Tuning the reversibility of hair artificial muscles by disulfide cross-linking for sensors, switches, and soft robotics.

Tensile and torsional artificial muscles from biocompatible and biodegradable materials are highly desired for soft robotics, sensors, and controllers in bio-related applications. Twisted fibers can be used to prepare tensile and torsional artificial muscles, while torsional tethering is always required to avoid release of the inserted twist, which adds complexity to the device design. Moreover, the tuning of the reversibility of twisted fiber artificial muscles has not been realized. Here disulfide cross-linking was used to prepare novel tether-free hygroresponsive tensile and torsional fiber artificial muscles in twisted hair fibers. Increasing the cross-linking level converted the fiber artificial muscle from irreversible to reversible actuation. Different types of actuations including rotation, contraction, and elongation were realized for the twisted, the homochirally coiled, and the heterochirally coiled hair fibers, respectively. A reversible torsional fiber artificial muscle showed 122.4° mm-1 rotation, homochiral and heterochiral fiber artificial muscles showed 94% contraction and 3000% elongation, respectively, and a maximum work capacity and energy density of 6.35 J kg-1 and 69.8 kJ m-3, respectively, were realized, on exposure to water fog. This work provides a new strategy for preserving the inserted twist in bio-fiber artificial muscles and for tuning of muscle reversibility, which show application perspectives in biocompatible smart materials, sensors, and robotics.

Parkinson's disease associated mutation E46K of α-synuclein triggers the formation of a distinct fibril structure.

Amyloid aggregation of α-synuclein (α-syn) is closely associated with Parkinson's disease (PD) and other synucleinopathies. Several single amino-acid mutations (e.g. E46K) of α-syn have been identified causative to the early onset of familial PD. Here, we report the cryo-EM structure of an α-syn fibril formed by N-terminally acetylated E46K mutant α-syn (Ac-E46K). The fibril structure represents a distinct fold of α-syn, which demonstrates that the E46K mutation breaks the electrostatic interactions in the wild type (WT) α-syn fibril and thus triggers the rearrangement of the overall structure. Furthermore, we show that the Ac-E46K fibril is less resistant to harsh conditions and protease cleavage, and more prone to be fragmented with an enhanced seeding capability than that of the WT fibril. Our work provides a structural view to the severe pathology of the PD familial mutation E46K of α-syn and highlights the importance of electrostatic interactions in defining the fibril polymorphs.

Torsional refrigeration by twisted, coiled, and supercoiled fibers.

Higher-efficiency, lower-cost refrigeration is needed for both large- and small-scale cooling. Refrigerators using entropy changes during cycles of stretching or hydrostatic compression of a solid are possible alternatives to the vapor-compression fridges found in homes. We show that high cooling results from twist changes for twisted, coiled, or supercoiled fibers, including those of natural rubber, nickel titanium, and polyethylene fishing line. Using opposite chiralities of twist and coiling produces supercoiled natural rubber fibers and coiled fishing line fibers that cool when stretched. A demonstrated twist-based device for cooling flowing water provides high cooling energy and device efficiency. Mechanical calculations describe the axial and spring-index dependencies of twist-enhanced cooling and its origin in a phase transformation for polyethylene fibers.

Amyloid fibril structure of α-synuclein determined by cryo-electron microscopy.

α-Synuclein (α-syn) amyloid fibrils are the major component of Lewy bodies, which are the pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. High-resolution structure of α-syn fibril is important for understanding its assembly and pathological mechanism. Here, we determined a fibril structure of full-length α-syn (1-140) at the resolution of 3.07 Å by cryo-electron microscopy (cryo-EM). The fibrils are cytotoxic, and transmissible to induce endogenous α-syn aggregation in primary neurons. Based on the reconstructed cryo-EM density map, we were able to unambiguously build the fibril structure comprising residues 37-99. The α-syn amyloid fibril structure shows two protofilaments intertwining along an approximate 21 screw axis into a left-handed helix. Each protofilament features a Greek key-like topology. Remarkably, five out of the six early-onset PD familial mutations are located at the dimer interface of the fibril (H50Q, G51D, and A53T/E) or involved in the stabilization of the protofilament (E46K). Furthermore, these PD mutations lead to the formation of fibrils with polymorphic structures distinct from that of the wild-type. Our study provides molecular insight into the fibrillar assembly of α-syn at the atomic level and sheds light on the molecular pathogenesis caused by familial PD mutations of α-syn.

