Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
The milk fat globule membrane(MFGM)is a complex structure with numerous functions,and its composition is affected by many factors.There have been few systematic investigations on goat MFGM proteome profiling during la...The milk fat globule membrane(MFGM)is a complex structure with numerous functions,and its composition is affected by many factors.There have been few systematic investigations on goat MFGM proteome profiling during lactation.Individual milk samples from 15 healthy dairy goats were obtained at six lactation time points for investigation of the MFGM proteome using both data-independent acquisition(DIA)and data-dependent acquisition(DDA)proteomics techniques combined with multivariate statistical analysis.Using the DIA method,890 variably abundant MFGM proteins were discovered throughout the lactation cycle.From 1 to 240 d,butyrophilin subfamily 1 member A1,lipoprotein lipase,perilipin-2,and adipose triglyceride lipase were upregulated,while APOE,complement C3,clusterin,and IgG were downregulated.Furthermore,from 1 to 90 d,annexin A1,annexin A2,and antithrombin-ll were downregulated,then upregulated by d 240.Albumin had a high degree of connectedness,indicating that it was a key protein,according to protein-protein interaction research.Overall,our findings gave new insights into the biological features of MFGM protein in goat milk throughout lactation,which may aid in the creation of specialized MFGM products and infant formula.展开更多
BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ...BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.展开更多
Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progre...Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.展开更多
Milk fat globule membrane(MFGM)possesses various nutritional and biological benefits for mammals,whereas its effects on neonatal gut microbiota and barrier integrity remained unclear.This study investigated the effect...Milk fat globule membrane(MFGM)possesses various nutritional and biological benefits for mammals,whereas its effects on neonatal gut microbiota and barrier integrity remained unclear.This study investigated the effects of MFGM administration on microbial compositions and intestinal barrier functions of neonatal piglets.Sixteen newborn piglets were randomly allocated into a CON group or MFGM group,orally administered with saline or MFGM solution(1 g/kg body weight)respectively during the first postnatal week,and all piglets were breastfed during the whole neonatal period.The present study found that the MFGM oral administration during the first postnatal week increased the plasma immunoglobulin(lg)G level,body weight and average daily gain of piglets(P<0.05)on 21 d.Addi-tionally,MFGM administration enriched fecal SCFA-producing bacteria(Ruminococaceae_UCG-002,Ruminococaceae_UCG-010,Ruminococaceae_UCG-004,Ruminococaceae_UCG-014 and[Ruminococcus]_gauvrearuii_group),SCFA concentrations(acetate,propionate and butyrate;P<0.05)and their receptor(G-protein coupled receptor 41,GPR41).Furthermore,MFGM administration promoted intestinal villus morphology(P<0.05)and barrier functions by upregulating genes of tight junctions(E-cadherin,claudin-1,occludin and zonula occludin 1[ZO-1]),mucins(mucin-13 and mucin-20)and interleukin(IL)-22(P<0.05).Positive correlation was found between the beneficial microbes and SCFA levels pairwise with the intestinal barrier genes(P<0.05).In conclusion,orally administrating MFGM during the first postnatal week stimulated SCFA-producing bacteria colonization and SCFA generation,enhanced intes-tinal barrier functions and consequently improved growth performance of neonatal piglets on 21 d.Our findings will provide new insights about MFGM intervention for microbial colonization and intestinal development of neonates during their early life.展开更多
With the excellent biocompatibility and osteo- conductivity, nano-hydroxyapatite （nHA） has shown significant prospect in the biomedical applications. Con- trolling the size, crystallinity and surface properties of n...With the excellent biocompatibility and osteo- conductivity, nano-hydroxyapatite （nHA） has shown significant prospect in the biomedical applications. Con- trolling the size, crystallinity and surface properties of nHA crystals is a critical challenge in the design of HA based biomaterials. With the graft copolymer of chitosan and poly（N-isopropylacrylamide） in coil and globule states as a template respectively, a novel composite from chitosan-g-poly（N-isopropylacrylamide） and nano-hydro- xyapatite （CS-g-PNIPAM/nHA） was prepared via co- precipitation. Zeta potential analysis, thermogravimetric analysis and X-ray diffraction were used to identify the formation mechanism of the CS-g-PNIPAM/nHA compo- site and its morphology was observed by transmission electron microscopy. The results suggested that the physical aggregation states of the template polymer could induce or control the size, crystallinity and morphology of HA crystals in the CS-g-PNIPAM/nHA composite. The CS-g-PNIPAM/nHA composite was then introduced to chitosan-gelatin （CS-Gel） polyelectronic complex and the cytocompatibility of the resulting CS- Gel/composite hybrid film was evaluated. This hybrid film was proved to be favorable for the proliferation of MC 3T3-E1 cells. Therefore, the CS-g-PNIPAM/nHA compo- site is a potential biomaterial in bone tissue engineering.展开更多
