The Effects of an Accelerated Auditory Matching Protocol for Early Intervention Students.

We employed a multiple probe design to test the effects of an accelerated auditory matching protocol with five toddlers receiving early intervention services (four males, one female) for developmental delays. All participants emitted poorly articulated vocal mands and tacts. The dependent variables were the number of full echoics, partial echoics, and incorrect responses within a set of 20 two-syllable words. The independent variable was an accelerated Auditory Matching Protocol that targets auditory discrimination using an iPad App. Each phase of the protocol targets different sound discriminations with growing complexity. Four out of five participants emitted more full or partial echoic responses upon mastery of the Auditory Matching Protocol. Moreover, compared to those who received the full dosage of the standard Auditory Matching Protocol in previous studies, the participants in this study required fewer learn units to master all phases and to demonstrate improvement. Supplementary Information: The online version contains supplementary material available at 10.1007/s40617-023-00882-1.

Impact of personality traits on learners' navigational behavior patterns in an online course: a lag sequential analysis approach.

Personality is considered as the internal factor that defines a person's behavior. Therefore, providing adaptive features and personalized support in online learning by considering learners' personalities can improve their learning experiences and outcomes. In this context, several research studies have investigated the impact of personality differences in online learning. However, little is known about how personality differences affect learners' behavior while learning. To fill this gap, this study applies a lag sequential analysis (LSA) approach to understand learners' navigational behavior patterns in an online three-months course of 65 learners based on their personalities. In this context, the five factor model (FFM) model was used to identify learners' personalities. The findings revealed that learners with different personalities use different strategies to learn and navigate within the course. For instance, learners high in extraversion tend to be extrinsically motivated. They therefore significantly navigated between viewing the course module and their personal achievements. The findings of this study can contribute to the adaptive learning field by providing insights about which personalization features can help learners with different personalities. The findings can also contribute to the field of automatic modeling of personality by providing information about differences in navigational behavior based on learners' personalities.

A senolysis-based theragnostic prodrug strategy towards chronic renal failure.

Selective elimination of senescent cells (senolysis) has become a promising therapeutic strategy for the management of chronic renal failure (CRF), but the senolytic molecular pathways towards CRF therapy are limited. Here, we present for the first time a senescence-associated ß-galactosidase (SA-ß-gal) activatable theragnostic prodrug strategy to pertinently and effectively treat CRF in mice with the aid of fluorescence-guided senolysis. The signs of premature senescence, including the overexpression of ß-gal, have been found in kidneys of mice with CRF, making this enzyme particularly suitable as a trigger of prodrugs for CRF therapy. With this unique design, our pioneering prodrug TSPD achieved the activation of a fluorophore for tracking and the specific release of the parent drug, gemcitabine, in ß-gal-enriched cells after activation with SA-ß-gal. In mice with CRF, abdominal administration of TSPD was effective for improvement of the kidney functions, supporting the feasibility of the SA-ß-gal-dependent senolysis therapy towards CRF.

Nicandra physalodes Extract Exerts Antiaging Effects in Multiple Models and Extends the Lifespan of Caenorhabditis elegans via DAF-16 and HSF-1.

The development of safe and effective therapeutic interventions is an important issue for delaying aging and reducing the risk of aging-related diseases. Chinese herbal medicines for the treatment of aging and other complex diseases are desired due to their multiple components and targets. Through screening for effects on lifespan of 836 Chinese herbal medicine extracts, Nicandra physalodes extract (HL0285) was found to exhibit lifespan extension activity in Caenorhabditis elegans (C. elegans). In further experiments, HL0285 improved healthspan, enhanced stress resistance, and delayed the progression of neurodegenerative diseases in C. elegans. Additionally, it ameliorated senescence in human lung fibroblasts (MRC-5 cells) and reversed liver function damage and reduced senescence marker levels in doxorubicin- (Dox-) induced aging mice. In addition, the longevity effect of HL0285 in C. elegans was dependent on the DAF-16 and HSF-1 signaling pathways, as demonstrated by the results of the mutant lifespan, gene level, and GFP level assays. In summary, we discovered that HL0285 had an antiaging effect in C. elegans, MRC-5 cells, and Dox-induced aging mice and deserves to be explored in the future studies on antiaging agents.

Crotamiton derivative JM03 extends lifespan and improves oxidative and hypertonic stress resistance in Caenorhabditis elegans via inhibiting OSM-9.

While screening our in-house 1072 marketed drugs for their ability to extend the lifespan using Caenorhabditis elegans (C. elegans) as an animal model, crotamiton (N-ethyl-o-crotonotoluidide) showed anti-aging activity and was selected for further structural optimization. After replacing the ortho-methyl of crotamiton with ortho-fluoro, crotamiton derivative JM03 was obtained and showed better activity in terms of lifespan-extension and stress resistance than crotamiton. It was further explored that JM03 extended the lifespan of C. elegans through osmotic avoidance abnormal-9 (OSM-9). Besides, JM03 improves the ability of nematode to resist oxidative stress and hypertonic stress through OSM-9, but not osm-9/capsaicin receptor related-2 (OCR-2). Then the inhibition of OSM-9 by JM03 reduces the aggregation of Q35 in C. elegans via upregulating the genes associated with proteostasis. SKN-1 signaling was also found to be activated after JM03 treatment, which might contribute to proteostasis, stress resistance and lifespan extension. In summary, this study explored a new small molecule derived from crotamiton, which has efficient anti-oxidative, anti-hypertonic, and anti-aging effects, and could further lead to promising application prospects.

Characterization of cellular senescence in doxorubicin-induced aging mice.

