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
In this work,we have developed a novel machine(deep)learning computational framework to determine and identify damage loading parameters(conditions)for structures and materials based on the permanent or residual plast...In this work,we have developed a novel machine(deep)learning computational framework to determine and identify damage loading parameters(conditions)for structures and materials based on the permanent or residual plastic deformation distribution or damage state of the structure.We have shown that the developed machine learning algorithm can accurately and(practically)uniquely identify both prior static as well as impact loading conditions in an inverse manner,based on the residual plastic strain and plastic deformation as forensic signatures.The paper presents the detailed machine learning algorithm,data acquisition and learning processes,and validation/verification examples.This development may have significant impacts on forensic material analysis and structure failure analysis,and it provides a powerful tool for material and structure forensic diagnosis,determination,and identification of damage loading conditions in accidental failure events,such as car crashes and infrastructure or building structure collapses.展开更多
Food allergy has become a significant public health problem affecting a large number of people worldwide.Maternal obesity causes inflammation and alters the immune system of offspring,which may exacerbate their food a...Food allergy has become a significant public health problem affecting a large number of people worldwide.Maternal obesity causes inflammation and alters the immune system of offspring,which may exacerbate their food allergy.The aim of this study was to determine whether offspring mice born to obese mothers would have more serve reactions to cow's milk protein-induced food allergy,and further investigate the underlying mechanisms.Female offspring BALB/c mice of mothers with normal and high-fat diets were sensitized withβ-lactoglobulin(BLG),respectively.Maternal obesity increased the serum immunoglobulin E and mouse mast cell protease levels,though did not have significant influence on anaphylactic symptom score,core temperature and diarrhea rate of offspring mice after BLG sensitization.Furthermore,maternal obesity led to a lower level of occludin mRNA expression in BLG-sensitized mice.The mice born to obese mothers exhibited increased mRNA expression levels of GATA-3,interleukin(IL)-4 and IL-10 in jejunum after BLG sensitization,indicating maternal obesity intensified Th2-type biased immune responses.In conclusion,maternal obesity exerted exacerbating effects on the responsiveness of their offspring to cow's milk protein sensitization.展开更多
Precise genome-editing platforms are versatile tools for generating specific,site-directed DNA insertions,deletions,and substitutions.The continuous enhancement of these tools has led to a revolution in the life scien...Precise genome-editing platforms are versatile tools for generating specific,site-directed DNA insertions,deletions,and substitutions.The continuous enhancement of these tools has led to a revolution in the life sciences,which promises to deliver novel therapies for genetic disease.Precise genome-editing can be traced back to the 1950s with the discovery of DNA’s doublehelix and,after 70 years of development,has evolved from crude in vitro applications to a wide range of sophisticated capabilities,including in vivo applications.Nonetheless,precise genome-editing faces constraints such as modest efficiency,delivery challenges,and off-target effects.In this review,we explore precise genome-editing,with a focus on introduction of the landmark events in its history,various platforms,delivery systems,and applications.First,we discuss the landmark events in the history of precise genome-editing.Second,we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human genome.Third,we introduce the current delivery systems used to deploy precise genome-editing components through DNA,RNA,and RNPs.Finally,we summarize the current applications of precise genome-editing in labeling endogenous genes,screening genetic variants,molecular recording,generating disease models,and gene therapy,including ex vivo therapy and in vivo therapy,and discuss potential future advances.展开更多
