Muramidase-released protein(MRP)is now being recognized as a critical indicator of the virulence and pathogenicity of Streptococcus suis(S.suis).However,the identification of viable therapeutics for S.suis infection w...Muramidase-released protein(MRP)is now being recognized as a critical indicator of the virulence and pathogenicity of Streptococcus suis(S.suis).However,the identification of viable therapeutics for S.suis infection was hindered by the absence of an explicit mechanism for MRP-actuated inflammation.Dihydroartemisinin(DhA)is an artemisinin derivative with potential anti-inflammatory activity.The modulatory effect of DhA on the inflammatory response mediated by the virulence factor MRP remains obscure.This research aimed to identify the signaling mechanism by which MRP triggers the innate immune response in mouse spleen and cultured macrophages.With the candidate mechanism in mind,we investigated DhA for its ability to dampen the pro-inflammatory response induced by MRP.The innate immune response in mice was drastically triggered by MRP,manifesting as splenic and systemic inflammation with splenomegaly,immune cell infiltration,and an elevation in pro-inflammatory cytokines.A crucial role for Toll-like receptor 4(TLR4)in coordinating the MRP-mediated inflammatory response via nuclear factor-kappa B(NF-kB)activation was revealed by TLR4 blockade.In addition,NFkB-dependent transducer and activator of transcription 3(STAT3)and mitogen-activated protein kinases(MAPKs)activation was required for the inflammatory signal transduction engendered by MRP.Intriguingly,we observed an alleviation effect of DhA on the MRP-induced immune response,which referred to the suppression of TLR4-mediated actuation of NF-kB-STAT3/MAPK cascades.The inflammatory response elicited by MRP is relevant to TLR4-dependent NF-kB activation,followed by an increase in the activity of STAT3 or MAPKs.DhA mitigates the inflammation process induced by MRP via blocking the TLR4 cascade,highlighting the therapeutic potential of DhA in targeting S.suis infection diseases.展开更多
Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural develop...Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural development of the mammary gland occurs during fetal growth, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones (particularly estrogen, growth hormone, insulin-like growth factor-I, progesterone, placental lactogen, and prolactin) in a species- and stage-dependent manner. Milk is essential for the growth, development, and health of neonates. Amino acids (AA), present in both free and peptide-bound forms, are the most abundant organic nutrients in the milk of farm animals. Uptake of AA from the arterial blood of the lactating dam is the ultimate source of proteins (primarily 13-casein and a-lactalbumin) and bioactive nitrogenous metabolites in milk. Results of recent studies indicate extensive catabolism of branched-chain AA (leucine, isoleucine and valine) and arginine to synthesize glutamate, glutamine, alanine, aspartate, asparagine, proline, and polyamines. The formation of polypeptides from AA is regulated not only by hormones (e.g., prolactin, insulin and glucocorticoids) and the rate of blood flow across the lactating mammary gland, but also by concentrations of AA, lipids, glucose, vitamins and minerals in the maternal plasma, as well as the activation of the mechanistic (mammalian) target rapamycin signaling by certain AA (e.g., arginine, branched-chain AA, and glutamine). Knowledge of AA utilization (including metabolism) by mammary epithelial cells will enhance our fundamental understanding of lactation biology and has important implications for improving the efficiency of livestock production worldwide.展开更多
Protein is quantitatively the most expensive nutrient in swine diets. Hence it is imperative to understand the physiological roles played by amino acids in growth, development, lactation, reproduction, and health of p...Protein is quantitatively the most expensive nutrient in swine diets. Hence it is imperative to understand the physiological roles played by amino acids in growth, development, lactation, reproduction, and health of pigs to improve their protein nutrition and reduce the costs of pork production. Due to incomplete knowledge of amino acid biochemistry and nutrition, it was traditionally assumed that neonatal, post-weaning, growing-finishing, and gestating pigs could synthesize sufficient amounts of all "nutritionally nonessential amino acids" (NEAA) to support maximum production performance. Therefore, over the past 50 years, much emphasis has been placed on dietary requirements of nutritionally essential amino acids as building blocks for tissue proteins. However, a large body of literature shows that NEAA, particularly glutamine, glutamate, arginine and proline regulate physiological functions via cell signaling pathways, such as mammalian target of rapamycin, AMP-activated protein kinase, extracellular signal-related kinase, Jun kinase, mitogen-activated protein kinase, and NEAA-derived gaseous molecules (e.g., nitric oxide, carbon monoxide, and hydrogen sulfide). Available evidence shows that under current feeding programs, only 70% and 55% of dietary amino acids are deposited as tissue proteins in 14-day-old sow-reared piglets and in 30-day-old pigs weaned at 21 days of age, respectively. Therefore, there is an urgent need to understand the robes and dietary requirements of NEAA in swine nutrition. This review highlights the basic biochemistry and physiology of absorption and utilization of amino acids in young pigs to enhance the efficacy of utilization of dietary protein and to minimize excretion of nitrogenous wastes from the body.展开更多
Maternal undernutrition or overnutrition during pregnancy alters organ structure, impairs prenatal and neonatal growth and development, and reduces feed efficiency for lean tissue gains in pigs. These adverse effects ...Maternal undernutrition or overnutrition during pregnancy alters organ structure, impairs prenatal and neonatal growth and development, and reduces feed efficiency for lean tissue gains in pigs. These adverse effects may be carried over to the next generation or beyond. This phenomenon of the transgenerational impacts is known as fetal programming, which is mediated by stable and heritable alterations of gene expression through covalent modifications of DNA and histones without changes in DNA sequences(namely, epigenetics). The mechanisms responsible for the epigenetic regulation of protein expression and functions include chromatin remodeling; DNA methylation(occurring at the 5′-position of cytosine residues within CpG dinucleotides); and histone modifications(acetylation, methylation, phosphorylation, and ubiquitination). Like maternal malnutrition, undernutrition during the neonatal period also reduces growth performance and feed efficiency(weight gain:feed intake; also known as weightgain efficiency) in postweaning pigs by 5–10%, thereby increasing the days necessary to reach the market bodyweight. Supplementing functional amino acids(e.g., arginine and glutamine) and vitamins(e.g., folate) play a key role in activating the mammalian target of rapamycin signaling and regulating the provision of methyl donors for DNA and protein methylation. Therefore, these nutrients are beneficial for the dietary treatment of metabolic disorders in offspring with intrauterine growth restriction or neonatal malnutrition. The mechanism-based strategies hold great promise for the improvement of the efficiency of pork production and the sustainability of the global swine industry.展开更多
