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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.

Abstract Background & Aims Although non-alcoholic fatty liver disease (NAFLD) remains an uncommon indication for liver transplantation (LT) in the Chinese, the prevalence of NAFLD is increasing. We aimed to determine the prevalence of de novo steatosis and metabolic dysfunction-associated fatty liver disease (MAFLD) after LT. Methods Transient elastography assessment for liver stiffness and controlled attenuation parameter (CAP) were performed after LT in 549 patients at median time of 77 months from LT. CAP was compared with implant liver biopsy, and also validated in 42 patients with post-LT liver biopsy. Longitudinal history including diabetes mellitus (DM), dyslipidemia, hypertension, and immunosuppressive regimen were recorded. Results The optimal cut-off level of CAP for diagnosing at least mild (≥ S1) and moderate-to-severe steatosis (≥ S2/3) was 266 and 293 dB/m respectively, with AUROC of 0.740 and 0.954 respectively. Using this newly derived cut-off, 28.9% patients have de novo NAFLD, of which 95.6% fulfilled the criteria for MAFLD. After multivariate analysis, BMI (HR 1.34), DM (HR 2.01), hypertension (HR 2.03), HDL-cholesterol (HR 0.25), LDL-cholesterol (HR 1.5) and cryptogenic cirrhosis (HR 4.85) were associated with the development of S2/3 graft steatosis. de novo NAFLD was associated with higher incidence of new-onset hypertension (p 40 U/L; p = 0.008), but not associated with graft fibrosis (defined as liver stiffness > 12 kPa; p = 0.761). Conclusion Although NAFLD remains an uncommon primary liver disease indication for LT in Chinese patients, post-transplant de novo graft steatosis is common and the majority is classified as MAFLD. Development of graft steatosis is not associated with an increase in graft fibrosis but was associated with worse metabolic control and graft dysfunction. Routine CAP measurement to detect de novo graft steatosis should be considered after LT regardless of the primary indication of LT.

COVID-19 continues to spread around the world. This is mainly because new variants of the SARS-CoV-2 virus emerge due to genomic mutations, evade the immune system and result in the effectiveness of current therapeutics being reduced. We previously established a series of detection platforms, comprising computational docking analysis, S-protein-based ELISA, pseudovirus entry, and 3CL protease activity assays, which allow us to screen a large library of phytochemicals from natural products and to determine their potential in blocking the entry of SARS-CoV-2. In this new screen, rutaecarpine (an alkaloid from Evodia rutaecarpa) was identified as exhibiting anti-SARS-CoV-2 activity. Therefore, we conducted multiple rounds of structure-activity-relationship (SAR) studies around this phytochemical and generated several rutaecarpine analogs that were subjected to in vitro evaluations. Among these derivatives, RU-75 and RU-184 displayed remarkable inhibitory activity when tested in the 3CL protease assay, S-protein-based ELISA, and pseudovirus entry assay (for both wild-type and omicron variants), and they attenuated the inflammatory response induced by SARS-CoV-2. Interestingly, RU-75 and RU-184 both appeared to be more potent than rutaecarpine itself, and this suggests that they might be considered as lead candidates for future pharmacological elaboration.

Feedback is a crucial component of student learning. As advancements in technology have enabled the adoption of digital learning environments with assessment capabilities, the frequency, delivery format, and timeliness of feedback derived from educational assessments have also changed progressively. Advanced technologies powered by Artificial Intelligence (AI) enable teachers to generate different types of feedback supporting student learning. Despite the rapid uptake of digital technologies in education, previous studies on educational feedback primarily focused on the theoretical underpinnings of feedback practices, which are limited in terms of their coverage of AI-based technologies. This paper aims to inform both researchers and practitioners about the present and future of AI applications in feedback practices, identify and organize potential areas for the use of AI for feedback purposes, and establish venues for AI research and practice in educational feedback. Furthermore, the role of the three branches of AI (i.e., natural language processing, educational data mining, and learning analytics) in feedback practices and potential areas for their future development are discussed.

Background: COVID-19 outbreaks in residential care homes for the elderly (RCHEs) and for persons with disability (RCHDs) have caused significant morbidity and mortality during 5th epidemic in Hong Kong. This article reviewed COVID-19 outbreaks situation and estimated the effectiveness of receiving at least two-dose of COVID-19 vaccine in preventing severe outcomes. Methods: To estimate attack rates and vaccination coverage, documentation on COVID-19 infection and their vaccination records of residential care homes (RCH) residents reported between December 31, 2021 and May 31, 2022 were reviewed, and infected cases were follow-up for 4 weeks for severe outcomes or death. Correlation between vaccination coverage against attack rate by types of homes was examined. Infected RCH residents with available information were included in the analysis of vaccine effectiveness against severe outcomes and death. Results: COVID-19 vaccination coverage was low in RCHDs (median 0.46, IQR: 0.24–0.76) and very low in RCHEs (median 0.08, IQR: 0.00–0.19). Higher attack rates were recorded among RCHE residents (median 0.84, IQR: 0.64–0.93) and higher case fatality rate (CFR: 28.1%) than in RCHDs (median 0.58, IQR: 0.31–0.84; CFR: 3.9%). The attack rate decreased when vaccination coverage increased for both RCHEs (ρ = −0.131, p < 0.001) and RCHDs (ρ = −0.333, p < 0.001). Comparing with infected residents who were unvaccinated/vaccinated with one-dose, receiving at least two-dose was estimated to be effective in reducing severe outcomes in 31% and 36% of infected RCHE and RCHD residents respectively; with greater reduction in mortality among RCHD than RCHE residents (54% and 38%, respectively). Vaccine effectiveness of two-dose of BNT162b2 against severe outcomes and death are higher than that of CoronaVac. Conclusions: Increasing COVID-19 vaccination could have significant impact on reducing the risk of COVID-19 outbreaks in RCHs. At least two-dose of COVID-19 vaccine is still effective in reducing severe outcomes and death among infected residents in RCHs during Omicron epidemic.