This paper studies the effect of ice resistance on the icebreaking capacity and speed of an icebreaking vessel.We combine an improved Correct Smoothed Particle Method(CSPM)with a material low-speed collision fracture ...This paper studies the effect of ice resistance on the icebreaking capacity and speed of an icebreaking vessel.We combine an improved Correct Smoothed Particle Method(CSPM)with a material low-speed collision fracture model to numerically simulate the continuous icebreaking and rolling process of crushed.Using this model,we investigate the icebreaking resistance and immersion resistance during the icebreaking process,taking into account the fluid(water)as the elastic boundary support and the fluid-solid coupling interaction.We compare the icebreaking resistance and broken ice fracture shapes obtained by the numerical calculation with the theoretical analytical results,and thus validate the improved CSPM method.Further,we compare the immersion resistance results from our simulation against that from Puntigliano[Puntigliano,Hamburgische Schiffbau-Versuchsanstalt GmbH(1995)],and demonstrate that the proposed method can accurately predict ice resistance.展开更多
A 4H-SiC trench gate metal-oxide-semiconductor field-effect transistor(UMOSFET)with semi-super-junction shiel-ded structure(SS-UMOS)is proposed and compared with conventional trench MOSFET(CT-UMOS)in this work.The adv...A 4H-SiC trench gate metal-oxide-semiconductor field-effect transistor(UMOSFET)with semi-super-junction shiel-ded structure(SS-UMOS)is proposed and compared with conventional trench MOSFET(CT-UMOS)in this work.The advantage of the proposed structure is given by comprehensive study of the mechanism of the local semi-super-junction structure at the bottom of the trench MOSFET.In particular,the influence of the bias condition of the p-pillar at the bottom of the trench on the static and dynamic performances of the device is compared and revealed.The on-resistance of SS-UMOS with grounded(G)and ungrounded(NG)p-pillar is reduced by 52%(G)and 71%(NG)compared to CT-UMOS,respectively.Additionally,gate ox-ide in the GSS-UMOS is fully protected by the p-shield layer as well as semi-super-junction structure under the trench and p-base regions.Thus,a reduced electric-field of 2 MV/cm can be achieved at the corner of the p-shield layer.However,the quasi-intrinsic protective layer cannot be formed in NGSS-UMOS due to the charge storage effect in the floating p-pillar,resulting in a large electric field of 2.7 MV/cm at the gate oxide layer.Moreover,the total switching loss of GSS-UMOS is 1.95 mJ/cm2 and is reduced by 18%compared with CT-UMOS.On the contrary,the NGSS-UMOS has the slowest overall switching speed due to the weakened shielding effect of the p-pillar and the largest gate-to-drain capacitance among the three.The proposed GSS-UMOS plays an important role in high-voltage and high-frequency applications,and will provide a valuable idea for device design and circuit applications.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.
文摘In this work,we have developed a novel machine(deep)learning computational framework to determine and identify damage loading parameters(conditions)for structures and materials based on the permanent or residual plastic deformation distribution or damage state of the structure.We have shown that the developed machine learning algorithm can accurately and(practically)uniquely identify both prior static as well as impact loading conditions in an inverse manner,based on the residual plastic strain and plastic deformation as forensic signatures.The paper presents the detailed machine learning algorithm,data acquisition and learning processes,and validation/verification examples.This development may have significant impacts on forensic material analysis and structure failure analysis,and it provides a powerful tool for material and structure forensic diagnosis,determination,and identification of damage loading conditions in accidental failure events,such as car crashes and infrastructure or building structure collapses.
基金supported by the National Key Research and Development Program of China(2019YFC1605000)the Beijing Dairy Industry Innovation Team(BAIC06-2021)。
文摘Food allergy has become a significant public health problem affecting a large number of people worldwide.Maternal obesity causes inflammation and alters the immune system of offspring,which may exacerbate their food allergy.The aim of this study was to determine whether offspring mice born to obese mothers would have more serve reactions to cow's milk protein-induced food allergy,and further investigate the underlying mechanisms.Female offspring BALB/c mice of mothers with normal and high-fat diets were sensitized withβ-lactoglobulin(BLG),respectively.Maternal obesity increased the serum immunoglobulin E and mouse mast cell protease levels,though did not have significant influence on anaphylactic symptom score,core temperature and diarrhea rate of offspring mice after BLG sensitization.Furthermore,maternal obesity led to a lower level of occludin mRNA expression in BLG-sensitized mice.The mice born to obese mothers exhibited increased mRNA expression levels of GATA-3,interleukin(IL)-4 and IL-10 in jejunum after BLG sensitization,indicating maternal obesity intensified Th2-type biased immune responses.In conclusion,maternal obesity exerted exacerbating effects on the responsiveness of their offspring to cow's milk protein sensitization.