Background: Endoplasmic reticulum(ER) stress is associated with multiple pathological processes of intestinal diseases. Despite a critical role of mechanistic target of rapamycin complex 1(m TORC1) in regulating cellu...Background: Endoplasmic reticulum(ER) stress is associated with multiple pathological processes of intestinal diseases. Despite a critical role of mechanistic target of rapamycin complex 1(m TORC1) in regulating cellular stress response, the crosstalk between m TORC1 and ER stress signaling and its contribution to the intestinal barrier function is unknown.Results: In the present study, we showed that intestinal epithelial cells(IEC-6) incubated with tunicamycin led to caspase-3-dependent apoptotic cell death. The induction of cell death was accompanied by activation of unfolded protein response as evidenced by increased protein levels for Bi P, p-IRE1α, p-e IF2α, p-JNK, and CHOP. Further study demonstrated that tunicamycin-induced cell death was enhanced by rapamycin, a specific inhibitor of m TORC1.Consistently, tunicamycin decreased transepithelial electrical resistance(TEER) and increased permeability of the cells. These effects of tunicamycin were exacerbated by m TORC1 inhibitor.Conclusions: Taken together, the data presented here identified a previously unknown crosstalk between an unfold protein response and m TORC1 signaling in the intestinal epithelium. This feed-back loop regulation on ER stress signaling by m TORC1 is critical for cell survival and intestinal permeability in epithelial cells.展开更多
Background: Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposi...Background: Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposition in high fat diet-fed Nile tilapia(Oreochromis niloticus).Results: In the present study, we found that dietary supplementation with 1% or 2% arginine decreased the deposition and concentration of fats in the liver;the concentrations of triglycerides, low-density lipoprotein, total cholesterol, and high-density lipoprotein in the serum;and the diameter of adipocytes in intraperitoneal adipose tissue. Compared with the un-supplementation control group, the hepatic activities of alanine aminotransferase,aspartate aminotransferase, and lactate dehydrogenase, and hepatic concentration of malondialdehyde were reduced but these for catalase and superoxide dismutase were enhanced by dietary supplementation with 2% arginine. Arginine supplementation reduced the total amounts of monounsaturated fatty acids, while increasing the total amounts of n-3 and n-6 polyunsaturated fatty acids in the liver. These effects of arginine were associated with reductions in mRNA levels for genes related to lipogenesis(sterol regulatory element-binding protein-1, acetyl-CoA carboxylase α, stearoyl-CoA desaturase, and fatty acid synthase) but increases in mRNA levels for genes involved in fatty acid β-oxidation(carnitine palmitoyltransferase 1α and peroxisome proliferator-activated receptor α). In addition, hepatic mRNA levels for Δ4 fatty acyl desaturase 2 and elongase 5 of very long-chain fatty acids were enhanced by arginine supplementation.Conclusion: These results revealed that dietary L-arginine supplementation to tilapia reduced high fat diet-induced fat deposition and fatty acid composition in the liver by regulating the expression of genes for lipid metabolism.展开更多
Background: Cinnamicaldehyde(CA) is a key flavor compound in cinnamon essential oil possessing various bioactivities. Tight junction(TJ) proteins are vital for the maintenance of intestinal epithelial barrier fun...Background: Cinnamicaldehyde(CA) is a key flavor compound in cinnamon essential oil possessing various bioactivities. Tight junction(TJ) proteins are vital for the maintenance of intestinal epithelial barrier function,transport, absorption and utilization of dietary amino acids and other nutrients. In this study, we tested the hypothesis that CA may regulate the expression of TJ proteins and amino acid transporters in intestinal porcine epithelial cells(IPEC-1) isolated from neonatal pigs.Results: Compared with the control, cells incubated with 25 μmol/L CA had increased transepithelial electrical resistance(TEER) and decreased paracellular intestinal permeability. The beneficial effect of CA on mucosal barrier function was associated with enhanced protein abundance for claudin-4, zonula occludens(ZO)-1, ZO-2, and ZO-3. Immunofluorescence staining showed that 25 μmol/L CA promoted the localization of claudin-1 and claudin-3 to the plasma membrane without affecting the localization of other TJ proteins, including claudin-4, occludin,ZO-1, ZO-2, and ZO-3, compared with the control cells. Moreover, protein abundances for rBAT, xCT and LAT2 in IPEC-1 cells were enhanced by 25 μmol/L CA, while that for EAAT3 was not affected.Conclusions: CA improves intestinal mucosal barrier function by regulating the distribution of claudin-1 and claudin-3 in enterocytes, as well as enhancing protein abundance for amino acid transporters rBAT, xCT and LAT2 in enterocytes. Supplementation with CA may provide an effective nutritional strategy to improve intestinal integrity and amino acid transport and absorption in piglets.展开更多
Recent years have witnessed growing interest in the role of peptides in animal nutrition. Chemical, enzymatic, or microbial hydrolysis of proteins in animal by-products or plant-source feedstuffs before feeding is an ...Recent years have witnessed growing interest in the role of peptides in animal nutrition. Chemical, enzymatic, or microbial hydrolysis of proteins in animal by-products or plant-source feedstuffs before feeding is an attractive means of generating high-quality small or large peptides that have both nutritional and physiological or regulatory functions in livestock, poultry and fish. These peptides may also be formed from ingested proteins in the gastrointestinal tract, but the types of resultant peptides can vary greatly with the physiological conditions of the animals and the composition of the diets. In the small intestine, large peptides are hydrolyzed to small peptides,which are absorbed into enterocytes faster than free amino acids(AAs) to provide a more balanced pattern of AAs in the blood circulation. Some peptides of plant or animal sources also have antimicrobial, antioxidant,antihypertensive, and immunomodulatory activities. Those peptides which confer biological functions beyond their nutritional value are called bioactive peptides. They are usually 2–20 AA residues in length but may consist of 〉20AA residues. Inclusion of some(e.g. 2–8%) animal-protein hydrolysates(e.g., porcine intestine, porcine mucosa,salmon viscera, or poultry tissue hydrolysates) or soybean protein hydrolysates in practical corn-and soybean mealbased diets can ensure desirable rates of growth performance and feed efficiency in weanling pigs, young calves,post-hatching poultry, and fish. Thus, protein hydrolysates hold promise in optimizing the nutrition of domestic and companion animals, as well as their health(particularly gut health) and well-being.展开更多
