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Background Dilated cardiomyopathy (DCM) is a common cause of sudden cardiac death and heart failure in children, its different etiologies are significantly associated with the prognosis of children with DCM. However, there is a lack of accurate etiologic diagnosis and effective risk stratification programs. Primary DCM has the highest prevalence and relatively poor prognosis, especially in children with genetic factors. Therefore, the analysis of mortality risk factors based on genetic background would be beneficial for the accurate prognosis and risk stratification of children with DCM. Objective To explore the proportion of genetic etiology, genetic characteristics and factors related to poor prognosis of primary DCM in children. Methods The clinical data and genetic testing results of 42 children with primary DCM who were hospitalized in Hebei Children's Hospital from July 2018 to December 2022 and completed genetic testing were retrospectively collected, and the included children were regularly followed up in the cardiology outpatient department of Hebei Children's Hospital after discharge. With the time of death or 2022-12-31 as the end point of follow-up, the children were divided into the death group (9 cases) and survival group (33 cases) according to the follow-up outcomes. Survival curves of the children were plotted using the Kaplan-Meier method, and comparisons between groups were performed using the Log-rank test. Multivariate COX proportional risk model was used to analyze the risk factors for death. Results The median age of first diagnosis was 12 (7, 96) months, and the median follow-up time was 24 (9, 36) months. The median follow-up time was 8 (0, 11) months in the death group and 30 (12, 39) months in the survival group, the difference was statistically significant (Z=-2.19, PT) in the dead children with negative gene mutation was classified as unclear clinical significance. The Kaplan-Meier survival curve of the children was plotted, and the Log-rank test results showed that the survival rate of children with negative gene mutation was higher than that of children with positive gene mutation (χ2=18.1, P

Dietary threonine (Thr) deficiency increases hepatic triglyceride content and reduces sebum and abdominal fat percentages in lean type (LT), but not in fatty type (FT) Pekin ducks. However, the molecular changes regarding the role of Thr in lipid metabolism in LT and FT ducks induced by Thr deficiency remains unknown. This study compared differential expression gene profiles related to lipid metabolism in FT and LT Pekin ducks affected by Thr deficiency. We performed transcriptomic profiling and scanned the gene expression in the liver, sebum, and abdominal fat of Pekin ducks fed either Thr-deficient or Thr-adequate diet for 21 days from 14 to 35 days of age. There were 187, 52, and 50 differentially expressed genes (DEGs) identified in the liver, sebum, and abdominal fat of LT ducks affected by Thr deficiency, of which 12, 9, and 5 genes were involved in lipid metabolism, respectively. Thr deficiency altered the expression of 27, 6, and 3 genes in FT ducks’ liver, sebum, and abdominal fat, respectively. None of the DEGs had a relationship with lipid metabolism in FT ducks. KEGG analysis showed that the DEGs in the LT ducks’ livers were enriched in lipid metabolism pathways (linolenic acid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism) and amino acid metabolism pathways (biosynthesis of amino acids, phenylalanine metabolism, β-alanine metabolism, and glycine, serine and threonine metabolisms). The DEGs in the sebum and abdominal fat of LT ducks were not enriched in lipid and amino acid metabolic pathways. Additionally, DEGs involved in lipid metabolism were found to be upregulated by Thr deficiency in LT ducks, such as malic enzyme 3 (ME3), acyl-CoA synthetase short-chain family member 2 (ACSS2) in liver, and lipase member M (LIPM) in sebum. In summary, dietary Thr deficiency regulated the gene expression involved in lipid metabolism in the liver, sebum, and abdominal fat of Pekin ducks in a genotype-dependent manner.

Domestic ducks are descended from the Mallard and have been bred for several purposes. Here the authors present three high-quality duck genome assemblies which recover previously missing genes and provide a rich resource of variants potentially related to domestication.

