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Abstract Background Low immunity and sleep disorders are prevalent suboptimal health conditions in contemporary populations, which render them susceptible to the infiltration of pathogenic factors. LJC, which has a long history in traditional Chinese medicine for nourishing the Yin and blood and calming the mind, is obtained by modifying Qiyuan paste. Dendrobium officinale Kimura et Migo has been shown to improve the immune function in sleep-deprived mice. In this study, based on the traditional Chinese medicine theory, LJC was prepared by adding D. officinale Kimura et Migo to Qiyuan paste decoction. Methods Indicators of Yin deficiency syndrome, such as back temperature and grip strength, were measured in each group of mice; furthermore, behavioral tests and pentobarbital sodium-induced sleep tests were performed. An automatic biochemical analyzer, enzyme-linked immunosorbent assay kit, and other methods were used to determine routine blood parameters, serum immunoglobulin (IgG, IgA, and IgM), cont (C3, C4), acid phosphatase (ACP) and lactate dehydrogenase (LDH) levels in the spleen, serum hemolysin, and delayed-type hypersensitivity (DTH) levels. In addition, serum levels of γ-aminobutyric acid (GABA) and glutamate (Glu) were detected using high-performance liquid chromatography (HPLC). Hematoxylin–eosin staining and Nissl staining were used to assess the histological alterations in the hypothalamus tissue. Western blot and immunohistochemistry were used to detect the expressions of the GABA pathway proteins GABRA1, GAD, GAT1, and GABAT1 and those of CD4+ and CD8+ proteins in the thymus and spleen tissues. Results The findings indicated that LJC prolonged the sleep duration, improved the pathological changes in the hippocampus, effectively upregulated the GABA content in the serum of mice, downregulated the Glu content and Glu/GABA ratio, enhanced the expressions of GABRA1, GAT1, and GAD, and decreased the expression of GABAT1 to assuage sleep disorders. Importantly, LJC alleviated the damage to the thymus and spleen tissues in the model mice and enhanced the activities of ACP and LDH in the spleen of the immunocompromised mice. Moreover, serum hemolysin levels and serum IgG, IgA, and IgM levels increased after LJC administration, which manifested as increased CD4+ content, decreased CD8+ content, and enhanced DTH response. In addition, LJC significantly increased the levels of complement C3 and C4, increased the number of white blood cells and lymphocytes, and decreased the percentage of neutrophils in the blood. Conclusions LJC can lead to improvements in immunocompromised mice models with insufficient sleep. The underlying mechanism may involve regulation of the GABA/Glu content and the expression levels of GABA metabolism pathway-related proteins in the brain of mice, enhancing their specific and nonspecific immune functions. Graphical Abstract

Abstract Dragon's blood, the red resin derived from the wounded Dracaena, is a precious traditional medicine used by different culture. Dracaena cochinchinensis is one of the main species of Dracaena, and is the endangered medicinal plants in China. The vulnerable status severely limits the medicinal value and wide application of dragon’s blood. Therefore, it’s essential to analyze the mechanisms that form dragon’s blood in order to increase artificial production. To clarify the mechanisms forming dragon’s blood, understanding gene expression in the flavonoid biosynthesis pathway is the foundation. However, reference genes of D. cochinchinensis haven’t been analyzed. In this study, expression profiles of seven commonly used housekeeping genes (Actin, α-EF, UBC, β-tubulin, 18S, GAPDH, His) were evaluated by using quantitative real-time PCR combined with the algorithms geNorm, NormFinder, BestKeeper, and RefFinder. On the basis of overall stability ranking, the best reference genes were the combinations β-tubulin +UBC for wounded stems and α-EF +18S + Actin for different organs. Reliability of the recommended reference genes was validated by normalizing relative expression of two key enzyme genes PAL1 and CHI1 in the flavonoid biosynthesis pathway. The results provide a foundation to study gene expression in future research on D. cochinchinensis or other Dracaena.

