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Graph convolutional network (GCN) outputs powerful representation by considering the structure information of the data to conduct representation learning, but its robustness is sensitive to the quality of both the feature matrix and the initial graph. In this article, we propose a novel multigraph fusion method to produce a high-quality graph and a low-dimensional space of original high-dimensional data for the GCN model. Specifically, the proposed method first extracts the common information and the complementary information among multiple local graphs to obtain a unified local graph, which is then fused with the global graph of the data to obtain the initial graph for the GCN model. As a result, the proposed method conducts the graph fusion process twice to simultaneously learn the low-dimensional space and the intrinsic graph structure of the data in a unified framework. Experimental results on real datasets demonstrated that our method outperformed the comparison methods in terms of classification tasks.

Endophytes can benefit the growth and stress resistance of host plants by secreting bioactive components. Thiamine is an essential vitamin involved in many metabolic pathways and can only be synthesized by microbes and plants. In this study, we found that thiamine could inhibit the development of the phytopathogen Magnaporthe oryzaeand decrease the rice blast index under field conditions. In the thiamine biosynthesis pathway, the key enzyme ShTHIC of an endophyte Streptomyces hygroscopicusOsiSh-2 and OsTHIC of rice (Oryza sativa) were highly homologous. Gene overexpression or knockout approaches revealed that both THIC contributed to thiamine synthesis and resistance to M. oryzae. Furthermore, S. hygroscopicusOsiSh-2 colonization led to a decrease in the thiamine synthesis level of rice but still maintained thiamine homeostasis in rice. However, inoculation with the ShTHIC knockout strain ΔTHICreduced the thiamine content in rice, although the thiamine synthesis level of rice was increased. After infection with M. oryzae, blast resistance was dramatically improved in OsiSh-2-inoculated rice but decreased in ΔTHIC-inoculated rice compared with non-inoculated rice. This result demonstrated that ShTHICcould regulate thiamine biosynthesis and consequently assist blast resistance in the OsiSh-2-rice symbiont. Our results revealed a novel blast-resistance mechanism mediated by a key thiamine biosynthetic enzyme from an endophyte OsiSh-2.

Graphic abstract:

Unsupervised feature selection (UFS) is a popular technique of reducing the dimensions of high-dimensional data. Previous UFS methods were often designed with the assumption that the whole information in the data set is observed. However, incomplete data sets that contain unobserved information can be often found in real applications, especially in industry. Thus, these existing UFS methods have a limitation on conducting feature selection on incomplete data. On the other hand, most existing UFS methods did not consider the sample importance for feature selection, i.e., different samples have various importance. As a result, the constructed UFS models easily suffer from the influence of outliers. This article investigates a new UFS method for conducting UFS on incomplete data sets to investigate the abovementioned issues. Specifically, the proposed method deals with unobserved information by using an indicator matrix to filter it out the process of feature selection and reduces the influence of outliers by employing the half-quadratic minimization technique to automatically assigning outliers with small or even zero weights and important samples with large weights. This article further designs an alternative optimization strategy to optimize the proposed objective function as well as theoretically and experimentally prove the convergence of the proposed optimization strategy. Experimental results on both real and synthetic incomplete data sets verified the effectiveness of the proposed method compared with previous methods, in terms of clustering performance on the low-dimensional space of the high-dimensional data.

Injuries to the skin are common in daily life, and a certain type or size of defect is not easily restored using conventional dressings or naturally. The repair of these defects requires restoration of function in regenerated tissues. In this study, a tissue engineered skin was designed and fabricated using a bio-3D printing system. Polycaprolactone and bacterial cellulose comprised the scaffold, due to their excellent biocompatibility and multifunctionality. Adipose-derived mesenchymal stem cells (Ad-MSCs) were seeded onto the scaffold to functionalize it as an artificial skin. The finished artificial skin had mechanical properties similar to that of natural skin, and its fibrous structure providing a unique micro-environment that could regulate the paracrine function of the Ad-MSCs. This effect could be greatly increased by changes in the characteristics of the biomaterials. The artificial skin exhibited high biological activity, strong induction of cell recruitment, migration, growth and up-regulation of gene expression of relevant factors, resulting in excellent wound healing characteristics. This study clarified novel design aspects of cell-material interactions in which the topographical characteristics of materials can be further developed to establish cell signaling or communication networks that take advantage of the paracrine actions of Ad-MSCs to promote specific tissue regeneration or repair characteristics.

