Silk Fibroin Improves the Biological Properties of Egg White-Based Bioink for the Bioprinting of Tissue Engineering Materials.

Egg white (EW) is a common nutritious food with excellent heat gelation and biocompatibility, but its application in biomaterials is considerably limited. Silk fibroin (SF) is a protein-based fiber with both excellent mechanical properties and biocompatibility, and its application in biomaterials has attracted much attention. Here, the EW/SF composite scaffold was first synthesized with GMA-modified EW/SF composite bioink (G-EW/SF). When homogenized EW and SF were individually grafted with glycidyl methacrylate (GMA), the grafted EW (G-EW) and SF (G-SF) were mixed in different proportions and then added to I2959. The resulting G-EW/SF composite bioink could be bioprinted into various EW/SF composite scaffolds. Among them, the compressive modulus of EW/SF (50%) composite scaffolds incorporating 50% G-SF was significantly improved. It had a three-dimensional (3D) polypore structure with an average pore size of 61 µm and was mainly composed of ß-sheet structures. Compared with the EW scaffold alone, the thermal decomposition temperature of the EW/SF scaffold was 10 °C higher, and the residual rate after 9 days of enzymatic hydrolysis had increased by about 18%. The scaffold prolonged the sustained release of insulin and promoted the adhesion, growth, and proliferation of the L-929 cells. Therefore, the EW/SF composite scaffolds with good cell proliferation ability and certain mechanical properties can be used in different applications including cells, drugs, and tissues. These results provide new prospects for the application of the EW protein to medical tissue engineering materials.

Encephalitis and poor neuronal death-mediated control of herpes simplex virus in human inherited RIPK3 deficiency.

Inborn errors of TLR3-dependent type I IFN immunity in cortical neurons underlie forebrain herpes simplex virus-1 (HSV-1) encephalitis (HSE) due to uncontrolled viral growth and subsequent cell death. We report an otherwise healthy patient with HSE who was compound heterozygous for nonsense (R422*) and frameshift (P493fs9*) RIPK3 variants. Receptor-interacting protein kinase 3 (RIPK3) is a ubiquitous cytoplasmic kinase regulating cell death outcomes, including apoptosis and necroptosis. In vitro, the R422* and P493fs9* RIPK3 proteins impaired cellular apoptosis and necroptosis upon TLR3, TLR4, or TNFR1 stimulation and ZBP1/DAI-mediated necroptotic cell death after HSV-1 infection. The patient's fibroblasts displayed no detectable RIPK3 expression. After TNFR1 or TLR3 stimulation, the patient's cells did not undergo apoptosis or necroptosis. After HSV-1 infection, the cells supported excessive viral growth despite normal induction of antiviral IFN-ß and IFN-stimulated genes (ISGs). This phenotype was, nevertheless, rescued by application of exogenous type I IFN. The patient's human pluripotent stem cell (hPSC)-derived cortical neurons displayed impaired cell death and enhanced viral growth after HSV-1 infection, as did isogenic RIPK3-knockout hPSC-derived cortical neurons. Inherited RIPK3 deficiency therefore confers a predisposition to HSE by impairing the cell death-dependent control of HSV-1 in cortical neurons but not their production of or response to type I IFNs.

Ultrashort-Pulse-Microwave Excited Whole-Breast Thermoacoustic Imaging With Uniform Field of Large Size Aperture Antenna for Tumor Screening.

Microwave-induced thermoacoustic imaging (MTAI) has been widely used in biomedical science, and has the potential as an auxiliary measure for clinical diagnosis and treatment. Recently, there are increasing interests in using ultrashort microwave-pumped thermoacoustic imaging techniques to obtain high-efficiency, high-resolution images. However, the traditional imaging system can only provide uniform radiation in a relatively small area, which limits their large field of view in clinical applications (such as whole-breast imaging, brain imaging). To address this problem, we propose an ultrashort pulse microwave thermoacoustic imaging device with a large size aperture antenna. The system can provide a microwave radiation area of 40 cm × 27 cm and a uniform imaging view of 14 cm × 14 cm. With 7 cm imaging depth and a 290 µm resolution. The practical feasibility of the system for breast tumor screening is tested in phantoms with different shapes and in an ex vivo human breast tumor which is embedded in the excised breast of an ewe (π × 5 cm × 5 cm). The tumor can be identified with a contrast of about 1:2. The results demonstrate that the dedicated MTAI system with the uniform large field of view, high imaging resolution, and large imaging depth have the potential for clinical routine breast screening.

A stimulated liquid-gas phase transition nanoprobe dedicated to enhance the microwave thermoacoustic imaging contrast of breast tumors.

Microwave-induced thermoacoustic imaging (MTAI), combining the advantages of the high contrast of microwave imaging and the high resolution of ultrasonic imaging, is a potential candidate for breast tumor detection. MTAI probes have been used to extend thermoacoustic imaging to molecular imaging. However, due to the high content of water molecules in tissues, the thermoelastic expansion-based probes used in conventional MTAI are not capable of adequate enhancement. Herein, an MTAI nanoprobe for amplification of thermoacoustic (TA) signals by the stimulated liquid-gas phase transition mechanism has been developed, providing significantly higher signal amplitude than that from the conventional mechanism of thermoelastic expansion. The nanoprobe consists of liquid perfluorohexane (PFH) and tungsten disulfide (WS2) nanoparticles rich in defect electric dipoles. When irradiated with pulsed microwaves, the defect electric dipoles in WS2 were repeatedly polarized by gigahertz. This results in localized transient heating and an acoustic shockwave, which destroys the van der Waals forces between PFH molecules. Ultimately, liquid PFH droplets undergo a liquid-gas phase transition, generating dramatically enhanced TA signals. The practical feasibility was tested in vitro and in a breast tumor animal model. The results show that the proposed nanoprobe can greatly improve the contrast of tumor imaging. It will be a new generation probe for MTAI.

Sodium N-lauryl amino acids derived from silk protein can form catanionic aggregates with cytarabine as novel anti-tumor drug delivery systems.

A sodium N-lauryl amino acids (shortly silk sericin surfactant, SSS) is synthesized with lauryl chloride and sericin amino acids recovered from silk industrial waste. The purpose of this study is to explore whether the sericin surfactant can be used as a potential drug delivery carrier. By controlling the proportion of cationic drugs, cytarabine hydrochloride (CH) and anionic SSS, the aggregation behavior, slow release capability and toxicological effects of catanionic aggregates or vesicles, formed through CH and SSS, have been investigated in detail. Dynamic light scattering (DLS), transmission electron microscopy (TEM), and zeta potential analysis showed that the aggregate solution could form a stable vesicle structure when the mass fraction of CH is less than or equal to 0.3. The drug release results showed that the cumulative release rate of the catanionic aggregation solution with CH mass fraction of 0.2 reached a maximum at 18 h, being approximately 9 times greater than that of pure cytarabine. The CH/SSS aggregates had a significant sustained release effect compared with the control group. At the same time, vesicles formed by SSS and CH have better anti-tumor effects compared with the pure drug group. In summary, sericin surfactant from silk industrial waste has a potential use as a drug delivery carrier.