Misfolded aggregation of the hyperphosphorylated microtubule binding protein Tau in the brain is a pathological hallmark of Alzheimer’s disease (AD). Tau aggregation downregulates brain-derived neurotrophic factor (BDNF)/tropomycin receptor kinase B (TRKB) signaling and leads to neurotoxicity. Therefore, enhancement of BDNF/TRKB signaling could be a strategy to alleviate Tau neurotoxicity. In this study, eight compounds were evaluated for the potential of inhibiting Tau misfolding in human neuroblastoma SH-SY5Y cells expressing the pro-aggregator Tau folding reporter (ΔK280 TauRD-DsRed). Among them, coumarin derivative ZN-015 and quinoline derivatives VB-030 and VB-037 displayed chemical chaperone activity to reduce ΔK280 TauRD aggregation and promote neurite outgrowth. Studies of TRKB signaling revealed that ZN-015, VB-030 and VB-037 treatments significantly increased phosphorylation of TRKB and downstream Ca2+/calmodulin-dependent protein kinase II (CaMKII), extracellular signal-regulated kinase 1/2 (ERK) and AKT serine/threonine kinase (AKT), to activate ribosomal S6 kinase (RSK) and cAMP response element-binding protein (CREB). Subsequently, p-CREB enhanced the transcription of pro-survival BDNF and BCL2 apoptosis regulator (BCL2), accompanied with reduced expression of anti-survival BCL2-associated X protein (BAX) in ΔK280 TauRD-DsRed-expressing cells. The neurite outgrowth promotion effect of ZN-015, VB-030 and VB-037 was counteracted by a RNA interference-mediated knockdown of TRKB, suggesting the role of these compounds acting as TRKB agonists. Tryptophan fluorescence quenching analysis showed that ZN-015, VB-030 and VB-037 interacted directly with a Pichia pastoris-expressed TRKB extracellular domain, indirectly supporting the role through TRKB signaling. The results of up-regulation in TRKB signaling open up the therapeutic potentials of ZN-015, VB-030 and VB-037 for AD.

Hyperphosphorylation and aggregation of the microtubule binding protein tau is a neuropathological hallmark of Alzheimer’s disease/tauopathies. Tau neurotoxicity provokes alterations in brain-derived neurotrophic factor (BDNF)/tropomycin receptor kinase B (TRKB)/cAMP-response-element binding protein (CREB) signaling to contribute to neurodegeneration. Compounds activating TRKB may therefore provide beneficial effects in tauopathies. LM-031, a coumarin derivative, has demonstrated the potential to improve BDNF signaling in neuronal cells expressing pro-aggregated ΔK280 tau mutant. In this study, we investigated if LM-031 analogous compounds provide neuroprotection effects through interaction with TRKB in SH-SY5Y cells expressing ΔK280 tauRD-DsRed folding reporter. All four LMDS compounds reduced tau aggregation and reactive oxygen species. Among them, LMDS-1 and -2 reduced caspase-1, caspase-6 and caspase-3 activities and promoted neurite outgrowth, and the effect was significantly reversed by knockdown of TRKB. Treatment of ERK inhibitor U0126 or PI3K inhibitor wortmannin decreased p-CREB, BDNF and BCL2 in these cells, implying that the neuroprotective effects of LMDS-1/2 are via activating TRKB downstream ERK, PI3K-AKT and CREB signaling. Furthermore, LMDS-1/2 demonstrated their ability to quench the intrinsic fluorescence of tryptophan residues within the extracellular domain of TRKB, thereby consolidating their interaction with TRKB. Our results suggest that LMDS-1/2 exert neuroprotection through activating TRKB signaling, and shed light on their potential application in therapeutics of Alzheimer’s disease/tauopathies.

Riboflavin is an essential micronutrient and a precursor of flavin mononucleotide and flavin adenine dinucleotide for maintaining cell homeostasis. Riboflavin deficiency (RD) induces cell apoptosis. Endoplasmic reticulum (ER) stress is considered to induce apoptosis, and C/EBP homologous protein (CHOP) is a key pathway involved in this process. However, whether RD-induced apoptosis is mediated by ER stress and the CHOP pathway remains unclear and needs further investigation. Therefore, the current study presents the effect of RD on ER stress and apoptosis in the human hepatoma cell line (HepG2). Firstly, cells were cultured in a RD medium (4.55 nM riboflavin) and a control (CON) medium (1005 nM riboflavin). We conducted an observation of cell microstructure characterization and determining apoptosis. Subsequently, 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, was used in HepG2 cells to investigate the role of ER stress in RD-induced apoptosis. Finally, CHOP siRNA was transfected into HepG2 cells to validate whether RD triggered ER stress-mediated apoptosis by the CHOP pathway. The results show that RD inhibited cell proliferation and caused ER stress, as well as increased the expression of ER stress markers (CHOP, 78 kDa glucose-regulated protein, activating transcription factor 6) (p < 0.05). Furthermore, RD increased the cell apoptosis rate, enhanced the expression of proapoptotic markers (B-cell lymphoma 2-associated X, Caspase 3), and decreased the expression of the antiapoptotic marker (B-cell lymphoma 2) (p < 0.05). The 4-PBA treatment and CHOP knockdown markedly alleviated RD-induced cell apoptosis. These results demonstrate that RD induces cell apoptosis by triggering ER stress and the CHOP pathway.

