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1.
Biomimetics (Basel) ; 9(2)2024 Jan 29.
Article En | MEDLINE | ID: mdl-38392127

Underwater bionic-legged robots encounter significant challenges in attitude, velocity, and positional control due to lift and drag in water current environments, making it difficult to balance operational efficiency with motion stability. This study delves into the hydrodynamic properties of a bionic crab robot's shell, drawing inspiration from the sea crab's motion postures. It further refines the robot's underwater locomotion strategy based on these insights. Initially, the research involved collecting attitude data from crabs during underwater movement through biological observation. Subsequently, hydrodynamic simulations and experimental validations of the bionic shell were conducted, examining the impact of attitude parameters on hydrodynamic performance. The findings reveal that the transverse angle predominantly influences lift and drag. Experiments in a test pool with a crab-like robot, altering transverse angles, demonstrated that increased transverse angles enhance the robot's underwater walking efficiency, stability, and overall performance.

2.
Oncogene ; 42(12): 869-880, 2023 03.
Article En | MEDLINE | ID: mdl-36721000

Targeting cyclin-dependent kinases (CDKs) has recently emerged as a promising therapeutic approach against cancer. However, the anticancer mechanisms of different CDK inhibitors (CDKIs) are not well understood. Our recent study revealed that selective CDK4/6 inhibitors sensitize colorectal cancer (CRC) cells to therapy-induced apoptosis by inducing Death Receptor 5 (DR5) via the p53 family member p73. In this study, we investigated if this pathway is involved in anticancer effects of different CDKIs. We found that less-selective CDKIs, including flavopiridol, roscovitine, dinaciclib, and SNS-032, induced DR5 via p73-mediated transcriptional activation. The induction of DR5 by these CDKIs was mediated by dephosphorylation of p73 at Threonine 86 and p73 nuclear translocation. Knockdown of a common target of these CDKIs, including CDK1, 2, or 9, recapitulated p73-mediated DR5 induction. CDKIs strongly synergized with 5-fluorouracil (5-FU), the most commonly used CRC chemotherapy agent, in vitro and in vivo to promote growth suppression and apoptosis, which required DR5 and p73. Together, these findings indicate p73-mediated DR5 induction as a potential tumor suppressive mechanism and a critical target engaged by different CDKIs in potentiating therapy-induced apoptosis in CRC cells. These findings help better understand the anticancer mechanisms of CDKIs and may help facilitate their clinical development and applications in CRC.


Antineoplastic Agents , Colonic Neoplasms , Humans , Cyclin-Dependent Kinases , Cell Line, Tumor , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis , Fluorouracil/pharmacology , Fluorouracil/therapeutic use
3.
Int J Mol Sci ; 23(23)2022 Nov 24.
Article En | MEDLINE | ID: mdl-36498997

Stearoyl-CoA desaturase-1 (SCD1) catalyzes the rate-liming step of monounsaturated fatty acid biosynthesis and is a key regulator of systemic glucose metabolism. Mice harboring either a global (GKO) or liver-specific deletion (LKO) of Scd1 display enhanced insulin signaling and whole-body glucose uptake. Additionally, GKO and LKO mice are protected from high-carbohydrate diet-induced obesity. Given that high-carbohydrate diets can lead to chronic metabolic diseases such as obesity, diabetes, and hepatic steatosis, it is critical to understand how Scd1 deficiency confers metabolically beneficial phenotypes. Here we show that insulin-like growth factor-binding protein 1 (IGFBP1), a hepatokine that has been reported to enhance insulin signaling, is significantly elevated in the liver and plasma of GKO and LKO mice fed a low-fat high-carbohydrate diet. We also observed that the expression of hepatic Igfbp1 is regulated by oleic acid (18:1n9), a product of SCD1, through the mTORC1-FGF21 axis both in vivo and in vitro.


