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Despite the increasing popularity of dual language education programs in Taiwan, limited research assesses their effectiveness. This study evaluated eight English Immersion Programs (EIPs) in Taiwan, representing a dual language education model, using the "Guiding Principles for Dual Language Education" (GPDLE) framework. Interviews with the management team and a questionnaire for Native English Teachers (NETs) assessed the alignment of program structure and instruction with the GPDLE. A quasi-experimental design, including pre-tests and post-tests, examined the English listening and reading outcomes of 74 fourth to sixth-grade students in two randomly-selected EIPs over a year. The findings reveal that 83% of the EIPs fully adhered to the program structure outlined in the GPDLE, while only 33% of teacher instruction exhibited full alignment, with an additional 57% demonstrating partial alignment. Notably, significant improvements in reading were observed among fourth-grade students, and both reading and listening skills showed substantial enhancements in the fifth and sixth-grade students. The study recommends adopting a financially sustainable, user-paid model for an after-school English immersion program, supporting Taiwan's 2030 Bilingual National Initiative.

Abstract Despite the widespread use of multimodal pedagogies in Content and Language Integrated Learning (CLIL) contexts, empirical studies specifically focusing on the impact of hands-on learning on target vocabulary and procedural knowledge acquisition in CLIL Social Studies, particularly in Taiwan, are relatively uncommon. Grounded in embodied learning theories, this study investigated the comparative impact of hands-on learning versus worksheet-based instruction on fourth graders’ target vocabulary acquisition and procedural knowledge within a CLIL Social Studies setting in Taiwan. The study also explored students’ perceptions of their learning experiences with these instructional methods. This quasi-experimental study involved four intact fourth-grade CLIL Social Studies classes from three elementary schools in Taiwan, comprising 40 students in the Experimental Group (EG), who engaged in hands-on learning, and 34 students in the Control Group (CG), who engaged in worksheet-based learning. Activities included Chinese dumpling making, bird’s nest building, and designing a pot of succulents. Data were collected through pre- and post-tests to assess target vocabulary acquisition and procedural knowledge, followed by learner experience surveys to evaluate students’ perceptions of their learning experiences. The analysis included paired-samples t-tests, independent-samples t-tests, and thematic analysis of open-ended survey responses. Results revealed that the EG significantly outperformed the CG in both target vocabulary acquisition and procedural knowledge across all three activities, with large effect sizes (d = 1.05–1.51 for target vocabulary and 0.95–2.89 for procedural knowledge), demonstrating the effectiveness of hands-on learning. However, while significant differences were observed in memory retention of target vocabulary and procedural knowledge from the survey results, no significant differences were found between the EG and CG in terms of perceived ease of learning. These findings suggest that hands-on learning offers substantial benefits over traditional worksheet-based instruction in CLIL settings, though the transition to hands-on methods may require additional support. Practical implications include the strategic selection of relevant vocabulary, the implementation of structured hands-on approaches, and the emphasis on behavioral reinforcement to enhance learning outcomes.

Abstract Background Aflatoxin B1 (AFB1) is a prevalent contaminant in agricultural products, presenting significant risks to animal health. CotA laccase from Bacillus licheniformis has shown significant efficacy in degrading mycotoxins in vitro test. The efficacy of Bacillus CotA laccase in animals, however, remains to be confirmed. A 2 × 2 factorial design was used to investigate the effects of Bacillus CotA laccase level (0 or 1 U/kg), AFB1 challenge (challenged or unchallenged) and their interactions on ducks. The purpose of this study was to evaluate the efficacy of Bacillus CotA laccase in alleviating AFB1 toxicosis of ducks. Results Bacillus CotA laccase alleviated AFB1-induced declines in growth performance of ducks accompanied by improved average daily gain (ADG) and lower feed/gain ratio (F/G). Bacillus CotA laccase ameliorated AFB1-induced gut barrier dysfunctions and inflammation testified by increasing the jejunal villi height/crypt depth ratio (VH/CD) and the mRNA expression of tight junction protein 1 (TJP1) and zonula occluden-1 (ZO-1) as well as decreasing the expression of inflammation-related genes in the jejunum of ducks. Amino acid metabolome showed that Bacillus CotA laccase ameliorated AFB1-induced amino acid metabolism disorders evidenced by increasing the level of glutamic acid in serum and upregulating the expression of amino acid transport related genes in jejunum of ducks. Bacillus CotA laccase ameliorated AFB1-induced liver injury testified by suppressing oxidative stress, inhibiting apoptosis, and downregulating the expression of hepatic metabolic enzyme related genes of ducks. Moreover, Bacillus CotA laccase degraded AFB1 in digestive tract of ducks, resulting in the reduced absorption level of AFB1 across intestinal epithelium testified by the decreased level of AFB1-DNA adduct in the liver, and the reduced content of AFB1 residues in liver and feces of ducks. Conclusions Bacillus CotA laccase effectively improved the growth performance, intestinal health, amino acid metabolism and hepatic aflatoxin metabolism of ducks fed AFB1 diets, highlighting its potential as an efficient and safe feed enzyme for AFB1 degradation in animal production. Graphical Abstract

