Clinical features, treatment, and follow-up of OPPG and high-bone-mass disorders: LRP5 is a key regulator of bone mass.

Osteoporosis-pseudoglioma syndrome (OPPG) and LRP5 high bone mass (LRP5-HBM) are two rare bone diseases with opposite clinical symptoms caused by loss-of-function and gain-of-function mutations in LRP5. Bisphosphonates are an effective treatment for OPPG patients. LRP5-HBM has a benign course, and age-related bone loss is found in one LRP5-HBM patient. PURPOSE: Low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the canonical Wnt signaling pathway. The gain-of-function mutation leads to high bone mass (LRP5-HBM), while the loss-of-function mutation leads to osteoporosis-pseudoglioma syndrome (OPPG). In this study, the clinical manifestations, disease-causing mutations, treatment, and follow-up were summarized to improve the understanding of these two diseases. METHODS: Two OPPG patients and four LRP5-HBM patients were included in this study. The clinical characteristics, biochemical and radiological examinations, pathogenic mutations, and structural analysis were summarized. Furthermore, several patients were followed up to observe the treatment effect and disease progress. RESULTS: Congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures were the main clinical manifestations of OPPG. Complex heterozygous mutations were detected in two OPPG patients. The c.1455G > T mutation in exon 7 was first reported. During the follow-up, BMD of two patients was significantly improved after bisphosphonate treatment. On the contrary, typical clinical features of LRP5-HBM included extremely high BMD without fractures, torus palatinus and normal vision. X-ray showed diffuse osteosclerosis. Two heterozygous missense mutations were detected in four patients. In addition, age-related bone loss was found in one LRP5-HBM patient after 12-year of follow-up. CONCLUSION: This study deepened the understanding of the clinical characteristics, treatment, and follow-up of OPPG and LRP5-HBM; expanded the pathogenic gene spectrum of OPPG; and confirmed that bisphosphonates were effective for OPPG. Additionally, it was found that Ala242Thr mutation could not protect LRP5-HBM patients from age-related bone loss. This phenomenon deserves further study.

FATTY ACID DESATURASE5 Is Required to Induce Autoimmune Responses in Gigantic Chloroplast Mutants of Arabidopsis.

Chloroplasts mediate genetically controlled cell death via chloroplast-to-nucleus retrograde signaling. To decipher the mechanism, we examined chloroplast-linked lesion-mimic mutants of Arabidopsis (Arabidopsis thaliana) deficient in plastid division, thereby developing gigantic chloroplasts (GCs). These GC mutants, including crumpled leaf (crl), constitutively express immune-related genes and show light-dependent localized cell death (LCD), mirroring typical autoimmune responses. Our reverse genetic approach excludes any potential role of immune/stress hormones in triggering LCD. Instead, transcriptome and in silico analyses suggest that reactive electrophile species (RES) generated via oxidation of polyunsaturated fatty acids (PUFAs) or lipid peroxidation-driven signaling may induce LCD. Consistent with these results, the one of the suppressors of crl, dubbed spcrl4, contains a causative mutation in the nuclear gene encoding chloroplast-localized FATTY ACID DESATURASE5 (FAD5) that catalyzes the conversion of palmitic acid (16:0) to palmitoleic acid (16:1). The loss of FAD5 in the crl mutant might attenuate the levels of RES and/or lipid peroxidation due to the reduced levels of palmitic acid-driven PUFAs, which are prime targets of reactive oxygen species. The fact that fad5 also compromises the expression of immune-related genes and the development of LCD in other GC mutants substantiates the presence of an intrinsic retrograde signaling pathway, priming the autoimmune responses in a FAD5-dependent manner.

Uncoupled Expression of Nuclear and Plastid Photosynthesis-Associated Genes Contributes to Cell Death in a Lesion Mimic Mutant.

