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Multimodal learning analytics (MMLA) offers the potential to provide evidence-based insights into complex learning phenomena such as collaborative learning. Yet, few MMLA applications have closed the learning analytics loop by being evaluated in real-world educational settings. This study evaluates the effectiveness of an MMLA solution in enhancing feedback and reflection within a complex and highly dynamic collaborative learning environment. A two-year longitudinal study was conducted with 399 students and 17 teachers, utilising an MMLA system in reflective debriefings in the context of healthcare education. We analysed the survey data of 74 students and 11 teachers regarding their perceptions of the MMLA system. We applied the Evaluation Framework for Learning Analytics, augmented by complexity, accuracy and trust measures, to assess both teachers' and students' perspectives. The findings illustrated that teachers and students both had generally positive perceptions of the MMLA solution. Teachers found the MMLA solution helpful in facilitating feedback provision and reflection during debriefing sessions. Similarly, students found the MMLA solution effective in providing clarity on the data collected, stimulating reflection on their learning behaviours, and prompting considerations for adaptation in their learning behaviours. However, the complexity of the MMLA solution and the need for qualitative measures of communication emerged as areas for improvement. Additionally, the study highlighted the importance of data accuracy, transparency, and privacy protection to maintain user trust. The findings provide valuable contributions to advancing our understanding of the use of MMLA in supporting feedback and reflection practices in intricate collaborative learning while identifying avenues for further research and improvement. We also provided several insights and practical recommendations for successful MMLA implementation in authentic learning contexts.

Creativity is an important skill in the 21st century, and design thinking has been proposed as a methodology for fostering creativity. Design creativity involves two non-rational aspects: motivation and empathy. However, little is known about how empathy and motivation work in synergy with creativity. This study explored the underlying mechanisms of empathy and motivation in creativity in design thinking. We built an explanatory model to examine the effect of empathy on motivation and creativity and the mediating effects of four aspects of motivation (i.e., attention, relevance, confidence, and satisfaction). In the study, 220 6th-grade students participated in an integrated STEM curriculum that centered on design thinking activities that lasted one semester, and then completed a questionnaire measuring their perceptions of empathy, motivation, and creativity at the end of the design activities. Partial least squares structural equation modelling was used to analyze the collected data. The results showed that empathy positively predicted creativity. In addition, empathy had a significant impact on creativity through the effect of intrinsic motivation, but not through that of extrinsic motivation. Among the four aspects of motivation, attention, relevance, and confidence each strengthened the association between empathy and creativity. However, satisfaction had a negative effect on creativity and a non-significant mediating effect. These findings increase our understanding of the internal mechanisms of design thinking and creativity. Some practical implications of empathy and motivation in creativity are also discussed.

Effective collaboration and teamwork skills are critical in high-risk sectors, as deficiencies in these areas can result in injuries and risk of death. To foster the growth of these vital skills, immersive learning spaces have been created to simulate real-world scenarios, enabling students to safely improve their teamwork abilities. In such learning environments, multiple dialogue segments can occur concurrently as students independently organise themselves to tackle tasks in parallel across diverse spatial locations. This complex situation creates challenges for educators in assessing teamwork and for students in reflecting on their performance, especially considering the importance of effective communication in embodied teamwork. To address this, we propose an automated approach for generating teamwork analytics based on spatial and speech data. We illustrate this approach within a dynamic, immersive healthcare learning environment centred on embodied teamwork. Moreover, we evaluated whether the automated approach can produce transcriptions and epistemic networks of spatially distributed dialogue segments with a quality comparable to those generated manually for research objectives. This paper makes two key contributions: (1) it proposes an approach that integrates automated speech recognition and natural language processing techniques to automate the transcription and coding of team communication and generate analytics; and (2) it provides analyses of the errors in outputs generated by those techniques, offering insights for researchers and practitioners involved in the design of similar systems.

Socio-spatial learning analytics (SSLA) is an emerging area within learning analytics research that seeks to uncover valuable educational insights from individuals' social and spatial data traces. These traces are captured automatically through sensing technologies in physical learning spaces, and the research is commonly based on the theoretical foundations of social constructivism and cultural anthropology. With its growing empirical basis, a systematic literature review is timely in order to provide educational researchers and practitioners with a detailed summary of the emerging works and the opportunities enabled by SSLA. This paper presents a systematic review of 25 peer-reviewed articles on SSLA published between 2011 and 2023. Descriptive, network, and thematic analyses were conducted to identify the citation networks, essential components, opportunities, and challenges enabled by SSLA. The findings illustrated that SSLA provides the opportunity to: (1) contribute unobtrusive and unsupervised research methodologies; (2) support educators' classroom orchestration through visualizations; (3) support learner reflection with continuous and reliable evidence; (4) develop novel theories about social and collaborative learning; and (5) empower educational stakeholders with the quantitative data to evaluate different learning spaces. These findings could support learning analytics and educational technology scholars and practitioners to better understand and utilize SSLA to support future educational research and practice.

Educational technology innovations leveraging large language models (LLMs) have shown the potential to automate the laborious process of generating and analysing textual content. While various innovations have been developed to automate a range of educational tasks (eg, question generation, feedback provision, and essay grading), there are concerns regarding the practicality and ethicality of these innovations. Such concerns may hinder future research and the adoption of LLMs-based innovations in authentic educational contexts. To address this, we conducted a systematic scoping review of 118 peer-reviewed papers published since 2017 to pinpoint the current state of research on using LLMs to automate and support educational tasks. The findings revealed 53 use cases for LLMs in automating education tasks, categorised into nine main categories: profiling/labelling, detection, grading, teaching support, prediction, knowledge representation, feedback, content generation, and recommendation. Additionally, we also identified several practical and ethical challenges, including low technological readiness, lack of replicability and transparency and insufficient privacy and beneficence considerations. The findings were summarised into three recommendations for future studies, including updating existing innovations with state-of-the-art models (eg, GPT-3/4), embracing the initiative of open-sourcing models/systems, and adopting a human-centred approach throughout the developmental process. As the intersection of AI and education is continuously evolving, the findings of this study can serve as an essential reference point for researchers, allowing them to leverage the strengths, learn from the limitations, and uncover potential research opportunities enabled by ChatGPT and other generative AI models.

