Explore the vast range of titles available.

The blood–brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among some of the limitations associated with current neurotherapeutics. In recent years, advances in nanodrug delivery have enabled the carrier system containing the active therapeutic drug to target the signaling pathways and pathophysiology that are closely linked to central nervous system (CNS) disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS), brain tumor, epilepsy, ischemic stroke, and neurodegeneration. At present, among the nano formulations, solid lipid nanoparticles (SLNs) have emerged as a putative drug carrier system that can deliver the active therapeutics (drug-loaded SLNs) across the BBB at the target site of the brain, offering a novel approach with controlled drug delivery, longer circulation time, target specificity, and higher efficacy, and more importantly, reducing toxicity in a biomimetic way. This paper highlights the synthesis and application of SLNs as a novel nontoxic formulation strategy to carry CNS drugs across the BBB to improve the use of therapeutics agents in treating major neurological disorders in future clinics.

Software engineering education plays an important role in keeping students educated with software technologies, processes, and practices that are needed by industries. Nevertheless, the nature of software engineering learning activities in traditional classrooms is limited in scope and time, making it more difficult to achieve a proper balance between theory and practice and address industrial demands. This makes scant provision for assisting students in keeping their software engineering knowledge current. To support software engineering education, flipped learning is a suitable strategy. Prior studies have shown that students’ perceptions in flipped learning environments are better than those in traditional learning environments. Nevertheless, in flipped learning, students may not have sufficient ability to conduct learning out of class. Therefore, the flipped learning strategy should aim to meet the needs of students to ensure that they get the appropriate support or feedback during the learning process before the class. The aim of this study was to propose a flipped learning diagnosis approach to promote students’ learning out of class in the flipped classroom. To explore students’ learning performance in software engineering courses, three classes of students were invited to learn with three different learning approaches (traditional learning approach, flipped learning approach, and flipped learning diagnosis approach). The results showed that the students who learned with the flipped learning diagnosis approach outperformed those students who learned with the flipped learning approach or the traditional learning approach.

The aim of software engineering education is to educate students in software technologies, developments, procedures, and scientific practices to enable them to cope with industrial demands. However, the implementation of software engineering education in traditional university classrooms is restricted by the semester structure, making it difficult to achieve a proper learning balance between theory and practice. To balance theoretical and practical learning, prior studies have indicated that flipped learning is a suitable classroom setting for students and teachers. In a flipped learning environment, it is important to enhance and capture students' learning performance before the class to facilitate teachers and students in proceeding with in-class instruction and learning. In this study, an e-book system named BookRoll was applied to support software engineering education in a flipped learning setting. The proposed approach supports and facilitates out-of-class and in-class learning by providing reading and learning analytic functions for teachers and students. To evaluate the proposed approach, two classes of students were allocated to an experimental group and a control group to participate in an experiment. In the flipped learning process, the experimental group was supported by the BookRoll system, while the control group did not use the BookRoll system. The results revealed that the proposed approach not only promoted students' learning achievements in software engineering education but also improved their learning motivation, attitude, and problem-solving ability. The reading behavior analysis further indicated that reading time was a statistically significant predictor of learning achievement.

Bee venom is a complex natural mixture with various pharmaceutical properties. Among these properties, its peptides and enzymes have potential medical therapy for pain relief and inflammation. In clinical settings, this therapy has been used widely to treat diseases by injecting into acupoints. In this article, we have conducted various research from PubMed, Cochrane Library, and Clinical Key from inception of July 2020. The results revealed that bee venom therapy has been reported effective in anti-inflammatory, antiapoptosis, and analgesic effects. Moreover, bee venom acupuncture has been commonly used for clinical disorders such as Parkinson disease, neuropathic pain, Alzheimer disease, intervertebral disc disease, spinal cord injury, musculoskeletal pain, arthritis, multiple sclerosis, skin disease and cancer.

Inflammation is a major root of several diseases such as allergy, cancer, Alzheimer’s, and several others, and the present state of existing drugs provoked researchers to search for new treatment strategies. Plants are regarded to be unique sources of active compounds holding pharmacological properties, and they offer novel designs in the development of therapeutic agents. Therefore, this study aimed to explore the anti-inflammatory mechanism of esculetin in lipoteichoic acid (LTA)-induced macrophage cells (RAW 264.7). The relative expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO) production and COX-2 expression were intensified in LTA-induced RAW cells. The phosphorylation status of mitogen-activated protein kinases (extracellular signal-regulated kinase (ERK)1/2, p38 MAPK, and c-Jun N-terminal kinase (JNK)) and nuclear factor kappa B (NF-κB) p65 were detected by using Western blot assay. The nuclear translocation of p65 was assessed by confocal microscopic image analysis. Esculetin significantly and concentration-dependently inhibited LTA-induced NO production and iNOS expression, but not COX-2 expression, in RAW cells. Esculetin was not effective in LTA-induced MAPK molecules (ERK, p38 and JNK). However, esculetin recovered LTA-induced IκBα degradation and NF-κB p65 phosphorylation. Moreover, esculetin at a higher concentration of 20 µM evidently inhibited the nuclear translocation of NF-κB p65. At the same high concentration, esculetin augmented Nrf2 expression and decreased DPPH radical generation in RAW 264.7 cells. This study exhibits the value of esculetin for the treatment of LTA-induced inflammation by targeting NF-κB signaling pathways via its antioxidant properties.