Abstract Background Doctors are at high risk of developing hemorrhoidal disease (HD), but it is unclear whether doctors are aware of this risk. The OASIS (dOctors AS patIentS) study was performed to examine the prevalence, awareness, diagnosis, and treatment of HD among doctors in big cities in China. Methods An online survey consisting of a structured questionnaire was carried out among doctors in grade-A tertiary hospitals in 29 provinces across China from August to October 2020. Results A total of 1227 questionnaire responses were collected. HD prevalence was 56.8%, with a significant difference between internists and surgeons (P = 0.01). 15.6% of doctors with HD didn’t have serious concerns about the recurrence and severity of HD. 91.5% of doctors adopted general treatments, and 83.0% considered oral medications only when topical medications were ineffective. Among the oral medications, Micronized Purified Flavonoid Fraction (MPFF) was most effective based on the scores from three important parameters, but only 17% of doctors received MPFF. Conclusions Doctors are at higher risk of developing HD with a high prevalence among Chinese doctors, but they are not fully aware or not concerned about HD. There is a deficiency in treatment recommendations and clinical management of HD even for doctors, including late initiation and inadequate oral drug therapy. Therefore, awareness and standardized treatment of HD should be improved among Chinese doctors, as well as in the general population.

Aim: Atractylodes macrocephala Rhizome (AM) has been used to treat hyperlipidemia for centuries, but its functional components and mechanisms are not clear. This research aimed to investigate the active components in AM and the mechanisms that underlie its anti-hyperlipidemia effect. Methods: SD rats were fed a high-sucrose high-fat diet in conjunction with alcohol (HSHFDAC) along with different AM extracts (AMW, AMO, AME, and AMP) for 4 weeks. AM's active components were analyzed using multiple databases, and their mechanisms were explored through network pharmacology. The relationship between AM's effect of enhancing serum HDL-c and regulating the expression of reverse cholesterol transport (RCT)-related proteins (Apo-A1, LCAT, and SR-BI) was further validated in the HSHFDAC-induced hyperlipidemic rats. The kidney and liver functions of the rats were measured to evaluate the safety of AM. Results: AMO, mainly comprised of volatile and liposoluble components, contributed the most significant anti-hyperlipidemia effect among the four extracts obtained from AM, significantly improving the blood lipid profile. Network pharmacology analysis also suggested that volatile and liposoluble components, comprise AM's main active components and they might act on signaling pathways associated with elevated HDL-c. Validation experiments found that AMO substantially and dose-dependently increased HDL-c levels, upregulated the expression of Apo-A1, SR-BI, and LCAT, improved the pathological changes in the kidney and liver, and significantly reduced the serum creatinine levels in rats with hyperlipidemia. Conclusion: The main anti-hyperlipidemia active components of AM are its volatile and liposoluble components, which may enhance serum HDL-c by increasing the expression of the RCT-related proteins Apo-A1, LCAT, and SR-BI.

Sesquiterpenes are characteristic components and important quality criterions for agarwood. Although sesquiterpenes are well-known to be biosynthesized by sesquiterpene synthases (TPSs), to date, only a few TPS genes involved in agarwood formation have been reported. Here, two new TPS genes, namely, TPS9 and TPS12, were isolated from Aquilaria sinensis (Lour.) Gilg, and their functions were examined in Escherichia coli BL21(DE3), with farnesyl pyrophosphate (FPP) and geranyl pyrophosphate (GPP) as the substrate of the corresponding enzyme activities. They were both identified as a multiproduct enzymes. After incubation with FPP, TPS9 liberated β-farnesene and cis-sesquisabinene hydrate as main products, with cedrol and another unidentified sesquiterpene as minor products. TPS12 catalyzes the formation of β-farnesene, nerolidol, γ-eudesmol, and hinesol. After incubation with GPP, TPS9 generated citronellol and geraniol as main products, with seven minor products. TPS12 converted GPP into four monoterpenes, with citral as the main product, and three minor products. Both TPS9 and TPS12 showed much higher expression in the two major tissues emitting floral volatiles: flowers and agarwood. Further, RT-PCR analysis showed TPS9 and TPS12 are typical genes mainly expressed during later stages of stress response, which is better known than that of chromone derivatives. This study will advance our understanding of agarwood formation and provide a solid theoretical foundation for clarifying its mechanism in A. sinensis.