Abstract During follicular development, changes in the composition of the follicular fluid are synchronized with the development of oocytes. Our aim was to screen the key factors affecting oocyte maturation and optimize the in vitro culture protocol by understanding the changes of proteins and metabolites in follicular fluid. Follicles are divided into three groups according to their diameter (small follicle fluid (SFF): 10 mm

Abstract Background The failure of proper recognition of the intricate nature of pathophysiology in colorectal cancer (CRC) has a substantial effect on the progress of developing novel medications and targeted therapy approaches. Imbalances in the processes of lipid oxidation and biosynthesis of fatty acids are significant risk factors for the development of CRC. Therapeutic intervention that specifically targets the peroxisome proliferator-activated receptor gamma (PPARγ) and its downstream response element, in response to lipid metabolism, has been found to promote the growth of tumors and has shown significant clinical advantages in cancer patients. Methods Clinical CRC samples and extensive in vitro and in vivo experiments were carried out to determine the role of ZDHHC6 and its downstream targets via a series of biochemical assays, molecular analysis approaches and lipid metabolomics assay, etc. Results To study the effect of ZDHHC6 on the progression of CRC and identify whether ZDHHC6 is a palmitoyltransferase that regulates fatty acid synthesis, which directly palmitoylates and stabilizes PPARγ, and this stabilization in turn activates the ACLY transcription-related metabolic pathway. In this study, we demonstrate that PPARγ undergoes palmitoylation in its DNA binding domain (DBD) section. This lipid-related modification enhances the stability of PPARγ protein by preventing its destabilization. As a result, palmitoylated PPARγ inhibits its degradation induced by the lysosome and facilitates its translocation into the nucleus. In addition, we have identified zinc finger-aspartate-histidine-cysteine 6 (ZDHHC6) as a crucial controller of fatty acid biosynthesis. ZDHHC6 directly interacts with and adds palmitoyl groups to stabilize PPARγ at the Cys-313 site within the DBD domain of PPARγ. Consequently, this palmitoylation leads to an increase in the expression of ATP citrate lyase (ACLY). Furthermore, our findings reveals that ZDHHC6 actively stimulates the production of fatty acids and plays a role in the development of colorectal cancer. However, we have observed a significant reduction in the cancer-causing effects when the expression of ZDHHC6 is inhibited in in vivo trials. Significantly, in CRC, there is a strong positive correlation between the high expression of ZDHHC6 and the expression of PPARγ. Moreover, this high expression of ZDHHC6 is connected with the severity of CRC and is indicative of a poor prognosis. Conclusions We have discovered a mechanism in which lipid biosynthesis is controlled by ZDHHC6 and includes the signaling of PPARγ-ACLY in the advancement of CRC. This finding provides a justification for targeting lipid synthesis by blocking ZDHHC6 as a potential therapeutic approach.

Abstract Background Clinical events such as angina pectoris, acute coronary syndrome, and sudden death caused by myocardial bridge (MB) have attracted increasing attention. It is still a challenge to diagnose whether MB can cause the symptoms of patients with MB. For most MB patients, medication remains the primary treatment. Case presentation This article reports a case of chest pain in a patient with MB in the middle segment of the left anterior descending artery (LADm) with moderate stenosis in the proximal segment (LADp). Through functional assessment, we found that neither MB nor fixed stenosis had sufficient effect on coronary blood flow to cause myocardial ischemia, but their synergistic effect resulted in myocardial ischemia. Finally, a stent was implanted in LADp and good clinical results were achieved. Conclusions For symptomatic patients with MB combined with fixed stenosis, functional evaluation may be necessary, which has significant guiding significance for treatment strategy selection. For asymptomatic patients, early detection of myocardial ischemia may also improve the prognosis of patients.

Abstract The driving force behind the Cenozoic India-Asia collision remains elusive. Using global-scale geodynamic modeling, we find that the continuous motion of the Indian plate is driven by a prominent upper-mantle flow pushing the thick Indian lithospheric root, originated from the northward rollover of the detached Neo-Tethyan slab and sinking slabs below East Asia. The maximum mantle drag occurs within the strong Indian lithosphere and is comparable in magnitude to that of slab pull (1013 N m−1). The thick cratonic root enhances both lithosphere-asthenosphere coupling and upper-plate compressional stress, thereby sustaining the topography of Tibetan Plateau. We show that the calculated resistant force from the India-Asia plate boundary is also close to that due to the gravitational potential energy of Tibetan Plateau. Here, we demonstrate that this mantle flow is key for the formation of the Tibetan Plateau and represents part of a hemispheric convergent flow pattern centered on central Asia.

Objective Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. Methods Herein, we constructed the high-fat diet-induced FLHS chicken model to investigate the genome-wide active enhancers and transcriptome by H3K27ac target chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-Seq) profiles of normal and FLHS liver tissues. Concurrently, an integrative analysis combining ChIP-seq with RNA-Seq and a comparative analysis with chicken FLHS, rat non-alcoholic fatty liver disease (NAFLD) and human NAFLD at the transcriptome level revealed the enhancer and super enhancer target genes and conservative genes involved in metabolic processes. Results In total, 56 and 199 peak-genes were identified in upregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange) ≥1) (PP) and downregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange)≤−1) (PN), respectively; then we screened key regulatory targets mainly distributing in lipid metabolism (PCK1, APOA4, APOA1, INHBE) and apoptosis (KIT, NTRK2) together with MAPK and PPAR signaling pathway in FLHS. Intriguingly, PCK1 was also significantly covered in up-regulated super-enhancers (SEs), which further implied the vital role of PCK1 during the development of FLHS. Conclusion Together, our studies have identified potential therapeutic biomarkers of PCK1 and elucidated novel insights into the pathogenesis of FLHS, especially for the epigenetic perspective.

