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This study provides a research-based approach to reimagining the world language classroom through open educational resources (OER), primarily in higher education. Using quantitative and qualitative analyses, we provide insight into students' perceptions of OER in world language education classrooms, with a specific focus on conversation courses. The results of the current investigation suggest that OER, and digital platforms in general, align with the values, behaviors, and learning styles observed in Generation Z students: environmental awareness (Falc, 2013), financial consciousness, and organic interconnectedness via social media. Most participants recruited for the study (n = 84) had used some type of online platform or digital resource while in college and said they were (or would be) comfortable using such resources in the world language classroom. To that end, most participants considered such materials to be more practical, engaging, entertaining, and relevant to everyday life than traditional textbooks. In fact, the survey items addressing the use of digital materials in world language courses were among the most highly ranked items in the survey. Consequently, the pedagogical implications of this study suggest that instructors consider using open educational resources that meet the interests, principles, and learning styles of Generation Z students, especially as they relate to world language learning.

Abstract Pigeon pea (Cajanus cajan L.) is one of the most important legume crops grown in subtropical and tropical regions with high nutritional quality. However, the consumption of pigeon pea is very limited worldwide owing to its high level of anti‐nutrients, hard texture, and unpleasant characteristic taste. The present review summarized the nutritional profile and health benefit of pigeon pea with special attention to its bioactive phytochemicals (e.g., cajanin, cajanol, and cajaninstilbene acid). Furthermore, some aspects that can help promote the application of pigeon pea in foods were highlighted from the perspectives of physical (i.e., thermal, extrusion, and ultrasound‐assisted), chemical (i.e., chemical modification and enzymatic hydrolysis), and biological treatment (i.e., sprouting and fermentation). The primary impact of physical methods was confined to the mitigation of anti‐nutrients. Chemical approaches were less explored and mainly targeted on the modification of starch and protein in pigeon pea. In contrast, the biological methods were found to decrease the level of anti‐nutritional factors, increase the production of bioactive phytochemicals, and improve the sensory properties of pigeon pea. Therefore, biological methods, especially sprouting techniques, are considered to be more promising.

The integrated community energy system (ICES) has emerged as a promising solution for enhancing the efficiency of the distribution system by effectively coordinating multiple energy sources. However, the concept and modeling of ICES still remain unclear, and operational optimization of ICES is hindered by the physical constraints of heterogeneous integrated energy networks. This paper, therefore, provides an overview of the state-of-the-art concepts for techno–economic modeling of ICES by establishing a Multi-Network Constrained ICES (MNC-ICES) model. The proposed model underscores the diverse energy devices at community and consumer levels and multiple networks for power, gas, and heat in a privacy-protection manner, providing a basis for practical network-constrained community operation tools. The corresponding operational optimization in the proposed model is formulated into a constrained Markov decision process (C-MDP) and solved by a Safe Reinforcement Learning (RL) approach. A novel Safe RL algorithm, Primal-Dual Twin Delayed Deep Deterministic Policy Gradient (PD-TD3), is developed to solve the C-MDP. By optimizing operations and maintaining network safety simultaneously, the proposed PD-TD3 method provides a solid backup for the ICESO and has great potential in real-world implementation. The non-convex modeling of MNC-ICES and the optimization performance of PD-TD3 is demonstrated in various scenarios. Compared with benchmark approaches, the proposed algorithm merits training speed, higher operational profits, and lower violations of multi-network constraints. Potential beneficiaries of this work include ICES operators and residents who could be benefited from improved ICES operation efficiency, as well as reinforcement learning researchers and practitioners who could be inspired for safe RL applications in real-world industry.

The turnover rate of melanogenesis in retinal pigment epithelium (RPE) and its molecular signaling remain unclear. This study aimed to investigate the role of cholinergic signaling in the process of melanogenesis of cultured RPE cells. Here, a human retinal pigment epithelia cell line, ARPE-19 cell, was used to study the process of melanogenesis. The mRNA and protein expressions of cholinergic molecules, e.g., acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and melanogenic molecules i.e., tyrosinase (TYR), microphthalmia-associated transcription factor (MITF), and melanin pigment were measured during melanogenesis of cultured ARPE-19 cells. Forskolin (a cAMP inducing agent), acetylcholine (ACh) and bethanechol (Bch; a muscarinic AChR agonist) were used to induce melanogenesis in the cultures. Muscarinic acetylcholine receptor (mAChR) antagonists were employed to identify the receptor subtype. During melanogenesis of ARPE-19 cells, the mRNA and protein expressions of cholinergic molecules, e.g., AChE and BChE, were increased along with melanogenic molecules, i.e., TYR, MITF and melanin pigment. Forskolin, ACh, and Bch induced an upregulation of melanogenesis in cultured ARPE-19 cultures: the induction was parallel to an increase of AChE expression. The Bch-induced enzymatic activities and mRNA levels of AChE and TYR were fully blocked by the treatments of gallamine (a M2 specific antagonist), tropicamide (a M4 specific antagonist) and atropine (non-specific antagonist for mAChRs). Cholinergic signaling via M2/M4 mAChRs regulates melanogenesis in cultured ARPE-19 cells through a cAMP-dependent pathway. This study provides insights into the regulation of RPE cell melanogenesis via a non-neuronal function of cholinergic system.

