A new type of "rigid and tough" hydrogel with excellent elasticity is designed by dense clustering of hydrogen bonds within a loose chemical network. The resultant hydrogel exhibits a good combination of high modulus (28 MPa), toughness (9300 J m(-3) ), extensibility (800%), and tensile stress (2 MPa). Furthermore, the gel displays good fatigue-resistance and complete and extremely fast recovery of shape and mechanical properties (3 min at 37°C).

Nonhuman proteins have valuable therapeutic properties, but their efficacy is limited by neutralizing antibodies. Recombinant immunotoxins (RITs) are potent anticancer agents that have produced many complete remissions in leukemia, but immunogenicity limits the number of doses that can be given to patients with normal immune systems. Using human cells, we identified eight helper T-cell epitopes in PE38, a portion of the bacterial protein Pseudomonas exotoxin A which consists of the toxin moiety of the RIT, and used this information to make LMB-T18 in which three epitopes were deleted and five others diminished by point mutations in key residues. LMB-T18 has high cytotoxic and antitumor activity and is very resistant to thermal denaturation. The new immunotoxin has a 93% decrease in T-cell epitopes and should have improved efficacy in patients because more treatment cycles can be given. Furthermore, the deimmunized toxin can be used to make RITs targeting other antigens, and the approach we describe can be used to deimmunize other therapeutically useful nonhuman proteins.deimmunization | protein engineering I mmunotoxins are chimeric proteins that combine the "magic bullet" specificity of an antibody with the high potency of a toxin. The high specificity of recombinant immunotoxins (RITs) leads to a dramatic decrease in side effects compared with chemotherapy. Moxetumomab Pasudotox (MP) is an RIT that consists of PE38, a fragment of Pseudomonas exotoxin A, fused to an anti-CD22 Fv (1). In a phase I trial for refractory hairy-cell leukemia (HCL), MP had an 86% response rate (2), with 46% complete remissions, and is now in phase III clinical trials (3).Immunogenicity is a stumbling block in the clinical success of many therapeutic proteins (4). Formation of neutralizing antidrug antibodies (5) inactivates the therapeutic agent and can cause serious adverse effects. Although MP had low immunogenicity in the immune-suppressed patients of the HCL trial, some patients did eventually develop antibodies. Consequently, fewer doses could be given to these patients, leading to a reduced response rate. Additionally, RITs targeting solid tumors are less effective than MP because of their high immunogenicity in patients with normal immune systems (6, 7).The role of helper T cells in mounting an immune response is well-established (8, 9). It was previously shown that elimination of murine T-cell epitopes reduced neutralizing antibody formation in mice (10), leading us to the hypothesis that reduction of human T-cell epitopes in the bacterial moiety of RITs would diminish its immunogenicity in humans, allowing more treatment cycles and better antitumor responses, as previously attempted for other therapeutic proteins like erythropoietin (11).To circumvent the immunogenicity of PE38, we previously used peptide pools to map the approximate location of the T-cell epitopes and found an immunodominant and promiscuous epitope that stimulated T cells in 42% of all donors (12). Here, we have done high-resolution mapping of the epitopes ...

Lead‐free halide double perovskite (HDP) nanocrystals are considered as one of the most promising alternatives to the lead halide perovskite nanocrystals due to their unique characteristics of nontoxicity, robust intrinsic thermodynamic stability, rich and tunable optoelectronic properties. Although lead‐free HDP variants with highly efficient emission are synthesized and characterized, the photoluminescent (PL) properties of colloidal HDP nanocrystals still have enormous challenges for application in light‐emitting diode (LED) devices due to their intrinsic and surface defects, indirect band, and disallowable optical transitions. Herein, recent progress on the synthetic strategies, ligands passivation, and metal doping/alloying for boosting efficiency and stability of HDP nanocrystals is comprehensive summarized. It begins by introducing the crystalline structure, electronic structure, and PL mechanism of lead‐free HDPs. Next, the limiting factors on PL properties and origins of instability are analyzed, followed by highlighting the effects of synthesis strategies, ligands passivation, and metal doping/alloying on the PL properties and stability of the HDPs. Then, their preliminary applications for LED devices are emphasized. Finally, the challenges and prospects concerning the development of highly efficient and stable HDP nanocrystals‐based LED devices in the future are proposed.