Abstract Kidney diseases represent a diverse range of conditions that compromise renal function and structure which characterized by a progressive deterioration of kidney function, may ultimately necessitate dialysis or kidney transplantation as end-stage treatment options. This review explores the complex landscape of kidney diseases, highlighting the limitations of existing treatments and the pressing need for innovative strategies. The paper delves into the role of extracellular vesicles (EVs) as emerging biomarkers and therapeutic agents in the context of kidney pathophysiology. Urinary extracellular vesicles (uEVs), in particular, offer a non-invasive means of assessing renal injury and monitoring disease progression. Additionally, mesenchymal stem cell-derived EVs (MSC-EVs) are examined for their immunomodulatory and tissue repair capabilities, presenting a promising avenue for novel therapeutic interventions. And discusses the potential of engineering EVs to enhance their targeting and therapeutic efficacy. This paper systematically integrates the latest research findings and aims to provide a comprehensive overview of the role of EVs in kidney disease, providing cutting-edge insights into their potential as a diagnostic and therapeutic tool.

Abstract Tumor cells remodel the phenotype and function of tumor microenvironment (TME) cells to favor tumor progression. Previous studies have shown that neutrophils in TME are polarized to N2 tumor-associated neutrophils (TANs) by tumor derived factors, thus promoting tumor growth and metastasis, angiogenesis, therapy resistance, and immunosuppression. Exosomes act as critical intercellular messengers in human health and diseases including cancer. So far, the biological roles of exosomes from N2 TANs in gastric cancer have not been well characterized. Herein, we represented the first report that exosomes from N2 TANs promoted gastric cancer metastasis in vitro and in vivo. We found that exosomes from N2 TANs transferred miR-4745-5p/3911 to gastric cancer cells to downregulate SLIT2 (slit guidance ligand 2) gene expression. Adenovirus-mediated overexpression of SLIT2 reversed the promotion of gastric cancer metastasis by N2 TANs derived exosomes. We further revealed that gastric cancer cells induced glucose metabolic reprogramming in neutrophils through exosomal HMGB1 (high mobility group protein B1)/NF-κB pathway, which mediated neutrophil N2 polarization and miR-4745-5p/3911 upregulation. We further employed ddPCR (droplet digital PCR) to detect the expression of miR-4745-5p/3911 in N2 TANs exosomes from human serum samples and found their increased levels in gastric cancer patients compared to healthy controls and benign gastric disease patients. Conclusively, our results indicate that N2 TANs facilitate cancer metastasis via regulation of SLIT2 in gastric cancer cells by exosomal miR-4745-5p/3911, which provides a new insight into the roles of TME cells derived exosomes in gastric cancer metastasis and offers a potential biomarker for gastric cancer diagnosis.