Chloroplast-to-nucleus retrograde signaling is essential for the coupled expression of photosynthesis-associated nuclear genes (PhANGs) and plastid genes (PhAPGs) to ensure the functional status of chloroplasts (Cp) in plants. Although various signaling components involved in the process have been identified in Arabidopsis (Arabidopsis thaliana), the biological relevance of such coordination remains an enigma. Here, we show that the uncoupled expression of PhANGs and PhAPGs contributes to the cell death in the lesion simulating disease1 (lsd1) mutant of Arabidopsis. A daylength-dependent increase of salicylic acid (SA) appears to rapidly up-regulate a gene encoding SIGMA FACTOR BINDING PROTEIN1 (SIB1), a transcriptional coregulator, in lsd1 before the onset of cell death. The dual targeting of SIB1 to the nucleus and the Cps leads to a simultaneous up-regulation of PhANGs and down-regulation of PhAPGs. Consequently, this disrupts the stoichiometry of photosynthetic proteins, especially in PSII, resulting in the generation of the highly reactive species singlet oxygen (1O2) in Cps. Accordingly, inactivation of the nuclear-encoded Cp protein EXECUTER1, a putative 1O2 sensor, significantly attenuates the lsd1-conferred cell death. Together, these results provide a pathway from the SA- to the 1O2-signaling pathway, which are intertwined via the uncoupled expression of PhANGs and PhAPGs, contributing to the lesion-mimicking cell death in lsd1.

Convenient Synthesis of a Ru Catalyst Containing Single Atoms and Nanoparticles on Nitrogen-Doped Carbon with Superior Hydrogen Evolution Reaction Activity in a Wide pH Range.

Ruthenium, which is relatively cheap in precious metals, has become a popular alternative for a hydrogen evolution reaction (HER) catalyst because of its corrosion resistance and appropriate metal-H bond strength. Convenient synthesis and active site regulation are conducive to stimulating the excellent catalytic performance of Ru as much as possible. Herein, using the mature mesoporous nitrogen-doped carbon material as the support, the catalytic materials containing both single atom Ru and Ru nanoparticles were synthesized by impregnation using the solid-phase reduction method. The effect of reduction temperature on the dispersion state and electronic structure of Ru species has been fully studied using electronic and spectroscopic characterizations. The sample reduced at 300 °C has excellent HER activity with overpotentials of 10.8 and 53.8 mV to deliver 10 mA/cm2 in alkaline and acidic media, respectively, which is among the best activities in the reported results. Electrochemical impedance analysis shows that the reduction temperature has a great influence on the number of active sites and charge transfer impedance of the catalyst.

Impact of a sleep promotion protocol on off-pump coronary artery bypass graft patients.

BACKGROUND: Sleep abnormalities frequently occur in intensive care unit (ICU) patients, and the consequences of sleep abnormalities in patients who undergo off-pump coronary artery bypass graft (OPCABG) surgery are particularly significant. Although many interventions have been reported to improve sleep, few sleep promotion protocols have been designed specifically for patients in cardiac ICUs. AIMS AND OBJECTIVES: This study aimed to explore the effects of an evidence-based sleep promotion protocol on patients who underwent OPCABG in a cardiac ICU. DESIGN: A quasi-experimental study was conducted in a comprehensive hospital in Shandong province of China. METHODS: Overall, 67 participants were recruited (37 in the control group and 30 in the intervention group). An evidence-based sleep promotion protocol was developed by a 10-member interprofessional collaborative team and then applied. Sound levels, light intensity, and the number of nocturnal interventions were compared between groups. The Chinese version of the Richards-Campbell Sleep Questionnaire (RCSQ) was used to compare intergroup sleep status on two consecutive postoperative nights. RESULTS: No significant differences were found for demographics or disease severity between the groups. In the intervention group, sound levels and light intensity were significantly lower at various times, and nocturnal interventions were significantly less frequent over the two consecutive nights. RCSQ scores were significantly higher in the intervention group for both nights. CONCLUSIONS: The sleep promotion protocol reduced sound levels, night-time light intensity, the number of nocturnal interventions, and improved sleep among OPCABG patients in a cardiac ICU. RELEVANCE TO CLINICAL PRACTICE: Evidence-based practice can help to promote good quality of care, improve patient outcomes, and advance nursing in clinical settings.

