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A microneedle (MN) is a painless and minimally invasive drug delivery device initially developed in 1976. As microneedle technology evolves, microneedles with different shapes (cone and pyramid) and forms (solid, drug-coated, hollow, dissolvable and hydrogel-based microneedles) have been developed. The main objective of this review is the applications of microneedles in biomedical areas. Firstly, the classifications and manufacturing of microneedle are briefly introduced so that we can learn the advantages and fabrications of different MNs. Secondly, research of microneedles in biomedical therapy such as drug delivery systems, diagnoses of disease, as well as wound repair and cancer therapy are overviewed. Finally, the safety and the vision of the future of MNs are discussed.

Although aberrant alveolar myofibroblasts (AMYFs) proliferation and differentiation are often associated with abnormal lung development and diseases, such as bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), epigenetic mechanisms regulating proliferation and differentiation of AMYFs remain poorly understood. Protein arginine methyltransferase 7 (PRMT7) is the only reported type III enzyme responsible for monomethylation of arginine residue on both histone and nonhistone substrates. Here we provide evidence for PRMT7’s function in regulating AMYFs proliferation and differentiation during lung alveologenesis. In PRMT7 -deficient mice, we found reduced AMYFs proliferation and differentiation, abnormal elastin deposition, and failure of alveolar septum formation. We further shown that oncogene forkhead box M1 (Foxm1) is a direct target of PRMT7 and that PRMT7-catalyzed monomethylation at histone H4 arginine 3 (H4R3me1) directly associate with chromatin of Foxm1 to activate its transcription, and thereby regulate of cell cycle-related genes to inhibit AMYFs proliferation and differentiation. Overexpression of Foxm1 in isolated myofibroblasts (MYFs) significantly rescued PRMT7 -deficiency-induced cell proliferation and differentiation defects. Thus, our results reveal a novel epigenetic mechanism through which PRMT7-mediated histone arginine monomethylation activates Foxm1 transcriptional expression to regulate AMYFs proliferation and differentiation during lung alveologenesis and may represent a potential target for intervention in pulmonary diseases.

The blood-spinal cord barrier (BSCB) plays significance roles in recovery following spinal cord injury (SCI), and diabetes mellitus (DM) impairs endothelial cell function and integrity of BSCS. Endoplasmic reticulum (ER) stress occurs in the early stages of SCI and affects prognosis and cell survival. However, the relationship between ER stress and the integrity of BSCB in diabetic rats after SCI remains unclear. Here we observed that diabetic rats showed increased extravasation of Evans Blue (EB) dye, and loss of endothelial cells and pericytes 1 day after SCI compared to non-diabetic rats. Diabetes was also shown to induce activation of ER stress. Similar effects were observed in human brain microvascular endothelial cells. 4-phenylbutyric acid (4-PBA), an ER stress inhibitor lowered the adverse effect of diabetes on SCI, reduced EB dye extravasation, and limited the loss of endothelial cells and pericytes. Moreover, 4-PBA treatment partially reversed the degradation of tight junction and adherens junction both in vivo and in vitro . In conclusion, diabetes exacerbates the disruption of BSCB after SCI via inducing ER stress, and inhibition of ER stress by 4-PBA may play a beneficial role on the integrity of BSCB in diabetic SCI rats, leading to improved prognosis.

Protein‐based hydrogels have attracted great attention due to their excellent biocompatible properties, but often suffer from weak mechanical strength. Conventional strengthening strategies for protein‐based hydrogels are to introduce nanoparticles or synthetic polymers for improving their mechanical strength, but often compromise their biocompatibility. Here, a new, general, protein unfolding‐chemical coupling (PNC) strategy is developed to fabricate pure protein hydrogels without any additives to achieve both high mechanical strength and excellent cell biocompatibility. This PNC strategy combines thermal‐induced protein unfolding/gelation to form a physically‐crosslinked network and a ‐NH2/‐COOH coupling reaction to generate a chemicallycrosslinked network. Using bovine serum albumin (BSA) as a globular protein, PNC‐BSA hydrogels show macroscopic transparency, high stability, high mechanical properties (compressive/tensile strength of 115/0.43 MPa), fast stiffness/toughness recovery of 85%/91% at room temperature, good fatigue resistance, and low cell cytotoxicity and red blood cell hemolysis. More importantly, the PNC strategy can be not only generally applied to silk fibroin, ovalbumin, and milk albumin protein to form different, high strength protein hydrogels, but also modified with PEDOT/PSS nanoparticles as strain sensors and fluorescent fillers as color sensors. This work demonstrates a new, universal, PNC method to prepare high strength, multi‐functional, pure protein hydrogels beyond a few available today. A new, robust, and universal, crosslinking strategy is proposed and demonstrated to prepare high strength, multi‐functional, pure protein hydrogels without any synthetic components. Such general crosslinking property makes use of general heat‐induced protein unfolding and ‐NH2/‐COOH coupling to produce pure protein hydrogels, beyond a few available today.

