Effects of supplemental octanoate on hepatic lipid metabolism, serum biochemical indexes, antioxidant capacity and inflammation-related genes expression of large yellow croaker (Larimichthys crocea) fed with high soybean oil diet

Dietary high soybean oil (SO) levels might cause hepatic lipid deposition, induce oxidative stress and inflammatory response in aquatic animals, while octanoate (OCT) is beneficial to metabolism and health in mammals. However, the effect of OCT has been studied rarely in aquatic animals. In this study, a 10-week feeding trial was conducted to investigate the effect of supplemental OCT on hepatic lipid metabolism, serum biochemical indexes, antioxidant capacity and inflammatory response of large yellow croaker (Larimichthys crocea) fed with high SO levels diet. The negative control diet contained 7% fish oil (FO), while the positive control diet contained 7% SO. The other four experimental diets were supplemented with 0.7, 2.1, 6.3 and 18.9 g/kg sodium octanoate (OCT) based on the positive control diet. Results showed that OCT supplementation effectively reduced the hepatic crude lipid, triglyceride (TG), total cholesterol (TC) and non-esterified free fatty acids contents, and alleviated lipid accumulation caused by the SO diet. Meanwhile, OCT supplementation decreased the serum TG, TC, alanine transaminase, aspartate transaminase and low-density lipoprotein cholesterol levels, increased the serum high-density lipoprotein cholesterol level, improved the serum lipid profiles and alleviated hepatic injury. Furthermore, with the supplementation of OCT, the mRNA expression of genes related to lipogenesis (acc1, scd1, fas, srebp1, dgat1 and cebpα) and fatty acid (FA) transport (fabp3, fatp and cd36) were down-regulated, while the mRNA expression of genes related to lipolysis (atgl, hsl and lpl) and FA β-oxidation (cpt1 and mcad) were up-regulated. Besides that, dietary OCT increased the total antioxidant capacity, activities of peroxidase, catalase and superoxide dismutase and the content of reduced glutathione, decreased the content of 8-hydroxy-deoxyguanosine and malondialdehyde and relieved hepatic oxidative stress. Supplementation of 0.7 and 2.1 g/kg OCT down-regulated the mRNA expression of genes related to pro-inflammatory cytokines (tnfα, il1β and ifnγ), and suppressed hepatic inflammatory response. In conclusion, supplementation with 0.7-2.1 g/kg OCT could reduce hepatic lipid accumulation, relieve oxidative stress and regulate inflammatory response in large yellow croaker fed the diet with high SO levels, providing a new way to alleviate the hepatic fat deposition in aquatic animals

Genome-wide identification of resistance genes and response mechanism analysis of key gene knockout strain to catechol in Saccharomyces cerevisiae

Engineering Saccharomyces cerevisiae for biodegradation and transformation of industrial toxic substances such as catechol (CA) has received widespread attention, but the low tolerance of S. cerevisiae to CA has limited its development. The exploration and modification of genes or pathways related to CA tolerance in S. cerevisiae is an effective way to further improve the utilization efficiency of CA. This study identified 36 genes associated with CA tolerance in S. cerevisiae through genome-wide identification and bioinformatics analysis and the ERG6 knockout strain (ERG6Δ) is the most sensitive to CA. Based on the omics analysis of ERG6Δ under CA stress, it was found that ERG6 knockout affects pathways such as intrinsic component of membrane and pentose phosphate pathway. In addition, the study revealed that 29 genes related to the cell wall-membrane system were up-regulated by more than twice, NADPH and NADP+ were increased by 2.48 and 4.41 times respectively, and spermidine and spermine were increased by 2.85 and 2.14 times, respectively, in ERG6Δ. Overall, the response of cell wall-membrane system, the accumulation of spermidine and NADPH, as well as the increased levels of metabolites in pentose phosphate pathway are important findings in improving the CA resistance. This study provides a theoretical basis for improving the tolerance of strains to CA and reducing the damage caused by CA to the ecological environment and human health

The response mechanism analysis of HMX1 knockout strain to levulinic acid in Saccharomyces cerevisiae

