The nuclear receptor FXR is the sensor of physiological levels of enterohepatic bile acids, the end products of cholesterol catabolism. Here we report crystal structures of the FXR ligand binding domain in complex with coactivator peptide and two different bile acids. An unusual A/B ring juncture, a feature associated with bile acids and no other steroids, provides ligand discrimination and triggers a pi-cation switch that activates FXR. Helix 12, the activation function 2 of the receptor, adopts the agonist conformation and stabilizes coactivator peptide binding. FXR is able to interact simultaneously with two coactivator motifs, providing a mechanism for enhanced binding of coactivators through intermolecular contacts between their LXXLL sequences. These FXR complexes provide direct insights into the design of therapeutic bile acids for treatment of hyperlipidemia and cholestasis.

The rapid emergence of antibiotic resistance in pathogenic microbes is becoming an imminent global public health problem. Local application of antibiotics might be a solution. In local application, materials need to act as the drug delivery system. The drug delivery system should be biodegradable and prolonged antibacterial effect should be provided to satisfy clinical demand. Hydrogel is a promising material for local antibacterial application. Hydrogel refers to a kind of biomaterial synthesized by a water-soluble natural polymer or a synthesized polymer, which turns into gel according to the change in different signals such as temperature, ionic strength, pH, ultraviolet exposure etc. Because of its high hydrophilicity, unique three-dimensional network, fine biocompatibility and cell adhesion, hydrogel is one of the suitable biomaterials for drug delivery in antimicrobial areas. In this review, studies from the past 5 years were reviewed, and several types of antimicrobial hydrogels according to different ingredients, different preparations, different antimicrobial mechanisms, different antimicrobial agents they contained and different applications, were summarized. The hydrogels loaded with metal nanoparticles as a potential method to solve antibiotic resistance were highlighted. Finally, future prospects of development and application of antimicrobial hydrogels are suggested.

Adenine flips out: A combination of X‐ray crystallography, 2‐aminopurine fluorescence labeling, and the use of aminoglycosides as ligands is exploited to demonstrate conformational transitions in the RNA domain that ensures accurate protein synthesis (see picture). The triggering of a conformational change of an adenine unit in the RNA by ligand binding can be used as the basis of a screening method to discover antibiotics.

Adenin dreht sich raus: Röntgenkristallographie, Fluoreszenzmarkierung mit 2‐Aminopurin und die Verwendung von Aminoglycosiden als Liganden ermöglichten den Nachweis von Konformationsänderungen an der RNA‐Domäne, die die richtige Proteinsynthese sicherstellt (siehe Bild). Das Auslösen einer Änderung der Konformation einer RNA‐Adenineinheit durch die Bindung von Liganden kann als Grundlage für eine Methode zur Suche nach Antibiotika dienen.

With the increasing application of orthopedic scaffolds, a dramatically increasing number of requirements for scaffolds are precise. The porous structure has been a fundamental design in the bone tissue engineering or orthopedic clinics because of its low Young's modulus, high compressive strength, and abundant cell accommodation space. The porous structure manufactured by additive manufacturing (AM) technology has controllable pore size, pore shape, and porosity. The single unit can be designed and arrayed with AM, which brings controllable pore characteristics and mechanical properties. This paper presents the current status of porous designs in AM technology. The porous structures are stated from the cellular structure and the whole structure. In the aspect of the cellular structure, non-parametric design and parametric design are discussed here according to whether the algorithm generates the structure or not. The non-parametric design comprises the diamond, the body-centered cubic, and the polyhedral structure, etc. The Voronoi, the Triply Periodic Minimal Surface, and other parametric designs are mainly discussed in parametric design. In the discussion of cellular structures, we emphasize the design, and the resulting biomechanical and biological effects caused by designs. In the aspect of the whole structure, the recent experimental researches are reviewed on uniform design, layered gradient design, and layered gradient design based on topological optimization, etc. These parts are summarized because of the development of technology and the demand for mechanics or bone growth. Finally, the challenges faced by the porous designs and prospects of porous structure in orthopedics are proposed in this paper.

The preorganized presentation of functional groups in the antibiotic neomycin (green) is exploited to obtain a conformationally restricted aminoglycoside (yellow) by regioselective intramolecular cyclization. X‐ray crystallography data show how the natural product and the derivative recognize the RNA target motif that is the binding site of aminoglycoside antibiotics.

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Porous metal is metal with special porous structures, which can offer high biocompatibility and low Young’s modulus to satisfy the need for orthopedic applications. Titanium and tantalum are the most widely used porous metals in orthopedics due to their excellent biomechanical properties and biocompatibility. Porous titanium and tantalum have been studied and applied for a long history until now. Here in this review, various manufacturing methods of titanium and tantalum porous metals are introduced. Application of these porous metals in different parts of the body are summarized, and strengths and weaknesses of these porous metal implants in clinical practice are discussed frankly for future improvement from the viewpoint of orthopedic surgeons. Then according to the requirements from clinics, progress in research for clinical use is illustrated in four aspects. Various creative designs of microporous and functionally gradient structure, surface modification, and functional compound systems of porous metal are exhibited as reference for future research. Finally, the directions of orthopedic porous metal development were proposed from the clinical view based on the rapid progress of additive manufacturing. Controllable design of both macroscopic anatomical bionic shape and microscopic functional bionic gradient porous metal, which could meet the rigorous mechanical demand of bone reconstruction, should be developed as the focus. The modification of a porous metal surface and construction of a functional porous metal compound system, empowering stronger cell proliferation and antimicrobial and antineoplastic property to the porous metal implant, also should be taken into consideration.