A method of combining headspace microextraction technique based on a polyurethane sponge-supported liquid film with gas chromatography-mass spectrometry (GC-MS) was developed for convenient and sensitive analysis of six polycyclic aromatic hydrocarbons (PAHs) in environmental water samples. The microextraction device consists of three parts, namely injector, polyurethane sponge, and headspace bottle. Firstly, the commercially available polyurethane sponge was specially tailored to be fitted into miniature cylinders that were compatible with the internal cavity of the 2.5 mL syringe needle. Then the extraction solvents were loaded to form a microextraction liquid film on the surface and inside of the sponge. After sealed with syringe barrel, the syringe needle was inserted into the septum of headspace bottle for headspace microextraction. The dynamic suction, heating assistance, and magnetic stirring were adopted to accelerate the volatilization process and transferring of the analytes in gas-liquid interface. Given the excellent elasticity of polyurethane sponge, the extraction solution could be successfully recovered through solvent elution and physical extrusion. The influence of the types and amounts of extraction solvents, suction time, heating (extraction) temperatures, stirring speeds, and eluent volumes on the enrichment efficiency of the monitored PAHs were systematically investigated. The results indicated that the satisfactory extraction efficiency could be achieved by using 40 µL of carbon tetrachloride as an extractant, which were loaded into a polyurethane sponge microcylinder with a bottom diameter and height of 4 mm, and followed by 150 cycles dynamic suction under extraction conditions of 65 ℃ and 1 000 r/min. Subsequently, physical extrusion was adopted to collect the extraction solution after elution with 30 µL of carbon tetrachloride. The validation results demonstrated that the proposed method achieves good relative recoveries of PAHs ranging from 94.7% to 113.2% at three spiked levels of 0.1, 0.5, and 1 μg/L. The intra- and inter-day precisions are in the range of 1.0%-8.1% and 4.2%-9.5%, respectively. Good linearities are observed for all monitored PAHs with the regression coefficients (R2) greater than 0.997 in the concentration range of 0.01-5 μg/L. The limits of detection (LODs) and quantification (LOQs) are in the range of 3-30 ng/L and 10-100 ng/L, respectively. This method is easy to operate, and has the advantages of low cost, high sensitivity as well as fast speed, having highly potential in the field of trace volatile analysis in environmental samples.

Abstract Multi‐agent reinforcement learning relies on reward signals to guide the policy networks of individual agents. However, in high‐dimensional continuous spaces, the non‐stationary environment can provide outdated experiences that hinder convergence, resulting in ineffective training performance for multi‐agent systems. To tackle this issue, a novel reinforcement learning scheme, Mutual Information Oriented Deep Skill Chaining (MioDSC), is proposed that generates an optimised cooperative policy by incorporating intrinsic rewards based on mutual information to improve exploration efficiency. These rewards encourage agents to diversify their learning process by engaging in actions that increase the mutual information between their actions and the environment state. In addition, MioDSC can generate cooperative policies using the options framework, allowing agents to learn and reuse complex action sequences and accelerating the convergence speed of multi‐agent learning. MioDSC was evaluated in the multi‐agent particle environment and the StarCraft multi‐agent challenge at varying difficulty levels. The experimental results demonstrate that MioDSC outperforms state‐of‐the‐art methods and is robust across various multi‐agent system tasks with high stability.

Content and Language Integrated Learning (CLIL) is increasingly adopted globally, including in Taiwan's educational initiatives, yet challenges remain in implementing effective CLIL practices, such as pedagogy and curriculum design. This study investigated the effectiveness of multimodal task designs, combining hands-on learning with poster presentations, in enhancing oral communicative competence within CLIL contexts. Employing a mixed-methods, quasi-experimental design with a comparative case study framework, the study assessed English oral communicative competence in four intact fourth-grade Taiwanese CLIL Social Studies classes. The hands-on learning group (EG, n = 40) engaged in activities like Chinese Dumpling Making, Bird's Nest Building, and Succulent Pot Designing, while the non-hands-on learning group (CG, n = 34) used traditional worksheets on the same topics. Both groups proceeded to poster presentations within their multimodal task design, where students' oral communicative competence was assessed using rubrics developed based on Coyle's 4Cs dimensions, focusing on Content, Communication, and Cognition. Additionally, students' cultural knowledge related to the hands-on topics was evaluated through written tests. To complement the quantitative data, qualitative data from self-reported reflections and video recordings documenting interventions were collected for the assessment of oral communicative competence within a CLIL framework. Results demonstrate that integrating hands-on activities significantly enhanced procedural content, communication (i.e., sentence complexity, pronunciation accuracy for target vocabulary, presentation fluency), and cognitive abilities, confirming the efficacy of multimodal learning approaches in fostering linguistic and cognitive engagement. Post-test comparisons show the EG's superiority in cultural knowledge acquisition across all three hands-on topics. Student reflections endorsed the enrichment of learning experiences through multimodal task design. Video analysis of both groups' interventions revealed that despite significant engagement and autonomy, EG students commonly utilized general English rather than target vocabulary, a pattern similar to that observed in the CG. These findings highlight the potential of diverse modalities in CLIL to enhance English content learning and oral skills, shaping future pedagogy and language strategies in Taiwan. The study also emphasizes the role of embodied learning, the interplay between physical actions and cognitive processes, to facilitate deeper understanding and engagement with subject matter within CLIL settings.

