Variation of microbiological and small molecule metabolite profiles of Nuodeng ham during ripening by high-throughput sequencing and GC-TOF-MS

The internal microbial diversity and small molecular metabolites of Nuodeng ham in different processing years(the first,second and third year sample)were analyzed by high-throughput sequencing technology and gas chromatography-time of flight mass spectrography(GC-TOF-MS)to study the effects of microorganisms and small molecular metabolites on the quality of ham in different processing years.The results showed that the dominant bacteria phyla of Nuodeng ham in different processing years were Proteobacteria and Firmicutes,the dominant fungi phyla were Ascomycota and Basidiomycota,while Staphylococcus and Aspergillus were the dominant bacteria and fungi of Nuodeng ham,respectively.Totally,252 kinds of small molecular metabolites were identified from Nuodeng ham in different processing years,and 12 different metabolites were screened through multivariate statistical analysis.Further metabolic pathway analysis showed that 23 metabolic pathways were related to ham fermentation,of which 8 metabolic pathways had significant effects on ham fermentation(Impact>0.01,P<0.05).The content of L-proline,phenyllactic acid,L-lysine,carnosine,taurine,D-proline,betaine and creatine were significantly positively correlated with the relative abundance of Staphylococcus and Serratia,but negatively correlated with the relative abundance of Halomonas,Aspergillus and Yamadazyma.

Overcoming neutrophil-induced immunosuppression in postoperative cancer therapy: Combined sialic acid-modified liposomes with scaffold-based vaccines

Immunotherapy is a promising approach for preventing postoperative tumor recurrence and metastasis. However, inflammatory neutrophils, recruited to the postoperative tumor site, have been shown to exacerbate tumor regeneration and limit the efficacy of cancer vaccines. Consequently, addressing postoperative immunosuppression caused by neutrophils is crucial for improving treatment outcomes. This study presents a combined chemoimmunotherapeutic strategy that employs a biocompatible macroporous scaffold-based cancer vaccine (S-CV) and a sialic acid (SA)-modified, doxorubicin (DOX)-loaded liposomal platform (DOX@SAL). The S-CV contains whole tumor lysates as antigens and imiquimod (R837, Toll-like receptor 7 activator)-loaded PLGA nanoparticles as immune adjuvants for cancer, which enhance dendritic cell activation and cytotoxic T cell proliferation upon localized implantation. When administered intravenously, DOX@SAL specifically targets and delivers drugs to activated neutrophils in vivo, mitigating neutrophil infiltration and suppressing postoperative inflammatory responses. In vivo and vitro experiments have demonstrated that S-CV plus DOX@SAL, a combined chemo-immunotherapeutic strategy, has a remarkable potential to inhibit postoperative local tumor recurrence and distant tumor progression, with minimal systemic toxicity, providing a new concept for postoperative treatment of tumors.

Multi-objective Design of Blending Fuel by Intelligent Optimization Algorithms

Fuel design is a complex multi-objective optimization problem in which facile and robust methods are urgently demanded.Herein,a complete workflow for designing a fuel blending scheme is presented,which is theoretically supported,efficient,and reliable.Based on the data distribution of the composition and properties of the blending fuels,a model of polynomial regression with appropriate hypothesis space was established.The parameters of the model were further optimized by different intelligence algorithms to achieve high-precision regression.Then,the design of a blending fuel was described as a multi-objective optimization problem,which was solved using a Nelder–Mead algorithm based on the concept of Pareto domination.Finally,the design of a target fuel was fully validated by experiments.This study provides new avenues for designing various blending fuels to meet the needs of next-generation engines.

