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Gaussian process regression (GPR) model of machine learning method was employed to identify the optimal process window for high-performance CoCrMo alloy in laser powder bed fusion (LPBF), considering density (≥99%) and surface roughness (≤7 μm) as key parameters. Additionally, the study examined the impact of LPBF parameters on morphology and distribution of defect and surface roughness. Results revealed a tongue-shaped optimal process window, with scanning speed having a greater influence on density than laser power. High laser power reduced surface roughness, and a combination of medium-to-high laser power (160–340 W) and moderate scanning speed (600–1500 mm/s) achieved low surface roughness (Ra ≤ 7 μm). The mean absolute error confirmed the reliability of the optimized process window predicted by GPR.

Contaminant-bearing polystyrene microplastics (PSMPs) may exert significantly different toxicity profiles from their contaminant-free counterparts, with the role of PSMPs in promoting contaminant uptake being recognized. However, studies investigating the environmentally relevant exposure and toxic mechanisms of aged PSMPs binding to Cr are limited. Here, we show that loading of chromium (Cr) markedly alters the physicochemical properties and toxicological profiles of aged PSMPs. Specifically, Cr-bearing aged PSMPs induced severe body weight loss, oxidative stress (OS), autophagy, intestinal barrier injury, inflammation–pyroptosis response, and enteropathogen invasion in mice. Mechanistic investigations revealed that PSMPs@Cr exacerbated the OS, resulting in intestinal barrier damage and inflammation–pyroptosis response via overactivated Notch signaling and autophagy/cathepsin B/IL-1β pathway, respectively, which ultimately elevated mortality related to bacterial pathogen infection. In vitro experiments confirmed that autophagy-mediated reactive oxygen species (ROS) overproduction resulted in severe pyroptosis and impaired intestinal stem cells differentiation alongside the overactivation of Notch signaling in PSMPs@Cr-exposed organoids. Overall, our findings provide an insight into autophagy-modulated ROS overproduction within the acidic environment of autophagosomes, accelerating the release of free Cr from PSMPs@Cr and inducing secondary OS, revealing that PSMPs@Cr is a stable hazard material that induces intestinal injury. These findings provided a potential therapeutic target for environmental MPs pollution caused intestinal disease in patients.

N6-methyladenosine (m6A) modification of mRNA plays an important role in regulating adipogenesis. However, its underlying mechanism remains largely unknown. Using Jinhua and Landrace pigs as fat and lean models, we presented a comprehensive transcriptome-wide m6A profiling in adipose tissues from these two pig breeds. Two differentially methylated genes were selected to explore the mechanisms of m6A-mediated regulation of gene function. The ratio of m6A/A in the layer of backfat (LB) was significantly higher in Landrace than that in Jinhua. Transcriptome-wide m6A profiling revealed that m6A modification on mRNA occurs in the conserved sequence motif of RRACH and that the pig transcriptome contains 0.53–0.91 peak per actively expressed transcript. The relative density of m6A peaks in the 3′UTR were higher than in 5′UTR. Genes with common m6A peaks from both Landrace (L-LB) and Jinhua (J-LB) were enriched in RNA splicing and cellular lipid metabolic process. The unique m6A peak genes (UMGs) from L-LB were mainly enriched in the extracellular matrix (ECM) and collagen catabolic process, whereas the UMGs from J-LB are mainly involved in RNA splicing, etc. Lipid metabolism processes were not significantly enriched in the UMGs from L-LB or J-LB. Uncoupling protein-2 (UCP2) and patatin-like phospholipase domain containing 2 (PNPLA2) were two of the UMGs in L-LB. Synonymous mutations (MUT) were conducted to reduce m6A level of UCP2and PNPLA2mRNAs. Adipogenesis test showed that UCP2-MUT further inhibited adipogenesis, while PNPLA2-MUT promoted lipid accumulation compared with UCP2-WT and PNPLA2-WT, respectively. Further study showed m6A negatively mediates UCP2 protein expression and positively mediates PNPLA2 protein expression. m6A modification affects the translation of PNPLA2 most likely through YTHDF1, whereas UCP2 is likely neither the target of YTHDF2 nor the target of YTHDF1. Our data demonstrated a conserved and yet dynamically regulated m6A methylome in pig transcriptomes and provided an important resource for studying the function of m6A epitranscriptomic modification in obesity development.

The DC voltage dynamics of droop-controlled voltage source converter based multi-terminal HVDC system (VSC-MTDC) are more complicated due to their transient overshoot and steady-state deviation. Firstly, to solve the DC voltage dynamic problems of the droop-controlled VSC-MTDC system with strong adjacent AC system, a practical reduced-order model of a VSC-MTDC system is established in DC voltage control timescale. Besides, the droop-based outer controller is considered as a droop admittance with lag-lead characteristic, which provides a physical explanation of DC voltage overshoot caused by droop controller coefficients. Moreover, the maximum DC voltage deviation that may occur under any power disturbance can be easily estimated by applying the frequency response analysis to the reduced-order model. Secondly, the damping of droop-controlled VSC can be easily enhanced by adding a simple compensator at the input of the DC voltage feedback loop. In this way, the droop admittance can present like a pure conductance for limiting DC voltage deviation under power disturbances. Finally, electromagnetic transient simulations are conducted to validate the accuracy of the reduced-order model of VSC-MTDC systems and the effectiveness of the proposed damping compensation method for DC voltage overshoot.

Image-guided thermal ablation (TA), which is less invasive, has been widely applied for treating various kinds of tumors. However, TA still poses the potential risk of thermal damage to sensitive tissue nearby. Therefore, an adjunctive thermoprotective hydrodissection technique with constant injection of 5% glucose (5% Glu) has currently been adopted for clinical application, but this may be hazardous to humans. In this study, a multifunctional hyaluronic acid-based hydrogel (HA-Dc) was developed for hydrodissection. Compared with 5% Glu (the most clinically used solution) and the previously reported F127 hydrogel, the HA-Dc hydrogel was studied in vitroin a porcine liver model and in vivoin a rabbit model and showed good injectability and better tissue retention, stability, and thermoprotective properties throughout the TA procedure. Furthermore, in the preclinical evaluation in a Macaca fascicularis (M. fascicularis)model, HA-Dc showed excellent performance in terms of stricter neuroprotection compared with 5% Glu. In addition, the HA-Dc hydrogel with good biocompatibility and controllable degradation behavior in vivocould be a promising platform for thermal protection during clinical TA procedures.