In this study,we sought to investigate the expression of the transcription factor E2F1 in chicken pulmonary arterial smooth muscle cells upon hypoxia exposure,as well as the role that E2F1 played in the regulation of ...In this study,we sought to investigate the expression of the transcription factor E2F1 in chicken pulmonary arterial smooth muscle cells upon hypoxia exposure,as well as the role that E2F1 played in the regulation of cell proliferation.Isolated chicken pulmonary arterial smooth muscle cells were subjected to hypoxia or normoxia for indicated time points.Cell viability,DNA synthesis,cell cycle profile,and expression of E2F1 were analyzed.The results showed that hypoxia promoted cell proliferation and DNA synthesis which was accompanied by an increased S phase entry and upregulation of E2F1 at mRNA and protein levels.Using siRNA technology,we demonstrated that gene inactivation of endogenous E2F1 abolished hypoxia-induced cell proliferation,DNA synthesis,and S phase entry compared with negative siRNA transfected cells.These results suggest that hypoxia-induced proliferation is mediated by inducing E2F1 in chicken pulmonary arterial smooth muscle cells.展开更多
The building blocks-based molecular network(BBMN)strategy was applied to the phytochemical investigation of Cleistocalyx operculatus,leading to the targeted isolation of eighteen novel cinnamoylphloroglucinol-terpene ...The building blocks-based molecular network(BBMN)strategy was applied to the phytochemical investigation of Cleistocalyx operculatus,leading to the targeted isolation of eighteen novel cinnamoylphloroglucinol-terpene adducts(CPTAs)with diverse skeleton types(cleistoperones A-R,1-18).Their structures including absolute configurations were determined by extensive spectroscopic methods,quantum chemical calculations,and single-crystal X-ray crystallographic experiments.Cleistoperone A(1),consisting of a cinnamoylphloroglucinol motif and two linear monoterpene moieties,represents an unprecedented macrocyclic CPTA,whose densely functionalized tricyclo[15.3.1.0^(3,8)]heneicosane bridge ring skeleton contains an enolizableβ,β′-triketone system and two different kinds of stereogenic elements(including five point and three planar chiralities).Cleistoperones B and C(2 and 3)are two new skeletal CPTAs with an unusual coupling pattern between the(nor)monoterpene moiety and the cinnamoyl chain of the cinnamoylphloroglucinol unit.Cleistoperone D(4)possesses an unprecedented cage-like 6/6/6/4/6-fused heteropentacyclic scaffold.The plausible biosynthetic pathways for 1-18 were also proposed.Notably,compounds 1,4,7,8,and 18 exhibited significant antiviral activity against respiratory syncytial virus(RSV).The most potent one,cleistoperone A(1)with IC_(50) value of 1.71±0.61μmol/L,could effectively inhibit virus replication via affecting the Akt/mTOR/p70S6K signaling pathway.展开更多
The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compound...The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compounds 1-5 featured new carbon skeletons in which phloroglucinol derivatives were coupled with lupane-and dammarane-type triterpenoids through different linkage patterns.Their structures and absolute configurations were elucidated by comprehensive analysis of spectroscopic data and quantum chemical calculations.Biosynthetic pathways for compounds 1-5 were proposed on the basis of the coexisting precursors.Guided by the biogenetic pathways,the biomimetic synthesis of compound 1 was also achieved.Additionally,compounds 2,3,and 5 exhibited potent antiviral activities against herpes simplex virus type-1(HSV-1)infection,and compounds 2 and 5 displayed significant anti-inflammatory activities on RAW264.7 cells.展开更多
This paper presents an experimental and numerical study of the aerodynamics of a moderate-scale rotor hovering in the Extreme Ground Effect(EGE)where rotor height-offground is below half the rotor radius.The tip vorte...This paper presents an experimental and numerical study of the aerodynamics of a moderate-scale rotor hovering in the Extreme Ground Effect(EGE)where rotor height-offground is below half the rotor radius.The tip vortex field was visualized by using the PIV technique.The aerodynamic performance,tip vortex trajectory,wall jet characteristics,surface pressure and velocity fields were measured and analyzed.To explore more deeply the flow mechanisms of the extreme ground effect,Detached Eddy Simulation(DES)was conducted on completely structured meshes.The results showed significant deviations of the rotor performance in EGE from that in Regular Ground Effect(RGE)with the rotor heights of more than half the rotor radius.Moreover,the flow structures of the rotor in EGE are considerably complex,such as the wall jet and groundwash flow separation.The rotor wake flow and tip vortices impact the ground more frequently,resulting in distinctive characteristics of the surface pressure and velocity fields in EGE.展开更多
Zearalenone(ZEA),a mycotoxin produced mainly by fungi belonging to Fusarium species in foods and feeds,causes a serious hazard to humans and animals.Numerous studies have revealed that ingesting ZEA can disrupt the re...Zearalenone(ZEA),a mycotoxin produced mainly by fungi belonging to Fusarium species in foods and feeds,causes a serious hazard to humans and animals.Numerous studies have revealed that ingesting ZEA can disrupt the reproductive function and impair the reproductive process in animals.This experiment was to investigate the toxicological effect and the mechanism of ZEA exposure on reproduction in pigs during early stages of pregnancy.In the present study,we treated with 0 to 80μmol/L ZEA for 12 or 24 h in trophoblast ectoderm(pTr)cells.The results showed that ZEA had significantly decreased cell proliferation(P<0.05),which was accompanied by DNA damage-related cell cycle arrest at G2/M phase,activation of the apoptosis and endoplasmic reticulum(ER)stress,as well as impairment of barrier function(P<0.05).Western blot analysis and transmission electron microscopy(TEM)showed that exposure to ZEA can activation of autophagy in pTr cells.Importantly,pretreatment with chloroquine(CQ)or 3-methyladenine(3-MA)led to increased apoptosis in pTr cells.Interestingly,pTr cells pretreated with 4-phenylbutyric acid(4-PBA),an inhibitor of ER stress,resulted in reduced cell death in pTr cells,indicating a critical role for ER stress in the activation of autophagy.In conclusion,these results reveal that ZEA-triggered ER stress is critical for the cell fate decision of pTr cells during early porcine embryonic development.Application of small molecules with ability of blocking ER stress might be therapeutic option to reduce the deleterious effect of ZEA in pregnant animals.展开更多
The inlet with scavenge duct is an important part of turboprop aircraft engine.This type of inlet normally has a complex shape,of which the design is challenging and directly affects the flow field quality of the engi...The inlet with scavenge duct is an important part of turboprop aircraft engine.This type of inlet normally has a complex shape,of which the design is challenging and directly affects the flow field quality of the engine entrance and thus the engine performance.In this paper,the parametric design method of a turboprop aircraft inlet with scavenge duct is established by extracting and controlling the transition law of the critical characteristic parameters.The inlet’s performance and internal flow characteristics are examined by wind-tunnel experiment and numerical simulation.The results indicate that a flow tendency of winding up on both sides is formed due to the induction of the inlet profile,as well as a vortex pair on the back side of the power output shaft.The vortex pair dominates the pressure distortion index on the Aerodynamic Interface Plane(AIP).In addition,with the increase of freestream angle of attack,the total-pressure recovery coefficient of the inlet increases gradually while the total pressure distortion index decreases slightly.On the basis of the experimental results under different working conditions,the parametric design method proposed in this paper is feasible.展开更多