Elastic-Modulus-Dependent Macroscopic Supramolecular Assembly of Poly(dimethylsiloxane) for Understanding Fast Interfacial Adhesion.

Macroscopic supramolecular assembly (MSA) is a new concept of supramolecular science with an emphasis on noncovalent interactions between macroscopic building blocks with sizes exceeding 10 µm. Owing to a similar noncovalently interactive nature with the phenomena of bioadhesion, self-healing, etc. and flexible features in tailoring and designing modular building blocks, MSA has been developed as a simplified model to interpret interfacial phenomena and a facile method to fabricate supramolecular materials. However, at this early stage, MSA has always been limited to hydrogel materials, which provide flowability for high molecular mobility to the interfacial binding. The extension to a wide range of materials for MSA is desired. Herein, we have developed a strategy of adjusting intrinsic properties (e.g., elastic modulus) of nonhydrogel materials to realize MSA, which could broaden the material choices of MSA. Using the widely used elastomer of poly(dimethylsiloxane) (PDMS) as building blocks, we have demonstrated the elastic-modulus-dependent MSA of PDMS based on the host/guest molecular recognition between supramolecular groups of ß-cyclodextrin and adamantane. In the varied elastic modulus range of 0.38 to 3.84 MPa, we obtained the trend of the MSA probability decreasing from 100% at 0.38 MPa to 0% at 3.84 MPa. Meanwhile, in situ measurements of interactive forces between PDMS building blocks have supported the observed assembly phenomena. The underlying reasons are interpreted with the low-modulus flexible surfaces favoring for high molecular mobility to achieve interactions between multiple sites at the interface based on the theory of multivalency. Taken together, we have demonstrated the feasibility of directly adjusting the modulus of bulk materials to realize MSA of nonhydrogel materials, which may provide clues to the fast wet adhesion and new solutions to the additive manufacture of elastomer materials.

Phase Demodulation Method for Fringe Projection Measurement Based on Improved Variable-Frequency Coded Patterns.

The phase-to-height imaging model, as a three-dimensional (3D) measurement technology, has been commonly applied in fringe projection to assist surface profile measurement, where the efficient and accurate calculation of phase plays a critical role in precise imaging. To deal with multiple extra coded patterns and 2π jump error caused to the existing absolute phase demodulation methods, a novel method of phase demodulation is proposed based on dual variable-frequency (VF) coded patterns. In this paper, the frequency of coded fringe is defined as the number of coded fringes within a single sinusoidal fringe period. First, the effective wrapped phase (EWP) as calculated using the four-step phase shifting method was split into the wrapped phase region with complete period and the wrapped phase region without complete period. Second, the fringe orders in wrapped phase region with complete period were decoded according to the frequency of the VF coded fringes and the continuous characteristic of the fringe order. Notably, the sampling frequency of fast Fourier transform (FFT) was determined by the length of the decoding interval and can be adjusted automatically with the variation in height of the object. Third, the fringe orders in wrapped phase region without complete period were decoded depending on the consistency of fringe orders in the connected region of wrapped phase. Last, phase demodulation was performed. The experimental results were obtained to confirm the effectiveness of the proposed method in the phase demodulation of both discontinuous objects and highly abrupt objects.

Impaired PSII Proteostasis Promotes Retrograde Signaling via Salicylic Acid.

