Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility

Bacterial or viral infections,such as Brucella,mumps virus,herpes simplex virus,and Zika virus,destroy immune homeostasis of the testes,leading to spermatogenesis disorder and infertility.Of note,recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells,leading to male reproductive dysfunction.Due to the many side effects associated with antibiotic therapy,finding alternative treatments for inflammatory injury remains critical.Here,we found that Dmrt1 plays an important role in regulating testicular immune homeostasis.Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells.Chromatin immunoprecipitation sequencing(ChIP-seq)and RNA sequencing(RNA-seq)revealed that Dmrt1 positively regulated the expression of Spry1,an inhibitory protein of the receptor tyrosine kinase(RTK)signaling pathway.Furthermore,immunoprecipitation-mass spectrometry(IP-MS)and co-immunoprecipitation(Co-IP)analysis indicated that SPRY1 binds to nuclear factor kappa B1(NF-κB1)to prevent nuclear translocation of p65,inhibit activation of NF-κB signaling,prevent excessive inflammatory reaction in the testis,and protect the integrity of the blood-testis barrier.In view of this newly identified Dmrt1-Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis,our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

基于灰色关联度与TOPSIS模型分析不同配伍比例的知母对石膏中6种无机元素溶出的影响

目的基于灰色关联度和逼近理想解排序(TOPSIS)法探讨配伍不同比例的知母对石膏中钾(K)、钛(Ti)、锶(Sr)、钡(Ba)、钙(Ca)、镁(Mg)6种无机元素溶出的影响,为临床提供一定参考。方法建立电感耦合等离子体质谱(ICP-MS)法同时分析石膏-知母药对中K、Ti、Sr、Ba、Ca、Mg 6种无机元素含量,并用灰色关联度法和TOPSIS综合分析,与不同比例知母配伍前后,石膏中6种无机元素溶出的变化。结果ICP-MS法测定石膏-知母药对中无机元素的线性、精密度、重复性和稳定性试验结果良好,平均加样回收率为81.78%~104.13%,RSD为2.10%~4.62%(n=6)。与不同比例知母配伍后石膏中6种无机元素的溶出均显著高于石膏单煎(P<0.05),石膏-知母30∶9配伍比例时石膏中6种无机元素溶出得分最高。结论ICP-MS法灵敏度高、准确性好,可用于石膏-知母药对中K、Ti、Sr、Ba、Ca、Mg等6种无机元素的溶出量测定。石膏-知母最佳配伍比例为30∶9时,可有效提高石膏中6种无机元素的溶出,为两者进一步的配伍研究提供依据。

An anisotropic micromechanics model for predicting the rafting direction in Ni-based single crystal superalloys

An anisotropic micromechanics model based on the equivalent inclusion method is developed to investigate the rafting direction of Ni-based single crystal superalloys. The micromechanical model considers actual cubic structure and orthogonal anisotropy properties. The von Mises stress, elastic strain energy density, and hydrostatic pressure in dif- ferent inclusions of micromechanical model are calculated when applying a tensile or compressive loading along the [001] direction. The calculated results can successfully pre- dict the rafting direction for alloys exhibiting a positive or a negative mismatch, which are in agreement with pervious experimental and theoretical studies. Moreover, the elastic constant differences and mismatch degree of the matrix and precipitate phases and their influences on the rafting direction are carefully discussed.

Molecular Dynamics Simulation of the Evolution of Interfacial Dislocation Network and Stress Distribution of a Ni-Based SingleCrystal Superalloy

The evolution of misfit dislocation network at γ/γ＇ phase interfaces and the stress distribution characteristics of Ni-based single-crystal superalloys under different temperatures of 0, 100 and 300 K are studied by molecular dynamics （MD） simulation. It was found that a closed three-dimensional misfit dislocation network appears on the γ/γ＇ phase interfaces, and the shape of the dislocation network is independent of the lattice mismatch. Under the influence of the temperature, the dislocation network gradually becomes irregular, a/2 [110] dislocations in the γ matrix phase emit and partly cut into the γ＇ phase with the increase in temperature. The dislocation evolution is related to the local stress field, a peak stress occurs at γ/γ＇ phase interface, and with the increase in temperature and relaxation times, the stress in the γ phase gradually increases, the number of dislocations in the γ phase increases and cuts into γ＇ phase from the interfaces where dislocation network is damaged. The results provide important information for understanding the temperature dependence of the dislocation evolution and mechanical properties of Ni-based single-crystal superalloys.

Orientation-Dependent Morphology and Evolution of Interfacial Dislocation Networks in Ni-Based Single-Crystal Superalloys:A Molecular Dynamics Simulation

In this paper,the morphology and evolution of interfacial dislocation networks of(100),(110)and(111)interphases of Ni-based single-crystal superalloys are studied by molecular dynamics(MD)simulations.Three-dimensional cubic-type and sandwich-type models are chosen to explore the orientation-dependent morphology of dislocation networks,and their respective advantages and disadvantages are compared.From the simulations,it is observed that various lattice orientations and model types lead to different morphologies of dislocation networks.Based on the analysis of average atomic energy and dislocation characteristics,the(100)orientation model has a more regular dislocation network,lower energy and better stability than the(110)and(111)orientation models after MD relaxation,which are supported by previous experimental and numerical simulations.Moreover,the cubic-type model has lower energy and better stability than the sandwich-type model.This will be helpful for choosing a more appropriate and reasonable model for simulating the interfacial dislocation networks of Ni-based single-crystal superalloys.