The site order parameter (SOP) has been adopted to analyze various orders of structure formation and distribution during the crystallization of a polyethylene globule simulated by molecular dynamics. The SOP not only ...The site order parameter (SOP) has been adopted to analyze various orders of structure formation and distribution during the crystallization of a polyethylene globule simulated by molecular dynamics. The SOP not only identifies different orders among the structures but also different phases. The results showed that intermediate structures with medium order exist unevenly in the early stage of nucleation, which differs from traditional models. We found that the nucleation relies on crystallinity fluctuations with increasing amplitude, and a baby nucleus with different shape and increasing size suddenly appears in the fluctuations. Once its size is large enough, the baby nucleus becomes the nucleus. In the growth stage, a number of lamellar mergences were observed and their selective behaviors were related to the orientation differences between the lamellae to be merged. The SOP distribution of all atoms in the system during crystallization had two peaks: one for the amorphous phase and the other for the crystalline phase. The intermediate structures with medium orders are located between the two peaks as an order promotion pathway. The data show that the medium order structure fluctuates at the growth front and is not always available, and that the medium order structure existing at the front is not always good for development. It is possibly caused by chain entanglement. Structure fluctuation at the growth front enables the system showing thousands of the most probable configurations to approach the precursor. The growth front is thus active for a while and inactive at other times.展开更多
Background: Milk lipids originate from cytoplasmic lipid droplets(LD) that are synthesized and secreted from mammary epithelial cells by a unique membrane-envelopment process. Butyrophilin 1 A1(BTN1 A1) is one of the ...Background: Milk lipids originate from cytoplasmic lipid droplets(LD) that are synthesized and secreted from mammary epithelial cells by a unique membrane-envelopment process. Butyrophilin 1 A1(BTN1 A1) is one of the membrane proteins that surrounds LD, but its role in bovine mammary lipid droplet synthesis and secretion is not well known.Methods: The objective was to knockout BTN1 A1 in bovine mammary epithelial cells(BMEC) via the CRISPR/Cas9 system and evaluate LD formation, abundance of lipogenic enzymes, and content of cell membrane phospholipid(PL) species. Average LD diameter was determined via Oil Red O staining, and profiling of cell membrane phospholipid species via liquid chromatography-tandem mass spectrometry(LC-MS/MS).Results: Lentivirus-mediated infection of the Cas9/sg RNA expression vector into BMEC resulted in production of a homozygous clone BTN1 A1^((-/-)). The LD size and content decreased following BTN1 A1 gene knockout. The m RNA abundance of fatty acid synthase(FASN) and peroxisome proliferator-activated receptor-gamma(PPARG) was downregulated in the BTN1 A1^((-/-))clone. Subcellular analyses indicated that BTN1 A1 and LD were co-localized in the cytoplasm. BTN1 A1 gene knockout increased the percentage of phosphatidylethanolamine(PE) and decreased phosphatidylcholine(PC), which resulted in a lower PC/PE ratio.Conclusions: Results suggest that BTN1 A1 plays an important role in regulating LD synthesis via a mechanism involving membrane phospholipid composition.展开更多
This study demonstrated that homogenization did not increase the activity of lipoprotein lipase (LPL) in spite of a fast accumulation of free fatty acids (FFA). Two homogenization pressures (100 and 170 bar) and two t...This study demonstrated that homogenization did not increase the activity of lipoprotein lipase (LPL) in spite of a fast accumulation of free fatty acids (FFA). Two homogenization pressures (100 and 170 bar) and two temperatures (40℃and 50℃) were examined. The activity of LPL was analyzed and the formation of FFA was measured with two different methods, the B.D.I.-method and a nonesterified fatty acids (NEFA) method. A homogenization temperature of 50℃ resulted in a decreased LPL activity compared to 40℃. No effect of homogenization pressure was found. Analyzing FFA concentration with the B.D.I.-method resulted in significant effect of homogenization temperature and no effect of pressure. The largest formation of FFA was found in milk homogenized at 40℃. Using the NEFA method, another result was obtained, indicating no effect of homogenization temperature and a larger FFA accumulation at 100 bar than at 170 bar. Both analytic methods demonstrated significant production of FFA during 60 min incubation at homogenization temperature after treatment. The level of FFA in the milk samples immediately after homogenization was very high, demonstrating that LPL cleaves the triglycerides very rapidly when the native membrane was damaged. The regression between the B.D.I.-method and the NEFA was fair in the interval between 4 and 14 mmol/100 g fat, whereas at higher concentrations, the correlation was poor.展开更多
