Non-invasive transdermal delivery of biomacromolecules with fluorocarbon-modified chitosan for melanoma immunotherapy and viral vaccines.

Transdermal drug delivery has been regarded as an alternative to oral delivery and subcutaneous injection. However, needleless transdermal delivery of biomacromolecules remains a challenge. Herein, a transdermal delivery platform based on biocompatible fluorocarbon modified chitosan (FCS) is developed to achieve highly efficient non-invasive delivery of biomacromolecules including antibodies and antigens. The formed nanocomplexes exhibits effective transdermal penetration ability via both intercellular and transappendageal routes. Non-invasive transdermal delivery of immune checkpoint blockade antibodies induces stronger immune responses for melanoma in female mice and reduces systemic toxicity compared to intravenous injection. Moreover, transdermal delivery of a SARS-CoV-2 vaccine in female mice results in comparable humoral immunity as well as improved cellular immunity and immune memory compared to that achieved with subcutaneous vaccine injection. Additionally, FCS-based protein delivery systems demonstrate transdermal ability for rabbit and porcine skins. Thus, FCS-based transdermal delivery systems may provide a compelling opportunity to overcome the skin barrier for efficient transdermal delivery of bio-therapeutics.

Transmucosal Delivery of Nasal Nanovaccines Enhancing Mucosal and Systemic Immunity.

Intranasal vaccines can induce protective immune responses at the mucosa surface entrance, preventing the invasion of respiratory pathogens. However, the nasal barrier remains a major challenge in the development of intranasal vaccines. Herein, a transmucosal nanovaccine based on cationic fluorocarbon modified chitosan (FCS) is developed to induce mucosal immunity. In our system, FCS can self-assemble with the model antigen ovalbumin and TLR9 agonist CpG, effectively promoting the maturation and cross-presentation of dendritic cells. More importantly, it can enhance the production of secretory immunoglobin A (sIgA) at mucosal surfaces for those intranasally vaccinated mice, which in the meantime showed effective production of immunoglobulin G (IgG) systemically. As a proof-of-concept study, such a mucosal vaccine inhibits ovalbumin-expressing B16-OVA melanoma, especially its lung metastases. Our work presents a unique intranasal delivery system to deliver antigen across mucosal epithelia and promote mucosal and systemic immunity.

Visualizing the multi-level assembly structures of conjugated molecular systems with chain-length dependent behavior.

It remains challenging to understand the structural evolution of conjugated polymers from single chains to solvated aggregates and film microstructures, although it underpins the performance of optoelectrical devices fabricated via the mainstream solution processing method. With several ensemble visual measurements, here we unravel the morphological evolution process of a model system of isoindigo-based conjugated molecules, including the hidden molecular assembly pathways, the mesoscale network formation, and their unorthodox chain dependence. Short chains show rigid chain conformations forming discrete aggregates in solution, which further grow to form a highly ordered film that exhibits poor electrical performance. In contrast, long chains exhibit flexible chain conformations, creating interlinked aggregates networks in solution, which are directly imprinted into films, forming interconnective solid-state microstructure with excellent electrical performance. Visualizing multi-level assembly structures of conjugated molecules provides a deep understanding of the inheritance of assemblies from solution to solid-state, accelerating the optimization of device fabrication.

Single-atom alloy Ir/Ni catalyst boosts CO2 methanation via mechanochemistry.

A new catalytic approach is pioneered to achieve CO2 methanation via a single atom alloy Ir/Ni catalyst using a ball-milling method. This Ir/Ni catalyst exhibits a TOFCH4 of 10244 h-1 and a 220 h lifetime at 350 °C without deactivation, illustrating excellent catalytic efficiency in the presence of mechanical energy.

A Novel Simulated Annealing-Based Hyper-Heuristic Algorithm for Stochastic Parallel Disassembly Line Balancing in Smart Remanufacturing.

Remanufacturing prolongs the life cycle and increases the residual value of various end-of-life (EoL) products. As an inevitable process in remanufacturing, disassembly plays an essential role in retrieving the high-value and useable components of EoL products. To disassemble massive quantities and multi-types of EoL products, disassembly lines are introduced to improve the cost-effectiveness and efficiency of the disassembly processes. In this context, disassembly line balancing problem (DLBP) becomes a critical challenge that determines the overall performance of disassembly lines. Currently, the DLBP is mostly studied in straight disassembly lines using single-objective optimization methods, which cannot represent the actual disassembly environment. Therefore, in this paper, we extend the mathematical model of the basic DLBP to stochastic parallel complete disassembly line balancing problem (DLBP-SP). A novel simulated annealing-based hyper-heuristic algorithm (HH) is proposed for multi-objective optimization of the DLBP-SP, considering the number of workstations, working load index, and profits. The feasibility, superiority, stability, and robustness of the proposed HH algorithm are validated through computational experiments, including a set of comparison experiments and a case study of gearboxes disassembly. To the best of our knowledge, this research is the first to introduce gearboxes as a case study in DLBP which enriches the research on disassembly of industrial equipment.