Purpose This qualitative study explores the meaning of life and end-of-life coping strategies among patients in China with advanced lung cancer. Methods We conducted in-depth interviews with 21 hospitalized patients with advanced lung cancer and analysed the data using the 7-step Colaizzi method. Results The analysis revealed themes in patients’ experiences and feelings about living with a terminal illness. These include: 1) The core of the meaning of life is “self-iteration,” which includes self-recognition and cherishing life; 2) The existence form of the meaning of life is “yu-wei,” including self-reliance and altruism; 3) The meaning of life is embodied in three levels: the past, present, and future. The past includes gratitude, guilt and remorse, and avoidance; the present includes using the support system, positive response, independence, and integrity; the future includes accompanying relatives, preparing for death, living a high quality of life, and worrying. Conclusion Meaning of life is a multidimensional and diverse concept among patients with advanced lung cancer. Medical care providers and family members can provide targeted professional guidance and psychological support according to patients’ characteristics to help them discover their meaning of life, improve their quality of life, and achieve a positive end-of-life perspective.

This paper is concerned with the existence of solutions for p-Laplace problems with non-local term. We prove the sub-supersolution theorem using the pseudomonotone operator theorem and Minty–Browder theorem with appropriate assumptions on M,gii=1,2. Then, using the sub-supersolution approach, we determine the existence of positive solutions to specific problems.

Many studies have incorporated concept maps into digital games to enable learners to make connections between subject concepts in the game. However, most learners do not associate spontaneously with the thematic concepts in the game but need to be facilitated by effective scaffolding mechanisms to reconceptualize the learning process and content. Therefore, this study proposed a knowledge check-based concept map-guided gaming strategy for chemistry learning for secondary-level learners. Specifically, the knowledge check-based concept map-guided gaming strategy was employed as a learning strategy while playing digital games. The knowledge check mechanism was developed based on the notation of two-tier testing. Moreover, the learning environment was a self-developed chemical classification-based digital game, in which learners learned through concept mapping guided gaming tasks with factual and conceptual questions to confirm that they can actually learn content and conceptual understanding in the game. To understand the effects of the proposed strategy, a quasi-experimental design was adopted to measure compare two groups' learning achievement, problem-solving awareness, critical thinking tendency, and germane cognitive load of seventh-grade students using the knowledge check-based concept map-guided gaming strategy and the conventional concept map-guided gaming strategy. The results of the study showed that learners' learning achievement, problem-solving awareness, critical thinking tendency, and germane cognitive load in chemistry learning were effectively improved by the knowledge check-based concept map-guided gaming strategy. Furthermore, this study implies that teachers can adjust their teaching scaffolds and provide strategies according to learners' learning behaviors in digital game-based learning.

This study explores the impact of an innovative approach that combines artificial intelligence (AI) chatbot support with collaborative note-taking (CNT) in the comprehension of semantic terms among English as a Foreign Language (EFL) learners. Given the significance of semantics in English language learning, traditional didactic methods often present challenges for EFL learners. The proposed AI chatbot-supported approach aims to foster learner interaction, while the CNT strategy focuses on enhancing knowledge retention and engagement with learning materials. Conducted as a quasiexperimental pre-test-post-test design, the study involved 60 English language and literature majors from a non-English-speaking area enrolled at a private university. Participants were divided into the AI chatbot-supported and CNT (AI-CNT) group and the conventional CNT (cCNT) group. Results indicated that the AI-CNT group outperformed the cCNT group across various dimensions of semantic learning outcomes, including performance, achievement, self-efficacy, metacognition, and anxiety reduction. This study highlights the potential of integrating AI chatbot support and the CNT strategy to significantly enhance the EFL semantic learning experience. The personalized and interaction-based linguistic practices, enriched with feedback and emotional support, offer a promising avenue for advancing language learning outcomes in the digital age.