CM-101 is a new peptide-based probe using the highly stable gadoterate meglumine chelate that is rapidly eliminated from plasma into urine, shows minimal accumulation of gadolinium in bone, and robustly depicted liver fibrosis in bile duct–ligated rat and CCl4mouse models.

GPR40 and GPR120 are fatty acid sensors that play important roles in glucose and energy homeostasis. GPR40 potentiates glucose-dependent insulin secretion and demonstrated in clinical studies robust glucose lowering in type 2 diabetes. GPR120 improves insulin sensitivity in rodents, albeit its mechanism of action is not fully understood. Here, we postulated that the antidiabetic efficacy of GPR40 could be enhanced by coactivating GPR120. A combination of GPR40 and GPR120 agonists in db/dbmice, as well as a single molecule with dual agonist activities, achieved superior glycemic control compared with either monotherapy. Compared with a GPR40 selective agonist, the dual agonist improved insulin sensitivity in ob/obmice measured by hyperinsulinemic-euglycemic clamp, preserved islet morphology, and increased expression of several key lipolytic genes in adipose tissue of Zucker diabetic fatty rats. Novel insights into the mechanism of action for GPR120 were obtained. Selective GPR120 activation suppressed lipolysis in primary white adipocytes, although this effect was attenuated in adipocytes from obese rats and obese rhesus, and sensitized the antilipolytic effect of insulin in rat and rhesus primary adipocytes. In conclusion, GPR120 agonism enhances insulin action in adipose tissue and yields a synergistic efficacy when combined with GPR40 agonism.

In lower organisms, NADP(H)‐dependent glutamate dehydrogenases (GDHs) have high affinities to ammonium and play important roles in nitrogen assimilation. Glutamate dehydrogenases in higher plants have lower affinities for ammonium so their nitrogen is mainly assimilated as ammonium by the glutamine synthetase (GS)/glutamate synthase (GOGAT) pathway. In present study, an NADP(H)‐dependent glutamate dehydrogenase gene (CeGDH) was cloned from the fungus Cylindrocarpon ehrenbergii(Ce) and ectopically expressed in rice (Oryza sativaL. ‘Kitaake’). Meanwhile, the enzyme activity of CeGDH was detected and the effects of CeGDH in transgenic rice were analyzed. The determination of enzymatic activity in vitro showed that CeGDH's aminating activity is higher than its deaminating activity, which was also confirmed by the results of enzymatic activity in vivo in CeGDHtransgenic rice. These results suggested that the CeGDH is inclined to convert 2‐Oxoglutarate to glutamate. Additionally, the nitrogen assimilation ability and grain yield were analyzed in CeGDHtransgenic plants. The hydroponic experiments revealed that the shoot and root lengths and nitrogen contents were improved obviously in transgenic plants compared with the wild‐type under low‐nitrogen conditions at seedling stage. In field conditions, the agronomic traits analysis showed that panicle numbers and grain yields of the transgenic plants also increased significantly under low‐nitrogen conditions. These results demonstrated that the introduction of CeGDHinto rice could enhance nitrogen utilization, improve growth, and increase grain yields, especially in low nitrogen fertility.