Electro-assisted photocatalytic reduction of CO_(2) in ambient air using Ag/TNTAs at the gas-solid interface

The direct conversion of atmospheric CO_(2) into fuel via photocatalysis exhibits significant practical application value in advancing the carbon cycle.In this study,we established an electro-assisted photocatalytic system with dual compartments and interfaces,and coated Ag nanoparticles on the titanium nanotube arrays(TNTAs)by polydopamine modification.In the absence of sacrificial agent and alkali absorption liquid conditions,the stable,efficient and highly selective conversion of CO_(2) to CO at the gas-solid interface in ambient air was realized by photoelectric synergy.Specifically,with the assistance of potential,the CO formation rates reached 194.9μmol h^(−1) m^(−2) and 103.9μmol h^(−1) m^(−2) under ultraviolet and visible light irradiation,respectively;the corresponding CO_(2) conversion rates in ambient air were 30%and 16%,respectively.The excellent catalytic effect is mainly attributed to the formation of P–N heterojunction during the catalytic process and the surface plasmon resonance effect.Additionally,the introduction of solid agar electrolytes effectively inhibits the hydrogen evolution reaction and improves the electron utilization rate.This system promotes the development of photocatalytic technology for practical applications and provides new insights and support for the carbon cycle.

核心保护区适度分类开展自然旅游的学理与法理

国家公园,顾名思义就是面向全体国民(及海外访客)的公共园区。作为公共物业,如果有某个部门宣布其中核心保护区“原则上禁止人为活动”,是不是欠考虑?这种规定符合科学原理吗?符合中国历史文化传统吗?会得到保护地当地政府和当地居民的支持吗?出现违反这一规定的“不法”行为会得到有效的依“法”处置吗?

Research progress and application of deep in-situ condition preserved coring and testing

With the depletion of shallow resources,the exploration of deep earth resources has become a global strategy.The study of the different patterns in the physical mechanical properties of rocks at different occurrence depths is the basis for exploring deep into the earth,with the core and premise being the acquisition and testing of deep in-situ core specimens.Based on the original idea of deep in-situ condition preserved coring(ICP-Coring)and testing,combined with theoretical modeling,numerical analysis,test platform development,indoor testing and engineering application,the principles and technologies of deep ICP-Coring are developed.This principle and technology consists of five parts:in-situ pressurepreserved coring(IPP-Coring),in-situ substance-preserved coring(ISP-Coring),in-situ temperaturepreserved coring(ITP-Coring),in-situ light-preserved coring(ILP-Coring),and in-situ moisturepreserved coring(IMP-Coring).The theory and technology of temperature and pressure reconstruction at different occurrence depths and in different environments are proposed,and prototype trial production was completed by following the principle of displacement and tests based on the in-situ reconstructed environment.The notable advances are as follows:(1)Deep in-situ coring system:A pressure-preserved controller with an ultimate bearing capacity greater than 140 MPa,highperformance(temperature-resistant,pressure-resistant,and low thermally conductive)temperaturepreserved materials,an active temperature control system,and high-barrier quality-preserved membrane materials were developed;a deep ICP-Coring capacity calibration platform was independently developed,a deep in-situ coring technology system was developed,and the acquisition of deep in-situ cores was realized.(2)In-situ storage displacement system:Following the dual-circuit hydraulic design idea,a single-drive source push-pull composite grabbing mechanism was designed;the design of the overall structure for the deep in-situ displacement storage system and ultrahigh pressure cabin structure was completed,which could realize docking the coring device and core displacement in the in-situ reconstructed environment.(3)Test analysis system:A noncontact acoustic-electric-magnetic test system was developed under the in-situ reconstructed environment,and the errors between the test results and traditional contact test results were mostly less than 10%;a detachable deep in-situ core true triaxial test system was developed,which could perform loading tests for deep in-situ cores.The relevant technological achievements were successfully applied to the exploration and development of deep resources,such as deep mines,deep-sea natural gas hydrates,and deep oil and gas.The research results provide technical and equipment support for the construction of a theoretical system for deep in-situ rock mechanics,the development of deep earth resources and energy,and the scientific exploration of different layers and occurrence depths(deep and ultradeep)of the Earth.

