Terpenoids from the Octocorals Menella sp. (Plexauridae) and Lobophytum crassum (Alcyonacea)

A new germacrane-type sesquiterpenoid, menelloide E (1), and a new cembrane-type diterpenoid, lobocrassin F (2), were isolated from the octocorals Menella sp. and Lobophytum crassum, respectively. The structures of terpenoids 1 and 2 were determined by spectroscopic and chemical methods and compound 2 was found to display a significant inhibitory effect on the release of elastase by human neutrophils

Metamorphic testing of Advanced Driver-Assistance System (ADAS) simulation platforms: Lane Keeping Assist System (LKAS) case studies

Context: Simulation-based testing is essential when developing Advanced Driver-Assistance Systems (ADASs) and autonomous driving (AD) systems, producing fast, high-quality test results, at relatively low cost. Simulation testing relies on the quality of the ADAS simulation platform: If the simulation platform is faulty, then the simulation results may be incorrect, and hence useless. However, because of the lack of suitable test oracles — mechanisms to determine the correctness of the software output or behavior — it can be too difficult (or expensive) to verify or validate ADAS/AD simulation platforms, a situation known as the oracle problem. Objective: To alleviate the oracle problem and better understand ADAS simulation software. Methods: We develop geometric-transformation-based metamorphic testing approaches, and report on empirical studies conducted on the verification and validation (V&V) of three popular simulation platforms for ADAS development: Simulink, CarMaker and 51Sim-One Cloud. Our examination focused on the platforms’ Lane Keeping Assist Systems (LKASs). Results: When tested with ordinary (traditional) test cases, no issues were identified on any simulation platform. However, after applying geometric-transformation-based metamorphic testing, issues were revealed, some of which were later confirmed by the MATLAB and IPG Automotive teams. To the best of our knowledge, this paper is the first to report on real bugs and issues in ADAS simulation platforms. Conclusion: Our research shows the simplicity, effectiveness and applicability of the proposed approach for ADAS simulation testing. This paper also provides successful examples of incorporating metamorphic testing into the testing of ADAS standards and protocols, and shows how practitioners can design effective metamorphic relations (MRs) inspired by using the symmetry metamorphic relation pattern

Recovery of walking ability in stroke patients through postacute care rehabilitation

Background: Walking entails orchestration of the sensory, motor, balance, and coordination systems, and walking disability is a critical concern after stroke. How and to what extent these systems influence walking disability after stroke and recovery have not been comprehensively studied. Methods: We retrospectively analyzed patients with stroke in the Post-acute care-Cerebrovascular Diseases (PAC-CVD) program. We compared the characteristics of patient groups stratified by their ability to complete the 5-m walk test across various time points of rehabilitation. We then used stepwise linear regression to examine the degree to which each stroke characteristic and functional ability could predict patient gait performance. Results: Five hundred seventy-three patients were recruited, and their recovery of walking ability was defined by the timing of recovery in a 5-m walk test. The proportion of patients who could complete the 5-m walk test at admission, at 3 weeks of rehabilitation, at 6 weeks of rehabilitation, between 7 and 12 weeks of rehabilitation, and who could not complete the 5-m walk test after rehabilitation was 52.2%, 21.8%, 8.7%, 8.7%, and 8.6%, respectively. At postacute care discharge, patients who regained walking ability earlier had a higher chance of achieving higher levels of walking activity. Stepwise linear regression showed that Berg Balance Scale (BBS) (β: 0.011, p < .001), age (β: −0.005, p = .001), National Institutes of Health Stroke Scale (NIHSS) (6a + 6b; β: −0.042, p = .018), Mini-Nutritional assessment (MNA) (β: −0.007, p < .027), and Fugl–Meyer upper extremity assessment (FuglUE) (β: 0.002, p = .047) scores predicted patient's gait speed at discharge. Conclusion: Balance, age, leg strength, nutritional status, and upper limb function before postacute care rehabilitation are predictors of walking performance after stroke

Ergosta-7, 9 (11), 22-trien-3β-ol Interferes with LPS Docking to LBP, CD14, and TLR4/MD-2 Co-Receptors to Attenuate the NF-κB Inflammatory Pathway In Vitro and Drosophila