Conjugated Polymers in Solution: A Physical Perspective.

Excellent progress has been made in the optoelectronic properties of conjugated polymers by controlling solution-state aggregation. However, due to the wide variety and complex structures of conjugated polymers, it is still challenging to fully understand the complex aggregation process and microstructures both in solution and in the solid state. This Perspective focuses on the chain conformations and the aggregation of conjugated polymers in solution. We discuss the factors in detail which affect solution-state aggregation and microstructures from the perspective of polymer physics in solutions, including chemical structures and environmental conditions. Based on the understanding of multiple interactions of conjugated polymers in solution, strategies to regulate solid-state microstructures and obtain high-performance polymer-based devices from solution-state aggregation are summarized.

ABC-Type, Bola-Form Giant Surfactants: Synthesis and Self-Assembly.

Due to the fast phase separation kinetics and small feature size, the self-assembly of giant molecules has attracted lots of attention. However, there is not much study on multicomponent giant surfactants. In this work, through a modular synthetic strategy, different polyhedral oligomeric silsesquioxane (POSS)-based molecular nanoparticles are installed with diverse functionalities (hydrophobic octavinyl POSS (VPOSS), hydrophilic dihydroxyl-functionalized POSS (DPOSS), and omniphobic perfluoroalkyl-chain-functionalized POSS (FPOSS)) on the ends of one polystyrene (PS) chain to build up a series of triblock bola-form giant surfactants denoted as XPOSS-PSn -FPOSS (X represents V or D). The target molecules are prepared by a combination of atom transfer radical polymerization (ATRP), esterification, as well as Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and thiol-ene "click" reactions. These macromolecules are thoroughly characterized by combined technologies including nuclear magnetic resonance (NMR), size exclusion chromatography (SEC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analyses. It is revealed by small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM) that VPOSS-PSn -FPOSS adopts a two-phase separation scenario where VPOSS and POSS are segregated in one phase. DPOSS-PSn -FPOSS with a third hydrophilic DPOSS shows a three-phase separation scenario, where highly ordered phase structures are difficult to develop owing to the competition of mutual phase separation processes and may be trapped in kinetically metastable states.

Experimental Study on the Grinding of an Fe-Cr-Co Permanent Magnet Alloy under a Small Cutting Depth.

A small cutting depth is the key parameter to realize precision in the machining process. The stability of the machining process will directly affect the quality of machining. In this study, dry grinding experiments using an Fe-Cr-Co permanent magnet alloy with small cutting depths (5 µm) were carried out. The relationship between the number of peaks and valleys and the quality control of the grinding force, wheel speed and feed speed were analyzed. The relationship between the peak and valley values of the grinding force signals and the peak and valley values of the grinding surface obtained using a white light interferometer was revealed. The influence of the grinding parameters on the grinding forces was analyzed by processing the grinding force signals with a low-pass filter based on the rotational speed of the grinding wheel. The experimental results indicated that the difference in grinding force between the peak and valley could be reduced by increasing the grinding wheel speed, which was mainly due to a decrease in average grinding force when the maximum undeformed cutting thickness of the single abrasive decreased. The actual height difference between the grinding surface peak and valley could be realized by increasing the grinding wheel speed. The feed speed of the worktable had no effect on the grinding force signal and the peaks and valleys of the surface morphology. Lower surface roughness could be achieved by reducing the feed speed and increasing the grinding wheel speed.

Self-Amplification of Tumor Oxidative Stress with Degradable Metallic Complexes for Synergistic Cascade Tumor Therapy.

The ferroptosis effect has been illuminated with a clear Fenton reaction mechanism that converts endogenous hydrogen peroxide (H2O2) into highly oxidative hydroxyl radicals (·OH) in ROS-amplified tumor therapy. This ferroptosis-related oxidation effect was then further enhanced by the enzyme-like roles of cisplatin (CDDP). This CDDP-induced apoptosis was promoted in reverse by ferroptosis via the depletion of glutathione (GSH) and prevention of DNA damage repair. Here, we have developed degradable metallic complexes (PtH@FeP) containing an Fe(III)-polydopamine (FeP) core and HA-cross-linked CDDP (PtH) shell, exaggerating in situ toxic ROS production via the synergistic effect of CDDP and Fe(III). Taken together, the rationally designed PtH@FeP provided a new strategy for self-amplified synergistic chemotherapy/ferroptosis/photothermal therapy (PTT) antitumor effects with a reduced dosage that facilitates clinical safety.

RECLAIM: Toward a New Era of Refurbishment and Remanufacturing of Industrial Equipment.