Membrane characteristics are determined by the fatty acids composition, which affects survival rates after freeze-drying. However, it is unknown which composition provides the greatest effect. In this study, we found that the addition of Tween 80 and Tween 20 significantly increased survival rates of Lactiplantibacillus plantarum, which reached a maximum of 93.1 %. Conversely, Tween 60 caused a significant decrease. We further found that the difference between the effects of adding Tween 80 and Tween 60 was the change in oleic acid contents. To verify the role of oleic acid, we used CRISPR-Cas9 to knock-out the key synthesis gene cla-er. The survival rates of L. plantarumAR113Δcla-erdeclined to 5.48 %. The addition of oleic acid restored the rates to those of wild type strains. Moreover, the membrane integrity and fluidity of knockout strains markedly decreased. This is the first confirmation that Tween 80 or Tween 20 increases the survival rate by increasing the content of oleic acid in the cell membrane. These findings also indicated that oleic acid in cell membranes has a substantial protective effect on L. plantarumduring freeze-drying.

Magnetic anomaly detection (MAD) is a method that uses magnetometers to find hidden ferromagnetic objects based on variations in magnetic field signals. Many methods use time–frequency fusion features to detect target signals, but these features are extracted using unlearnable methods in the preprocessing. This article proposes a network with adaptive time–frequency feature expression to detect magnetic anomalies. The network adaptively learns the time–frequency features of magnetic anomaly signal through optimization, and in the feature fusion step, it adaptively selects key features for classification. In experiments, we compared our proposed method with the state-of-the-art (SOTA) time–frequency fusion detection method in simulation, semireal, and real datasets. Results show that our method has better detection performance, with high accuracy (ACC), detection rate (DR), and area under receiver operating characteristic curve (AUC). In real datasets, the proposed method outperforms other methods in low signal-to-noise ratio (SNR) cases and has a low false alarm rate (FAR), demonstrating its good comprehensive detection ability and robustness.

Engineered probiotics can serve as therapeutics based on their ability of produce recombinant immune-stimulating properties. In this study, we built the recombinant Bacillus subtilisWB800 expressing antimicrobial peptide KR32 (WB800-KR32) using genetic engineering methods and investigated its protective effects of nuclear factor-E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway activation in intestinal oxidative disturbance induced by enterotoxigenic Escherichia coli(ETEC) K88 in weaned piglets. Twenty-eight weaned piglets were randomly distributed into four treatment groups with seven replicates fed with a basal diet. The feed of the control group (CON) was infused with normal sterilized saline; meanwhile, the ETEC, ETEC+WB800, and ETEC+WB800-KR32 groups were orally administered normal sterilized saline, 5×1010CFU (CFU: colony forming units) WB800, and 5×1010CFU WB800-KR32, respectively, on Days 1–14 and all infused with ETEC K88 1×1010CFU on Days 15–17. The results showed that pretreatment with WB800-KR32 attenuated ETEC-induced intestinal disturbance, improved the mucosal activity of antioxidant enzyme (catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)) and decreased the content of malondialdehyde (MDA). More importantly, WB800-KR32 downregulated genes involved in antioxidant defense (GPx and SOD1). Interestingly, WB800-KR32 upregulated the protein expression of Nrf2 and downregulated the protein expression of Keap1 in the ileum. WB800-KR32 markedly changed the richness estimators (Ace and Chao) of gut microbiota and increased the abundance of Eubacterium_rectale_ATCC_33656in the feces. The results suggested that WB800-KR32 may alleviate ETEC-induced intestinal oxidative injury through the Nrf2-Keap1 pathway, providing a new perspective for WB800-KR32 as potential therapeutics to regulate intestinal oxidative disturbance in ETEC K88 infection.

Probiotics can improve animal growth performance and intestinal health. Bacillusspecies, Lactobacillusspecies, Bifidobacteriumspecies, yeast etc. are the common types of probiotics. However, understanding the effects of probiotics on the immune status and gut microbiota of weaning piglets and how the probiotics exert their impact are still limited. This study aimed to investigate the effects of Bacillus amyloliquefaciens40 (BA40) on the performance, immune status and gut microbiota of piglets. A total of 12 litters of newborn piglets were randomly divided into 3 groups. Piglets in control group were orally dosed with phosphate buffered saline; BA40 group and probiotics group were orally gavaged with resuspension BA40 and a probiotics product, respectively. The results showed that BA40 treatment significantly decreased (P < 0.05) the diarrhea incidence (from d 5 to 40), diamine oxidase, D-lactate, interleukin (IL)-1β and interferon-γ concentrations compared with control group and probiotics group. Meanwhile BA40 dramatically increased the total antioxidant capacity, IL-10 and secretory immunoglobulin-A concentrations in contrast to control group. For the microbial composition, BA40 modulated the microbiota by improving the abundance of Bacteroides, Phascolarctobacterium(producing short-chain fatty acids) and Desulfovibrioand reducing the proliferation of pathogens (Streptococcus, Tyzzerella, Vellionellaand paraeggerthella). Meanwhile, a metabolic function prediction explained that carbohydrate metabolism and amino acid metabolism enriched in BA40 group in contrast to control group and probiotics group. For correlation analysis, the results demonstrated that BA40-enriched Phascolarctobacteriumand Desulfovibrioprovide insights into strategies for elevating the health status and performance of weaned piglets. Altogether, BA40 exerted stronger ability in decreasing diarrhea incidence and improved antioxidant activity, gut barrier function and immune status of piglets than the other treatments. Our study provided the experimental and theoretical basis for the application of BA40 in pig production.

This study was conducted to investigate the effects of fermented mixed feed (FMF) on growth performance, carcass traits, meat quality, muscle amino acid and fatty acid composition and mRNA expression levels of genes related to lipid metabolism in finishing pigs. In the present study, 144 finishing pigs (Duroc × Berkshire × Jiaxing Black) were randomly allocated to 3 dietary treatments with 4 replicate pens per group and 12 pigs per pen. The dietary treatments included a basal diet (CON), a basal diet + 5% FMF and a basal diet + 10% FMF. The experiment lasted 38 d after 4 d of acclimation. The results showed that 5% and 10% FMF significantly increased the average daily gain (ADG) of the females but not the males (P < 0.05), but FMF supplementation showed no impact on carcass traits. Moreover, 10% FMF supplementation increased the meat color45 minand meat color24 hvalues, while it decreased the shear force relative to CON (P < 0.05). In addition, 10% FMF significantly increased the contents of flavor amino acids (FAA), total essential AA (EAA), total non-EAA (NEAA) and total AA relative to CON (P < 0.05). Furthermore, the diet supplemented with 10% FMF significantly increased the concentration of n-3 polyunsaturated fatty acids (PUFA), n-6 PUFA and total PUFA, and the PUFA to saturated fatty acids ratio (P < 0.05), suggesting that FMF supplementation increased meat quality. Moreover, compared with the CON, 10% FMF supplementation increased the mRNA expression of lipogenic genes, including CEBPα, PPARγ, SREBP1and FABP4, and upregulated the expression of unsaturated fatty acid synthesis (ACAA1and FADS2). Together, our results suggest that 10% FMF dietary supplementation improved the female pigs’ growth performance, improved the meat quality and altered the profiles of muscle fatty acids and amino acids in finishing pigs. This study provides a reference for the production of high-quality pork.