With a rise in the need to develop anti-aging drugs, a growing number of in vivo studies evaluating the efficacy of potential drug candidates have used doxorubicin-induced aging mice. However, changes in the biomarkers of senescent cells have not been reported in detail in these animals. To lay a foundation for the use of doxorubicin-induced aging mice, we examined the biomarkers of hepatic and renal senescent cells in these mice. We found that the 5 mg/kg doxorubicin dose is optimal to induce cellular senescence in mice. Subsequently, using this dose, we found that doxorubicin-induced an increase in senescence-associated ß-galactosidase (SA-ß-gal) positive cells in the kidney and lipofuscin accumulation in the liver. Some markers of senescent cells (p21WAF1/CIP1, p16INK4A, and γH2AX) were also significantly upregulated by doxorubicin and then counteracted by metformin treatment. These preliminary findings support the application of doxorubicin-induced aging mice as an animal model to evaluate the efficacy of anti-aging drug candidates.

Anti-aging effects of chlorpropamide depend on mitochondrial complex-II and the production of mitochondrial reactive oxygen species.

Sulfonylureas are widely used oral anti-diabetic drugs. However, its long-term usage effects on patients' lifespan remain controversial, with no reports of influence on animal longevity. Hence, the anti-aging effects of chlorpropamide along with glimepiride, glibenclamide, and tolbutamide were studied with special emphasis on the interaction of chlorpropamide with mitochondrial ATP-sensitive K+ (mitoK-ATP) channels and mitochondrial complex II. Chlorpropamide delayed aging in Caenorhabditis elegans, human lung fibroblast MRC-5 cells and reduced doxorubicin-induced senescence in both MRC-5 cells and mice. In addition, the mitochondrial membrane potential and ATP levels were significantly increased in chlorpropamide-treated worms, which is consistent with the function of its reported targets, mitoK-ATP channels. Increased levels of mitochondrial reactive oxygen species (mtROS) were observed in chlorpropamide-treated worms. Moreover, the lifespan extension by chlorpropamide required complex II and increased mtROS levels, indicating that chlorpropamide acts on complex II directly or indirectly via mitoK-ATP to increase the production of mtROS as a pro-longevity signal. This study provides mechanistic insight into the anti-aging effects of sulfonylureas in C. elegans.

The Research on the Treatment of Metastatic Skin Cutaneous Melanoma by Huanglian Jiedu Decoction Based on the Analysis of Immune Infiltration Analysis.

OBJECTIVE: To explore the potential mechanism of Huanglian Jiedu Decoction (HJD) treatment and prevention of metastatic Cutaneous Melanoma (CM) occurrence and metastasis based on network pharmacological methods and immune infiltration analysis. METHODS: The GEO database was used to obtain metastatic CM disease targets, the TCMSP database and the HERB database were used to obtain HJD action targets, core genes were screened by protein interaction network, and the potential mechanism of HJD in the treatment of metastatic CM was explored by enrichment analysis, prognostic analysis and immune infiltration analysis. RESULTS: HJD treatment of metastatic CM involved 60 targets, enrichment analysis showed that HJD treatment of metastatic CM involved Chemokine signaling pathway, NF-kappa B signaling pathway, and Fluid shear stress and atherosclerosis, etc. Prognostic analysis revealed that HJD had a certain ability to improve the prognosis of metastatic CM patients. Immune infiltration analysis showed that HJD could inhibit the immune cell infiltration of metastatic CM patients by acting on related targets. CONCLUSIONS: Our study identified the potential mechanism of HJD in the treatment of metastatic CM through network pharmacology, and revealed the mechanism of HJD in the prevention of Skin Cutaneous Melanoma metastasis through immune infiltration analysis and prognostic analysis.

Head-on collision of compressional shocks in two-dimensional Yukawa systems.

The head-on collision of compressional shocks in two-dimensional dusty plasmas is investigated using both molecular dynamical and Langevin simulations. Two compressional shocks are generated from the inward compressional boundaries in simulations. It is found that, during the collision of shocks, there is a generally existing time delay of shocks τ, which diminishes monotonically with the increasing compressional speed of boundaries, corresponding to the time resolution of the studied system. Dispersive shock waves (DSWs) are generated around the shock front for some conditions. It is also found that the period of the DSW decreases monotonically with the inward compressional speed of boundaries, more substantially than the time delay of shocks τ. When the inward compressional speed of boundaries increases further, the DSWs gradually vanish. We speculate that, for these high compressional speeds of boundaries, the period of the DSW might be reduced to a comparable timescale of the time delay of shocks τ, i.e., the time resolution of our studied system, or even shorter, thus the DSW reasonably vanishes.

Game-Based Learning for Learners With Disabilities-What Is Next? A Systematic Literature Review From the Activity Theory Perspective.

The design, implementation, and outcome of game-based learning for learners with disabilities have not been sufficiently examined systematically. Particularly, learner-based and contextual factors, as well as the essential roles played by various stakeholders, have not been addressed when game-based learning applications are used in special education. Therefore, a systematic literature review using the Activity Theory (AT) was conducted to analyse studies about game-based learning for learners with disabilities. Content analysis of 96 studies reported relevant information with respect to each activity component-(a) subject (learners with disabilities), (b) technology (game-based learning applications), (c) object (target skills or behaviours), (d) rules (implementation procedure and performance measures), (e) community (learners with disabilities, special education professionals, and parents), (f) division of labour (among learners, professionals, and parents) and (g) outcome (performance of target skills or behaviours). Furthermore, this study identified existing gaps from the reviewed studies, including occasional lack of parental engagement, difficulty of standardising performance measures due to the heterogeneity of learner profiles and contradictions (e.g., opposing views among experts on the role of educational games in social interactions). Finally, recommendations were made under each activity component. The study concluded that both general and domain-specific guidelines should be created for each disability category proposed in this review to assist practitioners who wish to use game-based learning with learners with disabilities.