We assessed the effects of plantations of exotic trees (Pinus radiata, Eucalyptus globulus, and Populus nigra) on plant biodiversity in the temperate zone of the biodiversity hotspot of Central Chile. This region has ...We assessed the effects of plantations of exotic trees (Pinus radiata, Eucalyptus globulus, and Populus nigra) on plant biodiversity in the temperate zone of the biodiversity hotspot of Central Chile. This region has suffered from intense deforestation in favor of plantation establishment in the major part of the coastal area since the neoliberal turn in 1973. The approach presented aimed to analyze plant biodiversity on the α-, β- and γ-scale. Furthermore, a plantation evaluation index was applied in order to provide quantitative figures on management practices. Species richness is reduced by 50% below plantations. Diversity and evenness index values are also significantly reduced. Analyses on β-similarity indicate that plantations do not host species absent in adjacent native forests, and no additional habitat heterogeneity is gained. On the γ-scale, plantations lower the number of total species observed;especially of endemic species. The abundance of species considered as invasive is significantly higher and frequently, invasive plants dominate the understory. The evaluation index attests rather poor plantation management in Central Chile since plantations are grown as monocultures, natural elements and native species are lacking at specific sites and plantations are insufficiently connected to native plant formations at the landscape scale. Results give much concern since deforestation processes as observed in our study area is about to begin in Patagonia as well. If management practices from the temperate zone are adopted in Patagonia, a considerable decline in plant biodiversity has to be expected there.展开更多
DNA condensation is an important process in many fields including life sciences, polymer physics, and applied technology. In the nucleus, DNA is condensed into chromosomes. In polymer physics, DNA is treated as a semi...DNA condensation is an important process in many fields including life sciences, polymer physics, and applied technology. In the nucleus, DNA is condensed into chromosomes. In polymer physics, DNA is treated as a semi-flexible molecule and a polyelectrolyte. Many agents, including multi-valent cations, surfactants, and neutral poor solvents, can cause DNA condensation, also referred to as coil–globule transition. Moreover, DNA condensation has been used for extraction and gene delivery in applied technology. Many physical theories have been presented to elucidate the mechanism underlying DNA condensation, including the counterion correlation theory, the electrostatic zipper theory, and the hydration force theory. Recently several single-molecule studies have focused on DNA condensation, shedding new light on old concepts. In this document, the multi-field concepts and theories related to DNA condensation are introduced and clarified as well as the advances and considerations of single-molecule DNA condensation experiments are introduced.展开更多
Background: Characterising the regulation of milk component synthesis in response to macronutrient supply is critical for understanding the implications of nutritional interventions on milk production. Gene expression...Background: Characterising the regulation of milk component synthesis in response to macronutrient supply is critical for understanding the implications of nutritional interventions on milk production. Gene expression in mammary gland secretory cells was measured using RNA isolated from milk fat globules from 6 Holstein-Friesian cows receiving 5-d abomasal infusions of saline, essential amino acids(AA), or glucose(GG) or palm olein(LG)without(LAA) or with(HAA) essential AA, according to a 6 × 6 Latin square design. RNA was isolated from milk fat samples collected on d 5 of infusion and subjected to real-time quantitative PCR. We hypothesised that m RNA expression of genes involved in de novo milk fatty acid(FA) synthesis would be differently affected by GG and LG,and that expression of genes regulating transfer of tricarboxylic acid cycle intermediates would increase at the HAA level. We also hypothesised that the HAA level would affect genes regulating endoplasmic reticulum(ER)homeostasis but would not affect genes related to the mechanistic target of rapamycin complex 1(m TORC1) or the integrated stress response(ISR) network.Results: Infusion of GG did not affect de novo milk FA yield but decreased expression of FA synthase(FASN).Infusion of LG decreased de novo FA yield and tended to decrease expression of acetyl-Co A carboxylase 1(ACC1).The HAA level increased both de novo FA yield and expression of ACC1, and tended to decrease expression of mitochondrial phosphoenolpyruvate carboxykinase(PCK2). m RNA expression of m TORC1 signaling participants was not affected by GG, LG, or AA level. Expression of the ε subunit of the ISR constituent eukaryotic translation initiation factor 2 B(EIF2 B5) tended to increase at the HAA level, but only in the presence of LG. X-box binding protein 1(XBP1) m RNA was activated in response to LG and the HAA level.Conclusions: Results show that expression of genes involved in de novo FA synthesis responded to glucogenic,lipogenic, and aminogenic substrates, whereas genes regulating intermediate flux through the tricarboxylic acid cycle were not majorly affected. Results also suggest that after 5 d of AA supplementation, milk protein synthesis is supported by enhanced ER biogenesis instead of signaling through the mTORC1 or ISR networks.展开更多
To correct the light scattering property parameters of milk fat for improving the detection accuracy,the Mie-theory was used to establish a predictive model for light scattering properties of milk fat globule with mul...To correct the light scattering property parameters of milk fat for improving the detection accuracy,the Mie-theory was used to establish a predictive model for light scattering properties of milk fat globule with multi-diameter distributions, by means of Monte Carlo approach to simulate actual multi-diameter size distribution of milk fat globule in milk fat solution. Scattering coefficient and absorption coefficient of multidiameter distribution milk fat particles were calculated by simulating the particles size distribution in milk fat solution. And the light scattering properties of multi-diameter distribution was compared with that of volume mean diameter,Sauter mean diameter