We consider the renormalization-group evolution of the matrix element of 〈0|q¯(z)βz,0b(0)α|B¯〉, which can be used to define the distribution amplitudes for B meson and widely applied in studies of B ...meson decays. The contribution to the renormalization constant of the non-local operator q¯(z)βz,0b(0)α is considered up to one-loop order in QCD. Since the quark fields in this operator are not directly coupled fields, momentum can not flow freely through this non-local operator. Momentum involved in this operator can be treated stringently in coordinate space. We find that the ultraviolet divergences regulated by dimensional parameter ϵ cancel with each other, and the evolution effect vanishes. The matrix element 〈0|q¯(z)βz,0b(0)α|B¯〉 escapes from the renormalization-group evolution. We then apply the matrix element in calculating B→π transition form factor, where the matrix element is obtained by using the B meson wave function calculated in QCD-inspired potential model. By comparing with experimental data for the semileptonic decay of B→πℓν and light-cone sum rule calculation, we analyze the perturbative and non-perturbative contributions to B→π transition form factor in the frame work of perturbative QCD approach. We find that the effectiveness of the suppression of Sudakov factor to soft contribution depends on the end-point behavior of B meson wave function, and with the B-meson wave function used in this work, soft contribution can not be well suppressed. The hard contribution to the B→π transition form factor is about 59%, and soft contribution can be as large as 41% in the naive calculation. To make the perturbative calculation reliable, a soft momentum cutoff in the calculation and soft form factor have to be introduced.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Selective introduction of fluorine into molecules by the cleavage of inert C−H bonds is of central academic and synthetic interest, yet remains challenging. Given the central role of alcohols in ...organic chemistry as the most ubiquitous building blocks, a versatile and selective C(sp3)−H and C(sp2)−H fluorination of simple alcohols, enabled by novel designed exo‐directing groups, is described. C(sp2)−H bond fluorination was achieved by using a simple acetone oxime as auxiliary, whereas a new, modular and easily accessible bidentate auxiliary was developed for the efficient and site‐selective fluorination of various primary methyl, methylene, and benzylic C(sp3)−H bonds. Fluorinated alcohols can readily be accessed by the removal of auxiliaries, and significantly expands the synthetic prospect of the present procedure.
A versatile and selective C(sp3)−H and C(sp2)−H fluorination of simple alcohols, enabled by an exo‐directing group (DG) is described. C(sp2)−H bond fluorination was achieved by using simple acetone oxime as an auxiliary, whereas a new and modularly accessible bidentate auxiliary was developed for the efficient and site‐selective fluorination of C(sp3)−H bonds. The auxiliary is removable and demonstrates broad substrate scope and excellent selectivity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A microstructure‐based homogenization model is proposed for simulating the cyclic plasticity and predicting the low‐cycle fatigue (LCF) crack initiation life of GH4169 superalloy. Classical crystal ...plastic model (CPM) with a simple softening model is used at the grain level. Then, the transition from grain level to polycrystal level is based on the conservation of virtual work between the two levels. The Eshelby's formulation is applied in the model. Especially, local influences of grain interactions are considered by introducing the external Eshelby's tensor. Relatively precise macroresults and microresults as the finite element method can be provided by the present model with less computational cost. Grain volume averaged fatigue indicator parameters (FIPs) with considering the effect of inclusions are formed to predict the LCF crack initiation life, and a fold‐line fitting model is proposed to substitute for the cycle‐by‐cycle simulation. Predicted lives fit well with the experimental data for both the strain loading and stress loading simulations. Scatter of the life can also be predicted by the model and overwhelming influences of the incubation stage on the variability of LCF initiation life can be captured. It is shown that the inclusions and the inhomogeneous plastic strain are responsible for the scatter of the incubation stage.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Background
This study was designed to verify whether enhancer of zeste homolog 2 (EZH2) affects intervertebral disc degeneration (IVDD) development through regulation of microRNA (miR)‐129‐5p/MAPK1.
...Methods
Initially, we collected lumbar nucleus pulposus (NP) tissue samples from patients with juvenile idiopathic scoliosis (n = 14) and IVDD (n = 34). We measured the expression of related genes in clinical IVDD tissues and a lipopolysaccharide (LPS)‐induced NP cell model. After loss‐ and gain‐of‐function assays, NP cell proliferation and senescence were examined. The targeting relationship between miR‐129‐5p and MAPK1 was explored by dual luciferase reporter gene and RNA immunoprecipitation (RIP) assays. The enrichment of EZH2 and H3K27me3 in miR‐129‐5p promoter was verified by chromatin immunoprecipitation (ChIP). Finally, an IVDD rat model was established to test the effects of transduction with lentiviral vector carrying miR‐129‐5p agomir and/or oe‐EZH2 in vivo.