BackgroundMulti-slice spiral computerized tomography (MSCT) can be used as an auxiliary diagnosis of chest radiography in diagnosis of pneumoconiosis, but there are few studies on the correlations between interstitial images and stage classification of coal workers' pneumoconiosis in the existing literature. ObjectiveTo present MSCT imaging manifestations and distribution characteristics of coal workers' pneumoconiosis and complications, evaluate correlations between coal workers' pneumoconiosis stages and pulmonary interstitial lesions, and provide a reliable imaging diagnosis basis for pneumoconiosis interstitial lesions. MethodsFrom June 2022 to June 2023, a total of 1002 patients with coal workers' pneumoconiosis confirmed by the pneumoconiosis diagnostic and identification group in the Department of Occupational Diseases of the Emergency General Hospital were enrolled. MSCT was used to observe the abnormal imaging manifestations of the lungs of coal workers' pneumoconiosis patients and the diseases of pulmonary fibrosis related to their own diseases (thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, subpleural line, intralobular interstitial thickening, honeycomb, and subpleural interstitial thickening), the occurrence of coal workers' pneumoconiosis and complications (old tuberculosis, active tuberculosis, pneumonia, atelectasis, lung cancer, bronchiectasis), and the density, size, and location of pneumoconiosis nodules. Imaging data were analyzed and statistically processed. ResultsAll 1002 patients were male, with an average age of (60.71±6.87) years and an average dust exposure time of (23.01±7.80) years. Among them, there were 470 patients with stage I, 422 patients with stage II, and 110 patients with stage III. There were significant differences in the distribution of thickening of the interlobular septum, bronchial perivascular interstitial mass thickening, parenchymal banding, intralobular interstitial thickening, subpleural interstitial thickening, and honeycomb across different stages (P

Abstract Background The taxonomy of Taxus Linn. remains controversial due to its continuous phenotypic variation and unstable topology, thus adversely affecting the formulation of scientific conservation strategies for this genus. Recently, a new ecotype, known as Qinling type, is mainly distributed in the Qinling Mountains and belongs to a monophyletic group. Here, we employed multiple methods including leaf phenotype comparison (leaf shapes and microstructure), DNA barcoding identification (ITS + trnL-trnF + rbcL), and niche analysis to ascertain the taxonomic status of the Qinling type. Results Multiple comparisons revealed significant differences in the morphological characters (length, width, and length/width ratio) among the Qinling type and other Taxus species. Leaf anatomical analysis indicated that only the Qinling type and T. cuspidata had no papilla under the midvein or tannins in the epicuticle. Phylogenetic analysis of Taxus indicated that the Qinling type belonged to a monophyletic group. Moreover, the Qinling type had formed a relatively independent niche, it was mainly distributed around the Qinling Mountains, Ta-pa Mountains, and Taihang Mountains, situated at an elevation below 1500 m. Conclusions Four characters, namely leaf curvature, margin taper, papillation on midvein, and edges were put forward as primary indexes for distinguishing Taxus species. The ecotype Qingling type represented an independent evolutionary lineage and formed a unique ecological niche. Therefore, we suggested that the Qingling type should be treated as a novel species and named it Taxus qinlingensis Y. F. Wen & X. T. Wu, sp. nov.

Utilizing the Multi-Voltage Threshold method, All-Digital PET technology, characterized by "All-Digital" and "accurate sampling," facilitates hardware and software decoupling and modular "LEGO-like" system construction. This innovation addresses the limitations of traditional PET system architectures, enabling a broader range of innovative applications. This paper reviews recent advancements in application-specific All-Digital PET systems, highlighting their applications and advantages in proton therapy monitoring, clinical and basic brain science research, and plant metabolism studies. Furthermore, we explore the development trends of All-Digital PET technology to meet the increasing demands of PET imaging applications.

Background It is a research hotspot to study the changes of metabolites and metabolic pathways in the process of coal worker's pneumoconiosis (CWP) by metabonomics and to explore its pathogenesis. ObjectiveTo study the change of metabolites in bronchoalveolar lavage fluid (BALF) of patients with CWP and explore the metabolic regulation mechanism of the disease. MethodsPatients with CWP who met the national diagnostic criteria according to Diagnosis of occupational pneumoconiosis (GBZ 70-2015) and underwent massive whole lung lavage were selected as the case group, and patients with tracheostenosis who underwent bronchoscopy were selected as the control group. BALF samples were collected from the cases and the controls. After filtering out large particles and mucus, the supernatant was stored in a −80 ℃ refrigerator. The samples were detected and analyzed by liquid chromatography-mass spectrometry after adding extraction solution, cold bath ultrasonication, and high-speed centrifugation, and the metabolic profiles and related data of CWP patients were obtained. The differential metabolites related to the occurrence and development of CWP were screened by multiple statistical analysis; furthermore, we searched the Kyoto Encyclopedia of Genes and Genomes (KEGG) database for potential metabolic pathways involved in the progression. ResultsThere was no significant difference in the general conditions of the subjects, such as weight, height, age, and length of service among the stage I group, the stage II group, the stage III group, and the control group (P˃0.05). When comparing the CWP stage I group with the control group, 48 differential metabolites were screened out, among which 14 were up-regulated and 34 were down-regulated. A total of 66 differential metabolites were screened out between the patients with CWP stage II and the controls, 14 up-regulated and 52 down-regulated differential metabolites. Compared with the control group, 63 differential metabolites were screened out in the patients with CWP stage III, including 11 up-regulated and 52 down-regulated differential metabolites. There were 36 differential metabolites that may be related to the occurrence of CWP, among which 11 differential metabolites were up-regulated, and 25 were down-regulated. Four significant differential metabolic pathways were identified through KEGG database query: linoleic acid metabolic pathway, alanine metabolic pathway, sphingolipid metabolic pathway, and glycerophospholipid metabolic pathway. ConclusionThe metabolomic study of BALF show that there are 36 different metabolites in the occurrence and development of CWP, mainly associating with linoleic acid metabolism, alanine metabolism, sphingolipid metabolism, and glycerophospholipid metabolism pathways.