师范院校医学细胞生物学串联模块式教学设计与应用实践

探索师范院校医学细胞生物学串联模块式教学设计及实践应用效果对提高医学细胞生物学教学质量具有重要的现实意义。串联模块式教学是师范院校医学细胞生物学行之有效的教学方法,能够有效提高临床医学专业本科生的专业基础知识和技能水平,培养科研创新意识,推动医学教育事业的发展。

OsDA1 positively regulates grain width in rice

The size and shape of rice grains influence their yield and commercial value.We investigated the role of OsDA1,a rice homolog of the Arabidopsis DA1 gene,in regulating grain size and shape.OsDA1 was highly expressed in young spikelets and glumes.Its overexpression led to enlarged seeds with increased width and decreased length/width ratio(LWR)and knocking out OsDA1 reduced grain width and increased grain length and LWR.A R310K point mutation in the DA1-like domain is a potential target for breeding for increased grain width and length.OsDA1 interacted with TCP gene-family proteins to regulate grain size and shape.Our findings deepen our understanding of the molecular mechanisms underlying grain size regulation and provide useful information for improving grain yield.

The prediction of projectile-target intersection for moving tank based on adaptive robust constraint-following control and interval uncertainty analysis

To improve the hit probability of tank at high speed,a prediction method of projectile-target intersection based on adaptive robust constraint-following control and interval uncertainty analysis is proposed.The method proposed provides a novel way to predict the impact point of projectile for moving tank.First,bidirectional stability constraints and stability constraint-following error are constructed using the Udwadia-Kalaba theory,and an adaptive robust constraint-following controller is designed considering uncertainties.Second,the exterior ballistic ordinary differential equation with uncertainties is integrated into the controller,and the pointing control of stability system is extended to the impact-point control of projectile.Third,based on the interval uncertainty analysis method combining Chebyshev polynomial expansion and affine arithmetic,a prediction method of projectile-target intersection is proposed.Finally,the co-simulation experiment is performed by establishing the multi-body system dynamic model of tank and mathematical model of control system.The results demonstrate that the prediction method of projectile-target intersection based on uncertainty analysis can effectively decrease the uncertainties of system,improve the prediction accuracy,and increase the hit probability.The adaptive robust constraint-following control can effectively restrain the uncertainties caused by road excitation and model error.

A Constrained Local Neighborhood Approach for Efficient Markov Blanket Discovery in Undirected Independent Graphs

When learning the structure of a Bayesian network,the search space expands significantly as the network size and the number of nodes increase,leading to a noticeable decrease in algorithm efficiency.Traditional constraint-based methods typically rely on the results of conditional independence tests.However,excessive reliance on these test results can lead to a series of problems,including increased computational complexity and inaccurate results,especially when dealing with large-scale networks where performance bottlenecks are particularly evident.To overcome these challenges,we propose a Markov blanket discovery algorithm based on constrained local neighborhoods for constructing undirected independence graphs.This method uses the Markov blanket discovery algorithm to refine the constraints in the initial search space,sets an appropriate constraint radius,thereby reducing the initial computational cost of the algorithm and effectively narrowing the initial solution range.Specifically,the method first determines the local neighborhood space to limit the search range,thereby reducing the number of possible graph structures that need to be considered.This process not only improves the accuracy of the search space constraints but also significantly reduces the number of conditional independence tests.By performing conditional independence tests within the local neighborhood of each node,the method avoids comprehensive tests across the entire network,greatly reducing computational complexity.At the same time,the setting of the constraint radius further improves computational efficiency while ensuring accuracy.Compared to other algorithms,this method can quickly and efficiently construct undirected independence graphs while maintaining high accuracy.Experimental simulation results show that,this method has significant advantages in obtaining the structure of undirected independence graphs,not only maintaining an accuracy of over 96%but also reducing the number of conditional independence tests by at least 50%.This significant performance improvement is due to the effective constraint on the search space and the fine control of computational costs.