This paper focuscs on the recent progress in the adoption of active disturbance rejection control(ADRC)in thermal pro-cesses as a viable alternative to proportional-_integral-derivative(PID),especially in coa-fired po...This paper focuscs on the recent progress in the adoption of active disturbance rejection control(ADRC)in thermal pro-cesses as a viable alternative to proportional-_integral-derivative(PID),especially in coa-fired power plants.The profound interpretation of this paradigm shift,with backward compatibility,is discussed in detail.A few fundamental issues associated with ADRC's applications in thermal processes are discussed,such as implementation,tuning,and the structural changes.Examples and case studies are presented,encompassing coal-fired power plants,gas turbines and nuclear power plants,as well as highlighting results of field applications.Also discussed are future research opportunities brought by ADRC's entry as the baseline control technology in thermal processes.展开更多
Endoplasmic reticulum(ER)stress has been associated with the dysfunction of intestinal barrier in humans and animals.We have previously shown that oral administration of glycine to suckling-piglets improves ER stress-...Endoplasmic reticulum(ER)stress has been associated with the dysfunction of intestinal barrier in humans and animals.We have previously shown that oral administration of glycine to suckling-piglets improves ER stress-related intestinal mucosal barrier impairment and jejunal epithelial apoptosis.However,the underlying mechanism remains unknown.In this study,the protective effect and the mechanism of glycine on apoptosis and dysfunction in intestinal barrier induced by brefeldin A(BFA),an ER stress inducer,was explored in porcine intestinal epithelial cells(IPEC-1).The results showed that BFA treatment led to enhanced apoptosis and upregulation of proteins involved in ER stress signaling,including inositol-requiring enzyme 1a(IRE1a),activating transcription factor 6a(ATF6a),c-Jun N-terminal kinase(JNK),and C/EBP-homologous protein(CHOP).In addition,BFA induced a dysfunction in intestinal epithelial barrier,as evidenced by the increased paracellular permeability,decreased transepithelial electrical resistance(TEER),and reduced abundance of tight junction proteins(occludin,claudin-1,zonula occludens[ZO]-1,and ZO-2).These alterations triggered by BFA were significantly abolished by glycine treatment(P<0.05),indicating a protective effect of glycine on barrier function impaired by ER stress.Importantly,we found that the regulatory effect of glycine on intestinal permeability,proteins implicated in ER stress and apoptosis,as well as the morphological alterations of the ER were reversed by rapamycin.In summary,our results indicated that glycine alleviates ER stress-induced apoptosis and intestinal barrier dysfunction in IPEC-1 cells in a mammalian target of rapamycin complex 1(mTORC1)-dependent manner.The data provides in vitro evidence and a mechanism for the protective effect of glycine against the disruption of intestinal barrier integrity induced by ER stress.展开更多
Oxidative stress has been confirmed in relation to intestinal mucosa damage and multiple bowel diseases.Hydroxyproline (Hyp) is an imino acid abundant in sow's milk. Compelling evidence has beengathered showing th...Oxidative stress has been confirmed in relation to intestinal mucosa damage and multiple bowel diseases.Hydroxyproline (Hyp) is an imino acid abundant in sow's milk. Compelling evidence has beengathered showing the potential antioxidative properties of Hyp. However, the role and mechanism ofHyp in porcine intestinal epithelial cells in response to oxidative stress remains unknown. In this study,small intestinal epithelial cell lines of piglets (IPEC-1) were used to evaluate the protective effects of Hypon 4-hydroxy-2-nonenal (4-HNE)-induced oxidative DNA damage and apoptosis. IPEC-1 pretreated with0.5 to 5 mmol/L Hyp were exposed to 4-HNE (40 mmol/L) in the presence or absence of Hyp. Thereafter,the cells were subjected to apoptosis detection by Hoechst staining, flow cytometry, and Western blot orDNA damage analysis by comet assay, immunofluorescence, and reverse-transcription quantitative PCR(RT-qPCR). Cell apoptosis and the upregulation of cleaved-caspase-3 induced by 4-HNE (40 mmol/L) wereinhibited by 5 mmol/L of Hyp. In addition, 5 mmol/L Hyp attenuated 4-HNE-induced reactive oxygenspecies (ROS) accumulation, glutathione (GSH) deprivation and DNA damage. The elevation in transcriptionof GADD45a (growth arrest and DNA-damage-inducible protein 45 alpha) and GADD45b(growth arrest and DNA-damage-inducible protein 45 beta), as well as the phosphorylation of H2AX(H2A histone family, member X), p38 MAPK (mitogen-activated protein kinase), and JNK (c-Jun N-terminalkinase) in cells treated with 4-HNE were alleviated by 5 mmol/L Hyp. Furthermore, Hyp supplementationincreased the protein abundance of Krüppel like factor 4 (KLF4) in cells exposed to 4-HNE.Suppression of KLF4 expression by kenpaulone impeded the resistance of Hyp-treated cells to DNAdamage and apoptosis induced by 4-HNE. Collectively, our results indicated that Hyp serves to protectagainst 4-HNE-induced apoptosis and DNA damage in IPEC-1 cells, which is partially pertinent with theenhanced expression of KLF4. Our data provides an updated explanation for the nutritional values ofHyp-containing animal products.展开更多
基金supported by the National Key R&D Program of China(Grant Nos.:2022YFF1100104 and 2022YFF1100102)the National Natural Science Foundation of China(Grant Nos.:31625025,32172749,and 32202701)+1 种基金the 2115 Talent Development Program of China Agricultural University(Grant No.:00109016)the Zhengzhou 1125 Talent Program,China(Grant No.:2016XT016).
文摘Muramidase-released protein(MRP)is now being recognized as a critical indicator of the virulence and pathogenicity of Streptococcus suis(S.suis).However,the identification of viable therapeutics for S.suis infection was hindered by the absence of an explicit mechanism for MRP-actuated inflammation.Dihydroartemisinin(DhA)is an artemisinin derivative with potential anti-inflammatory activity.The modulatory effect of DhA on the inflammatory response mediated by the virulence factor MRP remains obscure.This research aimed to identify the signaling mechanism by which MRP triggers the innate immune response in mouse spleen and cultured macrophages.With the candidate mechanism in mind,we investigated DhA for its ability to dampen the pro-inflammatory response induced by MRP.The innate immune response in mice was drastically triggered by MRP,manifesting as splenic and systemic inflammation with splenomegaly,immune cell infiltration,and an elevation in pro-inflammatory cytokines.A crucial role for Toll-like receptor 4(TLR4)in coordinating the MRP-mediated inflammatory response via nuclear factor-kappa B(NF-kB)activation was revealed by TLR4 blockade.In addition,NFkB-dependent transducer and activator of transcription 3(STAT3)and mitogen-activated protein kinases(MAPKs)activation was required for the inflammatory signal transduction engendered by MRP.Intriguingly,we observed an alleviation effect of DhA on the MRP-induced immune response,which referred to the suppression of TLR4-mediated actuation of NF-kB-STAT3/MAPK cascades.The inflammatory response elicited by MRP is relevant to TLR4-dependent NF-kB activation,followed by an increase in the activity of STAT3 or MAPKs.DhA mitigates the inflammation process induced by MRP via blocking the TLR4 cascade,highlighting the therapeutic potential of DhA in targeting S.suis infection diseases.