Characterization of structure-antioxidant activity relationship of peptides in free radical systems using QSAR models: key sequence positions and their amino acid properties.

Antioxidative peptides have attracted increasing attention from researchers because of their antioxidant properties as natural materials in functional food and for applications in medicine. However, the relationship between structure and activity (SAR) remains unclear, especially in antioxidative peptides in free radical systems. Antioxidative peptides with different lengths were obtained from the literature, measured using different methods, and were organized into three databases, namely, Trolox-equivalent antioxidant capacity (TEAC), oxygen radical absorption capacity (ORAC), and superoxide radical (SOR). After the peptides were processed using the two-terminal position numbering method, quantitative SAR modeling was performed on antioxidative peptides in the three databases. The vectors of hydrophobic, steric, and electronic properties (VHSE) and the divided physicochemical property scores descriptors (DPPS) were selected from 17 physicochemical descriptors to express electronic, hydrophobic, and steric properties (or hydrogen bonding) of the three (or four) external amino acids in the N-terminal and C-terminal positions. Models were estimated using partial least squares regression and validated through full cross-validation and external validation (R(2)>0.7, Q(2)>0.5 for TEAC; R(2)>0.9, Q(2)>0.5 for ORAC and SOR). The results found a relationship between the physicochemical properties of the C-terminal and N-terminal regions and antioxidant potency. The properties of amino acids at C-terminal regions were more important than those at the N-terminal regions for predicting antioxidant activity. The properties of amino acids at C(2)>C(1) for TEAC, C(3)>C(4)>C(1) for ORAC, and C(4)>C(1)>N(1) for SOR were highly correlated with antioxidant activity. Although electronic property most significantly contributed to antioxidant activity in the three free radical systems, it had complex effects at each position. Bulky hydrophobic amino acids at the C-terminal were related to the antioxidant activity of peptides in the three free radical systems. For peptides in the TEAC database, the relationship between the N-terminal segment (N(2), N(3)) and the activity increased when longer peptides were included, which reflects the likely influence of stericity. This study contributes to the ongoing research on antioxidants in food and its application in medicine.

Structure-activity relationship study of antioxidative peptides by QSAR modeling: the amino acid next to C-terminus affects the activity.

Screening, isolation and in vitro assays have been used for characterization of antioxidative peptides derived from food proteins, and incompatible deductions of structural characteristics derived from the isolated peptides have been brought forward. However, there is still little information concerning the structure-activity relationship of antioxidative peptides. QSAR modeling was performed, respectively, on synthetic tripeptides and tetrapeptides related to LLPHH. According to cumulative squared multiple correlation coefficients (R(2)), cumulative cross-validation coefficients (Q(2)) and relative standard deviation for calibration set (RSD(c)), two credible models for tripeptide and tetrapeptide databases, respectively, have been built with partial least squares (PLS) regression (R(2) for models of tripeptide and tetrapeptide are 0.744 and 0.943, Q(2) are 0.631 and 0.414, and RSD(c) are 0.323 and 0.111, respectively). Meanwhile, according to the cumulative multiple correlation coefficient for the predictive set (R2(ext)) and the relative standard deviation for the predictive set (RSD(p)), the predictive ability of the model for tripeptides also is excellent (R2(ext)) and RSD(p) are 0.719 and 0.450, respectively). Hydrogen bond property and hydrophilicity of the amino acid residue next to the C-terminus, and the hydrophobicity as well as electronic propertyof the N-terminus are more significant; meanwhile, the electronic property of the C-terminus is beneficial for antioxidant activity. The structural characteristics we found are very useful in understanding and predicting the peptide structures responsible for activity and development of functional foods with peptides as active compounds, or antioxidative peptides as alternatives to other antioxidants.

[Analysis of 103 cases with adverse drug reactions induced by sanqizongzaogan injection].

To analyze the characteristics and relative factors of adverse drug reactions (ADR) induced by sanqizongzaogan injection, in order to provide reference for the clinical use of sanqizongzaogan injection properly. The 103 reported cases of ADR induced by sanqizongzaogan injection in China over 15 years were retrospectively analyzed. The 103 ADR cases, 41.7% occurred in patients aged above 60. The most common presentation of ADR was drug eruption, followed by allergic reactions (20.4%) and allergic shock (9.7%). The occurrence of ADR is affected by many factors. We should control the drug indication strictly, check patients drug allergy history carefully before prescription, monitor ADR afterwards, promote clinical rational drug-usage.