Photodamage of the PSII reaction center (RC) is an inevitable process in an oxygen-rich environment. The damaged PSII RC proteins (Dam-PSII) undergo degradation via the thylakoid membrane-bound FtsH metalloprotease, followed by posttranslational assembly of PSII. While the effect of Dam-PSII on gene regulation is described for cyanobacteria, its role in land plants is largely unknown. In this study, we reveal an intriguing retrograde signaling pathway by using the Arabidopsis (Arabidopsis thaliana) yellow variegated2-9 mutant, which expresses a mutated FtsH2 (FtsH2G267D) metalloprotease, specifically impairing its substrate-unfolding activity. This lesion leads to the perturbation of PSII protein homeostasis (proteostasis) and the accumulation of Dam-PSII. Subsequently, this results in an up-regulation of salicylic acid (SA)-responsive genes, which is abrogated by inactivation of either an SA transporter in the chloroplast envelope membrane or extraplastidic SA signaling components as well as by removal of SA. These results suggest that the stress hormone SA, which is mainly synthesized via the chloroplast isochorismate pathway in response to the impaired PSII proteostasis, mediates the retrograde signaling. These findings reinforce the emerging view of chloroplast function toward plant stress responses and suggest SA as a potential plastid factor mediating retrograde signaling.

Silk Fibroin-Based Materials for Catalyst Immobilization.

Silk fibroin is a widely and commercially available natural protein derived from silkworm cocoons. Thanks to its unique amino acid composition and structure, which lead to localized nanoscale pockets with limited but sufficient hydration for protein interaction and stabilization, silk fibroin has been studied in the field of enzyme immobilization. Results of these studies have demonstrated that silk fibroin offers an important platform for covalent and noncovalent immobilization of enzymes through serving as a stabilization matrix/support with high retention of the biological activity of the enzymes of interest. In the hope of providing suggestions for potential future research directions, this review has been written to briefly introduce and summarize key advances in silk fibroin-based materials for immobilization of both enzymes/biocatalysts (including alkaline phosphatase, ß-glucosidase, glucose oxidase, lipase, urease, uricase, horseradish peroxidase, catalase, xanthine oxidase, tyrosinase, acetylcholinesterase, neutral protease, α-chymotrypsin, amylase, organophosphorus hydrolase, ß-galactosidase, carbonic anhydrase, laccase, zymolyase, phenylalanine ammonia-lyase, thymidine kinase, and several others) and non-enzymatic catalysts (such as Au, Pd, Fe, α-Fe2O3, Fe3O4, TiO2, Pt, ZnO, CuO, Cu2O, Mn3O4, and MnO2).

Impact of Pesticide Type and Emulsion Fat Content on the Bioaccessibility of Pesticides in Natural Products.

There is interest in incorporating nanoemulsions into certain foods and beverages, including dips, dressings, drinks, spreads, and sauces, due to their potentially beneficial attributes. In particular, excipient nanoemulsions can enhance the bioavailability of nutraceuticals in fruit- and vegetable-containing products consumed with them. There is, however, potential for them to also raise the bioavailability of undesirable substances found in these products, such as pesticides. In this research, we studied the impact of excipient nanoemulsions on the bioaccessibility of pesticide-treated tomatoes. We hypothesized that the propensity for nanoemulsions to raise pesticide bioaccessibility would depend on the polarity of the pesticide molecules. Bendiocarb, parathion, and chlorpyrifos were therefore selected because they have Log P values of 1.7, 3.8, and 5.3, respectively. Nanoemulsions with different oil contents (0%, 4%, and 8%) were fabricated to study their impact on pesticide uptake. In the absence of oil, the bioaccessibility increased with increasing pesticide polarity (decreasing Log P): bendiocarb (92.9%) > parathion (16.4%) > chlorpyrifos (2.8%). Bendiocarb bioaccessibility did not depend on the oil content of the nanoemulsions, which was attributed to its relatively high water-solubility. Conversely, the bioaccessibility of the more hydrophobic pesticides (parathion and chlorpyrifos) increased with increasing oil content. For instance, for chlorpyrifos, the bioaccessibility was 2.8%, 47.0%, and 70.7% at 0%, 4%, and 8% oil content, respectively. Our findings have repercussions for the utilization of nanoemulsions as excipient foods in products that may have high levels of undesirable non-polar substances, such as pesticides.

Engineering Protein-Clay Nanosheets Composite Hydrogels with Designed Arginine-Rich Proteins.