Ergosta-7, 9 (11), 22-trien-3β-ol (EK100) was isolated from Cordyceps militaris, which has been used as a traditional anti-inflammatory medicine. EK100 has been reported to attenuate inflammatory diseases, but its anti-inflammatory mechanism is still unclear. We were the first to investigate the effect of EK100 on the Toll-like receptor 4 (TLR4)/nuclear factor of the κ light chain enhancer of B cells (NF-κB) signaling in the lipopolysaccharide (LPS)-stimulated RAW264.7 cells and the green fluorescent protein (GFP)-labeled NF-κB reporter gene of Drosophila. EK100 suppressed the release of the cytokine and attenuated the mRNA and protein expression of pro-inflammatory mediators. EK100 inhibited the inhibitor kappa B (IκB)/NF-κB signaling pathway. EK100 also inhibited phosphatidylinositol-3-kinase (PI3K)/Protein kinase B (Akt) signal transduction. Moreover, EK100 interfered with LPS docking to the LPS-binding protein (LBP), transferred to the cluster of differentiation 14 (CD14), and bonded to TLR4/myeloid differentiation-2 (MD-2) co-receptors. Compared with the TLR4 antagonist, resatorvid (CLI-095), and dexamethasone (Dexa), EK100 suppressed the TLR4/AKT signaling pathway. In addition, we also confirmed that EK100 attenuated the GFP-labeled NF-κB reporter gene expression in Drosophila. In summary, EK100 might alter LPS docking to LBP, CD14, and TLR4/MD-2 co-receptors, and then it suppresses the TLR4/NF-κB inflammatory pathway in LPS-stimulated RAW264.7 cells and Drosophila

Anti-Inflammatory and Antibacterial Activity Constituents from the Stem of Cinnamomum validinerve

One new dibenzocycloheptene, validinol (1), and one butanolide firstly isolated from the natural source, validinolide (2), together with 17 known compounds were isolated from the stem of Cinnamomum validinerve. Among the isolates, lincomolide A (3), secosubamolide (7), and cinnamtannin B1 (19) exhibited potent inhibition on both superoxide anion generation (IC50 values of 2.98 &plusmn; 0.3 &micro;M, 4.37 &plusmn; 0.38 &micro;M, and 2.20 &plusmn; 0.3 &micro;M, respectively) and elastase release (IC50 values of 3.96 &plusmn; 0.31 &micro;M, 3.04 &plusmn; 0.23 &micro;M, and 4.64 &plusmn; 0.71 &micro;M, respectively) by human neutrophils. In addition, isophilippinolide A (6), secosubamolide (7), and cinnamtannin B1 (19) showed bacteriostatic effects against Propionibacterium acnes in in vitro study, with minimal inhibitory concentration (MIC) values at 16 &mu;g/mL, 16 &mu;g/mL, and 500 &mu;g/mL, respectively. Further investigations using the in vivo ear P. acnes infection model showed that the intraperitoneal administration of the major component cinnamtannin B1 (19) reduced immune cell infiltration and pro-inflammatory cytokines TNF-&alpha; and IL-6 at the infection sites. The results demonstrated the potential of cinnamtannin B1 (19) for acne therapy. In summary, these results demonstrated the anti-inflammatory potentials of Formosan C. validinerve during bacterial infections

Osthole Antagonizes Microglial Activation in an NRF2-Dependent Manner

Microglia are neuroglia in the brain with an innate immune function and participate in the progress of neurodegenerative diseases. Osthole (OST) is a coumarin derivative extracted from Cnidium monnieri and bears a microglia-antagonizing ability. However, the underlying mechanism of the antagonism is not clear. The lipopolysaccharides-induced microglial BV2 cell line and amyloid-overexpressing fruit fly were used as models to study OST treatment. We found that OST treatment is sufficient to evoke NRF2 cascade under an LPS-induced inflammatory environment, and silencing NRF2 is sufficient to abolish the process. Moreover, we found that OST is sufficient to antagonize microglial activation in both LPS-induced BV2 cells and Aβ-overexpressing fruit flies, and silencing NRF2 abolishes OST’s antagonism. Furthermore, OST treatment rescued survival, climbing, and the learning ability of Aβ-overexpressing fruit flies and relieved oxidative stress. In conclusion, we proved that OST antagonizes microglial activation induced by either LPS or Aβ and that NRF2 is necessary for OST’s antagonism

Briarenolides F and G, New Briarane Diterpenoids from a Briareum sp. Octocoral

Two new briarane diterpenoids, briarenolides, F (1) and G (2), were isolated from an octocoral identified as Briareum sp. The structures of briaranes 1 and 2 were established by spectroscopic methods and by comparison of the spectroscopic data with those of known briarane analogues. Briarenolide F was proven to be the first 6-hydroperoxybriarane derivative and this compound displayed a significant inhibitory effect on the generation of superoxide anion by human neutrophils