Nanocage Ferritin Reinforced Polyacrylamide Hydrogel for Wearable Flexible Strain Sensors.

Biocomposite hydrogels are promising for applications in wearable flexible strain sensors. Nevertheless, the existing biocomposite hydrogels are still hard to meet all requirements, which limits the practical application. Here, inspired by the structure and composition of natural ferritin, we design a PAAm-Ferritin hybrid hydrogel through a facile method. Ferritin is uniformly distributed in the cross-linking networks and acts as a nanocage spring model, leading to the enhanced tensile strength of the hydrogel. The fracture stress is 99 kPa at 1400% maximum elongation. As fabricated PAAm-Ferritin hybrid hydrogels exhibit high toughness and low elastic modulus (21 kPa). The PAAm-Ferritin hybrid hydrogels present excellent biocompatibility and increased conductivity compared with PAAm hydrogel. Impressively, as a wearable flexible strain sensor, the PAAm-Ferritin hybrid hydrogels have high sensitivity (gauge factor = 2.06), excellent reliability, and cycling stability. This study indicates the feasibility of utilizing ferritin to synthesize functional materials, which is conducive to expanding the use of protein synthesis of materials technology and application fields.

Hydroxyapatite-reinforced alginate fibers with bioinspired dually aligned architectures.

Biological materials have excellent mechanical properties due to their organized structures from nano- to macro-scale. Artificial manufacture of materials with anisotropic microstructures still remains challenging. We described a stress-induced method to fabricate anisotropic alginate fibers. Organic-inorganic composite fibers were obtained by incorporating aligned hydroxyapatite (HAP) nanowires into the alginate fiber. Detailed structural characterization revealed the bone-like structure of the HAP-reinforced alginate fibers. Tensile test results showed that the maximum Young's modulus and tensile strength were 4.3 GPa and 153.8 MPa, respectively. A multiscale reinforcing mechanism is proposed after the discussion of the structure-property relationship: highly ordered and compacted nanofibrils aligned along the longitudinal direction at the microscale, and two kinds of alginate gels with different mechanical behaviors at the nanoscale coexisted (acidic alginate gel and calcium-alginate gel). This work validates the effectiveness of the bioinspired fabrication strategy, which inspires further manufacturing and optimization of materials for diverse applications.

Particle-attachment crystallization facilitates the occlusion of micrometer-sized Escherichia coli in calcium carbonate crystals with stable fluorescence.

Inspired from the occlusion of macromolecules in mineral crystals during the biomineralization process, the occlusion mechanism of functional guest species into a host matrix is gradually revealed in artificial systems. However, the guest species within calcite crystals are limited to the nanometer scale. Herein, using amorphous calcium carbonate (ACC) as a precursor and taking advantage of the crystallization of vaterite by the attachment of ACC nanoparticles, micrometer-sized modified Escherichia coli (E. coli) was incorporated into vaterite crystals. The occlusion content of bacteria within the vaterite crystal could reach up to 16 wt%. On the contrary, the occlusion of E. coli into calcite crystals, which proceeded via ion-by-ion addition growth, was only confined to the surface layer. Through modifying the surface structure or chemical composition of bacteria, the strong interaction between the surface of the bacteria and calcium carbonate has proved to be the key factor for successful occlusion. Interestingly, the genetically modified green fluorescent protein (GFP)-E. coli/vaterite composites exhibited stable fluorescence for more than six months with little attenuation and the lifetime could be more than 1.2 µs. It was demonstrated that a combination of the amorphous precursor crystallization pathway and a suitable surface structure of the foreign species can significantly enhance the occlusion efficiency of micrometer-sized species in crystals.

Knockdown of Latent Transforming Growth Factor-ß (TGF-ß)-Binding Protein 2 (LTBP2) Inhibits Invasion and Tumorigenesis in Thyroid Carcinoma Cells.