Results
miR‐129‐5p was underexpressed, and EZH2 and MAPK1 levels were overexpressed in lumbar nucleus pulposus from human IVDD patients and in LPS‐induced NP cells. miR‐129‐5p overexpression or silencing of MAPK1 promoted proliferation of NP cells, while inhibiting their senescence. EZH2 inhibited miR‐129‐5p through H3K27me3 modification in the miR‐129‐5p promoter. miR‐129‐5p could target the downregulation of MAPK1 expression. EZH2 overexpression increased the release of inflammatory factors and cell senescence factors, which was reversed by miR‐129‐5p agomir in vivo.
Conclusions
Taken together, EZH2 inhibits miR‐129‐5p through H3K27me3 modification, which upregulates MAPK1, thereby promoting the development of IVDD.
EZH2 can inhibit the transcription of miR‐129‐5p through epigenetic regulation of H3K27me3 modification in the miR‐129‐5p promoter, which upregulates the expression of MAPK1, inhibits the proliferation of NP cells, and promotes their senescence to promote IVDD development.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The pancreatic islet contains multiple hormone
endocrine lineages (α, β, δ, PP and ε cells), but the developmental processes that underlie endocrinogenesis are poorly understood. Here, we generated ...novel mouse lines and combined them with various genetic tools to enrich all types of hormone
cells for well-based deep single-cell RNA sequencing (scRNA-seq), and gene coexpression networks were extracted from the generated data for the optimization of high-throughput droplet-based scRNA-seq analyses. These analyses defined an entire endocrinogenesis pathway in which different states of endocrine progenitor (EP) cells sequentially differentiate into specific endocrine lineages in mice. Subpopulations of the EP cells at the final stage (EP4
and EP4
) show different potentials for distinct endocrine lineages. ε cells and an intermediate cell population were identified as distinct progenitors that independently generate both α and PP cells. Single-cell analyses were also performed to delineate the human pancreatic endocrinogenesis process. Although the developmental trajectory of pancreatic lineages is generally conserved between humans and mice, clear interspecies differences, including differences in the proportions of cell types and the regulatory networks associated with the differentiation of specific lineages, have been detected. Our findings support a model in which sequential transient progenitor cell states determine the differentiation of multiple cell lineages and provide a blueprint for directing the generation of pancreatic islets in vitro.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The activation of mixed lineage kinase-like (MLKL) by receptor-interacting protein kinase-3 (RIPK3) results in plasma membrane (PM) disruption and a form of regulated necrosis, called necroptosis. ...Here, we show that, during necroptosis, MLKL-dependent calcium (Ca2+) influx and phosphatidylserine (PS) exposure on the outer leaflet of the plasma membrane preceded loss of PM integrity. Activation of MLKL results in the generation of broken, PM “bubbles” with exposed PS that are released from the surface of the otherwise intact cell. The ESCRT-III machinery is required for formation of these bubbles and acts to sustain survival of the cell when MLKL activation is limited or reversed. Under conditions of necroptotic cell death, ESCRT-III controls the duration of plasma membrane integrity. As a consequence of the action of ESCRT-III, cells undergoing necroptosis can express chemokines and other regulatory molecules and promote antigenic cross-priming of CD8+ T cells.
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•Phosphatidylserine is exposed prior to loss of cell integrity during necroptosis•ESCRT-III facilitates the shedding of MLKL-damaged plasma membrane from intact cells•ESCRT-III supports cell survival and functions downstream of active MLKL•ESCRT-III allows necroptotic cells to signal surrounding cells
Cells undergoing necroptosis are not always headed towards death; ESCRT-III helps preserve the plasma membrane in these cells, contributing to survival.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Water is essential for the formation of granites, but its origin and role in granite generation (i.e., dehydration vs. water‐fluxed melting) remain uncertain. These issues are addressed by combining ...water abundances and other geochemical indices in zircons from Late Mesozoic granites generated during the destruction of the North China Craton (NCC). The water contents in zircons from the NCC Early Cretaceous granites (763 ppm, median) are much higher than those of the NCC Jurassic granites (424–513 ppm), upper mantle and continental arc magmas (92–477 ppm). More importantly, the higher water contents in the voluminous Early Cretaceous granites also have higher zircon saturation temperatures, εHf(t), and lower δ18O values. These observations suggest a predominantly mantle origin for the water, and water‐fluxed crustal melting, in which larger water ingression produced more voluminous melts. The high‐water flux was likely related to the subduction of the Paleo‐Pacific Plate, which ultimately destabilized the NCC.