and numerical mean diameter in milk fat solution. Theoretical simulation results indicate that the scattering coefficient and absorption coefficient of milk fat particles are determined by the particle size distribution in milk fat solution. There is a distinct difference in scattering characteristics between the milk fat particles with multi-diameter distribution and that with mean diameters. Compared to that with multi-diameter distribution,the scattering coefficient of the milk fat particles with mean diameter has a maximum mean deviation of 9042 m-1. The particle size distribution is not completely determined by the mean diameters. The dependence of the light scattering properties on the particle size distribution should be considered into the model and simulation. Therefore,it is found that the particle size distribution in milk fat solution is an essential and critical factor to significantly improve the detection accuracy of milk fat content.展开更多
We analyze large scale mapping observations of the molecular lines in the ^12CO（J= 2-1）,^12CO（J=3-2）,^13CO（J=2-1）,and ^13CO（J=3-2） transition emissions toward the Cepheus B molecular cloud with the KOSMA 3mtel...We analyze large scale mapping observations of the molecular lines in the ^12CO（J= 2-1）,^12CO（J=3-2）,^13CO（J=2-1）,and ^13CO（J=3-2） transition emissions toward the Cepheus B molecular cloud with the KOSMA 3mtelescope. The integrated intensity map of the ^12CO （J = 2 - 1） transition has shown a structure with a compact core and a compact ridge extended to the north-west of the core. The cloud is surrounded by an optically bright rim, where the radiation-driven implosion （RDI） may greatly change the gas properties. The intensities of the CO （J = 3 - 2） transition are higher than those of the CO （J = 2 - 1） transition along the rim area. We find characteristic RDI structure in position-velocity diagrams. Non-LTE large velocity gradient （LVG） model analysis shows that the density and temperature at the edge are higher than that in the center. Our results provide evidences that an RDI is taking place in the Cepheus B molecular cloud.展开更多
This study evaluated the expression of defense compounds from the secondary metabolism of Eucalyptus globulus plants, subjected to direct and indirect stimuli by the insect Ctenarytaina eucalypti (blue gum Psyllid). R...This study evaluated the expression of defense compounds from the secondary metabolism of Eucalyptus globulus plants, subjected to direct and indirect stimuli by the insect Ctenarytaina eucalypti (blue gum Psyllid). Results showed that defense responses were activated in plants in all tested cases. Were detected and identified thirty-two compounds in the leaves of treated plants, of which five compounds differed with the control, and all are part of the chemical defenses from the plants, three of them were oxygenated monoterpenes (borneol, exo-2-hydroxy cineole and thymol), a aromatic carboxylic acid (benzoic acid) and a quinone (6-acethyl-flaviolin). The plants induced by volatile compounds and by indirect entomological manner, showed its capability to synthesize defensive compounds without a wound that promotes these responses. Were also found some constitutive secondary metabolites over expressed in the different inductions compared with the control.展开更多
The conservation of the energy flux in turbulent jets that propagate in the interstellar medium (ISM) allows us to deduce the law of motion when an inverse power law decrease of density is considered. The back-reactio...The conservation of the energy flux in turbulent jets that propagate in the interstellar medium (ISM) allows us to deduce the law of motion when an inverse power law decrease of density is considered. The back-reaction that is caused by the radiative losses for the trajectory is evaluated. The velocity dependence of the jet with time/space is applied to the jet of HH34, for which the astronomical data of velocity versus time/space are available. The introduction of precession and constant velocity for the central star allows us to build a curved trajectory for the superjet connected with HH34. The bow shock that is visible in the superjet is explained in the framework of the theory of the image in the case of an optically thin layer.展开更多
Equilibrium guanidinium chloride （GdmCl）-induced unfolding of arginine kinase （AK） was investigated by enzymatic activity, intrinsic fluorescence, 8-anilinonaphthalene-1-sulfonic acid （ANS） fluorescence, circula...Equilibrium guanidinium chloride （GdmCl）-induced unfolding of arginine kinase （AK） was investigated by enzymatic activity, intrinsic fluorescence, 8-anilinonaphthalene-1-sulfonic acid （ANS） fluorescence, circular dichroism （CD） spectrum, and size-exclusion chromatography. The measurements showed that AK unfolded through two equilibrium intermediates： the molten globule state and the partly folded state. Both intermediates have no enzyme activity. The molten globule state exists at 0.4-0.8 mol/L GdmCi, perhaps after the N-terminal domain has unfolded but the C-terminal domain is still intact. The partly folded state occurs at 1.1-1.5 mol/L GdmCI with a hydrodynamic volume no more than 1.6-fold larger than the native state and a pronounced far UV-CD signal. Its ANS fluorescence intensity is about 50% of the molten globule state. This partly folded state shares similarities with the “burst” kinetic intermediate of protein folding.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
基金This work was supportedby theNational KeyR&D Program of China(2022YFD1301005)the Shandong Provincial Natural Science Foundation,China(ZR2022MC184)the High-level Talents Foundation of Qingdao Agricultural University,China(665/1120053,665/1120080).