Dinitrophenyl-oxadiazole compounds:Design strategy,synthesis,and properties of a series of new melt-cast explosives

Melt-cast explosives are the most widely used energetic materials in military composite explosives,researchers have been unremittingly exploring high-energy and insensitive melt-cast explosives.In this work,a series of dinitrophenyl-oxadiazole compounds were designed and prepared.These compounds have an ideal low melting point(80-97℃),good detonation performance(detonation velocity D=6455-6971 m/s,detonation pressure P=18-19 GPa)and extreme insensitive nature(impact sensitivity≥60 J,friction sensitivity>360 N).All these compounds were well characterized by nuclear magnetic resonance,fourier transform infrared spectroscopy,elemental analysis.Compounds 2,3 were unambiguously confirmed by X-ray single crystal diffraction analysis.As a result,their overall properties are superior to traditional melt-cast explosives trinitrotoluene(TNT)and dinitroanisole(DNAN)which may have excellent potential applications in insensitive melt-cast explosives.

A Study of the Effect of the Miller Cycle on the Combustion of a Supercharged Marine Diesel Engine

The Miller cycle is a program that effectively reduces NOx emissions from marine diesel engines by lowering the maximum combustion temperature in the cylinder,thereby reducing NOx emissions.To effectively investigate the impact of Miller cycle optimum combustion performance and emission capability under high load conditions,this study will perform a one-dimensional simulation of the performance of a marine diesel engine,as well as a threedimensional simulation of the combustion in the cylinder.A 6-cylinder four-stroke single-stage supercharged diesel engine is taken as the research object.The chassis dynamometer and other related equipment are used to build the test system,carry out the diesel engine bench test,and collect experimental data.The simulation results are compared with the test results,and the error is less than 5%.In this study,the authors will use simulation software to simulate several Miller cycle scenarios designed for early inlet valve closure and analyze the impact of the Miller cycle on combustion and emissions at 100%load conditions.By comparing the flow field distribution of the engine at 1500 r/min condition,it was found that proper EIVC can prolong the ignition latency period and homogeneous fuel-air mixture combustion acceleration,but it can reduce pressure and temperature within the piston chamber and NOx emission.However,the Miller cycle reduces end-of-compression temperatures,which increases combustion duration and exhaust temperatures,making it difficult to improve fuel economy at the optimum fuel consumption point,and closing the intake valves prematurely leads to excessive fuel expenditure.Furthermore,temperature and heat release rate within the piston chamber,NOx,and SOOT generation were significantly enhanced.

Preparation of activated carbon from cattail and its application for dyes removal

Activated carbon was prepared from cattail by H3PO4 activation. The effects influencing the surface area of the resulting activated carbon followed the sequence of activated temperature 〉 activated time 〉 impregnation ratio 〉 impregnation time. The optimum condition was found at an impregnation ratio of 2.5, an impregnation time of 9 hr, an activated temperature of 500℃, and an activated time of 80 min. The Brunauer-Emmett-Teller surface area and average pore size of the activated carbon were 1279 m^2/g and 5.585 nm, respectively. A heterogeneous structure in terms of both size and shape was highly developed and widely distributed on the carbon surface. Some groups containing oxygen and phosphorus were formed, and the carboxyl group was the major oxygen-containing functional group. An isotherm equilibrium study was carried out to investigate the adsorption capacity of the activated carbon. The data fit the Langmuir isotherm equation, with maximum monolayer adsorption capacities of 192.30 mg/g for Neutral Red and 196.08 mg/g for Malachite Green. Dye-exhausted carbon could be regenerated effectively by thermal treatment. The results indicated that cattail-derived activated carbon was a promising adsorbent for the removal of cationic dyes from aqueous solutions.

Theoretical prediction of wear of disc cutters in tunnel boring machine and its application

Predicting the cutter consumption and the exact time to replace the worn-out cutters in tunneling projects constructed with tunnel boring machine(TBM) is always a challenging issue. In this paper, we focus on the analyses of cutter motion in the rock breaking process and trajectory of rock breaking point on the cutter edge in rocks. The analytical expressions of the length of face along which the breaking point moves and the length of spiral trajectory of the maximum penetration point are derived. Through observation of rock breaking process of disc cutters as well as analysis of disc rock interaction, the following concepts are proposed: the arc length theory of predicting wear extent of inner and center cutters, and the spiral theory of predicting wear extent of gage and transition cutters. Data obtained from5621 m-long Qinling tunnel reveal that among 39 disc cutters, the relative errors between cumulatively predicted and measured wear values for nine cutters are larger than 20%, while approximately 76.9% of total cutters have the relative errors less than 20%. The proposed method could offer a new attempt to predict the disc cutter's wear extent and changing time.