Levulinic acid, a hydrolysis product of lignocellulose, can be metabolized into important compounds in the field of medicine and pesticides by engineered strains of Saccharomyces cerevisiae. Levulinic acid, as an intermediate product widely found in the conversion process of lignocellulosic biomass, has multiple applications. However, its toxicity to Saccharomyces cerevisiae reduces its conversion efficiency, so screening Saccharomyces cerevisiae genes that can tolerate levulinic acid becomes the key. By creating a whole-genome knockout library and bioinformatics analysis, this study used the phenotypic characteristics of cells as the basis for screening and found the HMX1 gene that is highly sensitive to levulinic acid in the oxidative stress pathway. After knocking out HMX1 and treating with levulinic acid, the omics data of the strain revealed that multiple affected pathways, especially the expression of 14 genes related to the cell wall and membrane system, were significantly downregulated. The levels of acetyl-CoA and riboflavin decreased by 1.02-fold and 1.44-fold, respectively, while the content of pantothenic acid increased. These findings indicate that the cell wall-membrane system, as well as the metabolism of acetyl-CoA and riboflavin, are important in improving the resistance of Saccharomyces cerevisiae to levulinic acid. They provide theoretical support for enhancing the tolerance of microorganisms to levulinic acid, which is significant for optimizing the conversion process of lignocellulosic biomass to levulinic acid

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

Virtual Network Function Migration Considering Load Balance and SFC Delay in 6G Mobile Edge Computing Networks

With the emergence of Network Function Virtualization (NFV) and Software-Defined Networks (SDN), Service Function Chaining (SFC) has evolved into a popular paradigm for carrying and fulfilling network services. However, the implementation of Mobile Edge Computing (MEC) in sixth-generation (6G) mobile networks requires efficient resource allocation mechanisms to migrate virtual network functions (VNFs). Deep learning is a promising approach to address this problem. Currently, research on VNF migration mainly focuses on how to migrate a single VNF while ignoring the VNF sharing and concurrent migration. Moreover, most existing VNF migration algorithms are complex, unscalable, and time-inefficient. This paper assumes that each placed VNF can serve multiple SFCs. We focus on selecting the best migration location for concurrently migrating VNF instances based on actual network conditions. First, we formulate the VNF migration problem as an optimization model whose goal is to minimize the end-to-end delay of all influenced SFCs while guaranteeing network load balance after migration. Next, we design a Deep Learning-based Two-Stage Algorithm (DLTSA) to solve the VNF migration problem. Finally, we combine previous experimental data to generate realistic VNF traffic patterns and evaluate the algorithm. Simulation results show that the SFC delay after migration calculated by DLTSA is close to the optimal results and much lower than the benchmarks. In addition, it effectively guarantees the load balancing of the network after migration

Metoda przetwarzania sygnału drganiowego i identyfikacji typu obciążenia młyna na podstawie ACMD-SVD

Green mine construction is the main melody of mining development and problems such as safe production, energy saving and consumption reduction need to be solved urgently. The working conditions of the mill are complex in the process of grinding. Aiming at the problems existing in the feature extraction and load prediction of the mill, a signal-processing method based on adaptive chirp mode decomposition (ACMD) and a standardized variable distance classifier (SVD) is proposed. Firstly, the recursive framework of the ACMD method is used to obtain the initial frequency of mill vibration signals. Secondly, the initial frequency is used to reconstruct the high-resolution component of the mill vibration signal through the iterative frame in the ACMD method. The frequency corresponding to the frequency domain peak of the reconstructed signal is then selected as the mill load feature vector. Finally, with consideration to the influence of standard deviation and standardized variable factors on the feature vectors, a standardized variable distance classifier is proposed. The feature vectors of the mill load are input into the SVD model for training, and the state types of the mill load are obtained. The method is applied to the grinding experiment and the results show that the frequency-domain features obtained by the mill vibration signal-processing method based on ACMD-SVD are obvious, which has high accuracy in the identification of mill load types, and provides a new idea for the extraction of mill load features and prediction of the mill load.Budowa zielonej kopalni jest główną melodią rozwoju górnictwa, a problemy takie jak: bezpieczna produkcja, oszczędność energii i redukcja zużycia wymagają pilnego rozwiązania. Warunki pracy młyna w procesie mielenia są złożone. Mając na celu rozwiązanie problemów występujących w ekstrakcji cech i przewidywaniu obciążenia młyna, zaproponowano metodę przetwarzania sygnału opartą na dekompozycji w trybie adaptacyjnym ACMD (Adaptive Chirp Made Decomposition) i znormalizowanym klasyfikatorze zmiennej odległości SVD (Variable Distance Classifier). Po pierwsze, rekurencyjna struktura metody ACMD jest wykorzystywana do uzyskania początkowej częstotliwości sygnałów drgań młyna. Po drugie, częstotliwość początkowa jest wykorzystywana do rekonstrukcji wysokorozdzielczej składowej sygnału drgań młyna poprzez ramkę iteracyjną w metodzie ACMD. Częstotliwość odpowiadająca pikowi w dziedzinie częstotliwości rekonstruowanego sygnału jest następnie wybierana jako wektor cech obciążenia młyna. Na koniec, biorąc pod uwagę wpływ odchylenia standardowego i standaryzowanych czynników zmiennych na wektory cech, zaproponowano standaryzowany klasyfikator odległości o zmiennej długości. Wektory cech obciążenia młyna są wprowadzane do modelu SVD w celu uczenia i uzyskiwane są typy stanu obciążenia młyna. Metodę zastosowano w eksperymencie mielenia, a wyniki pokazują, że cechy w dziedzinie częstotliwości uzyskane za pomocą metody przetwarzania sygnału drgań młyna opartej na ACMD-SVD są oczywiste, co ma wysoką dokładność w identyfikacji typów obciążeń młyna i zapewnia nowy pomysł na ekstrakcję cech obciążenia młyna i predykcję obciążenia młyna