文摘The milk fat globule membrane(MFGM)is a complex structure with numerous functions,and its composition is affected by many factors.There have been few systematic investigations on goat MFGM proteome profiling during lactation.Individual milk samples from 15 healthy dairy goats were obtained at six lactation time points for investigation of the MFGM proteome using both data-independent acquisition(DIA)and data-dependent acquisition(DDA)proteomics techniques combined with multivariate statistical analysis.Using the DIA method,890 variably abundant MFGM proteins were discovered throughout the lactation cycle.From 1 to 240 d,butyrophilin subfamily 1 member A1,lipoprotein lipase,perilipin-2,and adipose triglyceride lipase were upregulated,while APOE,complement C3,clusterin,and IgG were downregulated.Furthermore,from 1 to 90 d,annexin A1,annexin A2,and antithrombin-ll were downregulated,then upregulated by d 240.Albumin had a high degree of connectedness,indicating that it was a key protein,according to protein-protein interaction research.Overall,our findings gave new insights into the biological features of MFGM protein in goat milk throughout lactation,which may aid in the creation of specialized MFGM products and infant formula.
基金Supported by the National Natural Science Foundation of China,No.82100685the Scientific Research Fund of Xi’an Health Commission,No.2021yb08+1 种基金Scientific Research Fund of Xi’an Central Hospital,No.2022QN07Innovation Capability Support Plan of Xi’an Science and Technology Bureau,No.23YXYJ0097.
文摘BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.
基金Supported by a grant from Medical Technology Research Center for Health Development of China National Health and Family Planning Commission(No.W2012FZ007)
文摘Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.
基金the Beijing Municipal Natural Science Foundation(S170001)the National Natural Science Foundation of China(31630074,31902170,31972596 and 31902189)+2 种基金the National Key Research and Development Program of China(2016YFD0500506 and 2018YDF0501002)the Agriculture Research System of China(CARS-35)the Higher Education Discipline Innovation Project(B16044).
文摘Milk fat globule membrane(MFGM)possesses various nutritional and biological benefits for mammals,whereas its effects on neonatal gut microbiota and barrier integrity remained unclear.This study investigated the effects of MFGM administration on microbial compositions and intestinal barrier functions of neonatal piglets.Sixteen newborn piglets were randomly allocated into a CON group or MFGM group,orally administered with saline or MFGM solution(1 g/kg body weight)respectively during the first postnatal week,and all piglets were breastfed during the whole neonatal period.The present study found that the MFGM oral administration during the first postnatal week increased the plasma immunoglobulin(lg)G level,body weight and average daily gain of piglets(P<0.05)on 21 d.Addi-tionally,MFGM administration enriched fecal SCFA-producing bacteria(Ruminococaceae_UCG-002,Ruminococaceae_UCG-010,Ruminococaceae_UCG-004,Ruminococaceae_UCG-014 and[Ruminococcus]_gauvrearuii_group),SCFA concentrations(acetate,propionate and butyrate;P<0.05)and their receptor(G-protein coupled receptor 41,GPR41).Furthermore,MFGM administration promoted intestinal villus morphology(P<0.05)and barrier functions by upregulating genes of tight junctions(E-cadherin,claudin-1,occludin and zonula occludin 1[ZO-1]),mucins(mucin-13 and mucin-20)and interleukin(IL)-22(P<0.05).Positive correlation was found between the beneficial microbes and SCFA levels pairwise with the intestinal barrier genes(P<0.05).In conclusion,orally administrating MFGM during the first postnatal week stimulated SCFA-producing bacteria colonization and SCFA generation,enhanced intes-tinal barrier functions and consequently improved growth performance of neonatal piglets on 21 d.Our findings will provide new insights about MFGM intervention for microbial colonization and intestinal development of neonates during their early life.
