Genome-wide QTL mapping for stripe rust resistance in spring wheat line PI 660122 using the Wheat 15K SNP array

IntroductionStripe rust is a global disease of wheat. Identification of new resistance genes is key to developing and growing resistant varieties for control of the disease. Wheat line PI 660122 has exhibited a high level of stripe rust resistance for over a decade. However, the genetics of stripe rust resistance in this line has not been studied. A set of 239 recombinant inbred lines (RILs) was developed from a cross between PI 660122 and an elite Chinese cultivar Zhengmai 9023.MethodsThe RIL population was phenotyped for stripe rust response in three field environments and genotyped with the Wheat 15K single-nucleotide polymorphism (SNP) array.ResultsA total of nine quantitative trait loci (QTLs) for stripe rust resistance were mapped to chromosomes 1B (one QTL), 2B (one QTL), 4B (two QTLs), 4D (two QTLs), 6A (one QTL), 6D (one QTL), and 7D (one QTL), of which seven QTLs were stable and designated as QYrPI660122.swust-4BS, QYrPI660122.swust-4BL, QYrPI660122.swust-4DS, QYrPI660122.swust-4DL, QYrZM9023.swust-6AS, QYrZM9023.swust-6DS, and QYrPI660122.swust-7DS. QYrPI660122.swust-4DS was a major all-stage resistance QTL explaining the highest percentage (10.67%–20.97%) of the total phenotypic variation and was mapped to a 12.15-cM interval flanked by SNP markers AX-110046962 and AX-111093894 on chromosome 4DS.DiscussionThe QTL and their linked SNP markers in this study can be used in wheat breeding to improve resistance to stripe rust. In addition, 26 lines were selected based on stripe rust resistance and agronomic traits in the field for further selection and release of new cultivars

Facile discovery of surrogate cytokine agonists

Cytokines are powerful immune modulators that initiate signaling through receptor dimerization, but natural cytokines have structural limitations as therapeutics. We present a strategy to discover cytokine surrogate agonists by using modular ligands that exploit induced proximity and receptor dimer geometry as pharmacological metrics amenable to high-throughput screening. Using VHH and scFv to human interleukin-2/15, type-I interferon, and interleukin-10 receptors, we generated combinatorial matrices of single-chain bispecific ligands that exhibited diverse spectrums of functional activities, including potent inhibition of SARS-CoV-2 by surrogate interferons. Crystal structures of IL-2R:VHH complexes revealed that variation in receptor dimer geometries resulted in functionally diverse signaling outputs. This modular platform enabled engineering of surrogate ligands that compelled assembly of an IL-2R/IL-10R heterodimer, which does not naturally exist, that signaled through pSTAT5 on T and natural killer (NK) cells. This “cytokine med-chem” approach, rooted in principles of induced proximity, is generalizable for discovery of diversified agonists for many ligand-receptor systems

Ppm1b negatively regulates necroptosis through dephosphorylating ​Rip3

该研究论文发现蛋白磷酸酶Ppm1b 通过去磷酸化RIP3负调控程序性细胞坏死（necroptosis），阐明了RIP3磷酸化状态的精确调控对于细胞和机体在生理和病理状态下的存活至关重要。The auto-phosphorylation of murine ​receptor-interacting protein 3 (​Rip3) on Thr 231 and Ser 232 in the necrosome is required to trigger necroptosis. However, how ​Rip3 phosphorylation is regulated is still largely unknown. Here we identified ​protein phosphatase 1B (​Ppm1b) as a ​Rip3 phosphatase and found that ​Ppm1b restricts necroptosis in two settings: spontaneous necroptosis caused by ​Rip3 auto-phosphorylation in resting cells, and ​tumour necrosis factor-α (​TNF)-induced necroptosis in cultured cells. We revealed that ​Ppm1b selectively suppresses necroptosis through the dephosphorylation of ​Rip3, which then prevents the recruitment of ​mixed lineage kinase domain-like protein (​Mlkl) to the necrosome. We further showed that ​Ppm1b deficiency (​Ppm1bd/d) in mice enhanced ​TNF-induced death in a ​Rip3-dependent manner, and the role of ​Ppm1b in inhibiting necroptosis was evidenced by elevated ​Rip3 phosphorylation and tissue damage in the caecum of ​TNF-treated ​Ppm1bd/d mice. These data indicate that ​Ppm1b negatively regulates necroptosis through dephosphorylating ​Rip3 in vitro and in vivo

Extracellular vesicles in chronic kidney disease: diagnostic and therapeutic roles

Chronic kidney disease (CKD) is a progressive disorder characterized by structural and functional changes in the kidneys, providing a global health challenge with significant impacts on mortality rates. Extracellular vesicles (EVs), are vital in the physiological and pathological processes associated with CKD. They have been shown to modulate key pathways involved in renal injury, including inflammation, fibrosis, apoptosis, and oxidative stress. Currently, the application research of EVs in the diagnosis and treatment of CKD is highly prevalent. However, there is currently a lack of standardized guidelines for their application, and various methodologies have advantages and limitations. Consequently, we present an comprehensive summary elucidating the multifaceted involvement of EVs in both physiological and pathological aspects in CKD. Furthermore, we explore their potential as biomarkers and diverse therapeutic roles in CKD. This review provides an overview of the current state of research on application of EVs in the diagnosis and therapeutic management of CKD

Numerical Simulation of the Picking Process of Supernormal Jujube Branches

This paper elaborates on a digital simulation study on supernormal particle flow used to investigate and analyze the process of picking up jujube branches, which was a meaningful attempt to search for accurate and effective advanced numerical analogy methods in the agricultural field. In this paper, the meshless technology based on the element-free Galerkin method was used for the first time to present the effects of particle size, particle number and particle acting force on the movement of irregular particles, and the influence of the gear rotation speed, the feeding amount, and the jujube branch size on the movement behavior as well as the picking rate. It can describe not only the particles’ dynamic movement in the process of picking up jujube twigs, such as feeding, collision, throwing and rolling, but also the effect of the quality and shape caused by the particle size, which in turn affects the surface force of particles and interparticle acting force, thereby affecting the weight function in the analytical solution, the total feeding amount and the effect of the acting force resulting from the particles’ contact, roll and collision caused by gear rotation. The findings reveal that the digital simulation, based on the meshless Galerkin technology and Rocky software, is effective in dealing with issues related to supernormal particle flow. By eliminating the influence of geometric shapes on calculations, the method boasts an effective solution to the movement problems of irregularly shaped particles, which would be further applied in the agriculture field