This paper proposes a novel Distributed-Integrated Model Predictive Control (DI-MPC) strategy for the multi-vessel cooperative path following, formation control and obstacle avoidance. Each vessel is designed with an individually distributed controller based on the MPC theory and communication graph. Subject to actuator limitations and formation constraints, the motion control and thrust allocation are integrated into a dynamic model to achieve direct control to the thrusters. A bivariate thrust efficiency matrix is embedded into the model to consider the hydrodynamic interaction effects between adjacent thrusters. The Nominal System is introduced to generate the linearized predictive model. To achieve consensus among various vessels, a real-time iterative negotiation framework is established. The Kalman Filter is utilized to estimate the low-frequency state variables from the external disturbances of environment loads and measurement noises. Numerical simulations based on the proposed distributed strategy and the centralized strategy are carried out under the scenario of cooperative operation in the Huangpu River (in Shanghai). Comparative analysis results demonstrate the high control performance of both the strategies. DI-MPC mainly contributes to the system flexibility, computational cost reduction (67.65%), energy consumption reduction (5.03%) and fault-tolerant capability. Furthermore, DI-MPC also shows strong applicability to large-scale cooperative control problems.

Thrust allocation is of great importance for the application of Dynamic Positioning System (DPS). For dynamically positioned vessels, the thrust allocation is formulated as a nonlinear optimization problem, where the demanded forces and moments are distributed among the available thrusters. Both hydrodynamic interaction effects and physical limitations of thrusters affect the thrust generation. Therefore, the thrust allocation algorithm can be improved if these effects are considered. We propose a bivariate thrust efficiency function, dealing with both the forward thruster angle and the rear thruster angle, to describe the thrust loss. The thrust efficiency function is obtained from the model tests and approximated by the Radial Basis Function (RBF) neural network. The consequent thrust allocation problem is solved by the Sequential Quadratic Programming (SQP) algorithm with slack variables. The numerical simulations demonstrate a maximum power reduction of 16.03% compared with the forbidden zone algorithm. The proposed algorithm can also enhance system stability, highlighting the advantages of taking bivariate thrust efficiency function into account.

For dynamic positioning systems, a three degree-of-freedom motion control in the horizontal plane has usually been regarded as adequate for practical applications. However, for marine structures with a small water-plane area and low metacentric height, unintentional surge–pitch coupled motion will be induced by thruster actions. To effectively mitigate the thruster-induced pitch motion, we first apply a pitch damping controller for the dynamic positioning of a semisubmersible platform. Quantitative studies are conducted to select the optimal control coefficient for this damping controller, and its influence on surge–pitch coupled motion is analyzed theoretically and numerically. Furthermore, a novel adaptive fuzzy damping controller is proposed to improve the pitch mitigating effect. The fuzzy controller takes low-frequency pitch angle and pitch rate as inputs, and outputs time-varying damping control coefficient through fuzzy inference. Comparisons are made between the fixed damping controller and the proposed fuzzy damping controller. Finally, a parametric analysis is conducted to investigate the influence of the maximum damping control coefficient on pitch motion. The overall simulation results show that the proposed fuzzy damping controller has better performance than the fixed damping controller.

As conventional treatments for diabetic wounds often fail to achieve rapid satisfactory healing, the development of effective strategies to accelerate diabetic wound repair is highly demanded. Herein, fibroblast growth factor 21 (FGF21) and metformin co-loaded multifunctional polyvinyl alcohol (PVA) hydrogel were fabricated for improved diabetic wound healing. The in vitro results proved that the hydrogel was adhesive and injectable, and that it could particularly scavenge reactive oxygen species (ROSs), while the in vivo data demonstrated that the hydrogel could promote angiogenesis by recruiting endothelial progenitor cells (EPCs) through upregulation of Ang-1. Both ROSs’ removal and EPCs’ recruitment finally resulted in enhanced diabetic wound healing. This work opens a strategy approach to diabetic wound management by combining biological macromolecules and small chemical molecules together using one promising environmental modulating drug delivery system.

Thruster-assisted position mooring (PM) systems use both mooring lines and thrusters for station keeping of marine structures in ocean environments. To operate in an energy-efficient manner in moderate sea conditions, setpoints need to be appropriately chosen for the setpoint controller, so that the mooring system counteracts main environmental loads, while the thrusters reduce oscillatory motions of the marine structure. In this paper, reinforcement learning is used to design a decision-making agent for setpoint selection. In particular, a deep deterministic policy gradient (DDPG) approach is adopted with the powerful actor–critic architecture to continuously modify the setpoint setting at an optimal position. Extensive numerical experiments demonstrated that with the DDPG-based PM system, the intelligent agent is able to successfully identify the optimal positioning region in an unknown and stochastic environment, and the power consumption of the thrusters is maintained at a considerably low level.