文摘With the excellent biocompatibility and osteo- conductivity, nano-hydroxyapatite （nHA） has shown significant prospect in the biomedical applications. Con- trolling the size, crystallinity and surface properties of nHA crystals is a critical challenge in the design of HA based biomaterials. With the graft copolymer of chitosan and poly（N-isopropylacrylamide） in coil and globule states as a template respectively, a novel composite from chitosan-g-poly（N-isopropylacrylamide） and nano-hydro- xyapatite （CS-g-PNIPAM/nHA） was prepared via co- precipitation. Zeta potential analysis, thermogravimetric analysis and X-ray diffraction were used to identify the formation mechanism of the CS-g-PNIPAM/nHA compo- site and its morphology was observed by transmission electron microscopy. The results suggested that the physical aggregation states of the template polymer could induce or control the size, crystallinity and morphology of HA crystals in the CS-g-PNIPAM/nHA composite. The CS-g-PNIPAM/nHA composite was then introduced to chitosan-gelatin （CS-Gel） polyelectronic complex and the cytocompatibility of the resulting CS- Gel/composite hybrid film was evaluated. This hybrid film was proved to be favorable for the proliferation of MC 3T3-E1 cells. Therefore, the CS-g-PNIPAM/nHA compo- site is a potential biomaterial in bone tissue engineering.
文摘The site order parameter (SOP) has been adopted to analyze various orders of structure formation and distribution during the crystallization of a polyethylene globule simulated by molecular dynamics. The SOP not only identifies different orders among the structures but also different phases. The results showed that intermediate structures with medium order exist unevenly in the early stage of nucleation, which differs from traditional models. We found that the nucleation relies on crystallinity fluctuations with increasing amplitude, and a baby nucleus with different shape and increasing size suddenly appears in the fluctuations. Once its size is large enough, the baby nucleus becomes the nucleus. In the growth stage, a number of lamellar mergences were observed and their selective behaviors were related to the orientation differences between the lamellae to be merged. The SOP distribution of all atoms in the system during crystallization had two peaks: one for the amorphous phase and the other for the crystalline phase. The intermediate structures with medium orders are located between the two peaks as an order promotion pathway. The data show that the medium order structure fluctuates at the growth front and is not always available, and that the medium order structure existing at the front is not always good for development. It is possibly caused by chain entanglement. Structure fluctuation at the growth front enables the system showing thousands of the most probable configurations to approach the precursor. The growth front is thus active for a while and inactive at other times.
基金supported by the National Natural Science Foundation of China (U1904116)Special Funds for Modern Agricultural Industry Technology System (CARS-37)+1 种基金National Key Research and Development Program of China (Beijing, China2016YFD0500503)。
文摘Background: Milk lipids originate from cytoplasmic lipid droplets(LD) that are synthesized and secreted from mammary epithelial cells by a unique membrane-envelopment process. Butyrophilin 1 A1(BTN1 A1) is one of the membrane proteins that surrounds LD, but its role in bovine mammary lipid droplet synthesis and secretion is not well known.Methods: The objective was to knockout BTN1 A1 in bovine mammary epithelial cells(BMEC) via the CRISPR/Cas9 system and evaluate LD formation, abundance of lipogenic enzymes, and content of cell membrane phospholipid(PL) species. Average LD diameter was determined via Oil Red O staining, and profiling of cell membrane phospholipid species via liquid chromatography-tandem mass spectrometry(LC-MS/MS).Results: Lentivirus-mediated infection of the Cas9/sg RNA expression vector into BMEC resulted in production of a homozygous clone BTN1 A1^((-/-)). The LD size and content decreased following BTN1 A1 gene knockout. The m RNA abundance of fatty acid synthase(FASN) and peroxisome proliferator-activated receptor-gamma(PPARG) was downregulated in the BTN1 A1^((-/-))clone. Subcellular analyses indicated that BTN1 A1 and LD were co-localized in the cytoplasm. BTN1 A1 gene knockout increased the percentage of phosphatidylethanolamine(PE) and decreased phosphatidylcholine(PC), which resulted in a lower PC/PE ratio.Conclusions: Results suggest that BTN1 A1 plays an important role in regulating LD synthesis via a mechanism involving membrane phospholipid composition.
文摘This study demonstrated that homogenization did not increase the activity of lipoprotein lipase (LPL) in spite of a fast accumulation of free fatty acids (FFA). Two homogenization pressures (100 and 170 bar) and two temperatures (40℃and 50℃) were examined. The activity of LPL was analyzed and the formation of FFA was measured with two different methods, the B.D.I.-method and a nonesterified fatty acids (NEFA) method. A homogenization temperature of 50℃ resulted in a decreased LPL activity compared to 40℃. No effect of homogenization pressure was found. Analyzing FFA concentration with the B.D.I.-method resulted in significant effect of homogenization temperature and no effect of pressure. The largest formation of FFA was found in milk homogenized at 40℃. Using the NEFA method, another result was obtained, indicating no effect of homogenization temperature and a larger FFA accumulation at 100 bar than at 170 bar. Both analytic methods demonstrated significant production of FFA during 60 min incubation at homogenization temperature after treatment. The level of FFA in the milk samples immediately after homogenization was very high, demonstrating that LPL cleaves the triglycerides very rapidly when the native membrane was damaged. The regression between the B.D.I.-method and the NEFA was fair in the interval between 4 and 14 mmol/100 g fat, whereas at higher concentrations, the correlation was poor.