A linearly-independent higher-order extended numerical manifold method and its application to multiple crack growth simulation

The numerical manifold method(NMM)can be viewed as an inherent continuous-discontinuous numerical method,which is based on two cover systems including mathematical and physical covers.Higher-order NMM that adopts higher-order polynomials as its local approximations generally shows higher precision than zero-order NMM whose local approximations are constants.Therefore,higherorder NMM will be an excellent choice for crack propagation problem which requires higher stress accuracy.In addition,it is crucial to improve the stress accuracy around the crack tip for determining the direction of crack growth according to the maximum circumferential stress criterion in fracture mechanics.Thus,some other enriched local approximations are introduced to model the stress singularity at the crack tip.Generally,higher-order NMM,especially first-order NMM wherein local approximations are first-order polynomials,has the linear dependence problems as other partition of unit(PUM)based numerical methods does.To overcome this problem,an extended NMM is developed based on a new local approximation derived from the triangular plate element in the finite element method(FEM),which has no linear dependence issue.Meanwhile,the stresses at the nodes of mathematical mesh(the nodal stresses in FEM)are continuous and the degrees of freedom defined on the physical patches are physically meaningful.Next,the extended NMM is employed to solve multiple crack propagation problems.It shows that the fracture mechanics requirement and mechanical equilibrium can be satisfied by the trial-and-error method and the adjustment of the load multiplier in the process of crack propagation.Four numerical examples are illustrated to verify the feasibility of the proposed extended NMM.The numerical examples indicate that the crack growths simulated by the extended NMM are in good accordance with the reference solutions.Thus the effectiveness and correctness of the developed NMM have been validated.

Mechanism to remove oxide inclusions from molten aluminum by solid fluxes refining method

A novel flux charging method and a crucible quenching method were employed to study the mechanism of solid fluxes refining method regarding the removal of oxide inclusions(Al_2O_3) from molten aluminum. Electrochemical polishing method was adopted to prepare surfaces of the samples. Through experiments, the morphology of the residual solidified flux in the solidified samples as well as the wetting action of the molten flux during refining were observed for the first time. Three wetting regimes denoted by absorbing regime, engulfing regime and penetration regime correlating with the removal of oxide films(the most typical and common oxide inclusions in molten aluminum) were proposed in terms of different types and distributions of oxide films and different size ratios of the molten flux to oxide films. Particularly, from a thermodynamic point of view, for the first time, the penetration regime provided concrete evidence that the practical oxide inclusions can be wet by molten flux under ambient fluid of molten aluminum. A spreading model was proposed, according to which ingredients and size parameters of practical solid fluxes can be optimized.

Rotational failure analysis of spherical-cylindrical shell pressure controllers related to gas hydrate drilling investigations

In situ pressure-preserved coring(IPP-Coring)technology is considered one of the most efficient methods for assessing resources.However,seal failure caused by the rotation of pressure controllers greatly affects the success of pressure coring.In this paper,a novel spherical-cylindrical shell pressure controller was proposed.The finite element analysis model was used to analyze the stress distribution and deformation characteristics of the pressure controller at different rotation angles.The seal failure mechanism caused by the rotation of the pressure controller was discussed.The stress deviation rate was defined to quantitatively characterize the stress concentration.Based on the test equipment designed in this laboratory,the ultimate bearing strength of the pressure controller was tested.The results show that the rotation of the valve cover causes an increase in the deformation on its lower side.Furthermore,the specific sealing pressure in the weak zone is greatly reduced by a statistically significant amount,resulting in seal failure.When the valve cover rotates 5°around the major axis,the stress deviation rate is-92.6%.To prevent rotating failure of the pressure controller,it is necessary to control the rotation angle of the valve cover within 1°around the major axis.The results of this research can help engineers reduce failure-related accidents,provide countermeasures for pressure coring,and contribute to the exploration and evaluation of deep oil and gas resources.