Skeletal muscle fat infiltration is a common feature during ageing, obesity and several myopathies associated with muscular dysfunction and sarcopenia. However, the regulatory mechanisms of intramuscular adipogenesis and strategies to reduce fat infiltration in muscle remain unclear. Here, we identified the growth arrest and DNA damage‐inducible alpha (GADD45A), a stress‐inducible histone folding protein, as a critical regulator of intramuscular fat (IMAT) infiltration. To explore the role of GADD45A on IMAT infiltration and muscle regeneration, the gain or loss function of GADD45A in intramuscular preadipocytes was performed. The adipocyte‐specific GADD45A knock‐in (KI) mice and high IMAT‐infiltrated muscle model by glycerol injection (50 μL of 50% v/v GLY) were generated. RNA‐sequencing, histological changes, gene expression, lipid metabolism, mitochondrial function and the effect of dietary factor epigallocatechin‐3‐gallate (EGCG) treatment (100 mg/kg) on IMAT infiltration were studied. The unbiased transcriptomics data analysis indicated that GADD45A expression positively correlates with IMAT infiltration and muscle metabolic disorders in humans (correlation: young vs. aged people, Gadd45aand Cebpa, r2= 0.20, P< 0.05) and animals (correlation: wild‐type [WT] vs. mdxmice, Gadd45aand Cebpa, r2= 0.38, P< 0.05; NaCl vs. GLY mice, Gadd45aand Adipoq/Fabp4, r2= 0.80/0.71, both P< 0.0001). In vitro, GADD45A overexpression promotes intramuscular preadipocyte adipogenesis, upregulating the expression of adipogenic genes (Ppara: +47%, Adipoq: +28%, P< 0.001; Cebpa: +135%, Fabp4: +16%, P< 0.01; Pparg: +66%, Leptin: +77%, P< 0.05). GADD45A knockdown robustly decreased lipid accumulation (Pparg: −57%, Adipoq: −35%, P< 0.001; Fabp4: −37%, P< 0.01; Leptin: −28%, P< 0.05). GADD45A KI mice exhibit inhibited skeletal muscle regeneration (myofibres: −40%, P< 0.01) and enhanced IMAT infiltration (adipocytes: +20%, P< 0.05). These KI mice have impaired exercise endurance and mitochondrial function. Mechanistically, GADD45A affects ATP synthase F1 subunit alpha (ATP5A1) ubiquitination degradation (ubiquitinated ATP5A1, P< 0.001) by recruiting the E3 ubiquitin ligase TRIM25, which decreases ATP synthesis (ATP production: −23%, P< 0.01) and inactivates the cAMP/PKA/LKB1 signalling pathway (cAMP: −36%, P< 0.01; decreased phospho‐PKA and phospho‐LKB1 protein content, P< 0.01). The dietary factor EGCG can protect against muscle fat infiltration (triglyceride: −64%, P< 0.05) via downregulating GADD45A (decreased GADD45A protein content, P< 0.001). Our findings reveal a crucial role of GADD45A in regulating muscle repair and fat infiltration and suggest that inhibition of GADD45A by EGCG might be a potential strategy to combat fat infiltration and its associated muscle dysfunction.

In the process of rendering with NPR, there will often be a problem of reduced perception of the NPR effect caused by the fixed spatial structure of the static mesh. Therefore, this research first establishes a convolutional neural network to conduct supervised training on numerous hand-drawn target stylised images, and perform continuous angle recognition through stylised images then output its angle vector. Secondly, the displacement map is generated in real-time by inputting the observation angle through the fully connected neural network model. After that, the real-time displacement map is sampled to dynamically generate the deformation of the model. In the end, the goal of breaking the model's sense of space and enhancing the NPR rendering effect can be achieved. Besides, the experimental results of this study verify the effectiveness of the method.

The misuse of plastic products has led to serious environment problem. To alleviate such phenomenon, we need to recover the plastic waste with a precise distinction. In this work, we applied a deep learning model, e.g., Faster-RCNN, to identify the class of plastic bottle. We have designed a waste plastic bottle recycling system, which can cooperate with the manipulator and conveyor to automatically sort the bottles in the garbage. During the experiment, we established a data set containing 8400 images. Different backbone networks are used to train on the data set. The experimental results show that the skeleton network using Resnet-50 as Faster-RCNN has higher detection performance than other networks. The system can also be applied to the identification and classification of other solid wastes.

Based on preparation of co-fermented defatted rice bran (DFRB) using Bacillus subtilis, Saccharomyces cerevisiae, Lactobacillus plantarumand phytase, the present study aimed to evaluate the effects of co-fermented DFRB on growth performance, antioxidant capacity, immune status, gut microbiota and permeability in finishing pigs. Ninety finishing pigs (85.30 ± 0.97 kg) were randomly assigned to 3 treatments (3 replicates/treatment) with a basal diet (Ctrl), a basal diet supplemented with 10% unfermented DFRB (UFR), and a basal diet supplemented with 10% fermented DFRB (FR) for 30 d. Results revealed that the diet supplemented with FR notably (P < 0.05) improved the average daily gain (ADG), gain to feed ratio (G:F) and the digestibility of crude protein, amino acids and dietary fiber of finishing pigs compared with UFR. Additionally, FR supplementation significantly (P < 0.05) increased total antioxidant capacity, the activities of superoxide dismutase and catalase, and decreased the content of malonaldehyde in serum. Furthermore, FR remarkably (P < 0.05) increased serum levels of IgG, anti-inflammatory cytokines (IL-22 and IL-23) and reduced pro-inflammatory cytokines (TNF-α, IL-1β and INF-γ). The decrease of serum diamine oxidase activity and serum D-lactate content in the FR group (P < 0.05) suggested an improvement in intestinal permeability. Supplementation of FR also elevated the content of acetate and butyrate in feces (P < 0.05). Moreover, FR enhanced gut microbial richness and the abundance of fiber-degrading bacteria such as Clostridium butyricumand Lactobacillus amylovorus. Correlation analyses indicated dietary fiber in FR was associated with improvements in immune status, intestinal permeability and the level of butyrate-producing microbe C. butyricum, which was also verified by the in vitro fermentation analysis. These findings provided an experimental and theoretical basis for the application of fermented DFRB in finishing pigs.