基金supported by Texas A&M Agri Life Research (H-8200)The Agriculture and Food Research Initiative Competitive Grant from the Animal Growth & Nutrient Utilization Program of the USDA National Institute of Food and Agriculture (2014-67015-21770)+4 种基金National Basic Research Program of China (2012CB126305)National Natural Science Foundation of China (31572412 and 31272450)the 111 Project (B16044)Natural Science Foundation of Hubei Province (2013CFA097 and 2013CFB325)Hubei Hundred Talent program
文摘Milk is synthesized by mammary epithelial cells of lactating mammals. The synthetic capacity of the mammary gland depends largely on the number and efficiency of functional mammary epithelial cells. Structural development of the mammary gland occurs during fetal growth, prepubertal and post-pubertal periods, pregnancy, and lactation under the control of various hormones (particularly estrogen, growth hormone, insulin-like growth factor-I, progesterone, placental lactogen, and prolactin) in a species- and stage-dependent manner. Milk is essential for the growth, development, and health of neonates. Amino acids (AA), present in both free and peptide-bound forms, are the most abundant organic nutrients in the milk of farm animals. Uptake of AA from the arterial blood of the lactating dam is the ultimate source of proteins (primarily 13-casein and a-lactalbumin) and bioactive nitrogenous metabolites in milk. Results of recent studies indicate extensive catabolism of branched-chain AA (leucine, isoleucine and valine) and arginine to synthesize glutamate, glutamine, alanine, aspartate, asparagine, proline, and polyamines. The formation of polypeptides from AA is regulated not only by hormones (e.g., prolactin, insulin and glucocorticoids) and the rate of blood flow across the lactating mammary gland, but also by concentrations of AA, lipids, glucose, vitamins and minerals in the maternal plasma, as well as the activation of the mechanistic (mammalian) target rapamycin signaling by certain AA (e.g., arginine, branched-chain AA, and glutamine). Knowledge of AA utilization (including metabolism) by mammary epithelial cells will enhance our fundamental understanding of lactation biology and has important implications for improving the efficiency of livestock production worldwide.
基金supported by National Research Initiative Competitive Grants from the Animal Reproduction Program(2008-35203-19120)Animal Growth&Nutrient Utilization Program(2008-35206-18764)of the USDA National Institute of Food and Agriculture+6 种基金AHA(10GRNT4480020)Texas A&M AgriLife Research(H-8200)the National Basic Research Program of China(2013CB127302)the National Natural Science Foundation of China(30810103902,30972156,31172217,31272450,and 31272451)China Postdoctoral Science Foundation(2012T50163)Chinese Universities Scientific Funds(2012RC024)the Thousand-People Talent program at China Agricultural University
文摘Protein is quantitatively the most expensive nutrient in swine diets. Hence it is imperative to understand the physiological roles played by amino acids in growth, development, lactation, reproduction, and health of pigs to improve their protein nutrition and reduce the costs of pork production. Due to incomplete knowledge of amino acid biochemistry and nutrition, it was traditionally assumed that neonatal, post-weaning, growing-finishing, and gestating pigs could synthesize sufficient amounts of all "nutritionally nonessential amino acids" (NEAA) to support maximum production performance. Therefore, over the past 50 years, much emphasis has been placed on dietary requirements of nutritionally essential amino acids as building blocks for tissue proteins. However, a large body of literature shows that NEAA, particularly glutamine, glutamate, arginine and proline regulate physiological functions via cell signaling pathways, such as mammalian target of rapamycin, AMP-activated protein kinase, extracellular signal-related kinase, Jun kinase, mitogen-activated protein kinase, and NEAA-derived gaseous molecules (e.g., nitric oxide, carbon monoxide, and hydrogen sulfide). Available evidence shows that under current feeding programs, only 70% and 55% of dietary amino acids are deposited as tissue proteins in 14-day-old sow-reared piglets and in 30-day-old pigs weaned at 21 days of age, respectively. Therefore, there is an urgent need to understand the robes and dietary requirements of NEAA in swine nutrition. This review highlights the basic biochemistry and physiology of absorption and utilization of amino acids in young pigs to enhance the efficacy of utilization of dietary protein and to minimize excretion of nitrogenous wastes from the body.
基金supported by the National Basic Research Program of China(2013CB127302)the National Natural Science Foundation of China(31272450 and 31572412)+2 种基金Competitive Grants from the Animal Reproduction Program(no.2014-67015-21770)Animal Growth & Nutrient Utilization Programs(no.2015-67015-23276)of the USDA National Institute of Food and AgricultureTexas A&M AgriL ife Research(H-8200)
文摘Maternal undernutrition or overnutrition during pregnancy alters organ structure, impairs prenatal and neonatal growth and development, and reduces feed efficiency for lean tissue gains in pigs. These adverse effects may be carried over to the next generation or beyond. This phenomenon of the transgenerational impacts is known as fetal programming, which is mediated by stable and heritable alterations of gene expression through covalent modifications of DNA and histones without changes in DNA sequences(namely, epigenetics). The mechanisms responsible for the epigenetic regulation of protein expression and functions include chromatin remodeling; DNA methylation(occurring at the 5′-position of cytosine residues within CpG dinucleotides); and histone modifications(acetylation, methylation, phosphorylation, and ubiquitination). Like maternal malnutrition, undernutrition during the neonatal period also reduces growth performance and feed efficiency(weight gain:feed intake; also known as weightgain efficiency) in postweaning pigs by 5–10%, thereby increasing the days necessary to reach the market bodyweight. Supplementing functional amino acids(e.g., arginine and glutamine) and vitamins(e.g., folate) play a key role in activating the mammalian target of rapamycin signaling and regulating the provision of methyl donors for DNA and protein methylation. Therefore, these nutrients are beneficial for the dietary treatment of metabolic disorders in offspring with intrauterine growth restriction or neonatal malnutrition. The mechanism-based strategies hold great promise for the improvement of the efficiency of pork production and the sustainability of the global swine industry.