Insulin-Like Growth Factor Binding Protein 1 , Mechanistic Target of Rapamycin Complex 1 , Oleic Acid , Stearoyl-CoA Desaturase , Animals , Mice , Insulin/metabolism , Liver/metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Obesity/metabolism , Oleic Acid/metabolism , Stearoyl-CoA Desaturase/genetics , Stearoyl-CoA Desaturase/metabolism , Insulin-Like Growth Factor Binding Protein 1/metabolism , Dietary Carbohydrates/administration & dosage
4.
Int J Mol Sci ; 21(22)2020 Nov 16.
Article En | MEDLINE | ID: mdl-33207603

Stearoyl-CoA Desaturase-2 (SCD2) is a member of the Stearoyl-CoA Desaturase (SCD) family of enzymes that catalyze the rate-limiting step in monounsaturated fatty acid (MUFA) synthesis. The MUFAs palmitoleoyl-CoA (16:1n7) and oleoyl-CoA (18:1n9) are the major products of SCD2. Palmitoleoyl-CoA and oleoyl-CoA have various roles, from being a source of energy to signaling molecules. Under normal feeding conditions, SCD2 is ubiquitously expressed and is the predominant SCD isoform in the brain. However, obesogenic diets highly induce SCD2 in adipose tissue, lung, and kidney. Here we provide a comprehensive review of SCD2 in mouse development, metabolism, and various diseases, such as obesity, chronic kidney disease, Alzheimer's disease, multiple sclerosis, and Parkinson's disease. In addition, we show that bone mineral density is decreased in SCD2KO mice under high-fat feeding conditions and that SCD2 is not required for preadipocyte differentiation or the expression of PPARγ in vivo despite being required in vitro.


Adipocytes/enzymology , Cell Differentiation , Fatty Acids, Monounsaturated/metabolism , Neurodegenerative Diseases/enzymology , Obesity/enzymology , Renal Insufficiency, Chronic/enzymology , Stearoyl-CoA Desaturase/metabolism , Acyl Coenzyme A/biosynthesis , Acyl Coenzyme A/genetics , Animals , Diet, High-Fat/adverse effects , Mice , Mice, Knockout , Neurodegenerative Diseases/genetics , Obesity/chemically induced , Obesity/genetics , Obesity/metabolism , Palmitoyl Coenzyme A/biosynthesis , Palmitoyl Coenzyme A/genetics , Renal Insufficiency, Chronic/genetics , Stearoyl-CoA Desaturase/genetics
5.
Food Funct ; 9(8): 4153-4163, 2018 Aug 15.
Article En | MEDLINE | ID: mdl-30058657

Lysine is a common limiting amino acid in human and animal diets and plays an important role in cell proliferation and metabolism. Our previous study suggested that short-term lysine restriction improved feed intake. Herein, we further investigated the long-term effects of lysine restriction on intestinal microbial communities and metabolic profiles in pigs by 16S rDNA sequencing and metabolomic analysis. The results showed that 30% lysine limitation increased the feed intake in piglets but not in growing and finishing pigs. Microbiota sequencing was conducted, and we identified 12 differentiated microbes at the genus level in response to dietary lysine restriction. Metagenomic predictions by PICRUSt suggested that the altered microbiota was mainly involved in the host metabolism, especially in amino acid metabolism. Intestinal metabolomic study identified 20 differentiated metabolites in finishing pigs, which were mapped into 5 metabolic pathways including glutamine and glutamate metabolism, taurine metabolism, alanine, aspartate and glutamate metabolism, vitamin B6 metabolism, and pentose and glucoronate metabolism. Determination of serum amino acids and intestinal amino acid transporters further validated the results obtained from PICRUSt and metabolomic analyses, which showed that long-term lysine restriction influenced amino acid metabolism. Phosphorylation of mTOR in the intestine was not altered in lysine-restricted pigs, whereas lysine limitation markedly inhibited the AMPK signaling. In conclusion, long-term lysine restriction from piglets to finishing pigs affected the amino acid metabolism, which might be associated with gut microbiota and AMPK signaling.


Intestines/microbiology , Lysine/pharmacology , Swine/growth & development , Amino Acid Transport Systems/blood , Amino Acids/blood , Animals , Bacteria/genetics , Bacteria/isolation & purification , Dose-Response Relationship, Drug , Gastrointestinal Microbiome , Lysine/administration & dosage , Male , RNA, Bacterial/genetics , RNA, Ribosomal, 16S/genetics , Random Allocation , Real-Time Polymerase Chain Reaction , Swine/microbiology
6.
Protein Pept Lett ; 25(4): 405-416, 2018.
Article En | MEDLINE | ID: mdl-29623821