Dysregulation of the gut microbiota often leads to immune-related disorders, indigestion, or diarrhea. Here, Jiaxing Black (JXB) pig, a local Chinese pig breed known for its great tolerance and digestibility of nutrients, was employed for a metagenomic and transcriptomic integrative analysis to reveal the gut microbiota-genes and gut microbiota-pathway interactions. A total of 452 differentially expressed genes, and 174 phyla were found between the JXB and the Duroc?×?Landrace?×?Yorkshire (DLY) pigs. Detailed analysis revealed that the differences in colon gene expression signatures between the JXB and DLY are mainly enriched in metabolic and inflammatory responses, with Lactobacillusand Lachnospiraceae enriched in DLY and JXB, respectively. Notably, Pacebacteria, Streptophyta, and Aerophobetes were found to participate in the PI3K-Akt mediated immune response in both pig breeds; however, they only accelerated the metabolism in the intestines of JXB pigs. Moreover, the host could regulate microbe metabolism and immune response by Ig-like domain-containing protein and ITIH2, PAEP, and TDRD9, respectively. Taken together, our results revealed both common and breed-specific regulations of host genes by gut microbiota in two pig breeds. The colon contents of the Jiaxing Black (JXB) and the Duroc?×?Landrace?×?Yorkshire (DLY) pigs were collected for transcriptomic and metagenomic analyses. By using Weighted Gene Co-expression Network Analysis and sparse Canonical correlation analysis, we identified the potential interactions between host genes and gut microbes, indicating that host genes involved in the PI3K-Akt signaling pathway and metabolic pathways were regulated by gut microbes. The different colon gene expression signatures between the Jiaxing Black (JXB) and Duroc?×?Landrace?×?Yorkshire (DLY) are mainly enriched in metabolic and inflammatory responses.Lactobacilluswas dominant in DLY, while Lachnospiraceae was enriched in the JXB. Furthermore, Pacebacteria, Streptophyta, and Aerophobetes were identified as key bacteria associated with the PI3K-Akt mediated immune response.Ig-like domain-containing protein was involved in regulating the metabolism of intestinal microbiota, while ITIH2, PAEP, and TDRD9were involved in the NLR-mediated immune response of intestinal microbiota. The different colon gene expression signatures between the Jiaxing Black (JXB) and Duroc?×?Landrace?×?Yorkshire (DLY) are mainly enriched in metabolic and inflammatory responses. Lactobacilluswas dominant in DLY, while Lachnospiraceae was enriched in the JXB. Furthermore, Pacebacteria, Streptophyta, and Aerophobetes were identified as key bacteria associated with the PI3K-Akt mediated immune response. Ig-like domain-containing protein was involved in regulating the metabolism of intestinal microbiota, while ITIH2, PAEP, and TDRD9were involved in the NLR-mediated immune response of intestinal microbiota.

The effects of dietary metabolizable energy (ME) and crude protein (CP) on the growth performance, meat quality, and cecal microbiota of Taihe Silky Fowl (TSF) during fattening were investigated. In total, 900 twelve-week-old female fowl were randomly allocated to 9 treatments (5 replicates per group, 20 fowl per replicate), and were fed a 3 × 3 factorial arrangement of treatments diets (ME: 11.30, 11.93, or 12.56 MJ/kg; CP: 15%, 16%, or 17%). As ME increased, the average daily feed intake (ADFI, P<0.001), feed conversion ratio (FCR, P<0.001), pectoral and thigh shear forces (P<0.05), pectoral and thigh muscle fiber diameter (P<0.001) decreased significantly, while muscle fiber density increased (P<0.001). Pectoral muscle fiber diameter was lower and muscle fiber density higher at 16% CP than 15% or 17%. As ME increased, pectoral crude fat content increased significantly (P= 0.007). Pectoral crude protein, total amino acid (TAA), and essential amino acid (EAA) content were higher at 15% dietary CP than 16% or 17%. As ME increased, pectoral inosine monophosphate (IMP, P= 0.006), uridylic monophosphate (UMP, P= 0.003), guanylic monophosphate (GMP, P= 0.009), and adenosine monophosphate (AMP, P<0.001) decreased significantly, while hypoxanthine riboside (HxR, P= 0.045) increased. As dietary CP increased, IMP (P= 0.019), AMP (P<0.001), and HxR (P= 0.024) increased significantly. Cecal microbiota composition varied with dietary ME: 12.56 MJ/kg ME increased the abundance of Bifidobacteriaceae, and 15% CP increased that of Paraprevotella. These findings suggest that 12.56 MJ/kg dietary ME and 15% CP can enhance growth performance, improve meat quality by reducing shear force, enhancing flavor and nutritional value, and benefit for intestinal microbiota in fattening TSF.

Pyroptosis induced by lipopolysaccharide (LPS) has an obvious impact on intestinal inflammation and immune regulation. Enterotoxigenic Escherichia coli(ETEC) K88 has been proved to induce inflammatory responses in several models, but whether E. coliK88 participates in the same process of pyroptotic cell death as LPS remains to be identified. We conducted a pilot experiment to confirm that E. coliK88, instead of Escherichia coliO157 and Salmonella typhimurium, promotes the secretion of interleukin-1 beta (IL-1β) and interleukin-18 (IL-18) in macrophages. Further experiments were carried out to dissect the molecular mechanism both in vitroand in vivo. The Enzyme-Linked Immunosorbent Assay (ELISA) results suggested that E. coliK88 treatment increased the expression of pro-inflammatory cytokines IL-18 and IL-1β in both C57BL/6 mice and the supernatant of J774A.1 cells. Intestinal morphology observations revealed that E. coliK88 treatment mainly induced inflammation in the colon. Real-time PCR and Western blot analysis showed that the mRNA and protein expressions of pyroptosis-related factors, such as NLRP3, ASC, and Caspase1, were significantly upregulated by E. coliK88 treatment. The RNA-seq results confirmed that the effect was associated with the activation of NLRP3, ASC, Caspase1, GSDMD, IL-18, and IL-1β, and might also be related to inflammatory bowel disease and the tumor necrosis factor pathway. The pyroptosis-activated effect of E. coliK88 was significantly blocked by NLRP3 siRNA. Our data suggested that E. coliK88 caused inflammation by triggering pyroptosis, which provides a theoretical basis for the prevention and treatment of ETEC in intestinal infection.

This study investigates how Chinese logogriphs are comprehended by learners of Chinese as a foreign language (CFL) with different Chinese proficiencies and cultural backgrounds. Eighty-eight CFL learners from four cultures (South Koreans, Southeast Asians, Western Caucasians and Arabs) were divided into two Chinese proficiency groups according to their HSK scores, and 15 L1 Chinese speakers also took part in the experiment as a control group. The participants were asked to write down how they interpreted Chinese logogriphs in questionnaires. An ANOVA analysis was conducted to examine the effects of Chinese proficiency and cultural background on logogriph comprehension. The results indicate that the accuracy of logogriph comprehension and the frequency of adopting logogriph-solving strategies positively correlated with the learners’ Chinese proficiency, and that those with higher proficiency used more linguistic and cultural knowledge of the target language. As for cultural influence, Western Caucasians tended to think more visually than the other three cultural groups, and South Koreans and Southeast Asians were better at activating Chinese semantic knowledge. The closer the CFL learners’ culture is to Chinese culture, the more similar strategies they adopted to those of L1 Chinese participants. Moreover, the participants’ Chinese proficiency and cultural background show an interactive effect on their logogriph comprehension, with the former factor having a greater influence than the latter in this process.