The influence of the dynamic Stark effect on the dissociation of CsI is theoretically studied by the time-dependent wave-packet method. After a pump pulse induces a dissociating wave packet that propagates through both the ionic channel X0+(Cs+(1S0) + I+(1S0)) and the covalent channel A0+(Cs(2S1/2) + I(2P3/2)), a Stark pulse is applied to control the diabatic-dissociation dynamics. The first-order non-resonant non-perturbative dynamic Stark effect gives control over the break up, the dissociation probabilities in the two channels being controlled by the delay between the pump and Stark pulses. With a 720-fs delay, the dissociation probability through channel Ais greatly enhanced.

There has been concern for the crash safety of one kind of minibus in China because of its short, flat front-end structure. The minibus did not have enough crushable space for a frontal impact, and it had, in fact, failed to pass the Chinese vehicle safety regulations in frontal impact tests. This paper presents a method to improve the crashworthiness and occupant safety of this minibus. The design method, consisting of component tests and finite element analysis, focused both on the crashworthiness of the vehicle structure and occupant safety. An optimised design was obtained. The improved structural design has been implemented for the minibus. The time and cost of the redesign has been lowered substantially with the help of component tests and finite element analyses. We have shown that these procedures were effective for improving the crash safety of this minibus for the Chinese market.

Neuroglobin is a newly identified vertebrate globin that binds O2 and is expressed in cerebral neurons. We found recently that neuronal expression of neuroglobin is stimulated by hypoxia and ischemia and protects neurons from hypoxic injury. Here we report that, like hemoglobin and myoglobin, neuroglobin expression can also be induced by hemin. Induction was concentration dependent and time dependent, with maximal (about 4-fold) increases in neuroglobin mRNA and protein levels occurring with 50 μM hemin and at 8 to 24 hours. The inductive effect of hemin was attenuated by the protein kinase G inhibitor KT5823 and the soluble guanylate cyclase inhibitor LY83583, was mimicked by treatment with 8-bromo–cyclic guanosine 3′,5′-monophosphate, and was accompanied by a greater than 10-fold increase in cGMP levels, suggesting that it is mediated through protein kinase G and soluble guanylate cyclase. In contrast, hypoxic induction of neuroglobin was blocked by the mitogen-activated protein kinase/extracellular signal–regulated kinase kinase inhibitor PD98059, indicating that hemin and hypoxia regulate neuroglobin expression by different mechanisms. These results provide evidence for regulation of neuroglobin expression by at least 2 signal transduction pathways.

Neuroglobin is a newly identified vertebrate globin that binds O2and is expressed in cerebral neurons. We found recently that neuronal expression of neuroglobin is stimulated by hypoxia and ischemia and protects neurons from hypoxic injury. Here we report that, like hemoglobin and myoglobin, neuroglobin expression can also be induced by hemin. Induction was concentration dependent and time dependent, with maximal (about 4-fold) increases in neuroglobin mRNA and protein levels occurring with 50 μM hemin and at 8 to 24 hours. The inductive effect of hemin was attenuated by the protein kinase G inhibitor KT5823 and the soluble guanylate cyclase inhibitor LY83583, was mimicked by treatment with 8-bromo–cyclic guanosine 3′,5′-monophosphate, and was accompanied by a greater than 10-fold increase in cGMP levels, suggesting that it is mediated through protein kinase G and soluble guanylate cyclase. In contrast, hypoxic induction of neuroglobin was blocked by the mitogen-activated protein kinase/extracellular signal–regulated kinase kinase inhibitor PD98059, indicating that hemin and hypoxia regulate neuroglobin expression by different mechanisms. These results provide evidence for regulation of neuroglobin expression by at least 2 signal transduction pathways.