Refurbishment and remanufacturing are the industrial processes whereby used products or parts that constitute the product are restored. Remanufacturing is the process of restoring the functionality of the product or a part of it to "as-new" quality, whereas refurbishment is the process of restoring the product itself or part of it to "like-new" quality, without being as thorough as remanufacturing. Within this context, the EU-funded project RECLAIM presents a new idea on refurbishment and remanufacturing based on big data analytics, machine learning, predictive analytics, and optimization models using deep learning techniques and digital twin models with the aim of enabling the stakeholders to make informed decisions about whether to remanufacture, upgrade, or repair heavy machinery that is toward its end-of-life. The RECLAIM project additionally provides novel strategies and technologies that enable the reuse of industrial equipment in old, renewed, and new factories, with the goal of saving valuable resources by recycling equipment and using them in a different application, instead of discarding them after use. For instance, RECLAIM provides a simulation engine using digital twin in order to predict maintenance needs and potential faults of large industrial equipment. This simulation engine keeps the virtual twins available to store all available information during the lifetime of a machine, such as maintenance operations, and this information can be used to perform an economic estimation of the machine's refurbishment costs. The RECLAIM project envisages developing new technologies and strategies aligned with the circular economy and in support of a new model for the management of large industrial equipment that approaches the end of its design life. This model aims to reduce substantially the opportunity cost of retaining strategies (both moneywise and resourcewise) by allowing relatively old equipment that faces the prospect of decommissioning to reclaim its functionalities and role in the overall production system.

[Narrowing and sliding genioplasty procedure combined with mandibular outer cortex ostectomy technique to correct square jaw in short face].

OBJECTIVE: To evaluate the the feasibility and effectiveness of narrowing and sliding genioplasty combined with mandibular outer cortex ostectomy technique to reshape a square jaw in short face. METHODS: From July 2005 to October 2009, a total of 57 patients received narrowing and sliding genioplasty combined with mandibular outer cortex ostectomy procedure to correct square jaw in short face. All the patients had standard frontal and lateral cephalometric radiographs, panoramic radiographs, and were photographed preoperatively and postoperatively to assess their face contour. The alteration of mandibular angle, mental contour and width of lower face was observed for 6 to 24 months postoperatively. Questionnaires were used to assess the patients' satisfactory. RESULTS: It showed that the postoperative lower face had narrowed and become softer, slender and oval, with a slick mental region. The final aesthetic outcomes were quite satisfactory in all cases from both the view of surgeons and patients. CONCLUSIONS: Narrowing and sliding genioplasty combined with mandibular outer cortex ostectomy procedure could efficiently adjust the shape and position of chin to obtain a good proportion of the lower face, and to change square and short face to slender oval one by single operation in accordance with the fashionable aesthetics in orientals.

[Correction of low angel-square jaw with mandibular "V-Line" ostectomy combined with mandibular outer cortex ostectomy].

OBJECTIVE: To evaluate the feasibility of mandibular "V-Line" osteotomy combined with mandibular outer cortex osteotomy for correction of low angle-square jaw. METHODS: From Jul. 2005 to Nov. 2007, 31 patients with low angle-square jaw were corrected with mandibular "V-Line" osteotomy combined with mandibular outer cortex osteotomy. The patients were followed up for 6-24 months. Pre- and Post-operative standard images and X-ray cephalometric examination were used to assess the therapeutic effect. RESULTS: The wounds were healed primarily in all the 31 cases with no severe complication. The lower labial numbness was happened in 13 cases, which was recovered within 4 months. All the patients achieved esthetic improvement at the frontal and lateral view. The mandibular angle and the mandibular plane angle reached 110 degrees - 120 degrees and 25 degrees - 30 degrees after operation. The distance between the angles was decreased. CONCLUSIONS: The low angle-square jaw can be corrected satisfactorily with mandibular "V-Line" osteotomy combined with mandibular outer cortex osteotomy.

[Osteoblastic differentiation and gene expression profile change in rat bone marrow mesenchymal stem cells after a single period of mechanical strain].

OBJECTIVE: To evaluate the osteoblastic differentiation and compare the difference in the gene expression of rat bone marrow mesenchymal stem cells (MSCs) affected by a single period of mechanical strain. METHODS: Bone marrow MSCs were harvested from the femurs and tibiae of SD rats and cultured in vitro. A four-point bending apparatus were used to perform a single 40-minute period of 2,000 microepsilon mechanical strain on these MSCs. The proliferation of the MSCs was tested by MTT on scheduled date, and the osteoblastic differentiation of the MSCs was measured by testing the expression of osteocalcin and alkaline phosphate (ALP) activity of these cells. In addition, we have investigated the possible mechanisms underlying the action of the single 40-minute period of 2,000 microepsilon mechanical strain on these MSCs, after profile blotted and handled by bioinformation, the gene expressions of these two periods of MSCs were examined. RESULTS: The MSCs have grown well in vitro. Our experiment showed that mechanical environment did not weaken the proliferation of the MSCs. However, the ALP activity and the expression of osteocalcin were significantly up-regulated by the 2,000 microepsilon mechanical strain. Using the 27 K Rat Genome Array, 416 different expressions were found. The rate of different genes was 2.8%, of which the expressions of 247 genes increased (61 genes remarkably increased) and 169 genes decreased (74 genes remarkably decreased) in these two periods of MSCs. CONCLUSION: Mechanical strain induced the osteoblastic differentiation of the MSCs, which may be attributed to the different gene levels.