Granulin A synergizes with cisplatin to inhibit the growth of human hepatocellular carcinoma

OBJECTIVE Granulin A(GRN A),a cytokinesis protein,is derived from proteolysis of progranulin.The previous study in our laboratory has shown that GRN A is able to inhibit cancer cell growth significantly.This study aimed to investigate the effect of combination of GRN A and cisplatin on in vitro and in vivo on the growth of hepatocellular carcinoma.METHODS The in vitro and in vivo antitumor effects of combination of GRN A and Cisplatin were evaluated with MTS assay and subcuta.neous transplantation tumor model.Chou-Talalay method was used to calculate the combination index(CI).Colony formation assay and flow cytometry were used to detect the effects of GRN A on apoptosis.The expression of apoptosis-related proteins were detected by Western blot.RESULTS MTS assay showed that GRN A significantly inhibit hepatocellular carcinoma cells growth with the IC50 of 5.6 μmol·L^(-1),and GRN A combined with cisplatin synergistically inhibit hepatocellular carcinoma proliferation,with the CI<1.The colony-formation assay showed that GRN A significantly enhanced the inhibitory effects of cisplatin on cellular anchorage-independent growth.Flow cytometry showed that GRN A combined with cisplatin synergistically induced apoptosis,with the apoptotic rates of 5.87%,32.74%,35.67% and 67.15% in control,GRN A,Cisplatin,and combination of GRN A and Cisplatin groups,respectively.Western blot confirmed that the two drugs synergistically changed the expressions of proteins related to apoptosis.In vivo experiment indicated that combination of GRN A and cisplatin significantly suppressed tumor growth compared with single drug treatment groups.CONCLUSION The combination of GRN A and cisplatin resulted in synergistic antitumor effects against hepatocellular carcinoma both in vitro and in vivo.

Prior transfusion of umbilical cord mesenchymal stem cells can effectively alleviate symptoms of motion sickness in mice through interleukin 10 secretion

BACKGROUND Motion sickness(MS)is a disease that occurs during unbalanced movement,characterized by gastrointestinal symptoms and autonomic nervous system activation.Current clinical treatments for MS are limited.Recent evidence indicates that the levels of pro-inflammatory cytokines increase during MS and are associated with an inner ear immune imbalance.In the present study,mesenchymal stem cells(MSCs)have been shown to exert strong immunosuppressive effects.AIM To explore whether umbilical cord-derived mesenchymal stem cells(UC-MSCs)can prevent the occurrence of MS,and the underlying mechanism regulated by MSCs in a mouse model of MS.METHODS A total of 144(equal numbers of males and females)5wkold BALB/c mice were randomly divided into five groups:Normal group(n=16),MS group(n=32),MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32).The MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32)were preventively transplanted with UC-MSCs or AS101-treated UC-MSCs(1×106 cells/mouse).Mice in the MS(n=32),MS+MSCs,and MS+AS101/MSCs groups were subjected to rotation on a centrifuge for 10 min at 8×g/min for MS model establishment on days 3,5,8,and 10 after UC-MSCs injection.The Morris water maze(MWM)test was used to observe the symptom of dizziness.Enzyme-linked immunosorbent assay(ELISA)and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)were used to detect the levels of inflammatory cytokines in mice peripheral blood and the petrous part of the temporal bone samples.Western blot analysis was performed to analyze the JAK2/STAT3 signaling pathway in the cochlear tissues.Histological examination was performed by hematoxylin and eosin(HE)staining for conventional morphological evaluation in the petrous part of temporal bone samples.RESULTS The MWM test demonstrated that UC-MSCs improved the symptoms of MS.The MS+MSCs group was faster than the MS group on days 3 and 5(P=0.036 and P=0.002,respectively).ELISA and RT-qPCR showed that the serum and mRNA levels of interleukin-10(IL-10)in the cochlear tissues were increased after transplantation with UC-MSCs(MS+MSCs group vs MS group at 3 and 5 d,P=0.002 and cP<0.001,respectively).RT-qPCR results confirmed a significant increase in IL-10 levels at four time points(MS+MSCs group vs MS group,P=0.009,P=0.009,P=0.048,and P=0.049,respectively).This suggested that UCMSCs reduced the sensitivity of the vestibular microenvironment by secreting IL-10.Moreover,Western blot analysis showed that the MSCs activated the JAK2/STAT3 signaling pathway in the cochlear tissues.The levels of IL-10,IL-10RA,JAK2,STAT3,and phosphorylated JAK2 and STAT3 in the MS+MSCs group were increased compared to those of the MS group(P<0.05).The morphological changes in the four groups showed no significant differences.The role of IL-10 secretion on the ability of UC-MSCs to successfully improve the symptoms of MS was confirmed by the diminished therapeutic effects associated with treatment with the IL-10 inhibitor ammonium trichloro(dioxoethylene-o,o′)tellurate(AS101).CONCLUSION Prophylactic transplantation of UC-MSCs can alleviate the clinical symptoms of MS in mice,particularly at 3-5 d after preventive transplantation.The mechanism for UC-MSCs to reduce the sensitivity of vestibular cortex imbalance may be the secretion of IL-10.The next step is to demonstrate the possibility of curing MS in the vestibular environment by intermittent transplantation of MSCs.Above all,MSCs are expected to become a new method for the clinical prevention and treatment of MS.

