Knowledge mapping of nano drug delivery systems across blood - Brain barrier from 1996 to 2022: A bibliometric analysis.

Background: The blood-brain barrier (BBB) is a natural physiological barrier that protects the central nervous system from foreign substances and limits the delivery of drugs to the brain. Nanotechnology has opened up new possibilities for drug delivery in the brain. Over several decades, various Nanoparticle Drug Delivery Systems (NDDS) that can cross the BBB have been developed for targeted delivery in the brain. To gain a comprehensive understanding of the current research hotspots and trends of NDDS across the BBB, this paper employs bibliometric analysis of articles published in the core database of Web of Science (WOS) from 1996 to 2022. Method: A search for relevant research literature on NDDS that can cross the BBB was conducted in the Web of Science database, covering the period from 1996 to 2022. The Bibliometrix R-4.0 software package was used to analyze data related to the countries of publication, research institutions, journals, citations, and keywords. The analysis aimed to identify the co-occurrence of keywords in the documents, including their titles and abstracts. Additionally, cooperative network analyses of authors, institutions, and countries of publication were conducted. Results: A total of 436 articles were analyzed, originating from 174 journals and 13 books, with the majority published in Q1 and Q2 journals. Contributors from 53 countries or regions participated in the publication of these articles, with China, the United States, and India having the highest number of articles by correspondent authors, and China, the United States, and Germany being the most cited countries. Fudan University, Hacettepe University, and Sichuan University were the top three institutions with the most publications. Among the 436 articles analyzed, 1337 keywords and 1450 keywords plus were identified. Factor analysis grouped the keywords plus into two categories: drug delivery systems, polymeric nanoparticles, gold nanoparticles, transferrin, and others, and drug, delivery, efficiency, expression, and mechanism. Conclusion: The research on NDDS that can cross the BBB is gradually receiving attention, and the recognition and cooperation in this field have increased.

A Template Model Explains Jerboa Gait Transitions Across a Broad Range of Speeds.

For cursorial animals that maintain high speeds for extended durations of locomotion, transitions between footfall patterns (gaits) predictably occur at distinct speed ranges. How do transitions among gaits occur for non-cursorial animals? Jerboas (Jaculus) are bipedal hopping rodents that frequently transition between gaits throughout their entire speed range. It has been hypothesized that these non-cursorial bipedal gait transitions are likely to enhance their maneuverability and predator evasion ability. However, it is difficult to use the underlying dynamics of these locomotion patterns to predict gait transitions due to the large number of degrees of freedom expressed by the animals. To this end, we used empirical jerboa kinematics and dynamics to develop a unified spring Loaded Inverted Pendulum model with defined passive swing leg motions. To find periodic solutions of this model, we formulated the gait search as a boundary value problem and described an asymmetrical running gait exhibited by the jerboas that emerged from the numerical search. To understand how jerboas change from one gait to another, we employed an optimization approach and used the proposed model to reproduce observed patterns of jerboa gait transitions. We then ran a detailed numerical study of the structure of gait patterns using a continuation approach in which transitions are represented by bifurcations. We found two primary mechanisms to increase the range of speeds at which gait transitions can occur. Coupled changes in the neutral leg swing angle alter leg dynamics. This mechanism generates changes in gait features (e.g., touchdown leg angle and timings of gait events) that have previously been shown to induce gait transitions. This mechanism slightly alters the speeds at which existing gait transitions occur. The model can also uncouple the left and right neutral leg swing angle, which generates asymmetries between left and right leg dynamics. New gait transitions emerge from uncoupled models across a broad range of speeds. In both the experimental observations and in the model, the majority of the gait transitions involve the skipping and asymmetrical running gaits generated by the uncoupled neutral leg swing angle mechanism. This simulated jerboa model is capable of systematically reproducing all biologically relevant gait transitions at a broad range of speeds.

All common bipedal gaits emerge from a single passive model.

In this paper, we systematically investigate passive gaits that emerge from the natural mechanical dynamics of a bipedal system. We use an energetically conservative model of a simple spring-leg biped that exhibits well-defined swing leg dynamics. Through a targeted continuation of periodic motions of this model, we systematically identify different gaits that emerge from simple bouncing in place. We show that these gaits arise along one-dimensional manifolds that bifurcate into different branches with distinctly different motions. The branching is associated with repeated breaks in symmetry of the motion. Among others, the resulting passive dynamic gaits include walking, running, hopping, skipping and galloping. Our work establishes that the most common bipedal gaits can be obtained as different oscillatory motions (or nonlinear modes) of a single mechanical system with a single set of parameter values. For each of these gaits, the timing of swing leg motion and vertical motion is matched. This work thus supports the notion that different gaits are primarily a manifestation of the underlying natural mechanical dynamics of a legged system. Our results might explain the prevalence of certain gaits in nature, and may provide a blueprint for the design and control of energetically economical legged robots.

Toward Controllable Hydraulic Coupling of Joints in a Wearable Robot.

In this paper, we develop theoretical foundations for a new class of rehabilitation robot: body powered devices that route power between a user's joints. By harvesting power from a healthy joint to assist an impaired joint, novel bimanual and self-assist therapies are enabled. This approach complements existing robotic therapies aimed at promoting recovery of motor function after neurological injury. We employ hydraulic transmissions for routing power, or equivalently for coupling the motions of a user's joints. Fluid power routed through flexible tubing imposes constraints within a limb or between homologous joints across the body. Variable transmissions allow constraints to be steered on the fly, and simple valve switching realizes free space and locked motion. We examine two methods for realizing variable hydraulic transmissions: using valves to switch among redundant cylinders (digital hydraulics) or using an intervening electromechanical link. For both methods, we present a rigorous mathematical framework for describing and controlling the resulting constraints. Theoretical developments are supported by experiments using a prototype fluid-power exoskeleton.

Passive Dynamics Explain Quadrupedal Walking, Trotting, and Tölting.

This paper presents a simplistic passive dynamic model that is able to create realistic quadrupedal walking, tölting, and trotting motions. The model is inspired by the bipedal spring loaded inverted pendulum (SLIP) model and consists of a distributed mass on four massless legs. Each of the legs is either in ground contact, retracted for swing, or is ready for touch down with a predefined angle of attack. Different gaits, that is, periodic motions differing in interlimb coordination patterns, are generated by choosing different initial model states. Contact patterns and ground reaction forces (GRFs) evolve solely from these initial conditions. By identifying appropriate system parameters in an optimization framework, the model is able to closely match experimentally recorded vertical GRFs of walking and trotting of Warmblood horses, and of tölting of Icelandic horses. In a detailed study, we investigated the sensitivity of the obtained solutions with respect to all states and parameters and quantified the improvement in fitting GRF by including an additional head and neck segment. Our work suggests that quadrupedal gaits are merely different dynamic modes of the same structural system and that we can interpret different gaits as different nonlinear elastic oscillations that propel an animal forward.