基金supported the National Natural Science Foundation of China(No.31272451,31272450,31572410)Chinese University Scientific Fund(2015DK001)+3 种基金the 111 Project(B16044)the Program for New Century Excellent Talents in University(NCET-12-0522)the Agriculture and Food Research Initiative Competitive Grant from the USDA National Institute of Food and Agriculture(No.2014–67015-21770)Texas A&M Agri Life Research(H-8200)
文摘Background: Endoplasmic reticulum(ER) stress is associated with multiple pathological processes of intestinal diseases. Despite a critical role of mechanistic target of rapamycin complex 1(m TORC1) in regulating cellular stress response, the crosstalk between m TORC1 and ER stress signaling and its contribution to the intestinal barrier function is unknown.Results: In the present study, we showed that intestinal epithelial cells(IEC-6) incubated with tunicamycin led to caspase-3-dependent apoptotic cell death. The induction of cell death was accompanied by activation of unfolded protein response as evidenced by increased protein levels for Bi P, p-IRE1α, p-e IF2α, p-JNK, and CHOP. Further study demonstrated that tunicamycin-induced cell death was enhanced by rapamycin, a specific inhibitor of m TORC1.Consistently, tunicamycin decreased transepithelial electrical resistance(TEER) and increased permeability of the cells. These effects of tunicamycin were exacerbated by m TORC1 inhibitor.Conclusions: Taken together, the data presented here identified a previously unknown crosstalk between an unfold protein response and m TORC1 signaling in the intestinal epithelium. This feed-back loop regulation on ER stress signaling by m TORC1 is critical for cell survival and intestinal permeability in epithelial cells.
基金Supported by the National Natural Science Foundation of China (No. 31625025, 31572410, 31572412, 31272450, 31272451)the “111” Project (B16044)。
文摘Background: Excessive white fat accumulation in humans and other animals is associated with the development of multiple metabolic diseases. It is unknown whether dietary L-arginine supplementation reduces lipid deposition in high fat diet-fed Nile tilapia(Oreochromis niloticus).Results: In the present study, we found that dietary supplementation with 1% or 2% arginine decreased the deposition and concentration of fats in the liver;the concentrations of triglycerides, low-density lipoprotein, total cholesterol, and high-density lipoprotein in the serum;and the diameter of adipocytes in intraperitoneal adipose tissue. Compared with the un-supplementation control group, the hepatic activities of alanine aminotransferase,aspartate aminotransferase, and lactate dehydrogenase, and hepatic concentration of malondialdehyde were reduced but these for catalase and superoxide dismutase were enhanced by dietary supplementation with 2% arginine. Arginine supplementation reduced the total amounts of monounsaturated fatty acids, while increasing the total amounts of n-3 and n-6 polyunsaturated fatty acids in the liver. These effects of arginine were associated with reductions in mRNA levels for genes related to lipogenesis(sterol regulatory element-binding protein-1, acetyl-CoA carboxylase α, stearoyl-CoA desaturase, and fatty acid synthase) but increases in mRNA levels for genes involved in fatty acid β-oxidation(carnitine palmitoyltransferase 1α and peroxisome proliferator-activated receptor α). In addition, hepatic mRNA levels for Δ4 fatty acyl desaturase 2 and elongase 5 of very long-chain fatty acids were enhanced by arginine supplementation.Conclusion: These results revealed that dietary L-arginine supplementation to tilapia reduced high fat diet-induced fat deposition and fatty acid composition in the liver by regulating the expression of genes for lipid metabolism.
基金supported the National Natural Science Foundation of China(31572410,31572412,31625025)the 111 Project(B16044)+2 种基金the Program for New Century Excellent Talents in University(NCET-12-0522)the Agriculture and Food Research Initiative Competitive Grant from the USDA National Institute of Food and Agriculture(No.2014-6701521770)Texas A&M Agri Life Research(H-8200)
文摘Background: Cinnamicaldehyde(CA) is a key flavor compound in cinnamon essential oil possessing various bioactivities. Tight junction(TJ) proteins are vital for the maintenance of intestinal epithelial barrier function,transport, absorption and utilization of dietary amino acids and other nutrients. In this study, we tested the hypothesis that CA may regulate the expression of TJ proteins and amino acid transporters in intestinal porcine epithelial cells(IPEC-1) isolated from neonatal pigs.Results: Compared with the control, cells incubated with 25 μmol/L CA had increased transepithelial electrical resistance(TEER) and decreased paracellular intestinal permeability. The beneficial effect of CA on mucosal barrier function was associated with enhanced protein abundance for claudin-4, zonula occludens(ZO)-1, ZO-2, and ZO-3. Immunofluorescence staining showed that 25 μmol/L CA promoted the localization of claudin-1 and claudin-3 to the plasma membrane without affecting the localization of other TJ proteins, including claudin-4, occludin,ZO-1, ZO-2, and ZO-3, compared with the control cells. Moreover, protein abundances for rBAT, xCT and LAT2 in IPEC-1 cells were enhanced by 25 μmol/L CA, while that for EAAT3 was not affected.Conclusions: CA improves intestinal mucosal barrier function by regulating the distribution of claudin-1 and claudin-3 in enterocytes, as well as enhancing protein abundance for amino acid transporters rBAT, xCT and LAT2 in enterocytes. Supplementation with CA may provide an effective nutritional strategy to improve intestinal integrity and amino acid transport and absorption in piglets.
基金supported by the National Natural Science Foundation of China(31572416,31372319,31330075 and 31110103909)Hubei Provincial Key Project for Scientific and Technical Innovation(2014ABA022)+2 种基金Hubei Hundred Talent program,Natural Science Foundation of Hubei Province(2013CFA097)Agriculture and Food Research Initiative Competitive Grants(2014-67015-21770 and 2015-67015-23276)from the USDA National Institute of Food and AgricultureTexas A&M Agri Life Research(H-8200)
文摘Recent years have witnessed growing interest in the role of peptides in animal nutrition. Chemical, enzymatic, or microbial hydrolysis of proteins in animal by-products or plant-source feedstuffs before feeding is an attractive means of generating high-quality small or large peptides that have both nutritional and physiological or regulatory functions in livestock, poultry and fish. These peptides may also be formed from ingested proteins in the gastrointestinal tract, but the types of resultant peptides can vary greatly with the physiological conditions of the animals and the composition of the diets. In the small intestine, large peptides are hydrolyzed to small peptides,which are absorbed into enterocytes faster than free amino acids(AAs) to provide a more balanced pattern of AAs in the blood circulation. Some peptides of plant or animal sources also have antimicrobial, antioxidant,antihypertensive, and immunomodulatory activities. Those peptides which confer biological functions beyond their nutritional value are called bioactive peptides. They are usually 2–20 AA residues in length but may consist of 〉20AA residues. Inclusion of some(e.g. 2–8%) animal-protein hydrolysates(e.g., porcine intestine, porcine mucosa,salmon viscera, or poultry tissue hydrolysates) or soybean protein hydrolysates in practical corn-and soybean mealbased diets can ensure desirable rates of growth performance and feed efficiency in weanling pigs, young calves,post-hatching poultry, and fish. Thus, protein hydrolysates hold promise in optimizing the nutrition of domestic and companion animals, as well as their health(particularly gut health) and well-being.