BackgroundPneumoconiosis is a widespread occupational disease in China at present. As a type of lung diseases, its pathological damage is mainly irreversible fibrotic changes in the lungs. Several studies have shown that the occurrence and development of lung diseases such as coal workers' pneumoconiosis are closely related to intestinal flora. ObjectiveTo observe intestinal flora of coal workers' pneumoconiosis patients based on the results of 16SrDNA high-throughput sequencing and evaluate the changes of intestinal flora after treatment with tetrandrine tablets. MethodsA total of 80 patients with coal workers' pneumoconiosis attending the outpatient clinic of the Department of Occupational Diseases of the Emergency General Hospital from April to July 2022 were enrolled. All patients were treated with tetrandrine tablets for 4 weeks, with group A before the treatment of tetrandrine tablets and group B after the treatment. In the same period, 24 healthy controls (group C) were set up. Stool samples were collected before and after the treatment. Using 16SrDNA high-throughput sequencing, gene V3-V4 sequencing technology, and bioinformatic analysis platform, we evaluated the intestinal flora after treatment by groups. ResultsThe dominant flora at the phylum level and genus level were the same across three groups. The relative abundances of phylum Bacteroidetes, Bifidobacterium, Bacteroides, and Facealibacterium in groups B and C were higher than those in group A, and the relative abundances of phy-lum Actinobacteria, genus Blautia, and genus Romboutsia in groups B and C were lower than those in group A (P＜0.05). The relative abundances of genus Clostridium, genus Megamonas, and genus Lactobacillus in group C was lower than that in groups A and B (P＜0.05). The alpha diversity analysis showed that the Chao1 index was higher in group A than in group C (P＜0.01). Compared with group A, the Shannon index was higher in group B, and the increases of Simpson index were all statistically significant in stage I patients (P＜0.05), but the differences in Chao1 index were not statistically significant (P＞0.05). The differences in the values of Chao1 index, Shannon index, and Simpson index in stage Ⅱ and stage III patients were not statistically significant (P＞0.05). The beta diversity analysis showed that the difference in flora structure between group A and group C was statistically significant (P＜0.05); the differences in flora structure before and after treatment in the same stage patients were statistically significant (P＜0.05). The partial least squares discriminant analysis (PLS-DA) showed that there were significant differences between group A and group C, and between group A and group B. The LEfSe analysis showed that the significant markers contributing to the differences were basically the same in stage I, stage Ⅱ, and stage Ⅲ after treatment, which were mainly phylum Bacteroidetes and its subordinate groups, class Negativicutes, or-der Selenomonas, and genus Facealibacterium. ConclusionThere are differences in the distribution of flora between coal workers' pneumoconiosis patients and healthy individuals, and the structure and relative abundance of intestinal flora are changed and the number of beneficial flora is increased after treatment with tetrandrine tablets.

Abstract LIMA1 is a LIM domain and Actin binding 1 protein that acts as a skeleton protein to promote cholesterol absorption, which makes it an ideal target for interfering with lipid metabolism. However, the detailed regulation of LIMA1 remains unclear. Here, we identified that ring finger protein 40 (RNF40), an E3 ubiquitin ligase previously known as an epigenetic modifier to increase H2B ubiquitination, mediated the ubiquitination of LIMA1 and thereby promoted its degradation in a proteasome-dependent manner. Fraction studies revealed that the 1–166aa fragment of LIMA1 was indispensable for the interaction with RNF40, and at least two domains of RNF40 might mediate the association of RNF40 with LIMA1. Notably, treatment with simvastatin dramatically decreased the levels of CHO and TG in control cells rather than cells with overexpressed LIMA1. Moreover, RNF40 significantly decreased lipid content, which could be reversed by LIMA1 overexpression. These findings suggest that E3 ubiquitin ligase RNF40 could directly target LIMA1 and promote its protein degradation in cytoplasm, leading to the suppression of lipid accumulation mediated by LIMA1. Collectively, this study unveils that RNF40 is a novel E3 ubiquitin ligase of LIMA1, which underpins its high therapeutic value to combat dysregulation of lipid metabolism.

Retinoblastoma (RB) is the most common intraocular malignant tumor in children, primarily attributed to the bi-allelic loss of the RB1 gene in the developing retina. Despite significant progress in understanding the basic pathogenesis of RB, comprehensively unravelling the intricate network of genetics and epigenetics underlying RB tumorigenesis remains a major challenge. Conventional clinical treatment options are limited, and despite the continuous identification of genetic loci associated with cancer pathogenesis, the development of targeted therapies lags behind. This review focuses on the reported genomic and epigenomic alterations in retinoblastoma, summarizing potential therapeutic targets for RB and providing insights for research into targeted therapies.

