Search

Ferroptosis, an iron‐dependent form of cell death, plays a crucial role in the progression of liver injury in Wilson's disease (WD). Gandouling (GDL) has emerged as a potential therapeutic agent for preventing and treating liver injury in WD. However, the precise mechanisms by which GDL mitigates ferroptosis in WD liver injury remain unclear. In this study, we discovered that treating Toxic Milk (TX) mice with GDL effectively decreased liver copper content, corrected iron homeostasis imbalances, and lowered lipid peroxidation levels, thereby preventing ferroptosis and improving liver injury. Bioinformatics analysis and machine learning algorithms identified Hspb1 as a pivotal regulator of ferroptosis. GDL treatment significantly upregulated the expression of HSPB1 and its upstream regulatory factor HSF1, thereby activating the HSF1/HSPB1 pathway. Importantly, inhibition of this pathway by NXP800 reversed the protective effects of GDL on ferroptosis in the liver of TX mice. In conclusion, GDL shows promise in alleviating liver injury in WD by inhibiting ferroptosis through modulation of the HSF1/HSPB1 pathway, suggesting its potential as a novel therapeutic agent for treating liver ferroptosis in WD. [ABSTRACT FROM AUTHOR]

Purpose: Neuroinflammation is a main cause of neurological damage in Wilson's disease (WD). Ferroptosis is present in the WD pathological process, which is also closely related to the neuroinflammation. LCN2, a ferroptosis-related gene in WD, is linked with the activation of NLRP3 inflammasome. Our group has previously demonstrated that Gandouling (GDL) can effectively improve neuroinflammation in WD. This study aims to investigate the protective effect of GDL on neuroinflammation in animal and cell models of WD, and whether the pharmacological mechanism is related to the LCN2/NLRP3 signaling pathway. Methods: Toxic milk (TX) mice and HT22 cells stimulated by copper ions were selected as models. The pathology of hippocampal tissues in TX mice were observed by HE staining and transmission electron microscopy. High-throughput sequencing analysis was conducted to screen ferroptosis-related genes in WD. The expression of LCN2 and GPX4 in hippocampus of TX mice were detected by immunohistochemical. The expression of LCN2, NLRP3, GPX4, and SLC7A11 was determined in TX mice and HT22 cells by Western blotting and RT-qPCR. The levels of Fe2+, inflammatory factor indicators TNF-α, IL-1β and IL-6 and oxidative stress indicators 4-HNE, MAD, SOD, GSH and ROS were detected in each group by ELISA. Results: The results showed that GDL ameliorated pathological and mitochondrial damages in hippocampus of TX mice. The analysis of bioinformatics showed that LCN2 was a differential gene associated with ferroptosis in WD. The results of Western blotting and RT-qPCR indicated that GDL reduced the expression of LCN2 and NLRP3, and enhanced the expression of GPX4 and SLC711 in TX mice and HT22 cells. The ELISA results showed that GDL decreased the expression of Fe2+ and inflammatory factors TNF-α, IL-1β and IL-6 in TX mice with ferroptosis inducer intervention and copper ion-loaded HT22 cells. GDL decreased the expression of oxidative stress indicators ROS, 4-HNE and MDA, and increased the expression of oxidative stress indicators GSH and SOD in TX mice and copper ion-loaded HT22 cells. Conclusion: GDL has anti-inflammatory and antioxidant effects. LCN2 is a differential gene associated with ferroptosis in WD. GDL may alleviate ferroptosis by inhibiting the LCN2/NLPR3 signaling pathway, thereby improving neuroinflammatory responses and exerting neuroprotective effects in WD. [ABSTRACT FROM AUTHOR]

FOXG1 syndrome is a developmental encephalopathy caused by FOXG1 (Forkhead box G1) mutations, resulting in high phenotypic variability. However, the upstream transcriptional regulation of Foxg1 expression remains unclear. This report demonstrates that both deficiency and overexpression of Men1 (protein: menin, a pathogenic gene of MEN1 syndrome known as multiple endocrine neoplasia type 1) lead to autism‐like behaviors, such as social defects, increased repetitive behaviors, and cognitive impairments. Multifaceted transcriptome analyses revealed that Foxg1 signaling is predominantly altered in Men1 deficiency mice, through its regulation of the Alpha Thalassemia/Mental Retardation Syndrome X‐Linked (Atrx) factor. Atrx recruits menin to bind to the transcriptional start region of Foxg1 and mediates the regulation of Foxg1 expression by H3K4me3 (Trimethylation of histone H3 lysine 4) modification. The deficits observed in menin deficient mice are rescued by the over‐expression of Foxg1, leading to normalized spine growth and restoration of hippocampal synaptic plasticity. These findings suggest that menin may have a putative role in the maintenance of Foxg1 expression, highlighting menin signaling as a potential therapeutic target for Foxg1‐related encephalopathy. [ABSTRACT FROM AUTHOR]

When inquiry-based learning is designed for a collaborative context, the interactions that arise in the learning environment can become fairly complex. While the learning effectiveness of such learning environments has been reported in the literature, there have been fewer studies on the students' learning processes. To address this, the article presents a study of science learning in a computer-supported learning environment called Collaborative Science Inquiry (CSI), which integrates guided inquiry principles for activity design, employs modelling and visualisation tools for promoting conceptual understanding and incorporates key computer-supported collaborative learning (CSCL) elements for enabling students' collaboration. With the aim of understanding the process of students' conceptual changes supported by the CSI learning environment as used in a secondary school, data on students' test achievements, responses to learning tasks and peer discussions in collaboration were collected, analysed and discussed. The results of the qualitative and quantitative data analysis indicated that guided inquiry coupled with CSCL elements facilitated by the CSI system can engage students in inquiry activities and promote their conceptual understanding in a progressive way.