The increase in popularity of Generative Artificial Intelligence Chatbots, or GACs, has created a potentially fruitful opportunity to enhance teaching English as a Foreign Language (EFL). This study investigated the possibility of using GACs to give EFL students metalinguistic guidance (MG) in linguistics courses. Language competency gaps, a lack of individualized engagement, and low metacognitive abilities are common challenges EFL students face in linguistics courses. Feedback has been suggested as a potential solution to these issues in previous studies; nevertheless, conventional corrective feedback (CF) might not fully satisfy the demands of EFL students. In order to address these obstacles, the current study suggested a metalinguistic guiding (MG)-based GAC approach. Using a quasi-experimental approach with pretest and posttest setups, this study evaluated the learning achievement, reflective performance, perception, and metacognitive awareness of EFL students exposed to either CF-based GAC or MG-based GAC. According to the study's findings, the MG-based GAC group performed better than the CF-based GAC group in terms of learning achievement, reflective performance, and perceptual and metacognitive awareness. The GAC's immediate educational usefulness and potential as a pedagogical tool for shaping cognitive processes are highlighted by its successful application in helping EFL students gain metacognitive awareness. This study contributes significantly to the growing body of knowledge about the use of GAC in educational settings by providing empirical evidence of the effectiveness of GAC in terms of delivering MG to EFL students.

Laboratory courses can help students learn in a meaningful way. In the past, students encountered difficulties in chemistry laboratory courses due to limited access to equipment and space for practicing experimental operations. In recent years, virtual laboratories have allowed students to repeatedly practice in order to achieve their experimental goals. However, even when students follow the experimental protocol, some still cannot fully understand the principles and meaning of the experimental procedures. Therefore, when they encounter unexpected situations in experiments, they may not know how to handle them. Thus, this study incorporated a concept mapping-guided learning approach to facilitate students' understanding of the concepts of the experimental process and the relationship between experimental procedures before virtual laboratory practice. Using a quasi-experimental approach, 51 middle school students aged 12 to 13 years were assigned to an experimental group (M = 12, F = 14) using the concept mapping-guided virtual laboratory learning approach, and a control group (M = 12, F = 13) using the conventional virtual laboratory learning approach. The experimental group improved their science process skills, problem-solving awareness, and creative thinking tendency. Teachers can employ guided virtual laboratory learning approaches to help students experiment and understand concepts.

One of the main goals of the English as a Foreign Language (EFL) course is to facilitate the development of learners' reading comprehension and reflective skills in English, which can be developed with appropriate instruction. However, in EFL courses, many students are inactive in reflecting on their reading and are disengaged from learning. To fill this gap, a reflective reading-based e-learning approach was proposed to explore the impact of the suggested approach on reading comprehension, reflective thinking, and behavioral engagement. The study aimed to improve the comprehension of the student's reading using the proposed reflective e-learning approach. The study employed a quasi-experimental design in which the experimental group used reflective reading-based e-learning (n = 51) and the control group used conventional e-learning (n = 50) for a total of 13 weeks of participation. The experiment was designed to examine reading comprehension, reflective thinking, and behavioral engagement (e.g., reading time, Marker list, Quiz score, Memo list). The results revealed that the reflective reading-based e-learning approach could improve the comprehension and reflective thinking of the learners and promote behavioral engagement. These findings can be valuable for educators designing strategies to improve students' reading comprehension skills and stimulate behavioral engagement in e-learning systems.

This study explores the roles and research foci of AILEd (Artificial Intelligence in Language Education). The AILEd studies published from 1990 to 2020 in the WOS (Web of Science) database were included in the present study. Based on the well-recognized Technology-based Learning Review model, several dimensions, such as research methods, research sample groups, adopted technology, language skills, the role of AI in language education, and learning outcomes, were taken into account. The review results show that the main application domains of AILEd research were writing, reading, and vocabulary acquisition. In terms of applied technology and algorithms, AI in language education mostly adopted ITS (Intelligent Tutoring System) and NLP (Natural Language Processing). Besides, several commonly used AI algorithms were Statistical Learning, Data Mining, Machine Learning, and Natural Language Parsing. It was also found that some research focused on learning anxiety, willingness to communicate, knowledge acquisition, and classroom interaction. However, higher order thinking, complex problem solving, critical thinking ability, and collaborative learning tendencies were rarely considered in AILEd studies. Accordingly, several suggestions are provided to researchers, teachers, and decision makers for applying or studying AI applications in language education in the future.