The multifunctional tumor suppressor protein, p53, inhibits cell growth and promotes differentiation and programmed cell death. p53 activity is controlled by transcriptional, translational, and post-translational regulation. A major pathway for post-translational regulation of p53 comprises its nucleocytoplasmic transport and subsequent proteasomal degradation, which involves binding to the oncoprotein, murine double minute-2 (Mdm2). Hypoxia and other stress signals cause cellular injury partly through the action of p53. In this study, we show that hypoxia induces down-regulation of Mdm2 as well as serine 15 phosphorylation and nuclear accumulation of p53 in cultured cortical neurons from E16 mice. These effects are diminished by the p38 mitogen-activated protein kinase inhibitors SB203580 and SB202190, but not by the inactive analog SB202474, and by a dominant-interfering mutant of the p38-activating kinase mitogen-activated protein kinase kinase 3 (MKK3). Hypoxic neuronal death was also reduced by p38 inhibitors, by dominant-interfering MKK3, and by a p53-antisense oligodeoxynucleotide and was increased by a constitutively active form of p38 and by an Mdm2-antisense oligodeoxynucleotide. These results demonstrate that p38 and Mdm2 have roles in coupling hypoxic-ischemic neuronal insults to activation of p53 and hypoxic cell death.

Under disease stress, activation of defense response in plants often comes with the cost of a reduction in growth and yield, which is referred as the growth-defense trade-off. The microorganisms which can be recruited by plants to mitigate the growth-defense trade-off are of great value in crop breeding.

Heme is central to oxygen sensing and utilization in all living organisms. It directly regulates numerous molecular and cellular processes for systems that sense or use oxygen. In mammals, heme plays an indispensable role in erythroid cell differentiation. To investigate heme regulatory functions, we identified, by differential display, and confirmed, by quantitative RT-PCR and Northern blotting analysis, the genes whose expression is altered by heme during the early stage of K562 cell differentiation. These include genes encoding a GAP-associated p62 protein, histone H2A.Z, a subunit of the small nuclear ribonucleoprotein complex, and the chaperonin Tcp20, and a cellular immediate-early-response gene. The results suggest that heme initiates changes in key factors that control a wide array of processes ranging from cell cycle and Ras signaling to chromatin structure, splicing and protein folding. These key factors might act together to mediate heme action, which is critical for erythroid cell differentiation.

Drought and salinity are major environmental stresses that impair crop growth and productivity worldwide. Improving drought and salt tolerance of crops with microbial mutualists is an effective and environmentally sound strategy to meet the demands of the ever-growing world population. In the present study, we found that the Streptomyces albidoflavusOsiLf-2, a moderately salt-tolerant endophytic actinomycete, produced abundant osmolytes, including proline, polysaccharides, and ectoine. Inoculation with OsiLf-2 increased the osmotic-adjustment ability of the rice host by increasing the proline content (by 250.3% and 49.4%) and soluble sugar (by 20.9% and 49.4%) in rice under drought and salt conditions, relative to the uninoculated control. OsiLf-2 increased stress responses in the rice host at the physiological and biochemical levels (photosynthesis efficiency, osmolytes and antioxidant content), and the gene level (osmolytes synthesis, stress-responsive and ion-transport related genes), raising rice yields under both greenhouse and saline–alkaline soil conditions. The use of endophytic actinomycetes offers a promising biotechnological approach to developing stress-tolerant plants.

Fibrosis, or the accumulation of extracellular matrix, is a common feature of many chronic diseases. To interrogate core molecular pathways underlying fibrosis, we cross-examine human primary cells from various tissues treated with TGF-β, as well as kidney and liver fibrosis models. Transcriptome analyses reveal that genes involved in fatty acid oxidation are significantly perturbed. Furthermore, mitochondrial dysfunction and acylcarnitine accumulation are found in fibrotic tissues. Substantial downregulation of the PGC1α gene is evident in both in vitroand in vivofibrosis models, suggesting a common node of metabolic signature for tissue fibrosis. In order to identify suppressors of fibrosis, we carry out a compound library phenotypic screen and identify AMPK and PPAR as highly enriched targets. We further show that pharmacological treatment of MK-8722 (AMPK activator) and MK-4074 (ACC inhibitor) reduce fibrosis in vivo. Altogether, our work demonstrate that metabolic defect is integral to TGF-β signaling and fibrosis.