文摘We assessed the effects of plantations of exotic trees (Pinus radiata, Eucalyptus globulus, and Populus nigra) on plant biodiversity in the temperate zone of the biodiversity hotspot of Central Chile. This region has suffered from intense deforestation in favor of plantation establishment in the major part of the coastal area since the neoliberal turn in 1973. The approach presented aimed to analyze plant biodiversity on the α-, β- and γ-scale. Furthermore, a plantation evaluation index was applied in order to provide quantitative figures on management practices. Species richness is reduced by 50% below plantations. Diversity and evenness index values are also significantly reduced. Analyses on β-similarity indicate that plantations do not host species absent in adjacent native forests, and no additional habitat heterogeneity is gained. On the γ-scale, plantations lower the number of total species observed;especially of endemic species. The abundance of species considered as invasive is significantly higher and frequently, invasive plants dominate the understory. The evaluation index attests rather poor plantation management in Central Chile since plantations are grown as monocultures, natural elements and native species are lacking at specific sites and plantations are insufficiently connected to native plant formations at the landscape scale. Results give much concern since deforestation processes as observed in our study area is about to begin in Patagonia as well. If management practices from the temperate zone are adopted in Patagonia, a considerable decline in plant biodiversity has to be expected there.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.21204065 and 20934004)the Natural Science Foundation of Zhejiang Province,China(Grant No.Y4110357)
文摘DNA condensation is an important process in many fields including life sciences, polymer physics, and applied technology. In the nucleus, DNA is condensed into chromosomes. In polymer physics, DNA is treated as a semi-flexible molecule and a polyelectrolyte. Many agents, including multi-valent cations, surfactants, and neutral poor solvents, can cause DNA condensation, also referred to as coil–globule transition. Moreover, DNA condensation has been used for extraction and gene delivery in applied technology. Many physical theories have been presented to elucidate the mechanism underlying DNA condensation, including the counterion correlation theory, the electrostatic zipper theory, and the hydration force theory. Recently several single-molecule studies have focused on DNA condensation, shedding new light on old concepts. In this document, the multi-field concepts and theories related to DNA condensation are introduced and clarified as well as the advances and considerations of single-molecule DNA condensation experiments are introduced.
基金conducted by Wageningen University and Research(Wageningen Livestock Research, Wageningen, the Netherlands)commissioned and funded by the Ministry of Agriculture+2 种基金Nature and Food Quality (The Hague, the Netherlands) within the framework of Policy Support Research theme ‘Feed4 Foodure’(BO-31.03-005-001TKI-AF12039)by the Vereniging Diervoederonderzoek Nederland (Rijswijk, the Netherlands)。
文摘Background: Characterising the regulation of milk component synthesis in response to macronutrient supply is critical for understanding the implications of nutritional interventions on milk production. Gene expression in mammary gland secretory cells was measured using RNA isolated from milk fat globules from 6 Holstein-Friesian cows receiving 5-d abomasal infusions of saline, essential amino acids(AA), or glucose(GG) or palm olein(LG)without(LAA) or with(HAA) essential AA, according to a 6 × 6 Latin square design. RNA was isolated from milk fat samples collected on d 5 of infusion and subjected to real-time quantitative PCR. We hypothesised that m RNA expression of genes involved in de novo milk fatty acid(FA) synthesis would be differently affected by GG and LG,and that expression of genes regulating transfer of tricarboxylic acid cycle intermediates would increase at the HAA level. We also hypothesised that the HAA level would affect genes regulating endoplasmic reticulum(ER)homeostasis but would not affect genes related to the mechanistic target of rapamycin complex 1(m TORC1) or the integrated stress response(ISR) network.Results: Infusion of GG did not affect de novo milk FA yield but decreased expression of FA synthase(FASN).Infusion of LG decreased de novo FA yield and tended to decrease expression of acetyl-Co A carboxylase 1(ACC1).The HAA level increased both de novo FA yield and expression of ACC1, and tended to decrease expression of mitochondrial phosphoenolpyruvate carboxykinase(PCK2). m RNA expression of m TORC1 signaling participants was not affected by GG, LG, or AA level. Expression of the ε subunit of the ISR constituent eukaryotic translation initiation factor 2 B(EIF2 B5) tended to increase at the HAA level, but only in the presence of LG. X-box binding protein 1(XBP1) m RNA was activated in response to LG and the HAA level.Conclusions: Results show that expression of genes involved in de novo FA synthesis responded to glucogenic,lipogenic, and aminogenic substrates, whereas genes regulating intermediate flux through the tricarboxylic acid cycle were not majorly affected. Results also suggest that after 5 d of AA supplementation, milk protein synthesis is supported by enhanced ER biogenesis instead of signaling through the mTORC1 or ISR networks.
