抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

https://cyberleninka.org/article/n/933162.pdf

Hydrogels in drug delivery: progress and challenges

At present, strong requirements in orthopaedics are still to be met, both in bone and joint substitution and in the repair and regeneration of bone defects. In this framework, tremendous advances in the biomaterials field have been made in the last 50 years where materials intended for biomedical purposes have evolved through three different generations, namely first generation (bioinert materials), second generation (bioactive and biodegradable materials) and third generation (materials designed to stimulate specific responses at the molecular level). In this review, the evolution of different metals, ceramics and polymers most commonly used in orthopaedic applications is discussed, as well as the different approaches used to fulfil the challenges faced by this medical field.

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2008.0151

Biomaterials in orthopaedics.

Synthesis methods for nanosized hydroxyapatite with diverse structures.

The supramolecular crosslinking of polymer chains in water by specific, directional and dynamic non-covalent interactions has led to the development of novel supramolecular polymeric hydrogels. These aqueous polymeric networks constitute an interesting class of soft materials exhibiting attractive properties such as stimuli-responsiveness and self-healing arising from their dynamic behaviour and that are crucial for a wide variety of emerging applications. We present here a critical review summarising the formation of dynamic polymeric networks through specific non-covalent interactions, with a particular emphasis on those systems based on host–guest complex formation, as well as the characterisation of their physical characteristics. Aqueous supramolecular chemistry has unlocked a versatile toolbox for the design and fine-tuning of the material properties of these hydrogels (264 references).

Supramolecular polymeric hydrogels

Kinetics of hydroxyapatite precipitation at pH 10 to 11.

Erosion behaviour governs the use of physical hydrogels in biomedical applications ranging from controlled release to cell encapsulation. Genetically engineered protein hydrogels offer unique means of controlling the erosion rate by engineering their amino acid sequences and network topology. Here, we show that the erosion rate of such materials can be tuned by harnessing selective molecular recognition, discrete aggregation number and orientational discrimination of coiled-coil protein domains. Hydrogels formed from a triblock artificial protein bearing dissimilar helical coiled-coil end domains (P and A) erode more than one hundredfold slower than hydrogels formed from those bearing the same end domains (either P or A). The reduced erosion rate is a consequence of the fact that looped chains are suppressed because P and A tend not to associate with each other. Thus, the erosion rate can be tuned over several orders of magnitude in artificial protein hydrogels, opening the door to diverse biomedical applications.

Tuning the erosion rate of artificial protein hydrogels through control of network topology

We present a strategy to stabilize artificial protein hydrogels through covalent bond formation following physical association of terminal leucine zipper domains. Artificial proteins consisting of two terminal leucine zipper domains and a random coil central domain form transient networks above a certain concentration, but the networks dissolve when placed in excess buffer. Engineering of a cysteine residue into each leucine zipper domain allows formation of disulfide bonds templated by leucine zipper aggregation. Circular dichroism spectra show that the zipper domains remain helical after cysteine residues and disulfide bonds are introduced. Asymmetric placement of the cysteine residues in the leucine zipper domains suppresses intramolecular disulfide bonds and creates linked “multichains” composed of ca. 9 protein chains on average, as determined by multiangle light scattering measurements. These “multichains” act as the building units of the physical network formed by leucine zipper aggregation. The in...

Assembly of an artificial protein hydrogel through leucine zipper aggregation and disulfide bond formation

The dynamics for the hydraulic process of calcium phosphate cement (CPC) were investigated by X-ray diffraction quantitative analysis. The results show that the hardening process of CPC is initially controlled by the dissolution of reactants in a 4-h period and subsequently by diffusion through the product layer of hydroxyapatite (HAP) around the grains. The compressive strength rises approximately linearly with the increase of the extent of conversion in a 4-h period, and a maximum compressive strength of about 51 MPa, which is superior to those reported by the references, is obtained in 4 h. Then the compressive strength drops a little with an increase in the extent of conversion. The final product of setting reaction is acicular HAP crystal. Crystal seed not only reduces the setting time but also drops the compressive strength. The variation of pH in CPC slurry from 7.5 to 10.5 reveals that the control step of the dissolution process in the hardening process is the dissolution of dicalcium phosphate anhydrous and the presence of crystal seed will reduce the supersaturation to produce HAP.

Mechanism of the hardening process for a hydroxyapatite cement

Artificial protein hydrogels made from a triblock protein (designated AC10A, where A is an acidic zipper domain and C10 comprises 10 repeats of the nonapeptide sequence exhibit normalized plateau storage moduli (G′∞/nkT) less than 0.13 at all concentrations, pH values, and ionic strengths examined. These gels are surprisingly soft due to loop formation at the expense of bridges between physical junctions. Molecular-level evidence of loop formation is provided by strong fluorescence energy transfer (FRET) between distinct chromophores placed at the C- and N-termini of labelled chains diluted in an excess of unlabelled chains. The tendency to form loops originates from the compact size of the random coil midblock (mean RH(C10) ≈ 20 A, determined from quasi-elastic light scattering of C10), and is facilitated by the ability of the leucine zipper domains to form antiparallel aggregates. Although the aggregation number of the leucine zipper domains is small (tetrameric, determined from multi-angle static light scattering of AC10 diblock), the average center-to-center distance between aggregates is roughly 1.5 times the average end-to-end distance of the C10 domain in a 7% w/v network. To avoid stretching the C10 domain, the chains tend to form loops. Changes in pH or ionic strength that expand the polyelectrolyte midblock favor bridging, leading to greater G′∞ as long as leucine zipper endblocks do not dissociate. Understanding of the network structure provided successful design strategies to increase the rigidity of these hydrogels. In contrast to intuitive design concepts for rubber and gel materials, it was shown that increasing either the length or the charge density of the midblock increases rigidity, because fewer chains are wasted in loop formation.

/pdf/structure-and-mechanical-properties-of-artificial-protein-1l6f4bkr07.pdf

Wei Shen

Papers

Kinetics of hydroxyapatite precipitation at pH 10 to 11.

Tuning the erosion rate of artificial protein hydrogels through control of network topology

Assembly of an artificial protein hydrogel through leucine zipper aggregation and disulfide bond formation

Mechanism of the hardening process for a hydroxyapatite cement

Structure and mechanical properties of artificial protein hydrogels assembled through aggregation of leucine zipper peptide domains