Nasopharyngeal carcinoma (NPC) is an epithelia-derived malignancy with a distinctive geographic distribution. Cystathionine γ-lyase (CSE) is involved in cancer development and progression. Nevertheless, the role of CSE in the growth of NPC is unknown. In this study, we found that CSE levels in human NPC cells were higher than those in normal nasopharyngeal cells. CSE overexpression enhanced the proliferative, migrative, and invasive abilities of NPC cells and CSE downregulation exerted reverse effects. Overexpression of CSE decreased the expressions of cytochrome C, cleaved caspase (cas)-3, cleaved cas-9, and cleaved poly-ADP-ribose polymerase, whereas CSE knockdown exhibited reverse effects. CSE overexpression decreased reactive oxygen species (ROS) levels and the expressions of phospho (p)-extracellular signal-regulated protein kinase 1/2, p-c-Jun N-terminal kinase, and p-p38, but promoted the expressions of p-phosphatidylinositol 3-kinase (PI3K), p-AKT, and p-mammalian target of rapamycin (mTOR), whereas CSE knockdown showed oppose effects. In addition, CSE overexpression promoted NPC xenograft tumor growth and CSE knockdown decreased tumor growth by modulating proliferation, angiogenesis, cell cycle, and apoptosis. Furthermore, DL-propargylglycine (an inhibitor of CSE) dose-dependently inhibited NPC cell growth via ROS-mediated mitogen-activated protein kinase (MAPK) and PI3K/AKT/mTOR pathways without significant toxicity. In conclusion, CSE could regulate the growth of NPC cells through ROS-mediated MAPK and PI3K/AKT/mTOR cascades. CSE might be a novel tumor marker for the diagnosis and prognosis of NPC. Novel donors/drugs that inhibit the expression/activity of CSE can be developed in the treatment of NPC.

In biological responses, fatty acids (FA) are absorbed and metabolized in the form of substrates for energy production. The molecular structures (number of double bonds and chain length) and composition of dietary FA impact digestion, absorption and metabolism, and the biological roles of FA. Recently, increasing evidence indicates that FA are essentially utilized as an energy source and are signaling molecules that exert physiological activity of gut microbiota and immune responses. In addition, FA could serve as natural ligands for orphan G protein-coupled receptors (GPCR), also called free fatty acid receptors (FFAR), which intertwine metabolic and immune systems via multiple mechanisms. The present review explores the recent findings on FA absorption and its impact on gut health, particularly addressing the mechanism by which dietary FA potentially influences intestinal microbiota and epithelial functions. Also, this work attempts to uncover research ideas for devising future strategies for manipulating the composition of dietary FA to regulate gut health and support a normal immune system for metabolic and immune disorders.

ABSTRACT5-Methylcytosine (m5C) is a type of RNA modification that exists in tRNAs and rRNAs and was recently found in mRNA. Although mRNA m5C modification has been reported to regulate diverse biological process, its function in adipogenesis remains unknown. Here, we demonstrated that knockdown of NOL1/NOP2/Sun domain family member 2 (NSUN2), a m5C methyltransferase, increased lipid accumulation of 3T3-L1 preadipocytes through accelerating cell cycle progression during mitotic clonal expansion (MCE) at the early stage of adipogenesis. Mechanistically, we proved that NSUN2 directly targeted cyclin-dependent kinase inhibitor 1A (CDKN1A) mRNA, a key inhibitory regulator of cell cycle progression, and upregulated its protein expression in an m5C-dependent manner. Further study identified that CDKN1Awas the target of Aly/REF export factor (ALYREF), a reader of m5C modified mRNA. Upon NSUN2 deficiency, the recognition of CDKN1AmRNA by ALYREF was suppressed, resulting in the decrease of CDKN1AmRNA shuttling from nucleus to cytoplasm. Thereby, the translation of CDKN1A was reduced, leading to the acceleration of cell cycle and the promotion of adipogenesis. Together, these findings unveiled an important function and mechanism of the m5C modification on adipogenesis by controlling cell cycle progression, providing a potential therapeutic target to prevent obesity.

While being widely used to understand the chemical reactions in heterogeneous catalysis or other multidisciplinary systems, a great challenge that semilocal and hybrid density functional approximations (DFAs) are facing is to deliver a uniformly accurate description for both finite and extended systems. Herein, we perform reliable and well-converged periodic calculations of two doubly hybrid approximations (DHAs), XYG3 and XYGJ-OS, and demonstrate that the good accuracy of DHAs achieved for molecules is transferable to the semiconductors and insulators. Such an accuracy is not only for energetic properties but also for the first- and second-order response properties, which is general for different kinds of chemical environments, including simple cubic bulks, perovskite-type transition metal oxides like TiO2, and heterogeneous systems like CO adsorption on the NaCl(100) surface. The present finding has strengthened the predictive power of DFT, which not only will inspire the future development of the top-rung DFAs but also will boost their applications in multidisciplinary studies with high accuracy and efficiency.

ABSTRACTThe production of natural antimicrobial peptides has emerged as an important mechanism of innate immunity in animals. Defensins, members of a large family of antimicrobial peptides, have been suggested as effector molecules in host defence against bacteria, fungi, protozoa and enveloped viruses. However, the molecular mechanism underlying defensin upregulation in bacterial infection remains poorly understood. The modification of mRNA by N6-adenosine methylation (m6A) on internal bases influences gene expression in eukaryotes. Here, we show that β-defensin production triggered by Enterotoxigenic Escherichia coliK88 (E. coliK88) infection is controlled by the cellular m6A methyltransferase METTL3. Adding back with METTL3 robustly stimulated the re-expression of defensin, which further supports the conclusion. Furthermore, using a MeRIP-seq approach, we identified a functional connection between m6A dependent GPR161 signalling and the expression of defensins. Mechanistically, we found that the transcription factor FOXO6 interacted with METTL3 to trigger the transcription of GPR161 and the subsequent regulation of β-defensin expression. The study has shed light on the mechanisms by which enterotoxigenic Escherichia coliinfection promotes enteric defensin expression.