Abstract Background Sesarmid crabs dominate mangrove habitats as the major primary consumers, which facilitates the trophic link and nutrient recycling in the ecosystem. Therefore, the adaptations and mechanisms of sesarmid crabs to herbivory are not only crucial to terrestrialization and its evolutionary success, but also to the healthy functioning of mangrove ecosystems. Although endogenous cellulase expressions were reported in crabs, it remains unknown if endogenous enzymes alone can complete the whole lignocellulolytic pathway, or if they also depend on the contribution from the intestinal microbiome. We attempt to investigate the role of gut symbiotic microbes of mangrove-feeding sesarmid crabs in plant digestion using a comparative metagenomic approach. Results Metagenomics analyses on 43 crab gut samples from 23 species of mangrove crabs with different dietary preferences revealed a wide coverage of 127 CAZy families and nine KOs targeting lignocellulose and their derivatives in all species analyzed, including predominantly carnivorous species, suggesting the crab gut microbiomes have lignocellulolytic capacity regardless of dietary preference. Microbial cellulase, hemicellulase and pectinase genes in herbivorous and detritivorous crabs were differentially more abundant when compared to omnivorous and carnivorous crabs, indicating the importance of gut symbionts in lignocellulose degradation and the enrichment of lignocellulolytic microbes in response to diet with higher lignocellulose content. Herbivorous and detritivorous crabs showed highly similar CAZyme composition despite dissimilarities in taxonomic profiles observed in both groups, suggesting a stronger selection force on gut microbiota by functional capacity than by taxonomy. The gut microbiota in herbivorous sesarmid crabs were also enriched with nitrogen reduction and fixation genes, implying possible roles of gut microbiota in supplementing nitrogen that is deficient in plant diet. Conclusions Endosymbiotic microbes play an important role in lignocellulose degradation in most crab species. Their abundance is strongly correlated with dietary preference, and they are highly enriched in herbivorous sesarmids, thus enhancing their capacity in digesting mangrove leaves. Dietary preference is a stronger driver in determining the microbial CAZyme composition and taxonomic profile in the crab microbiome, resulting in functional redundancy of endosymbiotic microbes. Our results showed that crabs implement a mixed mode of digestion utilizing both endogenous and microbial enzymes in lignocellulose degradation, as observed in most of the more advanced herbivorous invertebrates.

Abstract Obesity, a global health challenge, is a major risk factor for multiple life-threatening diseases, including diabetes, fatty liver, and cancer. There is an ongoing need to identify safe and tolerable therapeutics for obesity management. Herein, we show that treatment with artesunate, an artemisinin derivative approved by the FDA for the treatment of severe malaria, effectively reduces body weight and improves metabolic profiles in preclinical models of obesity, including male mice with overnutrition-induced obesity and male cynomolgus macaques with spontaneous obesity, without inducing nausea and malaise. Artesunate promotes weight loss and reduces food intake in obese mice and cynomolgus macaques by increasing circulating levels of Growth Differentiation Factor 15 (GDF15), an appetite-regulating hormone with a brainstem-restricted receptor, the GDNF family receptor α-like (GFRAL). Mechanistically, artesunate induces the expression of GDF15 in multiple organs, especially the liver, in mice through a C/EBP homologous protein (CHOP)-directed integrated stress response. Inhibition of GDF15/GFRAL signalling by genetic ablation of GFRAL or tissue-specific knockdown of GDF15 abrogates the anti-obesity effect of artesunate in mice with diet-induced obesity, suggesting that artesunate controls bodyweight and appetite in a GDF15/GFRAL signalling-dependent manner. These data highlight the therapeutic benefits of artesunate in the treatment of obesity and related comorbidities.

As universities around the world have begun to use learning management systems (LMSs), more learning data have become available to gain deeper insights into students' learning processes and make data-driven decisions to improve student learning. With the availability of rich data extracted from the LMS, researchers have turned much of their attention to learning analytics (LA) applications using educational data mining techniques. Numerous LA models have been proposed to predict student achievement in university courses. To design predictive LA models, researchers often follow a data-driven approach that prioritizes prediction accuracy while sacrificing theoretical links to learning theory and its pedagogical implications. In this study, we argue that instead of complex variables (e.g., event logs, clickstream data, timestamps of learning activities), data extracted from online formative assessments should be the starting point for building predictive LA models. Using the LMS data from multiple offerings of an asynchronous undergraduate course, we analysed the utility of online formative assessments in predicting students' final course performance. Our findings showed that the features extracted from online formative assessments (e.g., completion, timestamps and scores) served as strong and significant predictors of students' final course performance. Scores from online formative assessments were consistently the strongest predictor of student performance across the three sections of the course. The number of clicks in the LMS and the time difference between first access and due dates of formative assessments were also significant predictors. Overall, our findings emphasize the need for online formative assessments to build predictive LA models informed by theory and learning design.