Abstract Renal interstitial fibrosis (RIF) is a prevalent consequence of chronic renal diseases, characterized by excessive extracellular matrix (ECM) deposition. A Disintegrin and Metalloprotease 17 (ADAM17), a transmembrane metalloproteinase, plays a central role in driving renal fibrosis progression by activating Notch 1 protein and the downstream TGF-β signaling pathway. Our study investigated potential therapeutic interventions for renal fibrosis, focusing on human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs). We found that hucMSC-EVs inhibit ADAM17, thereby impeding renal fibrosis progression. Analysis of hucMSC-EVs miRNA profiles revealed significant enrichment of miR-13474, which effectively targeted and inhibited ADAM17 mRNA expression, subsequently suppressing Notch1 activation, TGF-β signaling, and collagen deposition. Overexpression of miR-13474 enhanced hucMSC-EVs' inhibitory effect on renal fibrosis, while its downregulation abolished this protective effect. Our findings highlight the efficacy of hucMSC-EVs overexpressing miR-13474 in mitigating renal fibrosis via ADAM17 targeting. These insights offer potential therapeutic strategies for managing renal fibrosis.

Abstract Objective In this study, we compared the analgesic effects of intercostal nerve block (ICNB), ultrasound-guided paravertebral nerve block (PVB), and epidural block (EB) following single-port thoracoscopic lung surgery. Method A total of 120 patients who underwent single-hole thoracoscopic lung surgery were randomly and equally divided into three groups: ICNB group, the PVB group, and the EB group. ICNB was performed under direct thoracoscopic visualization before the conclusion of the surgery in the ICNB group, while PVB and EB were performed after general anesthesia in the PVB and EB groups, respectively. Patient-controlled intravenous analgesia (PCIA) was used following the surgery in all the groups. The following indicators were recorded: Intraoperative sufentanil dosage, anesthesia awakening time, postoperative intubation time, nerve block operation time, postoperative visual analog scale (VAS) pain scores during resting and coughing at regular intervals of 0, 2, 4, 8, 24, and 48 h, the time until first PCIA, number of effective compressions within 24 h postoperatively, number of rescue analgesia interventions, and the side effects. Results In comparison to the ICNB group, the PVB and EB groups had a lower intraoperative sufentanil dosage, significantly shorter anesthesia awakening time, and postoperative intubation time, but longer nerve block operation time, lower VAS scores when resting and coughing within 24 h postoperatively (all p-values less than 0.05). Conversely, there were no statistically significant differences in VAS scores during resting and coughing after 24 h (all p-values greater than 0.05). Time to first PCIA, number of effective compressions and number of rescue analgesia at the 24-hour mark postoperatively were significantly better in the PVB and EB groups than that in the ICNB group (P

Abstract Background Traumatic fractures occur frequently worldwide. However, research remains limited on the association between short-term exposure to temperature and traumatic fractures. This study aims to explore the impact of apparent temperature (AT) on emergency visits (EVs) due to traumatic fractures. Methods Based on EVs data for traumatic fractures and the contemporary meteorological data, a generalized Poisson regression model along with a distributed lag nonlinear model (DLNM) were undertaken to determine the impact of AT on traumatic fracture EVs. Subgroup analysis by gender and age and sensitivity analysis were also performed. Results A total of 25,094 EVs for traumatic fractures were included in the study. We observed a wide “J”-shaped relationship between AT and risk of traumatic fractures, with AT above 9.5 °C positively associated with EVs due to traumatic fractures. The heat effects became significant at cumulative lag 0–11 days, and the relative risk (RR) for moderate heat (95th percentile, 35.7 °C) and extreme heat (99.5th percentile, 38.8 °C) effect was 1.311 (95% CI: 1.132–1.518) and 1.418 (95% CI: 1.191–1.688) at cumulative lag 0–14 days, respectively. The cold effects were consistently non-significant on single or cumulative lag days across 0–14 days. The heat effects were higher among male and those aged 18–65 years old. The sensitivity analysis results remained robust. Conclusion Higher AT is associated with cumulative and delayed higher traumatic fracture EVs. The male and those aged 18–65 years are more susceptible to higher AT.