ABSTRACTPorcine fat deposition is an important economic trait of pig breeds, and understanding the gene regulatory network in adipocytes is essential for modern pig breeding. In a previous study, we demonstrated that miR-29a negatively regulates the differentiation of porcine adipocytes. In this study, we investigated the roles of miR-29b/c in porcine adipocytes and the underlying mechanisms. Using EdU staining and the CCK-8 assay, we observed that transfection with the miR-29b/c agomir promoted the proliferation of porcine intramuscular (IM) and subcutaneous (SC) adipocytes by altering the expression of cell-cycle-related genes. According to the results of oil red O staining and western blot analysis, transfection with the miR-29b/c agomir suppressed the differentiation of porcine SC and IM adipocytes via the AKT/PKA/MAPK signalling pathway. Furthermore, we proved that miR-29b/c regulates porcine adipocytes by directly targeting the 3ʹ-untranslated region (3ʹUTR) of CTRP6 using a dual-luciferase reporter assay. Finally, co-transfection with miR-29b/c and CTRP6 partially restored the changes of phenotype and gene expression induced by miR-29b/c overexpression in 3T3-L1 adipocytes. Taken together, our data demonstrate that both miR-29b and miR-29 c negatively regulate porcine adipogenesis by targeting CTRP6, which furthers our understanding of the gene network that regulates fat deposition in pigs.

High-frequency dc solid-state transformer (DCSST) plays an important role in DC bus connection, voltage conversion, electrical isolation, and bidirectional power transmission in dc distribution networks. In various DSSCT topologies, the dual-active-bridge (DAB) scheme becomes a typical solution for DCSST due to its various advantages. However, the DAB scheme still has drawbacks during practical applications. In this article, a DAB with half-bridge submodules (HSDAB) is proposed. By replacing the switches in front bridge arm with half-bridge submodules (SMs), the proposed HSDAB scheme maintains the advantages of conventional DAB and obtains bidirectional dc fault-handling capability, reducing the application of large dc capacitors and dc circuit breaker; therefore, the volume and construction cost of DCSST can be effectively reduced. Besides, a high-frequency-link (HFL) voltage regulation strategy for HSDAB is also proposed in this article. The HFL voltages can be adjusted to match the HFL transformer voltage ratio during the whole operating range, reducing the current stress, HFL reactive power, and power loss of DCSST. Moreover, the proposed HSDAB scheme can also be applied as a basic circuit to establish multiple modular architecture DCSST, flexibly connecting low-voltage dc, medium-voltage dc, and high-voltage dc buses in the dc distribution network. The topology, operation principle, control structure, corresponding bidirectional dc fault handling, and HFL voltage regulation strategy of the proposed HSDAB scheme are investigated. The experimental results verify the correctness and effectiveness of the analysis and proposed scheme.

The gut microbiota is comprised of a diverse array of microorganisms that interact with immune system and exert crucial roles for the health. Changes in the gut microbiota composition and functionality are associated with multiple diseases. As such, mobilizing a rapid and appropriate antimicrobial response depending on the nature of each stimulus is crucial for maintaining the balance between homeostasis and inflammation in the gut. Major players in this scenario are antimicrobial peptides (AMP), which belong to an ancient defense system found in all organisms and participate in a preservative co-evolution with a complex microbiome. Particularly increasing interactions between AMP and microbiota have been found in the gut. Here, we focus on the mechanisms by which AMP help to maintain a balanced microbiota and advancing our understanding of the circumstances of such balanced interactions between gut microbiota and host AMP. This review aims to provide a comprehensive overview on the interplay of diverse antimicrobial responses with enteric pathogens and the gut microbiota, which should have therapeutic implications for different intestinal disorders.

Transcriptome-wide mapping of N6-methyladenosine (m6A) at base resolution remains an issue, impeding our understanding of m6A roles at the nucleotide level. Here, we report a metabolic labeling method to detect mRNA m6A transcriptome-wide at base resolution, called ‘m6A-label-seq’. Human and mouse cells could be fed with a methionine analog, Se-allyl-l-selenohomocysteine, which substitutes the methyl group on the enzyme cofactor SAM with the allyl. Cellular RNAs could therefore be metabolically modified with N6-allyladenosine (a6A) at supposed m6A-generating adenosine sites. We pinpointed the mRNA a6A locations based on iodination-induced misincorporation at the opposite site in complementary DNA during reverse transcription. We identified a few thousand mRNA m6A sites in human HeLa, HEK293T and mouse H2.35 cells, carried out a parallel comparison of m6A-label-seq with available m6A sequencing methods, and validated selected sites by an orthogonal method. This method offers advantages in detecting clustered m6A sites and holds promise to locate nuclear nascent RNA m6A modifications.

ABSTRACTN6-methyladenosine (m6A), the most abundant internal modification on mRNAs in eukaryotes, play roles in adipogenesis. However, the underlying mechanism remains largely unclear. Here, we show that m6A plays a critical role in regulating macroautophagy/autophagy and adipogenesis through targeting Atg5and Atg7. Mechanistically, knockdown of FTO, a well-known m6A demethylase, decreased the expression of ATG5 and ATG7, leading to attenuation of autophagosome formation, thereby inhibiting autophagy and adipogenesis. We proved that FTO directly targeted Atg5and Atg7transcripts and mediated their expression in an m6A-dependent manner. Further study identified that Atg5and Atg7were the targets of YTHDF2 (YTH N6-methyladenosine RNA binding protein 2). Upon FTO silencing, Atg5and Atg7transcripts with higher m6A levels were captured by YTHDF2, which resulted in mRNA degradation and reduction of protein expression, thus alleviating autophagy and adipogenesis. Furthermore, we generated an adipose-selective ftoknockout mouse and find that FTO deficiency decreased white fat mass and impairs ATG5- and ATG7-dependent autophagy in vivo. Together, these findings unveil the functional importance of the m6A methylation machinery in autophagy and adipogenesis regulation, which expands our understanding of such interplay that is essential for development of therapeutic strategies in the prevention and treatment of obesity.Abbreviations3-MA: 3-methyladenine; ACTB: actin, beta; ATG: autophagy-related; Baf A1: bafilomycin A1; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; CEBPB: CCAAT/enhancer binding protein (C/EBP), beta; FABP4: fatty acid binding protein 4, adipocyte; FTO: fat mass and obesity associated; HFD: high-fat diet; LC-MS/MS: liquid chromatography-tandem mass spectrometry; MAP1LC3B/LC3: microtubule-associated protein 1 light chain 3 beta; m6A: N6-methyladenosine; MEFs: mouse embryo fibroblasts; MeRIP-qPCR: methylated RNA immunoprecipitation-qPCR; PPARG: peroxisome proliferator activated receptor gamma; RIP: RNA-immunoprecipitation; SAT: subcutaneous adipose tissue; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; ULK1: unc-51 like kinase 1; VAT: visceral adipose tissue; WAT: white adipose tissue; YTHDF: YTH N6-methyladenosine RNA binding protein

