Nigericin Boosts Anti-Tumor Immune Response via Inducing Pyroptosis in Triple-Negative Breast Cancer.

Although immune checkpoint inhibitors improved the clinical outcomes of advanced triple negative breast cancer (TBNC) patients, the response rate remains relatively low. Nigericin is an antibiotic derived from Streptomyces hydrophobicus. We found that nigericin caused cell death in TNBC cell lines MDA-MB-231 and 4T1 by inducing concurrent pyroptosis and apoptosis. As nigericin facilitated cellular potassium efflux, we discovered that it caused mitochondrial dysfunction, leading to mitochondrial ROS production, as well as activation of Caspase-1/GSDMD-mediated pyroptosis and Caspase-3-mediated apoptosis in TNBC cells. Notably, nigericin-induced pyroptosis could amplify the anti-tumor immune response by enhancing the infiltration and anti-tumor effect of CD4+ and CD8+ T cells. Moreover, nigericin showed a synergistic therapeutic effect when combined with anti-PD-1 antibody in TNBC treatment. Our study reveals that nigericin may be a promising anti-tumor agent, especially in combination with immune checkpoint inhibitors for advanced TNBC treatment.

Nanoparticles (NPs)-Meditated LncRNA AFAP1-AS1 Silencing to Block Wnt/ß-Catenin Signaling Pathway for Synergistic Reversal of Radioresistance and Effective Cancer Radiotherapy.

Resistance to radiotherapy is frequently encountered in clinic, leading to poor prognosis of cancer patients. Long noncoding RNAs (lncRNAs) play important roles in the development of radioresistance due to their functions in regulating the expression of target genes at both transcriptional and posttranscriptional levels. Exploring key lncRNAs and elucidating the mechanisms contributing to radioresistance are crucial for the development of effective strategies to reverse radioresistance, which however remains challenging. Here, actin filament-associated protein 1 antisense RNA1 (lncAFAP1-AS1) is identified as a key factor in inducing radioresistance of triple-negative breast cancer (TNBC) via activating the Wnt/ß-catenin signaling pathway. Considering the generation of a high concentration of reduction agent glutathione (GSH) under radiation, a reduction-responsive nanoparticle (NP) platform is engineered for effective lncAFAP1-AS1 siRNA (siAFAP1-AS1) delivery. Systemic delivery of siAFAP1-AS1 with the reduction-responsive NPs can synergistically reverse radioresistance by silencing lncAFAP1-AS1 expression and scavenging intracellular GSH, leading to a dramatically enhanced radiotherapy effect in both xenograft and metastatic TNBC tumor models. The findings indicate that lncAFAP1-AS1 can be used to predict the outcome of TNBC radiotherapy and combination of systemic siAFAP1-AS1 delivery with radiotherapy can be applied for the treatment of recurrent TNBC patients.

High-substitute nitrochitosan used as energetic materials: Preparation and detonation properties.

In order to develop new high-energy materials utilizing natural products, a high-substitute nitrochitosan was prepared with different methods. Prepared processes and detonation properties of the nitrochitosan samples were systematically studied. The nitration substitute degree, nitrogen content, exothermic decomposition enthalpy, heat of combustion, impact sensitivity, detonation velocity and detonation pressure of the prepared high-substitute nitrochitosan were 2.01, 16.67 %, -2226 J g-1, -7831.6 ±â€¯116.3 J g-1, >14.2 J, 7.81 km s-1, and 24.03 GPa, respectively. Compared with nitrocellulose (NC), the nitrogen content, impact sensitivity and detonation properties of the prepared nitrochitosan were significantly improved. Nitrochitosan and RDX can form a uniform composite in acetone. With the increase of RDX content, the impact sensitivity of composite increased, but the composite was more stable and not easy to decompose. High-substitute nitrochitosan presents a potential application in solid propellants.

Electrical stimulation affects neural stem cell fate and function in vitro.

Electrical stimulation (ES) has been applied in cell culture system to enhance neural stem cell (NSC) proliferation, neuronal differentiation, migration, and integration. According to the mechanism of its function, ES can be classified into induced electrical (EFs) and electromagnetic fields (EMFs). EFs guide axonal growth and induce directional cell migration, whereas EMFs promote neurogenesis and facilitates NSCs to differentiate into functional neurons. Conductive nanomaterials have been used as functional scaffolds to provide mechanical support and biophysical cues in guiding neural cell growth and differentiation and building complex neural tissue patterns. Nanomaterials may have a combined effect of topographical and electrical cues on NSC migration and differentiation. Electrical cues may promote NSC neurogenesis via specific ion channel activation, such as SCN1α and CACNA1C. To accelerate the future application of ES in preclinical research, we summarized the specific setting, such as current frequency, intensity, and stimulation duration used in various ES devices, as well as the nanomaterials involved, in this review with the possible mechanisms elucidated. This review can be used as a checklist for ES work in stem cell research to enhance the translational process of NSCs in clinical application.