Abstract Diabetic kidney disease (DKD), a chronic kidney disease, is characterized by progressive fibrosis caused due to persistent hyperglycemia. The development of fibrosis in DKD determines the patient prognosis, but no particularly effective treatment. Here, small extracellular vesicles derived from mesenchymal stem cells (MSC-sEV) have been used to treat DKD fibrosis. Single-cell RNA sequencing was used to analyze 27,424 cells of the kidney, we have found that a novel fibrosis-associated TGF-β1 +Arg1+ macrophage subpopulation, which expanded and polarized in DKD and was noted to be profibrogenic. Additionally, Actin+Col4a5+ mesangial cells in DKD differentiated into myofibroblasts. Multilineage ligand-receptor and cell-communication analysis showed that fibrosis-associated macrophages activated the TGF-β1/Smad2/3/YAP signal axis, which promotes mesangial fibrosis-like change and accelerates renal fibrosis niche. Subsequently, the transcriptome sequencing and LC-MS/MS analysis indicated that MSC-sEV intervention could restore the levels of the kinase ubiquitin system in DKD and attenuate renal interstitial fibrosis via delivering CK1δ/β-TRCP to mediate YAP ubiquitination degradation in mesangial cells. Our findings demonstrate the unique cellular and molecular mechanisms of MSC-sEV in treating the DKD fibrosis niche at a single-cell level and provide a novel therapeutic strategy for renal fibrosis.

We proposed a non-contact photoacoustic (PA) detection method using spectral domain optical coherence tomography (SDOCT). Two interference spectrums (A-lines) were acquired before and after the PA excitation with SDOCT. PA signal propagated within the sample causing the vibration. The vibration inner the sample introduced phase change between the acquired two A-lines. Thus, the PA signal can be detected by evaluating the difference in phase between the two A-lines. Based on the method, an OCT-PAM dual-mode imaging system was constructed. In the system, SDOCT served as the detection unit for PAM. Thus, the combination of the two imaging modalities was simplified. Another advantage of the system is that it realizes non-contact all-optic detection, which is attractive for biomedical imaging. Using the system, we imaged phantoms of carbon fibers, asparagus leaves and human hairs. Furthermore, the cortical vasculature of rat was imaged in vivo and the flow status was evaluated quantitatively.

Abstract Background Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. Methods A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. Results In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. Conclusions Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.

Abstract Cone‐beam computed tomography (CBCT) system can provide real‐time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Abstract The mesophilic purple sulfur phototrophic bacterium Allochromatium (Alc.) vinosum (bacterial family Chromatiaceae) has been a favored model for studies of bacterial photosynthesis and sulfur metabolism, and its core light-harvesting (LH1) complex has been a focus of numerous studies of photosynthetic light reactions. However, despite intense efforts, no high-resolution structure and thorough biochemical analysis of the Alc. vinosum LH1 complex have been reported. Here we present cryo-EM structures of the Alc. vinosum LH1 complex associated with reaction center (RC) at 2.24 Å resolution. The overall structure of the Alc. vinosum LH1 resembles that of its moderately thermophilic relative Alc. tepidum in that it contains multiple pigment-binding α- and β-polypeptides. Unexpectedly, however, six Ca ions were identified in the Alc. vinosum LH1 bound to certain α1/β1- or α1/β3-polypeptides through a different Ca2+-binding motif from that seen in Alc. tepidum and other Chromatiaceae that contain Ca2+-bound LH1 complexes. Two water molecules were identified as additional Ca2+-coordinating ligands. Based on these results, we reexamined biochemical and spectroscopic properties of the Alc. vinosum LH1–RC. While modest but distinct effects of Ca2+ were detected in the absorption spectrum of the Alc. vinosum LH1 complex, a marked decrease in thermostability of its LH1–RC complex was observed upon removal of Ca2+. The presence of Ca2+ in the photocomplex of Alc. vinosum suggests that Ca2+-binding to LH1 complexes may be a common adaptation in species of Chromatiaceae for conferring spectral and thermal flexibility on this key component of their photosynthetic machinery.