Clay nanosheets (CNSs) have been widely used in the design of nanocomposite biomaterials. CNSs display a disk-like morphology with strong negatively charged surfaces. It has been shown that guanidinium-containing molecules can bind CNSs through noncovalent salt-bridge interactions and thus serve as "molecular glues" for CNSs. Making use of the guanidinium side chain in arginine, here, we designed novel arginine-rich elastomeric proteins to engineer protein-CNS nanocomposite hydrogels. Our results showed that these arginine-rich proteins can interact with CNSs effectively and can cross-link CNSs into hydrogels. Rheological measurements showed that mechanical properties of the resultant hydrogels depended on the arginine content in the arginine-rich proteins as well as CNS/protein concentration. Compared with hydrogels constructed from CNSs or proteins alone, the novel protein-CNS nanocomposite hydrogels show much improved mechanical properties. Our work opens up a new avenue to engineer functional protein hydrogels for various applications.

Illustration and application of enhancing effect of arginine on interactions between nano-clays: self-healing hydrogels.

Nano-clays (NCs) as a representative type of nano-materials are a source of inspiration for design of new biomedical materials with excellent performances. Research has shown that guanidinium ions (Gu+) can form non-covalent salt-bridge interactions with NCs, serving as "molecular glue" in the fabrication of NC-based composites. However, synthesis of the Gu+-containing molecules is always not easy. Since the natural amino acid arginine (Arg) possesses Gu+, Arg could potentially be a replacement for the synthetic molecules. To prove this possibility, nano-composites were constructed by combining model anisotropic NCs with Arg-modified nano-hydroxyapatite (nHAP-Arg) and polyarginine (poly-Arg), respectively. Formation of molecular interactions between NCs and nHAP-Arg/poly-Arg was demonstrated by enhanced gelation behaviour of NCs. Through taking the unique advantage of Arg, this study can be readily implemented in constructing a variety of NC-based composites with diverse functionalities that are necessary for potential applications in tissue engineering and regenerative medicine.

Improved unwrapped phase retrieval method of a fringe projection profilometry system based on fewer phase-coding patterns.

In this paper, based on two additional phase-coding patterns, an improved phase demodulation method is proposed. First, six equally spaced coding phases in the interval [$ - \pi $-π, $\pi $π] are embedded in different periods of the coded fringes following a certain sequence. Subsequently, since a group of phase orders can be uniquely determined by the four adjacent coding phases, the phase-order map of the object can be generated. To ensure the accuracy of decoding results, the interference coding numbers should be corrected in advance. In the meantime, the connected regions exhibiting the same orders are classified and then labeled for simplifying the decoding process. The simulation results verify the feasibility of the proposed method. By two groups of 3D imaging experiments, the applicability of this method to multiple objects and discontinuous objects is confirmed.

Flexible calibration method of an FPP system based on a geometrical model and NLSM with fewer parameters.

Fringe projection profilometry (FPP) technology is an important method for 3D reconstruction. In this paper, we proposed a flexible calibration method of an FPP system based on the imaging principle and geometrical structure of the system. The target coordinates are only related to its pixel coordinates and phase. First, the fringe images are projected onto the calibration plate, and the phase can be calculated through the four-step phase-shifting method. Then, the pixel coordinates of the feature points can be located with the binarized fringe images and the centroid method. Finally, the calibration parameters are calculated by the nonlinear least-squares method (NLSM). The reconstructed experiment of 162 testing points was carried out, and the result shows that the maximum relative errors on coordinates X, Y, and h are 0.27%, 0.42%, and 0.59%, respectively. The other two surface reconstruction experiments also verify the feasibility of the calibration method.

Flexible calibration method of an FPP system based on a geometrical model and NLSM with fewer parameters: publisher's note.

This publisher's note amends the Funding section of Appl. Opt.58, A7 (2019)APOPAI0003-693510.1364/AO.58.0000A7.

Baicalein Enhances Migration and Invasion of Extravillous Trophoblasts via Activation of the NF-κB Pathway.