To evaluate the effects of gelatin and starch encapsulated vitamin A on growth performance, immune status and antioxidant capacity in weaned piglets, a total of 96 weaned piglets (body weight = 9.11 ± 0.03 kg, 30-d-old) were randomly allotted to 3 treatments with 4 replications of 8 piglets each. The 3 treatments were control diet (basal diet without addition of vitamin A), gelatin vitamin A diet (basal diet + 13,500 IU/kg gelatin encapsulated vitamin A), and starch vitamin A diet (basal diet + 13,500 IU/kg starch encapsulated vitamin A), respectively. The results showed that piglets fed starch vitamin A diet had significantly higher final body weight and average daily gain compared to those in control and gelatin vitamin A groups (P < 0.05). Gelatin and starch vitamin A supplementation both highly increased serum retinol concentration and immunoglobulin (Ig) M level when compared with the control group (P < 0.05). Additionally, serum IgA level and glutathione peroxidase (GSH-Px) activity were significantly increased by gelatin vitamin A diet on d 21 and starch vitamin A diet on d 42, respectively (P < 0.05). These results demonstrated that dietary supplementation of vitamin A could improve immune function and antioxidant capacity in weaned piglets, and starch vitamin A is better than gelatin vitamin A, especially in promoting the growth performance of piglets.

Diabetic wounds are a worldwide health problem causing extremely heavy public health burden and require effective treatment. Optimal strategies for treating nonhealing diabetic wounds include stem-cell-based therapy and delivery of novel drug substances, such as functional microRNAs (miRNAs); however, miRNA easily degrades in the wound microenvironment. Herein, we developed a human adipose stem-cell-derived exosome (hASC-exos)-based miRNA delivery strategy to enhance its therapeutic efficacy. The miR-21-5p mimics, as novel therapeutic candidates for diabetic wounds, were loaded into hASC-exos by electroporation, taking advantage of natural availability and biocompatibility of exosomes as extracellular miRNA transporting particles. The engineered exosomes (E-exos) exhibited excellent effects on promoting proliferation and migration of keratinocytes via Wnt/β-catenin signaling in vitro and accelerating diabetic wound healing by increasing re-epithelialization, collagen remodeling, angiogenesis, and vessel maturation in vivo. Results from this study would set the fundamentals of applying hASC-exos to deliver future drug substances and to develop cell-free therapy for wound-healing treatments.

The high prevalence of obesity and its associated metabolic diseases has heightened the importance of understanding control of adipose tissue development and energy metabolism. In mammals, 3 types of adipocytes with different characteristics and origins have been identified: white, brown, and beige. Beige and brown adipocytes contain numerous mitochondria and have the capability to burn energy and counteract obesity, while white adipocytes store energy and are closely associated with metabolic disorders and obesity. Thus, regulation of the development and function of different adipocytes is important for controlling energy balance and combating obesity and related metabolic disorders. Melatonin is a neurohormone, which plays multiple roles in regulating inflammation, blood pressure, insulin actions, and energy metabolism. This article summarizes and discusses the role of melatonin in white, beige, and brown adipocytes, especially in affecting adipogenesis, inducing beige formation or white adipose tissue browning, enhancing brown adipose tissue mass and activities, improving anti-inflammatory and antioxidative effects, regulating adipokine secretion, and preventing body weight gain. Based on the current findings, melatonin is a potential therapeutic agent to control energy metabolism, adipogenesis, fat deposition, adiposity, and related metabolic diseases.

As an alternative to antimicrobial growth promoters, fermented feed (FF) has been continuously developed for two decades; however, its effects on feed, performance, digestibility, and meat quality of pigs have yet to be systematically and comprehensively evaluated. This study aimed to (i) quantitatively evaluate the effects of fermentation on nutritional components of feed stuffs; (ii) quantitatively evaluate the effects of FF on pig growth performance, digestibility, and meat quality; and (iii) explore the dose-effect relationship. From PubMed and Web of Science (searched range from January 1, 2000 to April 4, 2019), we collected 3,271 articles, of which 30 articles (3,562 pigs) were included in our meta-analysis. Our analysis revealed that fermentation significantly increased the CP content in feed (P < 0.05). For weaned piglets and growing pigs, FF significantly improved ADG, G:F, DM digestibility, N digestibility, and energy digestibility (P < 0.05). However, compared with the basal diet, FF had no significant effects on growth performance and nutrient digestibility in finishing pigs (P > 0.05). In the subgroup analyses, fermented ingredients increased the growth performance of weaned piglets and growing pigs, and fermented additives promoted the growth of pigs at all stages. The dose-effect analysis confirmed that the optimal doses of fermented ingredients and additives were 8% and 0.15%, respectively. Furthermore, FF had beneficial impacts on meat quality through increased lightness, redness, marbling and flavor and reduced drip loss (P < 0.05). In conclusions, FF improved growth performance and meat quality primarily due to its positive effects on nutritive value and utilization.

ABSTRACTObesity is becoming a global problem. Research into the detailed mechanism of adipocyte development is crucial for the treatment of excess fat. Zinc finger protein 217 plays roles in adipogenesis. However, the underlying mechanism remains unclear. Here, we demonstrated that ZFP217 knockdown prevented the mitotic clonal expansion process and caused adipogenesis inhibition. Depletion of ZFP217 increased the expression of the m6A methyltransferase METTL3, which upregulated the m6A level of cyclin D1 mRNA. METTL3 knockdown rescued the siZFP217-inhibited MCE and promoted CCND1 expression. YTH domain family 2 recognized and degraded the methylated CCND1 mRNA, leading to the downregulation of CCND1. Consequently, cell-cycle progression was blocked, and adipogenesis was inhibited. YTHDF2 knockdown relieved siZFP217-inhibited adipocyte differentiation. These findings reveal that ZFP217 knockdown–induced adipogenesis inhibition was caused by CCND1, which was mediated by METTL3 and YTHDF2 in an m6A-dependent manner. We have provided novel insight into the underlying molecular mechanisms by which m6A methylation is involved in the ZFP217 regulation of adipogenesis.

The core physical behavior of reactors is essentially the result of multi-physical fields coupling feedback. High-fidelity neutronics/thermal-hydraulics (N/TH) analysis can simulate and predict nuclear reactor core phenomena realistically, providing advanced and reliable technical means during the design and safety analysis of nuclear reactor. In this work, an efficient and robustness coupling method using power density as the coupling parameter, Matrix-Free Newton Krylov (MFNK) method, is successfully developed and innovatively implemented in HNET for high-fidelity N/TH coupling simulation. To enhance the efficiency and stability, the multi-level generalized equivalence theory-based CMFD (ML-gCMFD) iterative acceleration method and ML-gCMFD coupling acceleration method are proposed. In addition, the nonlinear preconditioning and hybrid perturbation size formula are implemented to further improve the convergence. Finally, to evaluate the numerical accuracy, convergence, efficiency and stability of MFNK method, a series of representative problems, including a three-dimensional (3D) single fuel pin problem, VERA Benchmark Problem 6, and VERA Benchmark Problem 7, are analyzed by comparing with the current N/TH coupling methods. Numerical results indicate that MFNK method can obtain strong stability, high convergence performance, and relatively high computational efficiency while ensuring high accuracy. It demonstrates that MFNK method has significant performance advantages and potential for high-fidelity N/TH coupling simulation.

