Development and Validation of a Machine Learning Prognostic Model of m5C Related immune Genes in Lung Adenocarcinoma.

BACKGROUND: The aim of this retrospective research was to develop an immune-related genes significantly associated with m5C methylation methylation (m5C-IRGs)-related signature associated with lung adenocarainoma (LUAD). METHODS: We introduced transcriptome data to screen out m5C-IRGs in The Cancer Genome Atlas (TCGA)-LUAD dataset. Subsequently, the m5C-IRGs associated with survival were certificated by Kaplan Meier (K-M) analysis. The univariate Cox, least absolute shrinkage and selection operator (LASSO) regression, and xgboost.surv tool were adopted to build a LUAD prognostic signature. We further conducted gene functional enrichment, immune microenvironment and immunotherapy analysis between 2 risk subgroups. Finally, we verified m5C-IRGs-related prognostic gene expression in transcription level. RESULTS: A total of 76 m5C-IRGs were identified in TCGA-LUAD dataset. Furthermore, 27 m5C-IRGs associated with survival were retained. Then, a m5C-IRGs prognostic signature was build based on the 3 prognostic genes (HLA-DMB, PPIA, and GPI). Independent prognostic analysis suggested that stage and RiskScore could be used as independent prognostic factors. We found that 4104 differentially expressed genes (DEGs) between the 2 risk subgroups were mainly concerned in immune receptor pathways. We found certain distinction in LUAD immune microenvironment between the 2 risk subgroups. Then, immunotherapy analysis and chemotherapeutic drug sensitivity results indicated that the m5C-IRGs-related gene signature might be applied as a therapy predictor. Finally, we found significant higher expression of PPIA and GPI in LUAD group compared to the normal group. CONCLUSIONS: The prognostic signature comprised of HLA-DMB, PPIA, and GPI based on m5C-IRGs was established, which might provide theoretical basis and reference value for the research of LUAD. PUBLIC DATASETS ANALYZED IN THE STUDY: TCGA-LUAD dataset was collected from the TCGA (https://portal.gdc.cancer.gov/) database, GSE31210 (validation set) was retrieved from GEO (https://www.ncbi.nlm.nih.gov/geo/) database.

Thermoresponsive Polymer Brush Modulation on the Direction of Motion of Phoretically Driven Janus Micromotors.

We report a thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) brush functionalized Janus Au-Pt bimetallic micromotor capable of modulating the direction of motion with the change of the ambient temperature. The PNIPAM@Au-Pt micromotor moved along the Au-Pt direction with a speed of 8.5 µm s-1 in 1.5 % H2 O2 at 25 °C (below the lower critical solution temperature (LCST) of PNIPAM), whereas it changed the direction of motion (i.e., along the Pt-Au direction) and the speed decreased to 2.3 µm s-1 at 35 °C (above LCST). Below LCST, PNIPAM brushes grafted on the Au side were hydrophilic and swelled, which permitted the electron transfer and proton diffusion on the Au side, and thus the motion is regarded as a self-electrophoretic mechanism. However, PNIPAM brushes above LCST became hydrophobic and collapsed, and thus the driving mechanism switched to the self-diffusiophoresis like that of Pt-modified Janus silica motors. These motors could reversibly change the direction of motion with the transition of the hydrophobic and hydrophilic states of the grafted PNIPAM brushes. Such a thermoresponsive polymer brush functionalization method provides a new strategy for engineering the kinematic behavior of phoretically driven micro/nanomotors.

Macroscale Chemotaxis from a Swarm of Bacteria-Mimicking Nanoswimmers.

Inspired by the dynamics of bacterial swarming, we report a swarm of polymer-brush-grafted, glucose-oxidase-powered Janus gold nanoswimmers with a positive, macroscale chemotactic behavior. These nanoswimmers are prepared through the grafting of polymer brushes onto one side of gold nanoparticles, followed by functionalization with glucose oxidase on the other side. The resulting polymer-brush-functionalized Janus gold nanoswimmers exhibit efficient propulsion with a velocity of up to approximately 120 body lengths s-1 in the presence of glucose. The comparative analysis of their kinematic behavior reveals that the grafted polymer brushes significantly improve the translational diffusion of Janus gold nanoswimmers. Particularly, these bacteria-mimicking Janus gold nanoswimmers display a collectively chemotactic motion along the concentration gradient of a glucose resource, which could be observed at the macroscale.

pH-Sensitive Glucose-Powered Nanomotors for Enhanced Intracellular Drug Delivery and Ferroptosis Efficiency.