Latent transforming growth factor-ß (TGF-ß)-binding protein 2 (LTBP2) is one of four proteins in the LTBP family of proteins (LTBP1-4) and was shown to play a vital role in tumorigenesis. However, little is known regarding the functional role of LTBP2 in thyroid carcinoma. Therefore, the current study aimed to evaluate the effect of LTBP2 expression on the proliferation, invasion, and tumorigenesis in thyroid carcinoma cells and to explore the molecular mechanism of LTBP2 in tumor progression. Our results showed that the expression of LTBP2 is upregulated in human thyroid carcinoma and cell lines. Knockdown of LTBP2 inhibits the proliferation, invasion, and EMT phenotype in thyroid carcinoma cells. Furthermore, knockdown of LTBP2 attenuates thyroid carcinoma growth in nude mice. Finally, knockdown of LTBP2 inhibits activation of the PI3K/Akt pathway in thyroid carcinoma cells. In summary, the present study has provided further evidence that knockdown of LTBP2 inhibits invasion and tumorigenesis in thyroid carcinoma cells. Our findings may help to further elucidate the molecular mechanisms underlying thyroid carcinoma progression and provide candidate targets for the prevention and treatment of thyroid carcinoma.

4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to inhibit hepatocellular carcinoma cells.

The aim of the present study is to investigate the potential anti-hepatocellular carcinoma (HCC) cell activity by 4SC-202, a novel class I HDAC inhibitor (HDACi). The associated signaling mechanisms were also analyzed. We showed that 4SC-202 treatment induced potent cytotoxic and proliferation-inhibitory activities against established HCC cell lines (HepG2, HepB3, SMMC-7721) and patient-derived primary HCC cells. Further, adding 4SC-202 in HCC cells activated mitochondrial apoptosis pathway, which was evidenced by mitochondrial permeability transition pore (mPTP) opening, cytochrome C cytosol release and caspase-3/-9 activation. Inhibition of this apoptosis pathway, by caspase-3/-9 inhibitors, mPTP blockers, or by shRNA-mediated knockdown of cyclophilin-D (Cyp-D, a key component of mPTP), significantly attenuated 4SC-202-induced HCC cell death and apoptosis. Reversely, over-expression of Cyp-D enhanced 4SC-202's sensitivity in HCC cells. Further studies showed that 4SC-202 induced apoptosis signal-regulating kinase 1 (ASK1) activation, causing it translocation to mitochondria and physical association with Cyp-D. This mitochondrial ASK1-Cyp-D complexation appeared required for mediating 4SC-202-induced apoptosis activation. ASK1 stable knockdown by targeted-shRNAs largely inhibited 4SC-202-induced mPTP opening, cytochrome C release, and following HCC cell apoptotic death. Together, we suggest that 4SC-202 activates ASK1-dependent mitochondrial apoptosis pathway to potently inhibit human HCC cells.

[Study of BRCA1 and BRCA2 gene mutations in human sporadic breast cancers].

OBJECTIVE: To detect the mutations of BRCA1 and BRCA2 in sporadic breast cancer and study the relationship between BRCA1 and BRCA2 mutations and breast cancer. METHODS: Breast cancer tissues of 144 patients and breast tissues of 30 cases of healthy people who were treated from December 2000 to September 2005 were studied. DNA was extracted by the phenol-chloroform method. Fragments of exon 2, exon 3, exon 5, exon 6, exon 7, exon 8, exon 9, exon 10, exon 11, exon 12, exon 13, exon 14, exon 15, exon 16, exon 17, exon 18, exon 19, exon 20, exon 21, exon 22, exon 23 and exon 24 in the BRCA1 gene and exon 10 and exon 14 in the BRCA2 gene were amplified by polymerase chain reaction. Mutation screening was performed by single-strand conformation polymorphism analysis and alterations were confirmed by DNA sequencing. RESULTS: A total of 20 single nucleotide changes in BRCA1 were detected in the 144 cases of breast cancer patients. The total mutation rate was 13.9% and missense mutation rate was 11.1%. No mutation was detected in the BRCA2 and controls. CONCLUSIONS: Mutations in BRCA1 may play an important role in evaluation of sick risk, earlier diagnosis and gene therapy of breast cancer in southern Chinese populations.