Bamboo-eating giant panda (Ailuropoda melanoleuca) is an enigmatic species, which possesses a carnivore-like short and simple gastrointestinal tract (GIT). Despite the remarkable studies on giant panda, its diet adaptability status continues to be a matter of debate. To resolve this puzzle, we investigated the functional potential of the giant panda gut microbiome using shotgun metagenomic sequencing of fecal samples. We also compared our data with similar data from other animal species representing herbivores, carnivores, and omnivores from current and earlier studies. We found that the giant panda hosts a bear-like gut microbiota distinct from those of herbivores indicated by the metabolic potential of the microbiome in the gut of giant pandas and other mammals. Furthermore, the relative abundance of genes involved in cellulose- and hemicellulose-digestion, and enrichment of enzymes associated with pathways of amino acid degradation and biosynthetic reactions in giant pandas echoed a carnivore-like microbiome. Most significantly, the enzyme assay of the giant panda's feces indicated the lowest cellulase and xylanase activity among major herbivores, shown by an in-vitro experimental assay of enzyme activity for cellulose and hemicellulose-degradation. All of our results consistently indicate that the giant panda is not specialized to digest cellulose and hemicellulose from its bamboo diet, making the giant panda a good mammalian model to study the unusual link between the gut microbiome and diet. The increased food intake of the giant pandas might be a strategy to compensate for the gut microbiome functions, highlighting a strong need of conservation of the native bamboo forest both in high- and low-altitude ranges to meet the great demand of bamboo diet of giant pandas.

Based on the critical plane approach, a simple and efficient multiaxial fatigue damage parameter with no additional material constants is proposed for life prediction under uniaxial/multiaxial proportional and/or non-proportional loadings for titanium alloy TC4 and nickel-based superalloy GH4169. Moreover, two modified Ince-Glinka fatigue damage parameters are put forward and evaluated under different load paths. Results show that the generalized strain amplitude model provides less accurate life predictions in the high cycle life regime and is better for life prediction in the low cycle life regime; however, the generalized strain energy model is relatively better for high cycle life prediction and is conservative for low cycle life prediction under multiaxial loadings. In addition, the Fatemi–Socie model is introduced for model comparison and its additional material parameter k is found to not be a constant and its usage is discussed. Finally, model comparison and prediction error analysis are used to illustrate the superiority of the proposed damage parameter in multiaxial fatigue life prediction of the two aviation alloys under various loadings.

Diabetes is a major risk factor for the development of stroke. Glucagon-like peptide-1 receptor (GLP-1R) agonists have been in clinical use for the treatment of diabetes and also been reported to be neuroprotective in ischemic stroke. The quinoxaline 6,7-dichloro-2-methylsulfonyl-3-N-tert- butylaminoquinoxaline (DMB) is an agonist and allosteric modulator of the GLP-1R with the potential to increase the affinity of GLP-1 for its receptor. The aim of this study was to evaluate the neuroprotective effects of DMB on transient focal cerebral ischemia. In cultured cortical neurons, DMB activated the GLP-1R, leading to increased intracellular cAMP levels with an EC50 value about 100 fold that of exendin-4. Pretreatment of neurons with DMB protected against necrotic and apoptotic cell death was induced by oxygen-glucose deprivation (OGD). The neuroprotective effects of DMB were blocked by GLP-1R knockdown with shRNA but not by GLP-1R antagonism. In C57BL/6 mice, DMB was orally administered 30 min prior to middle cerebral artery occlusion (MCAO) surgery. DMB markedly reduced the cerebral infarct size and neurological deficits caused by MCAO and reperfusion. The neuroprotective effects were mediated by activation of the GLP-1R through the cAMP-PKA-CREB signaling pathway. DMB exhibited anti-apoptotic effects by modulating Bcl-2 family members. These results provide evidence that DMB, a small molecular GLP-1R agonist, attenuates transient focal cerebral ischemia injury and inhibits neuronal apoptosis induced by MCAO. Taken together, these data suggest that DMB is a potential neuroprotective agent against cerebral ischemia.