We developed a pyridine-catalyzed annulation of diaryl cyclopropenone with bromomethyl carbonyl compounds leading to 5-carbonyl furan-2(5H)-ones. Pyridinium, derived from the reaction of bromomethyl carbonyl and pyridine, triggered the reaction by the inter-molecular Michael addition to cyclopropenone. This procedure was sensitive neither to air nor moisture and proceeded at room temperature with broad substrate scopes and good functional group tolerance in moderate-to-good yields. As such, it represents a facile and practical pathway leading to 5-carbonyl furan-2(5H)-one derivatives. [ABSTRACT FROM AUTHOR]

Improving feed efficiency is important for decreasing feed cost in poultry production, because feed account for approximately 70% of the total production costs. The selection of feed efficiency may affect other important economic traits. Therefore, the objectives of this present study was to evaluate the relationships of the residual feed intake (RFI) with live body weight, carcass weight, carcass composition, and size of small intestines in a population of F2 Pekin ducks. Nine-hundred and eighty F2 ducks were derived from a cross between 40 Pekin ducks and 10 Mallard ducks. The results showed no significant correlation of RFI with live body weight and eviscerated carcass weight. RFI had negative effects on breast meat weight and gizzard weight. A positive correlation of RFI with abdominal fat weight, skin weight, and jejunum length was detected. Our results indicated that the selection of RFI could improve the feed efficiency of ducks without affecting their carcass compositions.

Power source structure has developed significantly because of the increasing share of renewable energy sources (RESs) in the power system. RESs bring inevitable impacts on power system frequency, voltage regulation, and power system stability. The conventional automatic generation control (AGC) loops which relay only on the synchronous generating units cannot meet the requirements of these new circumstances. This paper presents an ESS-integrated PV/wind station topology and its control structure for AGC auxiliary service in order to provide existing RESs the additional functionality of AGC auxiliary service without changing their control strategies conceived for MPPT mode. The shifting operation modes and external disturbances make ESSs in an ESS-integrated PV/wind station inherently nonlinear and time variable. Therefore, an adaptive robust sliding-mode control (ARSMC) system is proposed. The ARSMC colligates the advantages of adaptive control and SMC contains state feedback term, robust control term, and adaptive compensation term. The strictly logical and rigorous proof using Lyapunov stability analysis indicates the ARSMC system is insensitive to parametric uncertainties and external disturbances; meanwhile, it guarantees fast response speed and high control precision. The case studies on NI-PXI platform validate the effectiveness of the proposed approach.

Soil-dissolved organic matter (DOM) drives the carbon (C) and nitrogen (N) cycles in agroecosystems. Despite many studies on DOM dynamics, hardly any attention has been directed toward DOM quality, particularly DOM composition. The aim of this study was to elucidate how C and N management practices alter soil water-extractable organic matter (WEOM) in a loess soil agroecosystem. Field experiments were conducted with a winter wheat monoculture. Three N fertilization rates (0, 120, and 240 kg ha−1 year−1) were applied for 17 years (2002–2019), combined with five C practices (zero, low, and high rates of sheep manure or wheat straw) for three years (2016–2019). The results reveal that soil organic carbon (SOC) and water-extractable organic carbon (WEOC) concentrations in the topsoil (0–20 cm) were increased by organic amendments considerably but were not affected by N fertilization. The fluorescence excitation–emission matrix spectra (EEM) of WEOM were resolved to two humic-like components (C1 and C2) and two soluble microbial byproduct-like components (C3 and C4). The proportions of C1 and C2 were increased, while the proportion of C3 was decreased by both C and N management practices. In conclusion, organic amendments increased both WEOM quality and its proportion of humic-like components, whereas N fertilization increased the proportion of humic-like components without variations of WEOM quality in the topsoil of loess soil.