BACKGROUND: Our previous study suggested that short-term lysine restriction improved feed intake and gut microbiota in piglets. Thus, in this study, we further used proteomics technology to investigate the potential mechanism associated with long-term lysine restriction in pigs. In addition, blood biochemical parameters, meat quality, and muscle nutrient transporters were also evaluated in lysine restricted pigs. RESULTS: The results showed that 131 proteins in the liver were markedly altered in response to dietary lysine restriction, with 54 being downregulated and 77 being upregulated, which mainly involved in neurodegenerative diseases, oxidative phosphorylation, and metabolic pathways. In addition, lysine restriction markedly reduced serum BUN, CHOL, and HDL abundances. Dietary lysine restriction enhanced meat color lightness and upregulated SLC7A2 expression. CONCLUSION: Lysine restriction affected meat quality, blood biochemical parameters, and liver global protein expressions. This study is the first attempt to evaluate the liver protein profile of lysine restricted pigs, and the current results may provide valuable information with respect to better understanding the host response to lysine restriction in pigs.


Liver/metabolism , Lysine/administration & dosage , Meat/analysis , Proteins/metabolism , Swine/metabolism , Animal Feed , Animal Nutritional Physiological Phenomena , Animals , Diet/veterinary , Lysine/metabolism , Male
7.
Cell Physiol Biochem ; 44(5): 1749-1761, 2017.
Article En | MEDLINE | ID: mdl-29216634

BACKGROUND/AIMS: Our previous reports suggested that dietary supplementation with lysine influenced intestinal absorption and metabolism of amino acids. In this study, we further investigated the effect of lysine restriction (30%) on feed intake and we also tested the hypothesis that gut microbiome contributed to the potential mechanism of lysine restriction-mediated feeding behavior. Here, we profiled gut microbial communities by sequencing 16S ribosomal ribonucleic acid (rRNA) genes from gut samples as well as growth performance, serum hormones, and intestinal lysine transport in a piglet model. RESULTS: Piglets preferred to the lysine restricted diet when giving three diets and the feed intake was markedly higher in the lysine-restricted group than that in the control group. Altered hormones (leptin, CCK, and ghrelin) might contribute to the feeding behavior caused by lysine restriction. Meanwhile, lysine transporting ability (SLC7A1 and SLC7A2 expression, intestinal electrophysiological changes, and amino acid pool in mesenteric vein) was decreased in response to lysine restriction. Through deep sequencing of bacterial rRNA markers, we observed that bacterial diversity was enhanced in the lysine-restricted group (Shannon H, PD, and Chao1). At the phylum level, lysine restriction enhanced gut Actinobacteria, Saccharibacteria, and Synergistetes abundances. At the family level, Moraxellaceae, Halomonadaceae, Shewanellaceae, Corynebacteriaceae, Bacillaceae, Comamonadaceae, Microbacteriaceae, Caulobacteraceae, and Synergistaceae abundances were increased in response to lysine restriction. Predictive functional profiling of microbial communities by PICRUSt also confirmed that dietary lysine restriction affected gut microbiome, which might further mediate amino acid metabolism, membrane transport, and endocrine system. CONCLUSION: Our results indicated that lysine restriction inhibited intestinal lysine transport and promoted feed intake, which might be associated with gut microbiome.


Amino Acids/metabolism , Diet , Intestines/microbiology , Lysine/deficiency , Microbiota , Amino Acids/blood , Animals , Bacteria/genetics , Bacteria/isolation & purification , Cationic Amino Acid Transporter 1/genetics , Cationic Amino Acid Transporter 1/metabolism , Cationic Amino Acid Transporter 2/genetics , Cationic Amino Acid Transporter 2/metabolism , Eating , Enzyme-Linked Immunosorbent Assay , Gastrins/blood , Ghrelin/blood , Leptin/blood , Male , Principal Component Analysis , RNA, Ribosomal, 16S/chemistry , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolism , Real-Time Polymerase Chain Reaction , Sequence Analysis, DNA , Swine
9.
Se Pu ; 31(9): 894-7, 2013 Sep.
Article Zh | MEDLINE | ID: mdl-24392628