Traditional Chinese medicine Yiqi Huoxue recipe attenuates hepatic fibrosis via YAP/TAZ signaling

Background/Aims. The Yiqi Huoxue (YQHX) recipe has been shown to attenuate liver fibrosis, but precise mechanisms have not yet been elucidated. Recently, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling has been implicated in liver fibrogenesis. This study investigated whether the YAP/TAZ signaling is involved in the therapeutic effect of YQHX on hepatic fibrosis. Materials and Methods. Wistar rats were used to generate a model of carbon tetrachloride (CCl 4)-induced liver fibrosis. Chronic hepatitis B (CHB) patients with liver fibrosis were enrolled and assigned to receive either nucleoside/nucleotide analogues (NAs) or NAs plus YQHX. Histology, immunohistochemistry, qRT-PCR, and western blotting were conducted to mechanistically assess the therapeutic effects of YQHX on liver fibrosis. Results. YQHX markedly alleviated morphological alterations in CCl 4-induced liver fibrosis and decreased markers of hepatic fibrosis in rats. Furthermore, YQHX significantly suppressed CCl 4-meidated activation of the transforming growth factor-beta (TGF-β)/Smad signaling pathway. Notably, CCl 4 induced up-regulation of YAP, TAZ, and connective tissue growth factor (CTGF), which were significantly abrogated by YQHX. Consistent with the above major findings in rats, CHB patients treated with NAs plus YQHX had greater improvement in liver fibrosis than those given NAs alone (71.4% vs. 28.6%; P=0.057). In addition, hepatic and plasma levels of YAP were significantly decreased after YQHX treatment in CHB patients with liver fibrosis. Conclusion. YAP/TAZ signaling plays a role, at least in part, in the anti-fibrotic activity of YQHX. The findings may help to better understand the mechanisms of YQHX in the treatment of liver fibrosi

Boosting output performance of sliding mode triboelectric nanogenerator by charge space-accumulation effect

Improving the output performance of sliding mode triboelectric nanogenerators is a great challenge. Herein, a space charge accumulation effect, based on alternating shielding and blank-tribo areas, is demonstrated and effectively promotes charge density output

Exercise protects against chronic β-adrenergic remodeling of the heart by activation of endothelial nitric oxide synthase.

Extensive data have shown that exercise training can provide cardio-protection against pathological cardiac hypertrophy. However, how long the heart can retain cardio-protective phenotype after the cessation of exercise is currently unknown. In this study, we investigated the time course of the loss of cardio-protection after cessation of exercise and the signaling molecules that are responsible for the possible sustained protection. Mice were made to run on a treadmill six times a week for 4 weeks and then rested for a period of 0, 1, 2 and 4 weeks followed by isoproterenol injection for 8 days. Morphological, echocardiographic and hemodynamic changes were measured, gene reactivation was determined by real-time PCR, and the expression and phosphorylation status of several cardio-protective signaling molecules were analyzed by Western-blot. HW/BW, HW/TL and LW/BW decreased significantly in exercise training (ER) mice. The less necrosis and lower fetal gene reactivation induced by isoproterenol injection were also found in ER mice. The echocardiographic and hemodynamic changes induced by β-adrenergic overload were also attenuated in ER mice. The protective effects can be sustained for at least 2 weeks after the cessation of the training. Western-blot analysis showed that the alterations in the phosphorylation status of endothelial nitric oxide synthase (eNOS) (increase in serine 1177 and decrease in threonine 495) continued for 2 weeks after the cessation of the training whereas increases of the phosphorylation of Akt and mTOR disappeared. Further study showed that L-NG-Nitroarginine methyl ester (L-NAME) treatment abolished the cardio-protective effects of ER. Our findings demonstrate that stimulation of eNOS in mice through exercise training provides acute and sustained cardioprotection against cardiac hypertrophy