Optimizing the impact on the economy of control strategies aiming at containing the spread of COVID-19 is a critical challenge. We use daily new case counts of COVID-19 patients reported by local health administrations from different Metropolitan Statistical Areas (MSAs) within the US to parametrize a model that well describes the propagation of the disease in each area. We then introduce a time-varying control input that represents the level of social distancing imposed on the population of a given area and solve an optimal control problem with the goal of minimizing the impact of social distancing on the economy in the presence of relevant constraints, such as a desired level of suppression for the epidemics at a terminal time. We find that with the exception of the initial time and of the final time, the optimal control input is well approximated by a constant, specific to each area, which contrasts with the implemented system of reopening ‘in phases’. For all the areas considered, this optimal level corresponds to stricter social distancing than the level estimated from data. Proper selection of the time period for application of the control action optimally is important: depending on the particular MSA this period should be either short or long or intermediate. We also consider the case that the transmissibility increases in time (due e.g. to increasingly colder weather), for which we find that the optimal control solution yields progressively stricter measures of social distancing. We finally compute the optimal control solution for a model modified to incorporate the effects of vaccinations on the population and we see that depending on a number of factors, social distancing measures could be optimally reduced during the period over which vaccines are administered to the population.

Yilan, Taiwan is the first place in East Asia where freshwater glass eels, the juvenile stage of Anguilla species, arrive by ocean currents. We collected glass eels by fyke net in Lanyang River estuary twice a month from July 2010 to November 2023. By morphological examination and sequencing of the mitochondrial cytochrome b gene, we identified seven species of Anguilla . Most of the glass eels captured in Yilan belonged to the species A. japonica , A. marmorata , and A. bicolor pacifica . Only a few were A. luzonensis , and two A. celebesensis were recorded. In addition, two species were recorded for the time time from Taiwan; A. interioris and A. borneensis were confirmed by cytochrome b sequencing. Thus, we increase the number of Anguilla species in Taiwan from five to seven.

The current study aimed at investigating how mobile seamless technology can be used to enhance the pragmatic competence of learners of Chinese as a second language (CSL). 34 overseas CSL learners participated in this study. They were randomly assigned into two groups: the classroom group, executing language tasks in fake contexts in a traditional classroom; and the real-world group, executing identical tasks in real world with the support provided by a mobile seamless learning platform (MOSE). All the CSL learners were asked to make a plan of receiving a friend abroad after collecting the information about the shops or stores in the neighborhood of the campus. Both quantitative (Mandarin communication performance test) and qualitative data (videos recorded during the learning process) were collected and analyzed in this 4-week study. The analytical results show that both groups made significant improvements in the test-based Mandarin communication performance. However, according to the qualitative data, the CSL learners in the real-world group made significantly fewer errors when executing language tasks than did those in the classroom group. Furthermore, they did not depend on their first language to communicate with the people they visited in the real world and they had more peer cooperation with the support provided by the MOSE platform compared with those in the classroom group.

The cytochromes P450 are versatile enzymes found in all forms of life. Most P450s use dioxygen on a heme center to activate substrates, but one class of P450s utilizes hydrogen peroxide instead. Within the class of P450 peroxygenases, the P450 OleTJE isozyme binds fatty acid substrates and converts them into a range of products through the α-hydroxylation, β-hydroxylation and decarboxylation of the substrate. The latter produces hydrocarbon products and hence can be used as biofuels. The origin of these product distributions is unclear, and, as such, we decided to investigate substrate positioning in the active site and find out what the effect is on the chemoselectivity of the reaction. In this work we present a detailed computational study on the wild-type and engineered structures of P450 OleTJE using a combination of density functional theory and quantum mechanics/molecular mechanics methods. We initially explore the wild-type structure with a variety of methods and models and show that various substrate activation transition states are close in energy and hence small perturbations as through the protein may affect product distributions. We then engineered the protein by generating an in silico model of the double mutant Asn242Arg/Arg245Asn that moves the position of an active site Arg residue in the substrate-binding pocket that is known to form a salt-bridge with the substrate. The substrate activation by the iron(IV)-oxo heme cation radical species (Compound I) was again studied using quantum mechanics/molecular mechanics (QM/MM) methods. Dramatic differences in reactivity patterns, barrier heights and structure are seen, which shows the importance of correct substrate positioning in the protein and the effect of the second-coordination sphere on the selectivity and activity of enzymes.

Technology-enhanced learning and learning analytics have always been important topics in the field of education [...]