The work shown here describes a simple, fast and effective on-line solid phase extraction (on-line SPE) method for facilitative high-throughput sample desalting before the detection of mass spectrometry (MS) or liquid chromatography-mass spectrometry (LC-MS). This method includes single SPE column mode and dual SPE column mode. It accomplishes the on-line desalting with an Ultimate 3000 HPLC system equipped with a dual pump system (loading pump/analytical pump), an autosampler, a column oven equipped with a 2p-10p valve, controlled by a chromatography data system. In the single SPE column mode, sample loading and desalting were performed on the SPE column using the loading pump. The analytes were retained on the SPE column, and the salt in the sample solution was flushed out of the SPE column. After desalting, the retained analytes were eluted from the SPE column with the analytical pump. In the dual SPE column mode, two same SPE columns were used. Firstly, the sample loading and desalting were performed on the SPE column 1. The analytes were retained and the salt was flushed out. After desalting on the SPE column 1, the sample loading and desalting were performed on the SPE column 2. Meanwhile, the retained analytes were eluted from the SPE column 1 with the analytical pump. As both of the processes on the SPE columns 1 and 2 described above completed, the sample loading and desalting on the SPE column 1, and the elution of the analytes from the SPE column 2 started again. As the SPE columns 1 and 2 worked in turn, the on-line SPE desalting system was efficient. The eluted analytes from the SPE columns may be determined by MS directly, or separated on the analytical column and then determined by MS/UV.

10.
Se Pu ; 30(10): 1068-73, 2012 Oct.
Article Zh | MEDLINE | ID: mdl-23383497

An on-line solid phase extraction (SPE) system was used to eliminate the interferences sufficiently and fulfill the simple and sensitive determination of diquat and paraquat in tap and pond water. This on-line SPE system used two SPE cartridges. One was an Acclaim Mixed-Mode WAX-1 cartridge for the elimination of anionic interferences; the other one was an Acclaim Mixed-Mode WCX-1 cartridge for the enrichment of diquat and paraquat and the elimination of co-enriched cationic interferences. The baseline separation of diquat and paraquat was achieved on an Acclaim Trinity P1 column. A dual-gradient high performance liquid chromatographic (HPLC) system provided an efficient platform to fulfill the on-line SPE and separation, and the system operated under automatic control of chromatography data system software. The complete analysis only required 16 min, and the detection limits of the method were 0.12 microg/L for diquat and 0.10 microg/L for paraquat. The method is simple, rapid and sensitive, and can be applied to the determination of diquat and paraquat in drinking water and environmental water.


Chromatography, High Pressure Liquid/methods , Diquat/analysis , Drinking Water/analysis , Paraquat/analysis , Water Pollutants, Chemical/analysis , Fresh Water/analysis , Solid Phase Extraction/methods
11.
Amino Acids ; 39(5): 1477-86, 2010 Nov.
Article En | MEDLINE | ID: mdl-20473536

Recent work with young pigs shows that reducing dietary protein intake can improve gut function after weaning but results in inadequate provision of essential amino acids for muscle growth. Because acute administration of L-leucine stimulates protein synthesis in piglet muscle, the present study tested the hypothesis that supplementing L-leucine to a low-protein diet may maintain the activation of translation initiation factors and adequate protein synthesis in multiple organs of post-weaning pigs. Eighteen 21-day pigs (Duroc×Landrace×Yorkshire) were fed low-protein diets (16.9% crude protein) supplemented with 0, 0.27 or 0.55% L-leucine (total leucine contents in the diets being 1.34, 1.61 or 1.88%, respectively). At 35 days of age, protein synthesis was determined using the [2H] phenylalanine flooding-dose technique. Additionally, total and phosphorylated levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase 1 (S6K1), and eIF4E-binding protein-1 (4E-BP1) were measured in longissimus muscle and liver. Compared with the control group, dietary supplementation with 0.55% L-leucine for 2 weeks increased (P<0.05): (1) the phosphorylated levels of S6K1 and 4E-BP1; (2) protein synthesis in skeletal muscle, liver, the heart, kidney, pancreas, spleen, and stomach; and (3) daily weight gain by 61%. Dietary supplementation with 0.27% L-leucine enhanced (P<0.05) protein synthesis in proximal small intestine, kidney and pancreas. These novel findings provide a molecular basis for designing effective nutritional means to increase the efficiency of nutrient utilization for protein accretion in neonates.


Dietary Proteins/administration & dosage , Dietary Supplements , Leucine/administration & dosage , Muscle Proteins/biosynthesis , Amino Acids/blood , Animals , Blood Glucose/analysis , Eukaryotic Initiation Factor-4E/metabolism , Insulin/blood , Muscle, Skeletal/metabolism , Organ Size , Phosphorylation , Ribosomal Protein S6 Kinases/metabolism , Sirolimus/metabolism , Swine , Weaning
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