基金supported by the Yangtze River Scholar and Innovation Research Team Development Program(Project No.IRT0945)grants from the National Natural Science Foundation of China(NO.30700576,31172225,31272451)State Key Laboratory of Animal Nutrition(Project No.2004DA125184-0807)
文摘In this study,we sought to investigate the expression of the transcription factor E2F1 in chicken pulmonary arterial smooth muscle cells upon hypoxia exposure,as well as the role that E2F1 played in the regulation of cell proliferation.Isolated chicken pulmonary arterial smooth muscle cells were subjected to hypoxia or normoxia for indicated time points.Cell viability,DNA synthesis,cell cycle profile,and expression of E2F1 were analyzed.The results showed that hypoxia promoted cell proliferation and DNA synthesis which was accompanied by an increased S phase entry and upregulation of E2F1 at mRNA and protein levels.Using siRNA technology,we demonstrated that gene inactivation of endogenous E2F1 abolished hypoxia-induced cell proliferation,DNA synthesis,and S phase entry compared with negative siRNA transfected cells.These results suggest that hypoxia-induced proliferation is mediated by inducing E2F1 in chicken pulmonary arterial smooth muscle cells.
基金supported by the National Key R&D Program of China(No.2023YFC3503902,China)the National Natural Science Foundation of China(Nos.82293681(82293680)+6 种基金82321004,82204234,and 82273822,China)the Guangdong Basic and Applied Basic Research Foundation(Nos.2022B1515120015 and 2021A1515111021,China)the Guangdong Major Project of Basic and Applied Basic Research(No.2023B0303000026,China)the Guangdong-Hong Kong-Macao Universities Joint Laboratory for the Internationalization of Traditional Chinese Medicine(No.2023LSYS002,China)the Guangzhou Key Laboratory of Traditional Chinese Medicine&Disease Susceptibility(No.2024A03J090,China)the Science and Technology Projects in Guangzhou(No.202102070001,China)supported by the high-performance computing platform of Jinan University.
文摘The building blocks-based molecular network(BBMN)strategy was applied to the phytochemical investigation of Cleistocalyx operculatus,leading to the targeted isolation of eighteen novel cinnamoylphloroglucinol-terpene adducts(CPTAs)with diverse skeleton types(cleistoperones A-R,1-18).Their structures including absolute configurations were determined by extensive spectroscopic methods,quantum chemical calculations,and single-crystal X-ray crystallographic experiments.Cleistoperone A(1),consisting of a cinnamoylphloroglucinol motif and two linear monoterpene moieties,represents an unprecedented macrocyclic CPTA,whose densely functionalized tricyclo[15.3.1.0^(3,8)]heneicosane bridge ring skeleton contains an enolizableβ,β′-triketone system and two different kinds of stereogenic elements(including five point and three planar chiralities).Cleistoperones B and C(2 and 3)are two new skeletal CPTAs with an unusual coupling pattern between the(nor)monoterpene moiety and the cinnamoyl chain of the cinnamoylphloroglucinol unit.Cleistoperone D(4)possesses an unprecedented cage-like 6/6/6/4/6-fused heteropentacyclic scaffold.The plausible biosynthetic pathways for 1-18 were also proposed.Notably,compounds 1,4,7,8,and 18 exhibited significant antiviral activity against respiratory syncytial virus(RSV).The most potent one,cleistoperone A(1)with IC_(50) value of 1.71±0.61μmol/L,could effectively inhibit virus replication via affecting the Akt/mTOR/p70S6K signaling pathway.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515120066 and 2022A1515010010)the National Natural Science Foundation of China[Nos.82293681(82293680)and 82273822]+3 种基金the Science and Technology Key Project of Guangdong Province(No.2020B1111110004)the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(No.2017BT01Y036)the Fundamental Research Funds for the Central Universitiesthe support of K.C.Wong Education Foundation。
文摘The first phloroglucinol-triterpenoid hybrids,myrtphlotritins A-E(1-5),were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network(BBMN)strategy.Compounds 1-5 featured new carbon skeletons in which phloroglucinol derivatives were coupled with lupane-and dammarane-type triterpenoids through different linkage patterns.Their structures and absolute configurations were elucidated by comprehensive analysis of spectroscopic data and quantum chemical calculations.Biosynthetic pathways for compounds 1-5 were proposed on the basis of the coexisting precursors.Guided by the biogenetic pathways,the biomimetic synthesis of compound 1 was also achieved.Additionally,compounds 2,3,and 5 exhibited potent antiviral activities against herpes simplex virus type-1(HSV-1)infection,and compounds 2 and 5 displayed significant anti-inflammatory activities on RAW264.7 cells.
基金supported by the National Science and Technology Major Project,China(No.HT-J2019-V-0004-0095)the National Natural Science Foundation of China(No.12172174)the Civil Airplane Technology Development Program,China(No.MJ-2020-F-10).
文摘This paper presents an experimental and numerical study of the aerodynamics of a moderate-scale rotor hovering in the Extreme Ground Effect(EGE)where rotor height-offground is below half the rotor radius.The tip vortex field was visualized by using the PIV technique.The aerodynamic performance,tip vortex trajectory,wall jet characteristics,surface pressure and velocity fields were measured and analyzed.To explore more deeply the flow mechanisms of the extreme ground effect,Detached Eddy Simulation(DES)was conducted on completely structured meshes.The results showed significant deviations of the rotor performance in EGE from that in Regular Ground Effect(RGE)with the rotor heights of more than half the rotor radius.Moreover,the flow structures of the rotor in EGE are considerably complex,such as the wall jet and groundwash flow separation.The rotor wake flow and tip vortices impact the ground more frequently,resulting in distinctive characteristics of the surface pressure and velocity fields in EGE.
基金This work was supported by grants from the National Natural Science Foundation of China(No.31625025).
文摘Zearalenone(ZEA),a mycotoxin produced mainly by fungi belonging to Fusarium species in foods and feeds,causes a serious hazard to humans and animals.Numerous studies have revealed that ingesting ZEA can disrupt the reproductive function and impair the reproductive process in animals.This experiment was to investigate the toxicological effect and the mechanism of ZEA exposure on reproduction in pigs during early stages of pregnancy.In the present study,we treated with 0 to 80μmol/L ZEA for 12 or 24 h in trophoblast ectoderm(pTr)cells.The results showed that ZEA had significantly decreased cell proliferation(P<0.05),which was accompanied by DNA damage-related cell cycle arrest at G2/M phase,activation of the apoptosis and endoplasmic reticulum(ER)stress,as well as impairment of barrier function(P<0.05).Western blot analysis and transmission electron microscopy(TEM)showed that exposure to ZEA can activation of autophagy in pTr cells.Importantly,pretreatment with chloroquine(CQ)or 3-methyladenine(3-MA)led to increased apoptosis in pTr cells.Interestingly,pTr cells pretreated with 4-phenylbutyric acid(4-PBA),an inhibitor of ER stress,resulted in reduced cell death in pTr cells,indicating a critical role for ER stress in the activation of autophagy.In conclusion,these results reveal that ZEA-triggered ER stress is critical for the cell fate decision of pTr cells during early porcine embryonic development.Application of small molecules with ability of blocking ER stress might be therapeutic option to reduce the deleterious effect of ZEA in pregnant animals.