BACKGROUND Baicalein, one of the major flavonoids in the plant [i]Scutellaria baicalensis[/i], can regulate the invasive ability of cancer cells. The invasion of trophoblasts is similar to the invasion of tumor cells into host tissues. The appropriate invasion of trophoblast cells into the endometrium is an important factor for successful embryo implantation. In this research, we investigated the effect of baicalein on the invasion and migration of trophoblast cells and its possible molecular mechanism. MATERIAL AND METHODS We treated HTR-8/SVneo cells with different concentrations (0, 0.05, 0.1, and 0.5 µM) of baicalein. The invasion and migration abilities of HTR-8/SVneo cells were studied. Protein levels and gene expression related to invasion and migration were analyzed by Western blot analysis and reverse transcription-quantitative polymerase chain reaction, respectively. RESULTS Baicalein enhanced the migration and invasion of HTR-8/SVneo cells. In addition, gene expression and protein levels of MMP-9 in HTR-8/SVneo cells changed in the presence of baicalein. Moreover, the data show that baicalein activated the NF-κB pathway. Baicalein was also able to rescue effects of an NF-κB-specific inhibitor (JSH-23) on the migration and invasion of HTR-8/SVneo cells. CONCLUSIONS In conclusion, our results indicate that baicalein enhances migration and invasion of HTR-8/SVneo cells, which is important for successful pregnancy.

Physicochemical evolutions of starch/poly (lactic acid) composite biodegraded in real soil.

Plastic pollution is a major environmental problem and the waste disposal is a challenge in this case. Poly (lactic acid) (PLA) based biodegradable materials is one of the most attractive polymers which can fulfill the current demand. In this work, the degradation of starch/PLA composite was investigated in real soil environment. The weight loss results demonstrated that the degradation rate of PLA could be accelerated by starch. Scanning electrical microscopy (SEM) and Fourier transform infrared (FTIR) results showed that the samples degraded faster with the presence of starch. The mechanical strengths had an abrupt decrease for the starch/PLA composite while that of PLA only decreased in a low degree. The distribution of carboxyl group intensity and carbon atomic percent reflected the heterogeneity of biodegradation for starch/PLA composite in soil. Moreover, the variation of internal carbon atomic percent was higher than that on the surface, demonstrating that the degradation of starch/PLA composite was bulk degradation. Based on the role of starch played in starch/PLA composite and the physicochemical performance evolutions during biodegradation, it should create a scientific basis for people interested in studying the biodegradation of PLA, and provide some knowledge about controlling the biodegradation rate of PLA through adjusting the content of starch in the composite.

Synthesis, Characterization, and Identification of New in Vitro Covalent DNA Adducts of Divinyl Sulfone, an Oxidative Metabolite of Sulfur Mustard.

Divinyl sulfone (DVS) is an important oxidative metabolic product of sulfur mustard (SM) in vitro and in vivo. Although DVS is not a classical blister agent, its high reactivity and toxicity induced by vinyl groups can also cause blisters like SM upon contact with the skin, eyes, and respiratory organs. The purpose of this paper was to identify whether DVS could covalently bind to DNA bases to form new DNA adducts in cells in vitro. A series of adducts were synthesized and characterized using purine, nucleoside, or DNA, separately, as starting materials. The covalent site, pattern, and relative reactivity of adduct formation were identified and discussed in detail. The results showed that five high abundance site-specific DNA adducts, including two monoadducts and three cross-linked adducts, were obtained when DNA was used as a substrate. When HaCaT cells were exposed to 30 µM of DVS, four new DNA adducts containing monoadducts and cross-linked adducts were found and identified in cells, including N3-A monoadduct, N7-G monoadduct, N7G-N7G bis-adduct, and N3A-N7G cross-linked adduct. Among them, the abundance of N3-A monoadduct was 10 times higher than that of the other three adducts. DNA adduct formation with DVS showed significant differences from that observed with SM. The observation of these new DNA adduct in vitro cells revealed that DNA damage could be also induced by DVS.