Bionanotube/Poly(3,4-ethylenedioxythiophene) Nanohybrid as an Electrode for the Neural Interface and Dopamine Sensor.

Poly(3,4-ethylene dioxythiophene) (PEDOT) is a promising conductive material widely used for interfacing with tissues in biomedical fields because of its unique properties. However, obtaining high charge injection capability and high stability remains challenging. In this study, pristine carbon nanotubes (CNTs) modified by dopamine (DA) self-polymerization on the surface polydopamine (PDA@CNTs) were utilized as dopants of PEDOT to prepare hybrid films through electrochemical deposition on the indium tin oxide (ITO) electrode. The PDA@CNTs-PEDOT film of the nanotube network topography exhibited excellent stability and strong adhesion to the ITO substrate compared with PEDOT and PEDOT/ p-toulene sulfonate. The PDA@CNTs-PEDOT-coated ITO electrodes demonstrated lower impedance and enhanced charge storage capacity than the bare ITO. When applying exogenous electrical stimulation (ES), robust long neurites sprouted from the dorsal root ganglion (DRG) neurons cultured on the PDA@CNTs-PEDOT film. Moreover, ES promoted Schwann cell migration out from the DRG spheres and enhanced myelination. The PDA@CNTs-PEDOT film served as an excellent electrochemical sensor for the detection of DA in the presence of biomolecule interferences. Results would shed light into the advancement of conducting nanohybrids for applications in the multifunctional bioelectrode in neuroscience.

Advances in injectable self-healing biomedical hydrogels.

In recent years, implantable biomaterials have attracted significant interest owing to their potentials for use in the therapy of physical defects and traumas. Among the implantable biomaterials, hydrogels have received increasing attention for their tunable structures and good rheological behavior. However, the mechanical failures of traditional gel materials during normal operation remain a serious issue. To overcome this problem, hydrogel materials with self-healing and injectable abilities have been developed, with their potential for autonomous self-recovery and minimally invasive implantation. In this paper, the progress of injectable self-healing hydrogels is presented by combining developments in the fundamental knowledge of polymer designs and discussions on the practical biomedical applications of the materials. The mechanisms of different types of self-healing hydrogels are introduced first and their performances are then discussed, followed by a review of the self-healing hydrogels with injectability. The applications of the injectable self-healing hydrogels are discussed in the final section. STATEMENT OF SIGNIFICANCE: This paper provides an overview of the progress of a smart material, injectable self-healing hydrogel, during the past ten years and mainly focuses on its recent development. This paper presents developments in the fundamental knowledge in polymer designs and discussions on the practical biomedical application of the materials, which sheds more light on the advancement of injectable self-healing hydrogels. This paper should be of interest to the readers who are curious about the advances of injectable self-healing hydrogels.

Aromatic Nucleophilic Substitution of FOX-7: Synthesis and Properties of 1-Amino-1-Picrylamino-2,2-Dinitroethylene (APDE) and Its Potassium Salt [K(APDE)].

Two energetic compounds, 1-amino-1-picrylamino-2,2-dinitroethylene (APDE) and its potassium salt [K(APDE)] were synthesized through an aromatic nucleophilic substitution reaction between FOX-7 and picryl chloride. APDE and K(APDE) were characterized by elemental analysis, IR, NMR spectroscopy, and X-ray diffraction. APDE has a 3D wavy layered stacking structure similar to FOX-7. K(APDE) (peak temperature (Tip )=185.6 °C and impact sensitivity (IS)=19.6 J) presents better stability than APDE (tap =133.3 °C and IS=15.7 J). The reasons why the stability of APDE is lower than that of FOX-7 and picryl chloride are analyzed. The detonation velocity (D) and detonation pressure (P) of APDE (8.36 km s-1 and 31.3 Gpa) are close to those of FOX-7 and RDX. The thermal decomposition of K(APDE) is very violent, and its detonation performance (D=9.14 km s-1 and P=38.6 Gpa) is comparable to that of HMX, indicating that K(APDE) has good potential to be a high explosive.