Cr(VI) and phenol commonly coexist in wastewater, posing a great threat to the environment and human health. However, it is still a challenge for microorganisms to degrade phenol under high Cr(VI) stress. In this study, the phenol-degrading strain Bacillus cereus ZWB3 was co-cultured with the Cr(VI)-reducing strain Bacillus licheniformis MZ-1 to enhance phenol biodegradation under Cr(Ⅵ) stress. Compared with phenol-degrading strain ZWB3, which has weak tolerance to Cr(Ⅵ), and Cr(Ⅵ)-reducing strain MZ-1, which has no phenol-degrading ability, the co-culture of two strains could significantly increase the degraded rate and capacity of phenol. In addition, the co-cultured strains exhibited phenol degradation ability over a wide pH range (7–10). The reduced content of intracellular proteins and polysaccharides produced by the co-cultured strains contributed to the enhancement of phenol degradation and Cr(Ⅵ) tolerance. The determination coefficients R2, RMSE, and MAPE showed that the BP-ANN model could predict the degradation of phenol under various conditions, which saved time and economic cost. The metabolic pathway of microbial degradation of phenol was deduced by metabolic analysis. This study provides a valuable strategy for wastewater treatment containing Cr(Ⅵ) and phenol. HIGHLIGHTS Co-culture can degrade phenol under high concentrations of Cr(VI).; Co-culture improves the degraded rate and concentration of phenol under Cr(VI) stress.; Co-culture synergistically enhances the ability to resist phenol and Cr(VI) toxicity.; BP-ANN predicted the degradation of phenol under different conditions.;

Abstract Pediatric B-cell acute lymphoblastic leukemia (B-ALL) is a highly heterogeneous disease. According to large-scale RNA sequencing (RNA-seq) data, B-ALL patients can be divided into more than 10 subgroups. However, many genomic defects associated with resistance mechanisms have not yet been identified. As an individual clinical tool for molecular diagnostic risk classification, RNA-seq and gene expression pattern-based therapy could be potential upcoming strategies. In this study, we retrospectively analyzed the RNA-seq gene expression profiles of 45 children whose molecular diagnostic classifications were inconsistent with the response to chemotherapy. The relationship between the transcriptome and chemotherapy response was analyzed. Fusion gene identification was conducted for the included patients who did not have known high-risk associated fusion genes or gene mutations. The most frequently detected fusion gene pair in the high-risk group was the DHRSX duplication, which is a novel finding. Fusions involving ABL1, LMNB2, NFATC1, PAX5, and TTYH3 at onset were more frequently detected in the high-risk group, while fusions involving LFNG, TTYH3, and NFATC1 were frequently detected in the relapse group. According to the pathways involved, the underlying drug resistance mechanism is related to DNA methylation, autophagy, and protein metabolism. Overall, the implementation of an RNA-seq diagnostic system will identify activated markers associated with chemotherapy response, and guide future treatment adjustments.

Abstract Enhancing immune response activation through the synergy of effective antigen delivery and immune enhancement using natural, biodegradable materials with immune-adjuvant capabilities is challenging. Here, we present NAPS L.p that can activate the Toll-like receptor 4 (TLR4) pathway, an amphiphilic exopolysaccharide, as a potential self-assembly adjuvant delivery platform. Its molecular structure and unique properties exhibited remarkable self-assembly, forming a homogeneous nanovaccine with ovalbumin (OVA) as the model antigen. When used as an adjuvant, NAPS L.p significantly increased OVA uptake by dendritic cells. In vivo imaging revealed prolonged pharmacokinetics of NAPS L. p -delivered OVA compared to OVA alone. Notably, NAPS L.p induced elevated levels of specific serum IgG and isotype titers, enhancing rejection of B16-OVA melanoma xenografts in vaccinated mice. Additionally, NAPS L.p formulation improved therapeutic effects, inhibiting tumor growth, and increasing animal survival rates. The nanovaccine elicited CD4+ and CD8+ T cell-based immune responses, demonstrating the potential for melanoma prevention. Furthermore, NAPS L.p -based vaccination showed stronger protective effects against influenza compared to Al (OH)3 adjuvant. Our findings suggest NAPS L.p as a promising, natural self-adjuvanting delivery platform to enhance vaccine design across applications.

Abstract Background We recently reported that supplementing glycine to soybean meal-based diets is necessary for the optimum growth of 5- to 40-g (Phase-I) and 110- to 240-g (Phase-II) hybrid striped bass (HSB), as well as their intestinal health. Although glycine serves as an essential substrate for syntheses of creatine and glutathione (GSH) in mammals (e.g., pigs), little is known about these metabolic pathways or their nutritional regulation in fish. This study tested the hypothesis that glycine supplementation enhances the activities of creatine- and GSH-forming enzymes as well as creatine and GSH availabilities in tissues of hybrid striped bass (HSB; Morone saxatilis♀ × Morone chrysops♂). Methods Phase-I and Phase-II HSB were fed a soybean meal-based diet supplemented with 0%, 1%, or 2% glycine for 8 weeks. At the end of the 56-d feeding, tissues (liver, intestine, skeletal muscle, kidneys, and pancreas) were collected for biochemical analyses. Results In contrast to terrestrial mammals and birds, creatine synthesis occurred primarily in skeletal muscle from all HSB. The liver was most active in GSH synthesis among the HSB tissues studied. In Phase-I HSB, supplementation with 1% or 2% glycine increased (P 0.05) in these variables between the 1% and 2% glycine groups. In Phase-II HSB, supplementation with 1% and 2% glycine increased (P

The thermal evolution of the Earth’s interior and its dynamic effects are the focus of Earth sciences. However, the commonly adopted grid-based temperature solver is usually prone to numerical oscillations, especially in the presence of sharp thermal gradients, such as when modeling subducting slabs and rising plumes. This phenomenon prohibits the correct representation of thermal evolution and may cause incorrect implications of geodynamic processes. After examining several approaches for removing these numerical oscillations, we show that the Lagrangian method provides an ideal way to solve this problem. In this study, we propose a particle-in-cell method as a strategy for improving the solution to the energy equation and demonstrate its effectiveness in both one-dimensional and three-dimensional thermal problems, as well as in a global spherical simulation with data assimilation. We have implemented this method in the open-source finite-element code CitcomS, which features a spherical coordinate system, distributed memory parallel computing, and data assimilation algorithms.