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Abstract. Exendin-4 is now considered as a promising drug for the treatment of cerebral ischemia. To determine the neuroprotective effects of intranasal exendin-4, C57BL/6J mice were intranasally administered with exendin-4 daily for 7 days before middle cerebral artery occlusion (MCAO) surgery. Intranasally administered exendin-4 produced higher brain concentrations and lower plasma concentrations when compared to identical doses administered interperitoneally. Neurological deficits and volume of infarcted lesions were analyzed 24 h after ischemia. Intranasal administration of exendin-4 exhibited significant neuroprotection in C57BL/6 mice subjected to MCAO by reducing neurological deficit scores and infarct volume. The neuroprotective effects of exendin-4 were blocked by the knockdown of GLP-1R with shRNA. However, exendin-4 has no impact on glucose and insulin levels which indicated that the neuroprotective effect was mediated by the activation of GLP-1R in the brain. Exendin-4 intranasal administration restored the balance between pro-and anti-apoptotic proteins and decreased the expression of Caspase-3. The anti-apoptotic effect was mediated by the cAMP/PKA and PI3K/Akt pathway. These findings provided evidence that exendin-4 intranasal administration exerted a neuroprotective effect mediated by an anti-apoptotic mechanism in MCAO mice and protected neurons against ischemic injury through the GLP-1R pathway in the brain. Intranasal delivery of exendin-4 might be a promising strategy for the treatment of ischemic stroke.

As one of fracture critical components of an aircraft engine, accurate life prediction of a turbine blade to disk attachment is significant for ensuring the engine structural integrity and reliability. Fatigue failure of a turbine blade is often caused under multiaxial cyclic loadings at high temperatures. In this paper, considering different failure types, a new energy-critical plane damage parameter is proposed for multiaxial fatigue life prediction, and no extra fitted material constants will be needed for practical applications. Moreover, three multiaxial models with maximum damage parameters on the critical plane are evaluated under tension-compression and tension-torsion loadings. Experimental data of GH4169 under proportional and non-proportional fatigue loadings and a case study of a turbine disk-blade contact system are introduced for model validation. Results show that model predictions by Wang-Brown (WB) and Fatemi-Socie (FS) models with maximum damage parameters are conservative and acceptable. For the turbine disk-blade contact system, both of the proposed damage parameters and Smith-Watson-Topper (SWT) model show reasonably acceptable correlations with its field number of flight cycles. However, life estimations of the turbine blade reveal that the definition of the maximum damage parameter is not reasonable for the WB model but effective for both the FS and SWT models.

Plant innate immunity is capable of combating diverse and ever evolving pathogens. The plasticity of innate immunity could be boosted by RNA processing. Arabidopsis thaliana CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5 (CPR5), a key negative immune regulator, is a component of the nuclear pore complex. Here we further identified CPR5 as a component of RNA processing complexes. Through genetic screening, we found that RNA splicing activator NineTeen Complex and RNA polyadenylation factor CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR, coordinately function downstream of CPR5 to activate plant immunity. CPR5 and these two regulators forms a complex that is localized in nuclear speckles, an RNA processing organelle. Intriguingly, we found that CPR5 is an RNA-binding protein belonging to the Transformer 2 (Tra2) subfamily of the serine/arginine-rich family. The RNA recognition motif of CPR5 protein binds the Tra2-targeted RNA sequence in vitro and is functionally replaceable by those of Tra2 subfamily proteins. In planta, it binds RNAs of CPR5-regulated alternatively spliced genes (ASGs) identified by RNA-seq. ARGONAUTE 1 (AGO1) is one of the ASGs and, consistent with this, the ago1 mutant suppresses the cpr5 phenotype. These findings reveal that CPR5 is an RNA-binding protein linking RNA processing with plant immunity.

Bismuth sulfide nanorod array is directly grown on nickel foam (R‐Bi2S3/NF) to serve as a completely carbon and binder‐free 3D porous oxygen electrode material for lithium‐oxygen (Li‐O2) batteries. The synergistic effect of the fast kinetics of electron transport and gas and electrolyte diffusion provided by the continuous free‐standing network structure and the excellent electrocatalytic activity of the bismuth sulfide nanorod array enables outstanding performance of the oxygen electrode. Li‐O2 battery with the free‐standing R‐Bi2S3/NF oxygen electrode exhibits high energy efficiency (78.7%), good rate capability (4464 mA h g−1 at 1500 mA g−1), as well as excellent cyclability (146 cycles) while maintaining a moderate specific capacity of 1000 mA h g−1. The effect of cathodes with different reactant (O2) and intermediate (LiO2) adsorbability on the product (Li2O2) growth model is studied by first‐principle calculations. The strong O2 adsorption and weak LiO2 adsorption on Bi2S3 drives the growth of large‐size Li2O2 particles via solution growth model. Remarkably, the large‐area pouch‐type Li‐O2 battery delivers an energy density of 330 Wh kg−1. The present results open up a promising avenue toward developing novel electrode architecture for high‐performance Li‐O2 batteries through controlling morphology and functionality of porous electrodes.