Bio-orthogonal click chemistry strategy for PD-L1-targeted imaging and pyroptosis-mediated chemo-immunotherapy of triple-negative breast cancer.

BACKGROUND: The combination of programmed cell death ligand-1 (PD-L1) immune checkpoint blockade (ICB) and immunogenic cell death (ICD)-inducing chemotherapy has shown promise in cancer immunotherapy. However, triple-negative breast cancer (TNBC) patients undergoing this treatment often face obstacles such as systemic toxicity and low response rates, primarily attributed to the immunosuppressive tumor microenvironment (TME). METHODS AND RESULTS: In this study, PD-L1-targeted theranostic systems were developed utilizing anti-PD-L1 peptide (APP) conjugated with a bio-orthogonal click chemistry group. Initially, TNBC was treated with azide-modified sugar to introduce azide groups onto tumor cell surfaces through metabolic glycoengineering. A PD-L1-targeted probe was developed to evaluate the PD-L1 status of TNBC using magnetic resonance/near-infrared fluorescence imaging. Subsequently, an acidic pH-responsive prodrug was employed to enhance tumor accumulation via bio-orthogonal click chemistry, which enhances PD-L1-targeted ICB, the pH-responsive DOX release and induction of pyroptosis-mediated ICD of TNBC. Combined PD-L1-targeted chemo-immunotherapy effectively reversed the immune-tolerant TME and elicited robust tumor-specific immune responses, resulting in significant inhibition of tumor progression. CONCLUSIONS: Our study has successfully engineered a bio-orthogonal multifunctional theranostic system, which employs bio-orthogonal click chemistry in conjunction with a PD-L1 targeting strategy. This innovative approach has been demonstrated to exhibit significant promise for both the targeted imaging and therapeutic intervention of TNBC.

Ultrastretchable Electrically Self-Healing Conductors Based on Silver Nanowire/Liquid Metal Microcapsule Nanocomposites.

Stretchable conductive nanocomposites are essential for deformable electronic devices. These conductors currently face significant limitations, such as insufficient deformability, significant resistance changes upon stretching, and drifted properties during cyclic deformations. To tackle these challenges, we present an electrically self-healing and ultrastretchable conductor in the form of bilayer silver nanowire/liquid metal microcapsule nanocomposites. These nanocomposites utilize silver nanowires to establish their initial excellent conductivity. When the silver nanowire networks crack during stretching, the microcapsules are ruptured to release the encased liquid metal for recovering the electrical properties. This self-healing capability allows the nanocomposite to achieve ultrahigh stretchability for both uniaxial and biaxial strains, minor changes in resistance during stretching, and stable resistance after repetitive deformations. The conductors have been used to create skin-attachable electronic patches and stretchable light-emitting diode arrays with enhanced robustness. These developments provide a bioinspired strategy to enhance the performance and durability of conductive nanocomposites.

Human and monkey striatal interneurons are derived from the medial ganglionic eminence but not from the adult subventricular zone.

In adult rodent and monkey brains, newly born neurons in the subventricular zone (SVZ) in the wall of the lateral ventricle migrate into the olfactory bulb (OB) via the rostral migratory stream (RMS). A recent study reported that interneurons are constantly generating in the adult human striatum from the SVZ. In contrast, by taking advantage of the continuous expression of Sp8 from the neuroblast stage through differentiation into mature interneurons, we found that the adult human SVZ does not generate new interneurons for the striatum. In the adult human SVZ and RMS, very few neuroblasts were observed, and most of them expressed the transcription factor Sp8. Neuroblasts in the adult rhesus monkey SVZ-RMS-OB pathway also expressed Sp8. In addition, we observed that Sp8 was expressed by most adult human and monkey OB interneurons. However, very few Sp8+ cells were in the adult human striatum. This suggests that neuroblasts in the adult human SVZ and RMS are likely destined for the OB, but not for the striatum. BrdU-labeling results also revealed few if any newly born neurons in the adult rhesus monkey striatum. Finally, on the basis of transcription factor expression, we provide strong evidence that the vast majority of interneurons in the human and monkey striatum are generated from the medial ganglionic eminence during embryonic developmental stages, as they are in rodents. We conclude that, although a small number of neuroblasts exist in the adult human SVZ, they do not migrate into the striatum and become mature striatal interneurons.

Multifunctional Nanocomposite Yield-Stress Fluids for Printable and Stretchable Electronics.

Compliant materials are crucial for stretchable electronics. Stretchable solids and gels have limitations in deformability and durability, whereas active liquids struggle to create complex devices. This study presents multifunctional yield-stress fluids as printable ink materials to construct stretchable electronic devices. Ionic nanocomposites comprise silica nanoparticles and ion liquids, while electrical nanocomposites use the natural oxidation of liquid metals to produce gallium oxide nanoflake additives. These nanocomposite inks can be printed on an elastomer substrate and stay in a solid state for easy encapsulation. However, their transition into a liquid state during stretching allows ultrahigh deformability up to the fracture strain of the elastomer. The ionic inks produce strain sensors with high stretchability and temperature sensors with high sensitivity of 7% °C-1. Smart gloves are further created by integrating these sensors with printed electrical interconnects, demonstrating bimodal detection of temperatures and hand gestures. The nanocomposite yield-stress fluids combine the desirable qualities of solids and liquids for stretchable devices and systems.

