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The C-glycosidic bond that connects the sugar moiety with aglycone is difficult to be broken or made due to its inert nature. The knowledge of C-glycoside breakdown and synthesis is very limited. Recently, the enzyme DgpA/B/C cascade from a human intestinal bacterium PUE was identified to specifically cleave the C-glycosidic bond of puerarin (daidzein-8-C-glucoside). Here we investigated how puerarin is recognized and oxidized by DgpA based on crystal structures of DgpA with or without substrate and biochemical characterization. More strikingly, we found that apart from being a C-glycoside cleaving enzyme, DgpA/B/C is capable of efficiently converting O- to C-glycoside showing the activity as a structure isomerase. A possible mechanistic model was proposed dependently of the simulated complex structure of DgpB/C with 3″-oxo-daidzin and structure-based mutagenesis. Our findings not only shed light on understanding the enzyme-mediated C-glycosidic bond breakage and formation, but also may help to facilitate stereospecific C-glycoside synthesis in pharmaceutical industry.

ABSTRACT Enterobacter cloacae is a troublesome pathogen causing refractory infections of the lower respiratory tract, urethra and abdominal cavity, endocarditis, osteomyelitis, and neonatal septicemia. It is prone to developing resistance to ordinary antibiotics and has brought a serious problem to clinical treatment. An artful synergistic combination of an antibacterial natural product allicin and a newly isolated bacteriophage, named BD523, was constructed herein. This combination significantly lowered effective dosage of allicin and effectually overcame bacterial drug-resistance. We experimentally evidenced that allicin interacts with bacterial DNA in the groove region by inserting itself into the DNA double helix and, subsequently, disrupts the bacterial DNA by cleaving phosphate diester bonds of deoxynucleotides. Further, BD523 destroys the cell wall and membrane of bacteria by synthesizing lyase proteins, including holin and endolysins. Thus, the synergistic effect of the combination benefits from complementary targeting mechanisms of allicin and BD523. They cooperatively act on bacterial DNA, cell wall, and membrane to improve antibacterial efficiency and avoid drug-resistance. IMPORTANCE Bacterial drug-resistance is a serious problem afflicting pharmacologists all over the world. Many strategies have been developed and practiced to overcome it, but almost no one is satisfactory due to the continual change of bacteria. Combinations of antibiotics and bacteriophages are promising because of the cooperation of 2 bacterial killers with distinct mechanisms. The combination of allicin and an Enterobacter cloacae bacteriophage reported herein can significantly improve the effect of allicin against E. cloacae. Its synergistic effect was even superior to the combination of bacteriophage and neomycin, of which the MIC was significantly lower than allicin. It was ascribed to the complementary antibacterial and the possible resistance-proof mechanism of bacteriophage and allicin. This study provided a pragmatic way to conquer the cunning bacterium, and may offer reference for research and development of new bacterial killers.

Backgroud: Renal fibrosis is the common characteristic of chronic kidney disease. Circular RNA plays an essential role in the occurrence and development of Renal fibrosis, but its regulative mechanism remains elusive.Methods: The animal and cell model of Renal fibrosis was established, and RNA-sequencing and real-time polymerase chain reaction (qRT-PCR) experiments were implemented. Subsequently, experiments for detecting apoptosis and proliferation of cell, were carried out, and the isobaric tags for relative and absolute quantification proteomics analyses were performed accordingly.Results: It was found that a newly discovered Circular RNA (circRNA_0002158), is highly expressed in kidneys or cells with fibrosis, implying that this Circular RNA might be associated with the occurrence and development of Renal fibrosis. Subsequently, the overexpression and knockdown of circRNA_0002158 were conducted in the human kidney epithelial cell line (HK-2) cells, and the results indicated that the circRNA_0002158 could inhibit apoptosis, and promote proliferation of cells. The kidney injury-related factors, including Fibronectin and plasminogen activator inhibitor-1 (PAI-1), were decreased in HK-2 cells with overexpression of circRNA_0002158, while the results were reversed in cells with knockdown of circRNA_0002158. Finally, to explore the regulative mechanism of circRNA_0002158, the iTRAQ proteomics analyses were implemented for the cell samples with OE of circRNA_0002158 and its control, it showed that multiple genes and functional pathways were associated with the occurrence and development of Renal fibrosis.Conclusion: CircRNA_0002158 is associated with regulating Renal fibrosis, and may contribute to ameliorating the progression of Renal fibrosis in the future.

Abstract Kirigami, the ancient art of paper cutting, has evolved into a design and fabrication framework to engineer multi‐functional materials and structures at vastly different scales. By slit cutting with carefully designed geometries, desirable mechanical behaviors—such as accurate shape morphing, tunable auxetics, super‐stretchability, buckling, and multistability—can be imparted to otherwise inflexible sheet materials. In addition, the kirigami sheet provides a versatile platform for embedding different electronic and responsive components, opening up avenues for building the next generations of metamaterials, sensors, and soft robotics. These promising potentials of kirigami‐based engineering have inspired vigorous research activities over the past few years, generating many academic publications. Therefore, this review aims to provide insights into the recent advance in this vibrant field. In particular, this paper offers the first comprehensive survey of unique mechanical properties induced by kirigami cutting, their underlying physical principles, and their corresponding applications. The synergies between design methodologies, mechanics modeling, advanced fabrication, and material science will continue to mature this promising discipline.

Mechanical joints are the weakest links of composite materials and structures. The aim of this study is to investigate the effect of the pin profiles on the stress concentration and load-carry capacity of the pin-loaded single-lap joints subjected to tensile loading. Non-circular profiles of pins are numerically investigated to pursue a possible stress concentration reduction in both the net-tension and bearing stresses of composite single lap joints. Firstly, by varying the characteristic parameters, various round-corner squares are evaluated in terms of peak stresses. Secondly, the square-like profile is transferred to the racetrack-like one in order to gain optimal bearing stresses. Thirdly, the pin of the racetrack-like profile is investigated compared to the circular one, taking into account the through-thickness distributions of stresses. Lastly, the orthotropic effect and the load-carry capacity of the proposed profile are also discussed. Keywords: Composite single lap joints, Pin-loaded joints, Stress concentration, Net-tension stress, Bearing stress, Non-circular profile

This paper describes the design, working principle, as well as calibration of an air-floating six-axis force measurement platform, where the floating plate and nozzles were connected without contact, preventing inter-dimensional coupling and increasing precision significantly. The measurement repeatability error of the force size in the platform is less than 0.2% full scale (FS), which is significantly better than the precision of 1% FS in the six-axis force sensors on the current market. We overcame the difficulties of weight loading device in high-precision calibration by proposing a self-calibration method based on the floating plate gravity and met the calibration precision requirement of 0.02% FS. This study has general implications for the development and calibration of high-precision multi-axis force sensors. In particular, the air-floating six-axis force measurement platform could be applied to the calibration of some special sensors such as flexible tactile sensors and may be used as a micro-nano mechanical assembly platform for real-time assembly force testing. [ABSTRACT FROM AUTHOR]