To explore the effect of slightly acidic electrolyzed water (SAEW) on the storage quality of postharvest chives, the changes in the microbial load and storage quality of postharvest chives subjected to SAEW immersion treatment at different concentrations (0, 100, 200 and 300 mg/L) for 5 minutes were analyzed during low temperature ((4 ± 1) ℃) storage. The results showed that immersion treatment with 200 mg/L SAEW was more effective in maintaining the organoleptic quality of chives and inhibiting the increase of the total number of colonies when compared with the other groups. Furthermore, 200 mg/L SAEW treatment was able to inhibit the increase of mass loss and rot rate, slow down the decrease of chlorophyll, vitamin C, soluble sugar, and soluble protein contents, and reduce the accumulation of total free amino acids, malondialdehyde (MDA) and nitrite in chives. It is evident that immersion treatment with 200 mg/L SAEW can not only effectively inhibit microbial growth on chives during low-temperature storage, but also effectively delay the loss of nutrients in chives, thus improving the quality preservation of chives. Therefore, SAEW can be used as an effective sterilization and preservation method to maintain the storage quality and delay the aging process of postharvest chives.

Abstract Background Intravascular lithotripsy (IVL) represents a novel approach in the management of coronary calcification. This technique employs acoustic pressure waves, generated by a shockwave balloon, to effectively fracture both superficial and deep calcification in situ. The efficacy and safety of IVL have been convincingly demonstrated through the Disrupt CAD I-IV studies. While IVL is associated with the occurrence of atrial and ventricular arrhythmias, there is no evidence to indicate it causes myocardial ischemia. Case Description A 71-year-old man was admitted presenting with chest pain. His previous coronary angiography revealed stenosis and calcification in the left anterior descending branch. An attempt to predilate the lesion using two Lacrosse non-slip element balloons was unsuccessful. Ventricular premature beats and transient ST-segment depression were captured during the utilization of IVL. The operator gradually extended the pulse emission interval across two consecutive cycles to mitigate myocardial ischemia. Notably, when the interval reached 30s, the patient had no chest pain or ST-segment changes. Subsequent images of intravascular ultrasound confirmed calcification ruptures. Therapeutic intervention included the placement of a stent and the application of a drug-coated balloon in the left anterior descending branch. A telephonic follow-up six months later indicated the patient had no discomfort. Conclusions This case underscores the effectiveness of gradually extending the pulse emission interval as a strategic complement to the clinical application of IVL. In certain clinical scenarios, it may become imperative to suspend the pulse delivery to improve myocardial blood supply.

Abstract Background Mobile health (mHealth) may be an ideal solution for breast cancer (BC) patients in China to access weight management interventions. User retention and engagement are the main challenges faced by mHealth applications. A user persona, which is a user-centered design process, can lead to the development of mHealth that is more acceptable to the needs of target users. This study aimed to investigate the variety of experiences in weight management and the behavioral preferences of BC patients receiving chemotherapy to develop users’ personal information and persona development for the design and implementation of mHealth interventions. Methods Sixteen individual semi-structured in-depth interviews were conducted with BC patients receiving chemotherapy. We employed the thematic analysis method to analyze the interview transcripts in NVivo 11 software. The themes obtained from the analysis were used as the subdomains of personas. A proforma was designed to extract each participant’s experience in each subdomain. Patients who exhibited similar experience in subdomains were grouped into a persona using affinity diagrams. The personas were named according to their prominent features. A questionnaire survey was conducted to validate the personas and to test whether the personas that were generated from the qualitative interview data were applicable to the Chinese population with BC. Results Four themes were identified as subdomains of weight management personas: the perception of weight management while undergoing chemotherapy, symptoms and emotional disturbance, changes in diet and exercise, and health literacy and information seeking. Five personas were ultimately obtained: (1) positive weight controllers, (2) patients who were inactive due to fatigue, (3) young patients who avoided communication, (4) overweight patients with treatment priority, and (5) patients who engaged in irregular exercise. Finally, the quantitative study showed that 51.58% of patients chose one of these five personas to represent themselves in weight management. None of the patient reported selecting options that were not explicitly outlined in the questionnaire and provided personalized descriptions of their weight management characteristics. Conclusions The selected personas were developed from in-depth interviews on biopsychosocial areas. They highlight different weight management patterns in Chinese BC patients and provide implications for both the design of mHealth systems and traditional interventions.

Abstract Designing two-dimensional halide perovskites for high-performance optoelectronic applications requires deep understanding of the structure-property relationship that governs their excitonic behaviors. However, a design framework that considers both intra and interlayer structures modified by the A-site and spacer cations, respectively, has not been developed. Here, we use pressure to synergistically tune the intra and interlayer structures and uncover the structural modulations that result in improved optoelectronic performance. Under applied pressure, (BA)2(GA)Pb2I7 exhibits a 72-fold boost of photoluminescence and 10-fold increase of photoconductivity. Based on the observed structural change, we introduce a structural descriptor χ that describes both the intra and interlayer characteristics and establish a general quantitative relationship between χ and photoluminescence quantum yield: smaller χ correlates with minimized trapped excitons and more efficient emission from free excitons. Building on this principle, we design a perovskite (CMA)2(FA)Pb2I7 that exhibits a small χ and an impressive photoluminescence quantum yield of 59.3%.

Abstract Background Chimeric antigen receptor T (CAR-T) cell therapy, as an emerging anti-tumor treatment, has garnered extensive attention in the study of targeted therapy of multiple tumor-associated antigens in hepatocellular carcinoma (HCC). However, the suppressive microenvironment and individual heterogeneity results in downregulation of these antigens in certain patients’ cancer cells. Therefore, optimizing CAR-T cell therapy for HCC is imperative. Methods In this study, we administered FGFR4-ferritin (FGFR4-HPF) nanoparticles to the alpaca and constructed a phage library of nanobodies (Nbs) derived from alpaca, following which we screened for Nbs targeting FGFR4. Then, we conducted the functional validation of Nbs. Furthermore, we developed Nb-derived CAR-T cells and evaluated their anti-tumor ability against HCC through in vitro and in vivo validation. Results Our findings demonstrated that we successfully obtained high specificity and high affinity Nbs targeting FGFR4 after screening. And the specificity of Nbs targeting FGFR4 was markedly superior to their binding to other members of the FGFR family proteins. Furthermore, the Nb-derived CAR-T cells, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in both experiments when in vitro and in vivo. Conclusions In summary, the results of this study suggest that the CAR-T cells derived from high specificity and high affinity Nbs, targeting FGFR4, exhibited significantly enhanced anti-tumor efficacy in vitro and in vivo. This is an exploration of FGFR4 in the field of Nb-derived CAR-T cell therapy for HCC, holding promise for enhancing safety and effectiveness in the clinical treatment of HCC in the future.