Stretchable MXene/Carbon Nanotube Bilayer Strain Sensors with Tunable Sensitivity and Working Ranges.

Stretchable strain sensors have gained increasing popularity as wearable devices to convert mechanical deformation of the human body into electrical signals. Two-dimensional transition metal carbides (Ti3C2Tx MXene) are promising candidates to achieve excellent sensitivity. However, MXene films have been limited in operating strain ranges due to rapid crack propagation during stretching. In this regard, this study reports MXene/carbon nanotube bilayer films with tunable sensitivity and working ranges. The device is fabricated using a scalable process involving spray deposition of well-dispersed nanomaterial inks. The bilayer sensor's high sensitivity is attributed to the cracks that form in the MXene film, while the compliant carbon nanotube layer extends the working range by maintaining conductive pathways. Moreover, the response of the sensor is easily controlled by tuning the MXene loading, achieving a gauge factor of 9039 within 15% strain at 1.92 mg/cm2 and a gauge factor of 1443 within 108% strain at 0.55 mg/cm2. These tailored properties can precisely match the operation requirements during the wearable application, providing accurate monitoring of various body movements and physiological activities. Additionally, a smart glove with multiple integrated strain sensors is demonstrated as a human-machine interface for the real-time recognition of hand gestures based on a machine-learning algorithm. The design strategy presented here provides a convenient avenue to modulate strain sensors for targeted applications.

Optical levitation of a non-spherical particle in a loosely focused Gaussian beam.

The optical force on a non-spherical particle subjected to a loosely focused laser beam was calculated using the dynamic ray tracing method. Ellipsoidal particles with different aspect ratios, inclination angles, and positions were modeled, and the effects of these parameters on the optical force were examined. The vertical component of the optical force parallel to the laser beam axis decreased as the aspect ratio decreased, whereas the ellipsoid with a small aspect ratio and a large inclination angle experienced a large vertical optical force. The ellipsoids were pulled toward or repelled away from the laser beam axis, depending on the inclination angle, and they experienced a torque near the focal point. The behavior of the ellipsoids in a viscous fluid was examined by analyzing a dynamic simulation based on the penalty immersed boundary method. As the ellipsoids levitated along the direction of the laser beam propagation, they moved horizontally with rotation. Except for the ellipsoid with a small aspect ratio and a zero inclination angle near the focal point, the ellipsoids rotated until the major axis aligned with the laser beam axis.

Hydrodynamic interaction of dorsal fin and caudal fin in swimming tuna.

Tuna, which are known for high-performance swimming, possess a large crescent dorsal fin (DF) and a caudal fin (CF) that differ from those of other fishes. The hydrodynamic interaction between the DF and CF in tuna, which are represented by two tandem 3D flapping plates, is numerically explored in the present study. Hydrodynamic properties and wake structures of the models with and without a DF are compared to investigate the effects of the DF. The thrust on the CF is substantially enhanced by the DF, whereas the force on the DF is not affected by the CF. The constructive interaction between the leading-edge vortex (LEV) on the CF and the vortices shed from the dorsal fin (DFVs) is identified from 3D wake topology and 2D vorticity distributions. The circulation of spanwise vorticity quantitatively reveals that the LEV on the CF is strengthened by the same-signed DFV. The effect of the flapping phase of the CF is examined. The DF-CF interaction is sensitive to the flapping phase at a short spacing, whereas a long spacing between the two fins enables a robust constructive interaction in tuna swimming. A systematic study is carried out to explore the effects of the Strouhal number (St) and the Reynolds number (Re) on the interaction of the fins. The enhancement of thrust due to the DF is diminished at St = 0.63, whereas the Re does not substantially influence the constructive DF-CF interaction.

Lateral migration of an elastic capsule by optical force in a uniform flow.

The lateral migration of an elastic capsule under an optical force in a uniform flow was studied to show the separation characteristics according to the elastic properties in the cross-type optical separator. The initially spherical capsule was moved through the fluid flow using a laser beam with a Gaussian distribution focused along the direction normal to the flow device surface. To simulate such a system, a penalty immersed boundary method was adopted to enable fluid-membrane coupling, and a dynamic ray tracing method was applied to the optical force calculation. The effects of the elastic properties of the capsule membrane (the surface Young's modulus and the bending modulus) on the lateral migration were studied. By increasing the surface Young's modulus, the capsule deformed less and the migration distance increased; however, buckling occurred in the capsule with a high surface Young's modulus. Buckling could be suppressed by increasing the bending rigidity. The effects of the flow velocity and the laser beam power were also examined. In the simulation, the S number, i.e., the ratio of the optical force to the viscous force, was adjusted by decreasing the flow velocity or increasing the laser beam power. The migration distance increased as the S number increased, and a constant lateral migration distance was obtained for a rigid particle for a given S number. An elastic capsule under conditions intermediate between a fixed flow velocity and a fixed laser beam power, however, did not yield a constant lateral migration distance due to the extent of the deformation in the different situations. To predict the lateral migration distance of an elastic capsule, a nondimensional parameter, S_{e}, was defined to include the effects of the optical force, the elastic force, and the fluid viscous force. A unified tendency of the lateral migration distance with S_{e} was obtained for capsules with intermediate elasticity, by varying either the flow velocity or the laser beam power.