Self-directed learning (SDL) ability, its usefulness in higher education and life-long learning have been highlighted in previous literature. However, there has been much less understanding of the effects of SDL ability in the school settings, specifically the effects on learners' SDL behaviors and processes. To address this limitation, this study investigated the relations between SDL ability, SDL behaviors, and reading outcomes and further explored the process of planning behaviors in SDL. This study examined the context of SDL for extensive reading using a goal-oriented active learning system, GOAL. The results showed that the high SDL ability students demonstrated significantly more reading outcomes in terms of books completed and the number of days read than those with low SDL ability. The high SDL ability students engaged significantly more in planning behaviors, that were found to be significantly correlated with reading outcomes, than the low SDL ability students. Cluster analysis and transition analysis also differentiate groups of learners with different planning behaviors. These findings suggested that the learning behaviors and outcomes facilitated by the environment were affected to varying degrees by the levels of students' SDL ability, and personalized feedback can be created using the SDL behavioral variables and patterns in the environment.

Fostering students' competence in applying interdisciplinary knowledge to solve problems has been recognized as an important and challenging issue globally. This is why STEM (Science, Technology, Engineering, Mathematics) education has been emphasized at all levels in schools. Meanwhile, the use of robotics has played an important role in STEM learning design. The purpose of this study was to fill a gap in the current review of research on Robotics-based STEM (R-STEM) education by systematically reviewing existing research in this area. This systematic review examined the role of robotics and research trends in STEM education. A total of 39 articles published between 2012 and 2021 were analyzed. The review indicated that R-STEM education studies were mostly conducted in the United States and mainly in K-12 schools. Learner and teacher perceptions were the most popular research focus in these studies which applied robots. LEGO was the most used tool to accomplish the learning objectives. In terms of application, Technology (programming) was the predominant robotics-based STEM discipline in the R-STEM studies. Moreover, project-based learning (PBL) was the most frequently employed learning strategy in robotics-related STEM research. In addition, STEM learning and transferable skills were the most popular educational goals when applying robotics. Based on the findings, several implications and recommendations to researchers and practitioners are proposed.

This study aims to identify the bibliometric outcomes of articles and research trends in specific areas. This study revealed research on the use of e-books for EFL education published in selected journals of the Web of Science from 2011 to 2020, and discusses the trends of the top-cited countries, journals, the most used keywords, and the popular subjects, learning strategies, target skills, and the research outcomes. A total of 53 selected articles were manually and systematically analyzed. The results revealed that the most productive country was Taiwan, and the most cited journal was Computers & Education. The most used keywords were "engagement." The bibliometric analysis can be reflected in the content analysis as preschoolers and elementary school students were the most common participants, guided learning were the most frequently used strategy, and the main target skill was reading. This review study provides an overview of the research agenda for the last 10 years, and highlights the trends in the field by analyzing relevant past research. When the use of e-books in EFL education studies was examined, reading comprehension, teaching/learning strategies, and learning engagement were found to be crucial in the studies. Therefore, there is a need to develop more useful features of e-books to support EFL teaching practices. It is therefore suggested that future research focus more on pedagogical aspects and e-book feature development.

This study investigates the role of self-efficacy in an asynchronous online English course enriched with interactive features. Self-efficacy is a strong predictor of academic achievement in conventional classrooms. However, when learning happens in an online environment, the students' learning achievement is also affected by their psychological perceptions of online learning. In this study, the relationship between self-efficacy and affective factors (i.e., learner autonomy, learner-content interaction, and perceptions toward transactional distance) was investigated. The aims of this study were to identify the influence of different levels of self-efficacy on these factors and to explore their relationships in an online EFL course. In total, 286 students were administered the questionnaires before and after the curriculum to probe their self-perception of these affective variables. When asynchronous interactive learning materials came into play, learners with different levels of self-efficacy make statistically different learning achievements. The statistically significant differences were also found between the student's self-efficacy level, their learner autonomy, and their perception toward the interactive contents. However, the difference was not significant between self-efficacy and transactional distance. The cost of asynchronous learning is an increasing transactional distance due to the lack of instructor-learner interaction. This study suggests that interactive content triggered an opposite effect by making the instructor's role invisible rather than absent. A good online course must balance the student's self-determined learning and flexibility with the course structure. Interactive learning content can keep the balance between developing learner autonomy and fostering engagement by dissolving the teacher's role into interactive course material.