Drug repurposing offers an efficient approach to therapeutic development. In this study, our bioinformatic analysis first predicted an association between obesity and lansoprazole (LPZ), a commonly prescribed drug for gastrointestinal ulcers. We went on to show that LPZ treatment increased energy expenditure and alleviated the high-fat diet-induced obesity, insulin resistance, and hepatic steatosis in mice. Treatment with LPZ elicited thermogenic gene expression and mitochondrial respiration in primary adipocytes, and induced cold tolerance in cold-exposed mice, suggesting the activity of LPZ in promoting adipose thermogenesis and energy metabolism. Mechanistically, LPZ is an efficient inhibitor of adipose phosphocholine phosphatase 1 (PHOSPHO1) and produces metabolic benefits in a PHOSPHO1-dependent manner. Our results suggested that LPZ may stimulate adipose thermogenesis by inhibiting the conversion of 2-arachidonoylglycerol-lysophosphatidic acid (2-AG-LPA) to 2-arachidonoylglycerol (2-AG) and reduce the activity of the thermogenic-suppressive cannabinoid receptor signaling. In summary, we have uncovered a novel therapeutic indication and mechanism of LPZ in managing obesity and its related metabolic syndrome, and identified a potential metabolic basis by which LPZ improves energy metabolism.

With the rapid expansion of artificial light in the global nocturnal environment, the ecological impacts of artificial light at night (ALAN) on plant communities have garnered increasing research interest. However, the role of phyllosphere microorganisms as mediators in the regulation between ALAN and plants remains unclear. In this study, we conducted a field experiment in natural grassland plots, employing two treatments: one with no artificial light at night (control) and another with artificial light at night (ALAN). We then investigated the response of phyllosphere microorganisms in three grassland plant species (Leymus chinensis, Vicia sepium, and Aster altaicus) to ALAN exposure. The results revealed that the constructive species L. chinensis demonstrated a markedly higher diversity of phyllosphere bacteria and fungi compared to V. sepium and A. altaicus and thus had the most abundant microbial community. However, ALAN exposure reduced the diversity of phyllosphere bacteria and fungi in all three plant species to varying degrees. ALAN induced certain changes to the phyllosphere bacterial community composition, particularly manifesting in a reduction in the abundance of beneficial bacteria, including Sphingomonas, Hymenobacter, Methylobacterium-Methylorubrum, and Bacillus. Compared with phyllosphere bacterial communities, the alterations in phyllosphere fungal communities were more sensitive, characterized by a significant decrease in the abundance of certain fungi, including Zymoseptoria, Mycosphaerella, Cladosporium, and Epicoccum. The functional predictions of phyllosphere bacteria and fungi further corroborate these conclusions. In summary, ALAN exposure may suppress the functional capacity of phyllosphere microorganisms in grassland plants while decreasing the probability of fungal pathogen occurrence.

ABSTRACT Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.IMPORTANCEIn addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.

This study explores the mechanism by which obstructive jaundice (OJ) induces liver damage through pyroptosis. We induced OJ in rats via bile duct ligation and assessed liver damage using serum biochemical markers and histological analysis of liver tissue. Pyroptosis was investigated through immunofluorescence, ELISA, Western blot, and quantitative RT-PCR techniques. Additionally, we examined intestinal function and fecal microbiota alterations in the rats using 16S rDNA sequencing. In vitro experiments involved co-culturing Kupffer cells and hepatocytes, which were then exposed to bile and lipopolysaccharide (LPS). Our findings indicated that OJ modified the gut microbiota, increasing LPS levels, which, in conjunction with bile, initiated a cycle of inflammation, fibrosis, and cell death in the liver. Mechanistically, OJ elevated necrotic markers such as ATP, which in turn activated pyroptotic pathways. Increased levels of pyroptosis-related molecules, including NLRP3, caspase-1, gasdermin D, and IL-18, were confirmed. In our co-cultured cell model, bile exposure resulted in cell death and ATP release, leading to the activation of the NLRP3 inflammasome and its downstream effectors, caspase-1 and IL-18. The combination of bile and LPS significantly intensified pyroptotic responses. This study is the first to demonstrate that LPS and bile synergistically exacerbate liver injury by promoting necrosis and pyroptosis, unveiling a novel mechanism of OJ-associated hepatic damage and suggesting avenues for potential preventive or therapeutic interventions.

Summary: CXCR4 binding of its endogenous agonist CXCL12 leads to diverse functions, including bone marrow retention of hematopoietic progenitors and cancer metastasis. However, the structure of the CXCL12-bound CXCR4 remains unresolved despite available structures of CXCR4 in complex with antagonists. Here, we present the cryoelectron microscopy (cryo-EM) structure of the CXCL12-CXCR4-Gi complex at an overall resolution of 2.65 Å. CXCL12 forms a 1:1 stoichiometry complex with CXCR4, following the two-site model. The first 8 amino acids of mature CXCL12 are crucial for CXCR4 activation by forming polar interactions with minor sub-pocket residues in the transmembrane binding pocket. The 3.2-Å distance between V3 of CXCL12 and the “toggle switch” W6.48 marks the deepest insertion among all chemokine-receptor pairs, leading to conformational changes of CXCR4 for G protein activation. These results, combined with functional assays and computational analysis, provide the structural basis for CXCR4 activation by CXCL12.