We propose a glucose-powered Janus nanomotor where two faces are functionalized with glucose oxidase (GOx) and polydopamine-Fe3+ chelates (PDF), respectively. In the glucose fuel solution, the GOx on the one side of these Janus nanomotors catalytically decomposes glucose fuels into gluconic acid and hydrogen peroxide (H2 O2 ) to drive them at a speed of 2.67 µm/s. The underlying propulsion mechanism is the glucose-based self-diffusiophoresis owing to the generated local glucose concentration gradient by the enzymatic reaction. Based on the enhanced diffusion motion, such nanomotors with catalytic activity increase the uptake towards cells and subsequently exhibit excellent capabilities for Fe3+ ions delivery and H2 O2 generation for enhancing ferroptosis efficiency for inducing cancer cell death. In particular, the Fe3+ ions are released from nanomotors in a slightly acidic environment, and subsequently generate toxic hydroxyl radicals via Fenton reactions, which accumulation reactive oxygen species (ROS) level (~300 %) and further lipid peroxidation (LPO) strengthened ferroptosis therapy for cancer treatment. The as-developed glucose-powered Janus nanomotor with efficient diffusion and Fe ions delivery capabilities show great promise as a potential in biomedical applications.

pH-Responsive Calcium Ions and Crocetin Releasing Hydrogel for Accelerating Skin Wound Healing.

The ideal and highly anticipated dressing for skin wounds should provide a moist environment, possess antibacterial properties, and ensure sustained drug release. In the present work, a hyaluronic acid-based hydrogel was formed by cross-linking crocetin and CaCO3@polyelectrolyte materials (CaCO3@PEM) microspheres with HA hydrogels via hydrogen bond and amido bonding (CaCO3@PEM@Cro@HA hydrogel, CPC@HA hydrogel). Moreover, the CPC@HA hydrogel had the capability of sustained, controlled release of calcium ions and crocetin via pH-sensitive and accelerated skin wound healing. The experiment results showed that the CPC@HA hydrogel exhibited porous network structures, stable physical properties, and had antibacterial properties and biocompatibility in vitro. In addition, the CPC@HA hydrogel covering on the skin wound could reduce inflammation and promote wound healing. The high expression of angiogenic cytokines (CD31) and epidermal terminal differentiation markers (Loricrin) of wound healing tissue suggested the CPC@HA hydrogel also had the function of promoting the remodeling of regenerated skin. Overall, CPC@HA hydrogel has promising potential for clinical applications in accelerating skin wound repair.

Biosafety evaluation of dual-responsive neutrobots.

The toxicity effects of paclitaxel (PTX)-loaded magnetic neutrophil-hybrid swimming microrobots ("neutrobots") in vivo were assessed after intravenous administration to mice. The mice after 72 hours exhibited minimal immunotoxicity and liver and kidney toxicity at an administration dose of 3 × 106 PTX-loaded neutrobots. The minor toxicity of drug-loaded neutrobots holds considerable promise for biomedical applications.

Preparation and characterization of a dual cross-linking injectable hydrogel based on sodium alginate and chitosan quaternary ammonium salt.

The development of cheap and easily available injectable hydrogel is an urgent problem in the field of biomedical engineering. Herein, we used chitosan quaternary ammonium salt and sodium alginate to prepare a dual crosslinking hydrogel. The hydrogel formed in-situ crosslinking and can be injected continuously. Interestingly, the formed hydrogel possessed a homogeneous 3D network structure and exhibited reasonable mechanical properties. Moreover, the hydrogels had excellent injectability, and the compression strength of the hydrogel (Gel-0.5) was up to 27.65 kPa. Additionally, the hydrogel showed good biocompatibility that evaluated by cytotoxicity. Notably, the hydrogel was nontoxic toward NIH-3T3 cells. In summary, the hydrogel we produced can be used as an ideal biomaterial for further applications in the field of biomedical engineering.

Continuously Variable Regulation of the Speed of Bubble-Propelled Janus Microcapsule Motors Based on Salt-Responsive Polyelectrolyte Brushes.

The engineering of self-propelled micro-/nanomotors (MNMs) with continuously variable speeds, akin to macroscopic automobiles equipped with a continuously variable transmission, is still a huge challenge. Herein, after grafting with salt-responsive poly[2-(methacryloyloxy)ethyltrimethylammonium chloride] (PMETAC) brushes, bubble-propelled Janus microcapsule motors with polyelectrolyte multilayers exhibited adjustable speeds when the type and concentration of the counterion was changed. Reversible switching between low- and high-speed states was achieved by modulating the PMETAC brushes between hydrophobic and hydrophilic configurations by ion exchange with ClO4 - and polyphosphate anions. This continuously variable regulation enabled control of the speed in an accurate and predictable manner and an autonomous response to the local chemical environment. This study suggests that the integration of polymer brushes with precisely adjustable responsiveness offers a promising route for motion control of smart MNMs that act like their counterparts in living systems.