Tetrandrine prevents monocrotaline-induced pulmonary arterial hypertension in rats through regulation of the protein expression of inducible nitric oxide synthase and cyclic guanosine monophosphate-dependent protein kinase type 1.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a persistent elevation of pulmonary artery pressure and ventricular hypertrophy. Tetrandrine is a bisbenzylisoquinoline alkaloid that can decrease blood pressure, inhibit the proliferation of vascular smooth muscle cells, and block cardiac hypertrophy, but whether it has a therapeutic effect on PAH remains poorly defined. This study was undertaken to investigate the efficacy of tetrandrine on PAH. METHODS: Forty-eight male Sprague-Dawley rats were randomly and equally divided into four groups. The control group was injected with normal saline; the others were injected with monocrotaline (MCT) to induce PAH, then treated with saline, tetrandrine, and vardenafil, respectively, from day 21 to day 42. On day 43, we measured the mean pulmonary artery pressure under general anesthesia, dissected the rat, and calculated the right ventricular hypertrophy index [right ventricle/(left ventricle plus septum)]. Later we observed the changes in the pulmonary vascular wall; measured the expression of cyclic guanosine monophosphate-dependent protein kinase type 1 and inducible nitric oxide synthase; measured the levels of superoxide dismutase, glutathione, malondialdehyde, and catalase; and then compared the results among groups. RESULTS: Compared with the MCT group, rats treated with tetrandrine had attenuated mean pulmonary artery pressure (20.48 ± 1.49 vs 30.07 ± 1.51; P < .01) and right ventricular hypertrophy index (49.19 ± 2.45 vs 68.50 ± 1.95; P < .01), inhibited proliferation of pulmonary artery smooth muscle cells, and improved endothelial function. Tetrandrine also upregulated the expression of protein kinase type 1 (90.86 ± 1.95 vs 67.34 ± 1.50; P < .01); downregulated the expression of inducible nitric oxide synthase (74.76 ± 1.48 vs 80.19 ± 0.28; P < .01); increased levels of superoxide dismutase (245.54 ± 12.98 vs 166.16 ± 21.42; P < .01), glutathione (0.699 ± 0.032 vs 0.514 ± 0.056; P < .01), and catalase (32.13 ± 2.33 vs 27.19 ± 2.72; P < .01); and decreased malondialdehyde (1.027 ± 0.039 vs 1.462 ± 0.055; P < .01). CONCLUSIONS: Tetrandrine alleviated MCT-induced PAH through regulation of nitric oxide signaling pathway and antioxidant and antiproliferation effects.

Designed biomaterials to mimic the mechanical properties of muscles.

The passive elasticity of muscle is largely governed by the I-band part of the giant muscle protein titin, a complex molecular spring composed of a series of individually folded immunoglobulin-like domains as well as largely unstructured unique sequences. These mechanical elements have distinct mechanical properties, and when combined, they provide the desired passive elastic properties of muscle, which are a unique combination of strength, extensibility and resilience. Single-molecule atomic force microscopy (AFM) studies demonstrated that the macroscopic behaviour of titin in intact myofibrils can be reconstituted by combining the mechanical properties of these mechanical elements measured at the single-molecule level. Here we report artificial elastomeric proteins that mimic the molecular architecture of titin through the combination of well-characterized protein domains GB1 and resilin. We show that these artificial elastomeric proteins can be photochemically crosslinked and cast into solid biomaterials. These biomaterials behave as rubber-like materials showing high resilience at low strain and as shock-absorber-like materials at high strain by effectively dissipating energy. These properties are comparable to the passive elastic properties of muscles within the physiological range of sarcomere length and so these materials represent a new muscle-mimetic biomaterial. The mechanical properties of these biomaterials can be fine-tuned by adjusting the composition of the elastomeric proteins, providing the opportunity to develop biomaterials that are mimetic of different types of muscles. We anticipate that these biomaterials will find applications in tissue engineering as scaffold and matrix for artificial muscles.