基金supported by the National Science Foundation of China(Grant numbers 82200265,82070324,82270249)the USA National Institutes of Health(Grant numbers R00HL143194,R21HD108460).
文摘Precise genome-editing platforms are versatile tools for generating specific,site-directed DNA insertions,deletions,and substitutions.The continuous enhancement of these tools has led to a revolution in the life sciences,which promises to deliver novel therapies for genetic disease.Precise genome-editing can be traced back to the 1950s with the discovery of DNA’s doublehelix and,after 70 years of development,has evolved from crude in vitro applications to a wide range of sophisticated capabilities,including in vivo applications.Nonetheless,precise genome-editing faces constraints such as modest efficiency,delivery challenges,and off-target effects.In this review,we explore precise genome-editing,with a focus on introduction of the landmark events in its history,various platforms,delivery systems,and applications.First,we discuss the landmark events in the history of precise genome-editing.Second,we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human genome.Third,we introduce the current delivery systems used to deploy precise genome-editing components through DNA,RNA,and RNPs.Finally,we summarize the current applications of precise genome-editing in labeling endogenous genes,screening genetic variants,molecular recording,generating disease models,and gene therapy,including ex vivo therapy and in vivo therapy,and discuss potential future advances.
文摘This paper studies the effect of ice resistance on the icebreaking capacity and speed of an icebreaking vessel.We combine an improved Correct Smoothed Particle Method(CSPM)with a material low-speed collision fracture model to numerically simulate the continuous icebreaking and rolling process of crushed.Using this model,we investigate the icebreaking resistance and immersion resistance during the icebreaking process,taking into account the fluid(water)as the elastic boundary support and the fluid-solid coupling interaction.We compare the icebreaking resistance and broken ice fracture shapes obtained by the numerical calculation with the theoretical analytical results,and thus validate the improved CSPM method.Further,we compare the immersion resistance results from our simulation against that from Puntigliano[Puntigliano,Hamburgische Schiffbau-Versuchsanstalt GmbH(1995)],and demonstrate that the proposed method can accurately predict ice resistance.
基金supported by the National Natural Science Foundation of China(Grant No.62104222)the Natural Science Foundation of Fujian Province of China for Distinguished Young Scholars(Grant No.2020J06002)+3 种基金the Science and Technology Project of Fujian Province of China(Grant No.2020I0001)the Science and Technology Key Projects of Xiamen(Grant No.3502ZCQ20191001)Shenzhen Science and Technology Program(Grant No.JSGG20201102-155800003)Jiangxi Provincial Natural Science Foundation(Grant No.20212ACB212005).
文摘A 4H-SiC trench gate metal-oxide-semiconductor field-effect transistor(UMOSFET)with semi-super-junction shiel-ded structure(SS-UMOS)is proposed and compared with conventional trench MOSFET(CT-UMOS)in this work.The advantage of the proposed structure is given by comprehensive study of the mechanism of the local semi-super-junction structure at the bottom of the trench MOSFET.In particular,the influence of the bias condition of the p-pillar at the bottom of the trench on the static and dynamic performances of the device is compared and revealed.The on-resistance of SS-UMOS with grounded(G)and ungrounded(NG)p-pillar is reduced by 52%(G)and 71%(NG)compared to CT-UMOS,respectively.Additionally,gate ox-ide in the GSS-UMOS is fully protected by the p-shield layer as well as semi-super-junction structure under the trench and p-base regions.Thus,a reduced electric-field of 2 MV/cm can be achieved at the corner of the p-shield layer.However,the quasi-intrinsic protective layer cannot be formed in NGSS-UMOS due to the charge storage effect in the floating p-pillar,resulting in a large electric field of 2.7 MV/cm at the gate oxide layer.Moreover,the total switching loss of GSS-UMOS is 1.95 mJ/cm2 and is reduced by 18%compared with CT-UMOS.On the contrary,the NGSS-UMOS has the slowest overall switching speed due to the weakened shielding effect of the p-pillar and the largest gate-to-drain capacitance among the three.The proposed GSS-UMOS plays an important role in high-voltage and high-frequency applications,and will provide a valuable idea for device design and circuit applications.