Plain Language Summary
The fact that water is essential in generating granites has been known for a long time. However, its detailed role is poorly understood due to heterogeneous source and complex melting reactions involved in the generation of granites. As a fundamental issue of granite genesis, it remains a long‐standing problem to distinguish the two major mechanisms, that is, hydrous‐mineral‐dehydration melting versus external‐water‐added melting. In this study, the water content of zircon combined with other lines of clues of I‐type granites that generated during the destruction of North China Craton (NCC) in Late Mesozoic collectively points to water‐added crustal melting rather than dehydration melting. The isotope composition of zircon suggests a mantle provenance of water. The highest water contents occurred in the Early Cretaceous granites, corresponding to the climax of the NCC destruction. Higher zircon water contents in Early Cretaceous granites indicate higher water‐flux into thelithospheric mantle and overlying crust by the subduction of the paleo‐Pacific plate. Accordingly, water played a significant role in cratonic destruction.
Key Points
Water contents of zircons from North China Craton Jurassic granites are comparable with continental arc magmas
Higher zircon water contents are found in voluminous Early Cretaceous granites generated during the climax of cratonic destruction
Early Cretaceous granites were generated by water‐fluxed crustal melting, the water in which has a predominant mantle origin
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
In this paper, a collocation method with mixed degrees of freedom (DOFs) is proposed for heterogeneous structures. Local tractions of the outer and interface boundaries are introduced as DOFs ...in the mixed collocation scheme. Then, the equilibrium equations of all the nodes and the outer boundary conditions are discretized and assembled into the global stiffness matrix. A local force equilibrium equation for modeling the stress discontinuity through the interface is developed and added into the global stiffness matrix as well. With those contributions, a statically determined stiffness matrix is obtained. Numerical examples show that the present method is superior to the classical mixed collocation method in the heterogeneous structure because it improves the accuracy and the convergence and remains the efficiency. Besides, almost constant convergence rates of displacements and stresses are found in all the examples, even for three‐dimensional problems.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In respiratory diseases, there is an increased expression of multiple inflammatory proteins in the respiratory tract, including cytokines, chemokines, and adhesion molecules. Chemokines have been ...shown to regulate inflammation and immune cell differentiation. Moreover, many of the known inflammatory target proteins, such as matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A2 (cPLA2), are associated with airway and lung inflammation in response to various stimuli. Injuriously environmental stimuli can access the lung through either the airways or the pulmonary and systemic circulations. The time course and intensity of responses by resident and circulating cells may be regulated by various inflammatory signalings, including Src family kinases (SFKs), protein kinase C (PKC), growth factor tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species (ROS), PI3K/Akt, MAPKs, nuclear factor-kappa B (NF-κB), activator protein-1 (AP-1), and other signaling molecules. These signaling molecules regulate both key inflammatory signaling transduction pathways and target proteins involved in airway and lung inflammation. Here, we discuss the mechanisms involved in the expression of inflammatory target proteins associated with the respiratory diseases. Knowledge of the mechanisms of inflammation regulation could lead to the pharmacological manipulation of anti-inflammatory drugs in the respiratory diseases.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Elevated glucose metabolism in immune cells represents a hallmark feature of many inflammatory diseases, such as sepsis. However, the role of individual glucose metabolic pathways during immune cell ...activation and inflammation remains incompletely understood. Here, we demonstrate a previously unrecognized anti-inflammatory function of the O-linked β-N-acetylglucosamine (O-GlcNAc) signaling associated with the hexosamine biosynthesis pathway (HBP). Despite elevated activities of glycolysis and the pentose phosphate pathway, activation of macrophages with lipopolysaccharide (LPS) resulted in attenuated HBP activity and protein O-GlcNAcylation. Deletion of O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, led to enhanced innate immune activation and exacerbated septic inflammation. Mechanistically, OGT-mediated O-GlcNAcylation of the serine-threonine kinase RIPK3 on threonine 467 (T467) prevented RIPK3-RIPK1 hetero- and RIPK3-RIPK3 homo-interaction and inhibited downstream innate immunity and necroptosis signaling. Thus, our study identifies an immuno-metabolic crosstalk essential for fine-tuning innate immune cell activation and highlights the importance of glucose metabolism in septic inflammation.
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•LPS treatment causes a decrease in HBP activity and protein O-GlcNAcylation•OGT deficiency increases activation of innate immune response and necroptosis•O-GlcNAcylation of RIPK3 on T467 inhibits RIPK3-RIPK1 and RIPK3-RIPK3 interaction
The role of individual glucose metabolic pathways in innate immunity remains largely unknown. Li et al. demonstrate that attenuated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling enhances TLR-induced innate immune response and necroptosis. Mechanistically, O-GlcNAcylation of the kinase RIPK3 blocks RHIM-domain-mediated protein interaction and downstream signaling activation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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