基金Sponsored by the National Natural Science Foundation of China(Grant No.51206038)the Scientific Research Fund of Heilongjiang Provincial Education Department(Grant No.12521122)
文摘To correct the light scattering property parameters of milk fat for improving the detection accuracy,the Mie-theory was used to establish a predictive model for light scattering properties of milk fat globule with multi-diameter distributions, by means of Monte Carlo approach to simulate actual multi-diameter size distribution of milk fat globule in milk fat solution. Scattering coefficient and absorption coefficient of multidiameter distribution milk fat particles were calculated by simulating the particles size distribution in milk fat solution. And the light scattering properties of multi-diameter distribution was compared with that of volume mean diameter,Sauter mean diameter and numerical mean diameter in milk fat solution. Theoretical simulation results indicate that the scattering coefficient and absorption coefficient of milk fat particles are determined by the particle size distribution in milk fat solution. There is a distinct difference in scattering characteristics between the milk fat particles with multi-diameter distribution and that with mean diameters. Compared to that with multi-diameter distribution,the scattering coefficient of the milk fat particles with mean diameter has a maximum mean deviation of 9042 m-1. The particle size distribution is not completely determined by the mean diameters. The dependence of the light scattering properties on the particle size distribution should be considered into the model and simulation. Therefore,it is found that the particle size distribution in milk fat solution is an essential and critical factor to significantly improve the detection accuracy of milk fat content.
文摘We analyze large scale mapping observations of the molecular lines in the ^12CO（J= 2-1）,^12CO（J=3-2）,^13CO（J=2-1）,and ^13CO（J=3-2） transition emissions toward the Cepheus B molecular cloud with the KOSMA 3mtelescope. The integrated intensity map of the ^12CO （J = 2 - 1） transition has shown a structure with a compact core and a compact ridge extended to the north-west of the core. The cloud is surrounded by an optically bright rim, where the radiation-driven implosion （RDI） may greatly change the gas properties. The intensities of the CO （J = 3 - 2） transition are higher than those of the CO （J = 2 - 1） transition along the rim area. We find characteristic RDI structure in position-velocity diagrams. Non-LTE large velocity gradient （LVG） model analysis shows that the density and temperature at the edge are higher than that in the center. Our results provide evidences that an RDI is taking place in the Cepheus B molecular cloud.
文摘This study evaluated the expression of defense compounds from the secondary metabolism of Eucalyptus globulus plants, subjected to direct and indirect stimuli by the insect Ctenarytaina eucalypti (blue gum Psyllid). Results showed that defense responses were activated in plants in all tested cases. Were detected and identified thirty-two compounds in the leaves of treated plants, of which five compounds differed with the control, and all are part of the chemical defenses from the plants, three of them were oxygenated monoterpenes (borneol, exo-2-hydroxy cineole and thymol), a aromatic carboxylic acid (benzoic acid) and a quinone (6-acethyl-flaviolin). The plants induced by volatile compounds and by indirect entomological manner, showed its capability to synthesize defensive compounds without a wound that promotes these responses. Were also found some constitutive secondary metabolites over expressed in the different inductions compared with the control.
文摘The conservation of the energy flux in turbulent jets that propagate in the interstellar medium (ISM) allows us to deduce the law of motion when an inverse power law decrease of density is considered. The back-reaction that is caused by the radiative losses for the trajectory is evaluated. The velocity dependence of the jet with time/space is applied to the jet of HH34, for which the astronomical data of velocity versus time/space are available. The introduction of precession and constant velocity for the central star allows us to build a curved trajectory for the superjet connected with HH34. The bow shock that is visible in the superjet is explained in the framework of the theory of the image in the case of an optically thin layer.
基金Supported by the National High-Tech Research and Development (863) Program of China (No. 2003AA603430) and the National Natural Science Foundation of China (No. 30371092)
文摘Equilibrium guanidinium chloride （GdmCl）-induced unfolding of arginine kinase （AK） was investigated by enzymatic activity, intrinsic fluorescence, 8-anilinonaphthalene-1-sulfonic acid （ANS） fluorescence, circular dichroism （CD） spectrum, and size-exclusion chromatography. The measurements showed that AK unfolded through two equilibrium intermediates： the molten globule state and the partly folded state. Both intermediates have no enzyme activity. The molten globule state exists at 0.4-0.8 mol/L GdmCi, perhaps after the N-terminal domain has unfolded but the C-terminal domain is still intact. The partly folded state occurs at 1.1-1.5 mol/L GdmCI with a hydrodynamic volume no more than 1.6-fold larger than the native state and a pronounced far UV-CD signal. Its ANS fluorescence intensity is about 50% of the molten globule state. This partly folded state shares similarities with the “burst” kinetic intermediate of protein folding.