Dietary flavonoids are abundant in natural plants and possess multiple pharmacological and nutritional activities. In this study, apigenin, luteolin, and baicalein were chosen to evaluate their anti-diabetic effect in high-glucose and dexamethasone induced insulin-resistant (IR) HepG2 cells. All flavonoids improves the glucose consumption and glycogen synthesis abilities in IR-HepG2 cells via activating glucose transporter protein 4 (GLUT4) and phosphor-glycogen synthase kinase (GSK-3β). These flavonoids significantly inhibited the production of reactive oxygen species (ROS) and advanced glycation end-products (AGEs), which were closely related to the suppression of the phosphorylation form of NF-κB and P65. The expression levels of insulin receptor substrate-1 (IRS-1), insulin receptor substrate-2 (IRS-2) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in IR-HepG2 cells were all partially activated by the flavonoids, with variable effects. Furthermore, the intracellular metabolic conditions of the flavonoids were also evaluated.

To investigate the impact of extrusion parameters on the formation of Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL) and acrylamide in plant-based meat analogues (PBMAs), the content changes and the correlations of compounds related to their formation were studied. The extrusion promoted CML, CEL and acrylamide formation, with more CEL being formed than CML. Variations in the moisture level and barrel temperature exerted a greater influence on the CML, CEL, acrylamide and α-dicarbonyl compounds than the screw speed and the feed rate. An increase in the moisture content led to a decrease in the CEL content, whereas it enhanced CML formation. The impact of moisture on acrylamide formation varied depending on whether low- or high-moisture extrusion was applied. Elevated temperatures promoted the accumulation of CEL, methylglyoxal and 2,3-butanedione while diminishing the accumulation of CML, acrylamide, glyoxal and 3-deoxyglucosone. CML and CEL were positively correlated with glyoxal and methylglyoxal, respectively. CEL and methylglyoxal were negatively correlated with protein and water content, whereas CML, glyoxal and 3-deoxyglucosone displayed positive correlations. In summary, higher moisture levels and feed rates and lower screw speeds and barrel temperatures are advantageous for producing PBMAs with lower CEL and total advanced glycation end-products contents, while lower or higher moisture contents, a lower feed rate and a higher barrel temperature are beneficial to reducing the acrylamide content.

Variants (pathogenic) of the LMNA gene are a common cause of familial dilated cardiomyopathy (DCM), which is characterised by early-onset atrioventricular (AV) block, atrial fibrillation and ventricular tachyarrhythmias (VTs), and progressive heart failure. The unstable internal nuclear lamina observed in LMNA-related DCM is a consequence of the disassembly of lamins A and C. This suggests that LMNA variants produce truncated or alternative forms of protein that alter the nuclear structure and the signalling pathway related to cardiac muscle diseases. To date, the pathogenic mechanisms and phenotypes of LMNA-related DCM have been studied using different platforms, such as patient-specific induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs) and transgenic mice. In this review, point variants in the LMNA gene that cause autosomal dominantly inherited forms of LMNA-related DCM are summarised. In addition, potential therapeutic targets based on preclinical studies of LMNA variants using transgenic mice and human iPSC-CMs are discussed. They include mitochondria deficiency, variants in nuclear deformation, chromatin remodelling, altered platelet-derived growth factor and ERK1/2-related pathways, and abnormal calcium handling.

Soybean (Glycine max L.) is a globally important industrial legume crop that provides several important dietary components but faces growth challenges under various stresses, that cause production and economic losses. Isoflavone reductase (IFR) is a key gene involved in isoflavonoid biosynthesis and response to plant growth and stresses. However, IFR genes remain unexplored in the soybean genome. In this study, 37 IFR genes were identified and comprehensively characterized for the first time in the soybean genome. All GmIFR proteins contained NmrA conserved domains with diverse physicochemical properties including 1 to 9 motifs, and 1 to 10 exons. Chromosomal distribution revealed 11 GmIFR genes located on chromosomes 1 and 11. Cis-element analysis unveiled GmIFR genes role in phytohormones and stress responses. Synteny analysis identified 13 segmental and 2 tandem GmIFR duplicates under purifying selection. Additionally, 118 gma-miRNAs from 76 families were identified to be targeting all 37 GmIFR genes. Potential transcription factors including ERF, MYB, Dof, BBR-BPC, and bHLHs were predicted and visualized in a network interacting with GmIFR genes. The annotation results exhibit that GmIFR genes were highly related to the biosynthesis of metabolites, phenylpropanoid pathway, and response to stresses. FPKM expression data highlighted the significant upregulation of GmIFR genes in soybean tissues under different stress conditions. qRT-PCR results exhibited that most GmIFR genes, mainly GmIFR9/17 and GmIFR36 were highly upregulated in soybean cotyledon followed by hypocotyl and root tissues under spermidine and ultrasonication treatments than control, suggesting their key role in growth and developmental processes in soybean. These findings laid the foundation for further functional studies of GmIFR genes to elucidate their contributions to soybean improvement under adverse conditions.