Background/purpose: This study aimed to summarize the survival and complication profiles of the compress® endoprosthesis (CPS) through a systematic review and meta-analysis. Methods: Online databases (PubMed, EMBASE and Web of Science) were searched from inception to November 2023. Trials were included that involved the use of CPS for endoprosthetic replacement in patients with massive segmental bone defects. Patients’ clinical characteristics and demographic data were extracted using a standardized form. The methodological quality of included 13 non-comparative studies was assessed on basis of the Methodological Index for Non-Randomized Studies (MINORS). All the available Kaplan-Meier curves in the included studies were digitized and combined using Engauge-Digitizer software and the R Project for Statistical Computing. Results: The meta-analysis of thirteen included studies indicated: the all-cause failure rates of CPS were 26.3 % after surgery, in which the occurrence rates of aseptic loosening were 5.8 %. And the incidences of other complications were as follows: soft tissue failure (1.8 %), structure failure (8.2 %), infection (9.5 %), tumor progression (1.1 %). The 1-, 4-, and 8-year overall survival rates for all-cause failure with 95 % CI were 89 % (86 %-92 %), 75 % (71 %-79 %) and 65 % (60 %-70 %), respectively. The estimated mean survival time of all-cause failure was 145 months (95 % CI, 127–148 months), and the estimated median survival time of all-cause failure was 187 months (95 % CI, 135–198 months). The 1-, 4-, and 8-year overall survival rates of aseptic loosening with 95 % CI were 96 % (94 %-98 %), 91 % (87 %-95 %) and 88 % (83 %-93 %), respectively. The estimated mean survival time of aseptic loosening was 148 months (95 % CI, 137–153 months). Conclusion: CPS’s innovative spring system promotes bone ingrowth by providing immediate and high-compression fixation, thereby reducing the risk of aseptic loosening caused by stress shielding and particle-induced osteolysis. CPS requires less residual bone mass for reconstructing massive segmental bone defects and facilitates easier revision due to its non-cemented fixation. In addition, the survival rate, estimated mean survival time, and complication rates of CPS are not inferior to those of common endoprosthesis.

In the era of increasing environmental pollution and energy crisis, the development of thermoelectric materials to achieve the reuse of waste heat energy is of great significance. SnTe, as an environmentally friendly thermoelectric material, its high electronic-thermal conductivity and coupled high electrical conductivity originated from intrinsic high carrier hole concentration leads to the unsatisfactory thermoelectric properties. With a lot of research going on to optimize thermoelectric performance by decoupling the thermo-electrical contradiction, the entropy engineering strategy, which can independently modulate lattice thermal conductivity is proved to be feasible by increasing the internal configurational entropy through doping. However, due to the uncontrollable growth microscopic process and the perturbation of film quality, the desired precise phase doping remains a challenge. In this work, we report an instantiation of the entropy increase of SnSe-doped SnTe alloy thin films prepared by two-step magnetron sputtering and selenization method. The microstructure and physical properties of thin films were investigated for replaying and controlling the growth evolution of in-situ selenization substitution. When the reaction temperature and duration were adjusted to 300℃ and 30 mins respectively, the desired pure phase doping was obtained. This work provides a new method of doping modification of SnTe materials, and the product as a new functional material expands the thermoelectric material library. In particular, it has positive reference significance for the development of synthesis controllability and structure establishment of complex polycrystalline materials.

This study investigated the effects of different types of short video addiction on social adaptation. The aim of this study was to identify the various types of short video addiction among freshmen and the correlations with career adaptability, insomnia, and depressive symptoms. We recruited 931 freshmen and used latent profile analysis to classify participants based on different characteristics of short video addiction. Based on the results of a short video addiction questionnaire, participants were found to exhibit distinct answer patterns, categorized into five types. Class 1 exhibited minimal signs of addiction. Class 2 displayed fluctuations with stronger tendencies towards withdrawal or escape. Class 3 demonstrated a moderate inability to control cravings for short videos. Class 4 showed fluctuations but with less anxiety and feelings of lost. Finally, Class 5 presented the most pronounced symptoms of short video addiction. Freshmen with varying degrees of short video addiction exhibited significant differences in career adaptability, sleep quality, and depressive symptoms. Class 1 students showed strong career adaptability and sound sleep, whereas Class 5 students had the highest depression rates. Overall, our findings suggest that the characteristics of short video addiction in first-year students also indicate poor social adaptation, which is mainly manifested as weak career adaptability, decreased sleep quality, and depressive symptoms. One way to guide first-year students to adapt to campus life is for educators to provide timely interventions for students with severe short video addiction.

Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling. Endothelial-to-mesenchymal transition (EndMT) is an important manifestation and mechanism of pulmonary vascular remodeling. Resolvin D1 (RvD1) is an endogenous lipid mediator promoting the resolution of inflammation. However, the role of RvD1 on EndMT in PH remains unknown. Here, we aimed to investigate the effect and mechanisms of RvD1 on the treatment of PH. We showed that RvD1 and its receptor FPR2 expression were markedly decreased in PH patients and both chronic hypoxia-induced PH (CH-PH) and sugen 5416/hypoxia-induced PH (SuHx-PH) mice models. RvD1 treatment decreased right ventricular systolic pressure (RVSP) and alleviated right ventricular function, and reduced pulmonary vascular remodeling and collagen deposition in the perivascular of both two PH mice models. Then, RvD1 inhibited EndMT in both the lungs of PH mice models and primary cultured human umbilical vein endothelial cells (HUVECs) treated with TGF-β and IL-1β. Moreover, RvD1 inhibited EndMT by downregulating Smad2/3 phosphorylation in vivo and in vitro via FPR2. In conclusion, our date suggest that RvD1/FPR2 axis prevent experimental PH by inhibiting endothelial-mensenchymal-transition and may be a therapeutic target for PH.