Peripartal rumen-protected methionine supplementation to higher energy diets elicits positive effects on blood neutrophil gene networks, performance and liver lipid content in dairy cows

Background： Main objectives were to determine to what extent Smartamine M（SM） supplementation to a prepartal higher-energy diet could alter neutrophil（PMN） and liver tissue immunometabolic biomarkers, and whether those responses were comparable to those in cows fed a prepartal lower-energy diet（CON）.Results： Twenty-eight multiparous Holstein cows were fed CON（NEL= 1.24 Mcal/kg DM） during d-50 to d-22 relative to calving. From d-21 to calving, cows were randomly assigned to a higher-energy diet（OVE, n = 9; NEL= 1.54 Mcal/kg DM）, OVE plus SM（OVE ＋ SM, n = 10; SM = 0.07 % of DM） or remained on CON（n = 9）. Al cows received the same basal lactation diet（NEL= 1.75 Mcal/kg DM）. Supplementation of SM（OVE ＋ SM） continued until 30 d postpartum. Liver biopsies were harvested at d-10, 7, and 21 relative to parturition. Blood PMN isolated at-10, 3, and 21 d relative to calving was used to evaluate gene expression. As expected, OVE increased liver lipid content postpartum; however,cows fed OVE ＋ SM or CON had lower concentrations than OVE. Compared with OVE, cows in CON and OVE ＋ SM had greater DMI postpartum and milk production. Furthermore, cows fed OVE ＋ SM had the greatest milk protein and fat percentage and lowest milk SCC despite having intermediate PMN phagocytic capacity. Adaptations in PMN gene expression in OVE ＋ SM cows associated with the lower SCC were gradual increases from-10 to 21 d in genes that facilitate migration into inflammatory sites（SELL, ITGAM）, enzymes essential for reducing reactive oxygen metabolites（SOD1, SOD2）, and a transcription factor（s） required for controlling PMN development（RXRA）. The greater expression of TLR4 on d 3, key for activation of innate immunity due to inflammation, in OVE compared with CON cows suggests a more pronounced inflammatory state. Feeding OVE ＋ SM dampened the upregulation of TLR4, despite the fact that these cows had similar expression of the pro-inflammatory genes NFKB1 and TNF as OVE. Cows in CON had lower overall expression of these inflammation-related genes and GSR, which generates reduced glutathione, an important cellular antioxidant.Conclusions： Although CON cows appeared to have a less stressful transition into lactation, SM supplementation was effective in alleviating negative effects of energy-overfeeding. As such, SM was beneficial in terms of production and appeared to boost the response of PMN in a way that improved overall cow health.