The widespread use of colloidal copper oxide nanoparticles (CuONPs) poses substantial health risks to humans. CuONPs can penetrate the blood–testis barrier and induce spermatocide, and the understanding of the adverse effects of asthenospermia on spermatogenesis, embryonic development, and transgenerational inheritance is limited. In this study, male mice were orally administered different doses of CuONPs via continuous exposure for one spermatozoon development period (35 days) and then exposed without CuONPs for another 35 days. The CuONPs that accumulated in the testes induced oxidative stress (OS), affected the progress of spermatogenesis and sperm capacitation, and compromised epigenetic modifications, resulting in asthenospermia and embryonic development anomalies in male offspring. In a mechanism, CuONP exposure impaired the self-renewal and differentiation of spermatogonial stem cells (SSCs) via the GDNF/PI3K/AKT signaling pathway under OS. Importantly, CuONP exposure was found to potentially lower H3K9me3 levels in paternal sperm, which would further transgenerational transmission and interfere with sperm mitochondrial energy metabolism and motility, leading to asthenospermia and subfertility in the offspring. Collectively, these data reveal a molecular mechanism by which CuONP exposure disturbs H3K9me3 levels via the OS pathway, which further mediates the asthenospermic effects of reproductive failure by interfering with mitochondrial arrangement and formation in the next generation.

Accurate description of the static correlation poses a persistent challenge in electronic structure theory, particularly when it has to be concurrently considered with the dynamic correlation. We develop here a method in the generalized Kohn–Sham density functional theory (DFT) framework, named R-xDH7-SCC15, which achieves an unprecedented accuracy in capturing the static correlation, while maintaining a good description of the dynamic correlation on par with the state-of-the-art DFT and wave function theory methods, all grounded in the same single-reference black-box methodology. Central to R-xDH7-SCC15 is a general-purpose static correlation correction (SCC) model applied to the renormalized XYG3-type doubly hybrid method (R-xDH7). The SCC model development involves a hybrid machine learning strategy that integrates symbolic regression with nonlinear parameter optimization, aiming to achieve a balance between generalization capability, numerical accuracy, and interpretability. Extensive benchmark studies confirm the robustness and broad applicability of R-xDH7-SCC15 across a diverse array of main-group chemical scenarios. Notably, it displays exceptional aptitude in accurately characterizing intricate reaction kinetics and dynamic processes in regions distant from equilibrium, where the influence of static correlation is most profound. Its capability to consistently and efficiently predict the whole energy profiles, activation barriers, and reaction pathways within a user-friendly “black-box” framework represents an important advance in the field of electronic structure theory.

Neuroblastoma is a pediatric malignancy arising from the developing peripheral nervous system. p53 and downstream effector miR-34b/chave critical tumor suppressing functions. TP53Arg72Pro (rs1042522 C > G) and miR-34b/crs4938723 (T > C) polymorphisms have been known to modify cancer susceptibility. This study was performed to validate the association of these two polymorphisms and neuroblastoma risk with 819 cases and 1780 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to assess the strength of the associations. False positive report possibility analysis was adopted to dissect out real significant associations from chance findings. We found that both TP53Arg72Pro (CG/GG vs. CC: adjusted OR = 0.82, 95% CI = 0.69-0.98) and miR-34b/crs4938723 (TC/CC vs. TT: adjusted OR = 0.64, 95% CI = 0.54-0.75) were associated with decreased neuroblastoma susceptibility. Stratify analyses further confirmed the protective effect among some subgroups. Moreover, subjects with variant alleles of both polymorphisms were associated with more significantly decreased neuroblastoma risk (CG/TC vs. CC/TT: adjusted OR = 0.38, 95% CI = 0.28-0.50; GG/TC vs. CC/TT: adjusted OR = 0.43, 95% CI = 0.30-0.63) than those carrying variant allele of either one polymorphism (CC/TC vs. CC/TT: adjusted OR = 0.51, 95% CI = 0.37-0.69; CG/TT vs. CC/TT: adjusted OR = 0.71, 95% CI = 0.55-0.92), suggesting cumulative effects of the polymorphisms. False positive report possibility analysis further verified that our findings are noteworthy. Overall, we confirmed that miR-34b/crs4938723 and TP53Arg72Pro conferred decreased neuroblastoma risk and two polymorphisms exerted stronger protective effects against neuroblastoma than either one alone.

Hybrid high-voltage direct current (HVDC) transmission systems employ a new type of HVDC transmission topology that combines the advantages of the line-commutated converter system and the voltage-source converter system. They can improve the efficiency and reliability of long-distance power transmission. However, realizing alternating-current (AC) grid-fault ride through on the inverter side of a hybrid HVDC transmission system is a challenge considering that a voltage-source converter based HVDC (VSC-HVDC) is used on the inverter side. In this study, a control strategy for an overvoltage fixed trigger angle based on the power-balance method is developed by fully utilizing the operation characteristics of a hybrid HVDC transmission system. The strategy reduces the inverter-side overvoltage of the HVDC system under a fault in the inverter-side AC system. Simulations based on Gezhou Dam are conducted to validate the effectiveness of the proposed strategy.

A new method for regulating the synthesis of NiMgFe hydrotalcites (NMF LDHs) with the addition of hydroxyl compounds was proposed. A series of NMF LDHs were prepared by the above method, and then were calcined to obtain the NiMgFeOx(NMFOx) samples. The NMFOxsamples were characterized by XRD, SEM, TG-DTG, XPS and CO2-TPD, respectively. The catalytic performance of NMFOxfor depolymerizing calcium lignosulfonate (CLS) was evaluated by hydrothermal reaction. The results showed that the addition of hydroxyl compounds favored reducing the particle sizes of NMF LDHs. For the depolymerization of CSL, the yield of liquid product increased from 45% to 75.8% with the addition of NMFOx-ethanol (NMFOx-ET). The liquid products were mainly phenolics, aromatics, ketones and esters. The total selectivity of oxy-containing compounds was over 90.6%, among them, the phenolics were approximately 35.2%. The valence of Ni and Fe, crystalline phase and basicity almost remained unchanged. The NMFOx-ET samples were recycled for the depolymerization of CLS, moreover, the NMFOx-ET samples had high activity and stability after 4 cycles.