downstream interactor of ß-catenin, Pangolin which is the homologous protein of the T cell factor/lymphoid enhancer factor (TCF/LEF) in vertebrates is less understood in the research field of immunity. In this study, two isoforms of Litopenaeus vannamei Pangolin (LvPangolin1 and LvPangolin2) were identified. Phylogenetic tree analysis revealed that all of the Pangolin proteins from invertebrates were represented the same lineage. The mRNA expression profiles of the LvPangolin1 and LvPangolin2 genes differed across different tissues. The expression of LvPangolin1 and the amount of LvPangolin1and LvPangolin2 combined (LvPangolinComb) were significantly increased in the haemocyte, intestine and gill but reduced in the hepatopancreas after white spot syndrome virus (WSSV) challenge. The inhibition of LvPangolin1 but not LvPangolinComb significantly reduced the survival rates of L. vannamei after WSSV infection, while significantly higher WSSV viral loads in both LvPangolin1-inhibited and LvPangolinComb-inhibited L. vannamei were observed. Knockdown of LvPangolin by RNAi could distinctly decrease the expression of antimicrobial peptide (AMP) genes and their related transcription factors. All of these results indicate that LvPangolin plays a positive role in the response to WSSV infection and that this may be mediated through regulating the immune signalling pathways which control the expression of AMPs with antiviral abilities.

Comparison between his-bundle pacing and left bundle branch pacing in patients with atrioventricular block.

BACKGROUND: Pacing the cardiac conduction system has been explored in patients with conduction system disease, but comprehensive comparisons between different pacing modalities are not well investigated. OBJECTIVE: To compare pacing characteristics and ventricular synchrony between His-bundle pacing (HBP) and left bundle branch pacing (LBBP) in patients with atrioventricular block (AVB). METHODS: Fifty pacemaker-indicated patients with AVB were enrolled. Twenty-five patients underwent HBP, and another 25 patients underwent LBBP. Success rate, procedural and fluoroscopy duration, pacing parameters, and echocardiographic data were perioperatively assessed and at 3-month follow-up. RESULTS: HBP was successful in 19 of 25 (76.0%) patients, whereas LBBP was successful in 22 of 25 (88.0%) patients. Compared with HBP, LBBP capture threshold was significantly lower (0.76 ± 0.25 V/0.4 ms vs. 1.27 ± 0.61 V/1.0 ms, P = 0.003) and R-wave amplitude was significantly higher with LBBP (11.7 ± 6.6 vs. 4.9 ± 2.4 mV, P < 0.001) at implant. The mean procedural time (74.3 ± 17.8 vs. 63.2 ± 12.3 min, P = 0.029) and fluoroscopy duration (10.3 ± 4.5 vs. 6.8 ± 2.2 min, P = 0.005) were significantly longer in the HBP group compared to LBBP. At 3-month follow-up, pacing capture threshold remained more stable in LBBP than in HBP group while left ventricular synchrony was similar between both groups. CONCLUSION: Despite similar impact on ventricular synchrony compared with HBP, LBBP featured a significantly lower pacing capture threshold, higher R-wave amplitude, and less time to achieve similar success rate in patients with AVB. These findings indicate LBBP as a physiological pacing strategy for AVB patients.

GSK3ß Plays a Negative Role During White Spot Syndrome Virus (WSSV) Infection by Regulating NF-κB Activity in Shrimp Litopenaeus vannamei.

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 GSK3ß homologs from other species in Litopenaeus vannamei (designated as LvGSK3ß) was obtained. LvGSK3ß 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 LvGSK3ß expression was in immune tissues including the hemocyte, intestine, gill and hepatopancreas. The inhibition of LvGSK3ß resulted in significantly higher survival rates of L. vannamei during WSSV infection than the control group, and significantly lower WSSV viral loads in LvGSK3ß-inhibited L. vannamei were observed. Knockdown of LvGSK3ß 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 LvGSK3ß 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 LvGSK3ß. The interaction between LvGSK3ß and LvDorsal or LvCactus was confirmed using co-immunoprecipitation (Co-IP) assays. In addition, the expression of LvGSK3ß was dramatically reduced by knockdown of LvDorsal. In summary, the results presented in this study indicated that LvGSK3ß had a negative effect on L. vannamei by mediating a feedback regulation of the NF-κB pathway when it is infected by WSSV.

Clinical implications of sarcomere and nonsarcomere gene variants in patients with left ventricular noncompaction cardiomyopathy.

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.

Titin-truncating variants are associated with heart failure events in patients with left ventricular non-compaction cardiomyopathy.

BACKGROUND: Titin-truncating variants (TTNtv) have been recognized as the most prevalent genetic cause of dilated cardiomyopathy. However, their effects on phenotypes of left ventricular non-compaction cardiomyopathy (LVNC) remain largely unknown. HYPOTHESIS: The presence of TTNtv may have an effect on the phenotype of LVNC. METHODS: TTN was comprehensively screened by targeted sequencing in a cohort of 83 adult patients with LVNC. Baseline and follow-up data of all participants were collected. The primary endpoint was a composite of death and heart transplantation. The secondary endpoint was heart failure (HF) events, a composite of HF-related death, heart transplantation, and HF hospitalization. RESULTS: Overall, 13 TTNtv were identified in 13 patients, with 9 TTNtv located in the A-band of titin. There was no significant difference in baseline characteristics between patients with and without TTNtv. During a median follow-up of 4.4 years, no significant difference in death and heart transplantation between the two groups was observed. However, more HF events occurred in TTNtv carriers than in non-carriers (P = 0.006). Multivariable analyses showed that TTNtv were associated with an increased risk of HF events independent of sex, age, and baseline cardiac function (hazard ratio: 3.25, 95% confidence interval: 1.50-7.01, P = 0.003). Sensitivity analysis excluding non-A-band TTNtv yielded similar results, but with less strength. CONCLUSIONS: The presence of TTNtv may be a genetic modifier of LVNC and confer a higher risk of HF events among adult patients. Studies of larger cohorts are needed to confirm our findings.

Genotype-Positive Status Is Associated With Poor Prognoses in Patients With Left Ventricular Noncompaction Cardiomyopathy.

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 , MYH 7, MYBPC 3, 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 , MYH 7, MYBPC 3, 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.