基金co-supported by the Civil Airplane Technology Development Program,China(No.MJ-2020-F-10)the National Science and Technology Major Project,China(No.HT-J2019-V-0004-0095).
文摘The inlet with scavenge duct is an important part of turboprop aircraft engine.This type of inlet normally has a complex shape,of which the design is challenging and directly affects the flow field quality of the engine entrance and thus the engine performance.In this paper,the parametric design method of a turboprop aircraft inlet with scavenge duct is established by extracting and controlling the transition law of the critical characteristic parameters.The inlet’s performance and internal flow characteristics are examined by wind-tunnel experiment and numerical simulation.The results indicate that a flow tendency of winding up on both sides is formed due to the induction of the inlet profile,as well as a vortex pair on the back side of the power output shaft.The vortex pair dominates the pressure distortion index on the Aerodynamic Interface Plane(AIP).In addition,with the increase of freestream angle of attack,the total-pressure recovery coefficient of the inlet increases gradually while the total pressure distortion index decreases slightly.On the basis of the experimental results under different working conditions,the parametric design method proposed in this paper is feasible.
基金This work was supported by the Science&Technology Research Project in Henan Province of China(No.212102311052)the National Key Research and Development Program of China(No.2016YFB0901405)the National Natural Science Foundation of China(No.61473265).
文摘This paper focuscs on the recent progress in the adoption of active disturbance rejection control(ADRC)in thermal pro-cesses as a viable alternative to proportional-_integral-derivative(PID),especially in coa-fired power plants.The profound interpretation of this paradigm shift,with backward compatibility,is discussed in detail.A few fundamental issues associated with ADRC's applications in thermal processes are discussed,such as implementation,tuning,and the structural changes.Examples and case studies are presented,encompassing coal-fired power plants,gas turbines and nuclear power plants,as well as highlighting results of field applications.Also discussed are future research opportunities brought by ADRC's entry as the baseline control technology in thermal processes.
基金This work was supported by the National Natural Science Foundation of China(No.31625025,32172749,31572410,31272451)the Zhengzhou 1125 Talent Program,Jingxinnong Animal Science Development Foundation,and the“111”Project(B16044).
文摘Endoplasmic reticulum(ER)stress has been associated with the dysfunction of intestinal barrier in humans and animals.We have previously shown that oral administration of glycine to suckling-piglets improves ER stress-related intestinal mucosal barrier impairment and jejunal epithelial apoptosis.However,the underlying mechanism remains unknown.In this study,the protective effect and the mechanism of glycine on apoptosis and dysfunction in intestinal barrier induced by brefeldin A(BFA),an ER stress inducer,was explored in porcine intestinal epithelial cells(IPEC-1).The results showed that BFA treatment led to enhanced apoptosis and upregulation of proteins involved in ER stress signaling,including inositol-requiring enzyme 1a(IRE1a),activating transcription factor 6a(ATF6a),c-Jun N-terminal kinase(JNK),and C/EBP-homologous protein(CHOP).In addition,BFA induced a dysfunction in intestinal epithelial barrier,as evidenced by the increased paracellular permeability,decreased transepithelial electrical resistance(TEER),and reduced abundance of tight junction proteins(occludin,claudin-1,zonula occludens[ZO]-1,and ZO-2).These alterations triggered by BFA were significantly abolished by glycine treatment(P<0.05),indicating a protective effect of glycine on barrier function impaired by ER stress.Importantly,we found that the regulatory effect of glycine on intestinal permeability,proteins implicated in ER stress and apoptosis,as well as the morphological alterations of the ER were reversed by rapamycin.In summary,our results indicated that glycine alleviates ER stress-induced apoptosis and intestinal barrier dysfunction in IPEC-1 cells in a mammalian target of rapamycin complex 1(mTORC1)-dependent manner.The data provides in vitro evidence and a mechanism for the protective effect of glycine against the disruption of intestinal barrier integrity induced by ER stress.
基金the National Natural Science Foundation of China(No.31625025,31301979)the Zhengzhou 1125 Talent Program,and the Jinxinnong Animal Science Development Foundation.
文摘Oxidative stress has been confirmed in relation to intestinal mucosa damage and multiple bowel diseases.Hydroxyproline (Hyp) is an imino acid abundant in sow's milk. Compelling evidence has beengathered showing the potential antioxidative properties of Hyp. However, the role and mechanism ofHyp in porcine intestinal epithelial cells in response to oxidative stress remains unknown. In this study,small intestinal epithelial cell lines of piglets (IPEC-1) were used to evaluate the protective effects of Hypon 4-hydroxy-2-nonenal (4-HNE)-induced oxidative DNA damage and apoptosis. IPEC-1 pretreated with0.5 to 5 mmol/L Hyp were exposed to 4-HNE (40 mmol/L) in the presence or absence of Hyp. Thereafter,the cells were subjected to apoptosis detection by Hoechst staining, flow cytometry, and Western blot orDNA damage analysis by comet assay, immunofluorescence, and reverse-transcription quantitative PCR(RT-qPCR). Cell apoptosis and the upregulation of cleaved-caspase-3 induced by 4-HNE (40 mmol/L) wereinhibited by 5 mmol/L of Hyp. In addition, 5 mmol/L Hyp attenuated 4-HNE-induced reactive oxygenspecies (ROS) accumulation, glutathione (GSH) deprivation and DNA damage. The elevation in transcriptionof GADD45a (growth arrest and DNA-damage-inducible protein 45 alpha) and GADD45b(growth arrest and DNA-damage-inducible protein 45 beta), as well as the phosphorylation of H2AX(H2A histone family, member X), p38 MAPK (mitogen-activated protein kinase), and JNK (c-Jun N-terminalkinase) in cells treated with 4-HNE were alleviated by 5 mmol/L Hyp. Furthermore, Hyp supplementationincreased the protein abundance of Krüppel like factor 4 (KLF4) in cells exposed to 4-HNE.Suppression of KLF4 expression by kenpaulone impeded the resistance of Hyp-treated cells to DNAdamage and apoptosis induced by 4-HNE. Collectively, our results indicated that Hyp serves to protectagainst 4-HNE-induced apoptosis and DNA damage in IPEC-1 cells, which is partially pertinent with theenhanced expression of KLF4. Our data provides an updated explanation for the nutritional values ofHyp-containing animal products.