With advancements made in mobile technology, increasing emphasis has been paid to how to leverage the affordances of mobile technology to improve science learning and instruction. This paper reports on a science curriculum supported by an inquiry-based framework and mobile technologies. It was developed by teachers and researchers in a multiyear program of school-based research. The foci of this paper is on the design principles of the curriculum and its enactment, and the establishment of a teacher learning community. Through elucidating the design features of the innovative curriculum and evaluating teacher and student involvement in science instruction and learning, we introduce the science curriculum, called Mobilized 5E Science Curriculum (M5ESC), and present a representative case study of how one experienced teacher and her class adopted the curriculum. The findings indicate the intervention promoted this teacher's questioning competency, enabled her to interact with students frequently and flexibly in class, and supported her technology use for promoting different levels of cognition. Student learning was also improved in terms of test achievement and activity performance in and out of the classroom. We propose that the study can be used to guide the learning design of mobile technology-supported curricula, as well as teacher professional development for curriculum enactment.

The research literature reports on designs of ubiquitous and seamless learning environments enabled by the integration of mobile technology into learning. However, the lack of good pedagogical designs that provide for sustainability and the inadequate investigation of learning outcomes remain major gaps in the current studies on mobile learning. This paper seeks to contribute to addressing these issues by reporting on a study concerning the principles of integrating mobile learning into a standards-based science curriculum. It also explores how mobile learning activities have impacted students' academic and activity performances in and out of the classroom over a whole academic year. Mixed methods were used to examine students' performances, and a yearly comparison was made for assessing students' progression in their conceptual understanding in science. Data analysis on students' test results, mobile learning artifacts, and their activity performances in the classroom suggested that they had improved in their conceptual understanding and self-reflection on these conceptual changes. Students were engaged in mobile learning activities both in the classroom and out of the classroom through sustained exposure to and experience of the mobilized science curriculum.

Metastases to the thyroid gland (MTT) are uncommon in clinical practice. The ultrasound (US) features are easily confused with primary thyroid malignancy, Hashimoto's thyroiditis, and other thyroid diseases. Therefore, this study aimed to assess the role of US and analysis of prognosis of MTT. A total of 45 patients with MTT in the database between July 2009 and February 2022 at the Fujian Cancer Hospital were reviewed. US examinations were performed only on 20 patients, who were finally included in our study. Among the 20 patients, nine were male, and eleven were female. According to US characteristics, metastases to the thyroid gland were divided into nodular and diffuse types (17 and 3 cases, respectively). Three lesions (17.6%) had circumscribed margins, and 14 (82.4%) were uncircumscribed. Three lesions (17.6%) were regular in shape, and 14 (82.4%) were irregular. Nine metastases (52.9%) were a taller-than-wide shape, and eight (47.1%) were not a taller-than-wide shape. Ten lesions (58.8%) had rich vascularity, and seven (41.2%) had absence/not rich vascularity. The mean overall survival (OS) from the time of MTT diagnosis was 22 months (95% confidence interval: 5.95–38.05). The 1-, 3-, and 5-year OS after metastasis was 68.1%, 25.5%, and 17%, respectively. The prognosis of MTT was poor, which is closely related to the characteristics of the primary tumor and metastatic disease. The US findings and US-guided core needle biopsy may be useful in diagnosing MTT in patients with a history of the malignant tumors. [ABSTRACT FROM AUTHOR]

Though discussion of the teacher factor in ICT-enabled science learning abounds in the literature, the investigation of Teacher Enactments (TEs) of ICT-facilitated lessons through exploring teaching practices is still under-explored and under-recognized. Current studies are still lacking in evidence-based findings of TEs based on the investigation of teaching practices. This study explores the TEs of science lessons supported by a web-based learning platform, namely, Collaborative Science Inquiry (CSI), by two experienced teachers in their respective classes. The CSI system is built on a model-based inquiry framework integrated with Computer-Supported Collaborative Learning (CSCL) elements. The CSI lessons selected were on the topic of "Diffusion and Osmosis" in Grade 7. Through examining the ways in which teachers instructed, questioned, and interacted with the students, we identified the commonalities and differences in TEs that subsequently influenced students' conceptual understanding and their involvement in collaborative inquiry. The factors that contributed to these discrepancies were then discussed. Implications were proposed to inform the use of complex ICT tools in the science classroom.

Newcastle disease (ND) and infectious bursal disease (IBD) are two key infectious diseases that significantly threaten the health of the poultry industry. Although existing vaccinations can effectively prevent and treat these two diseases through multiple immunizations, frequent immunization stresses significantly impact chicken growth. In this study, three recombinant adenoviruses, rAd5-F expressing the NDV (genotype VII) F protein, rAd5-VP2 expressing the IBDV VP2 protein, and rAd5-VP2-F2A-F co-expressing F and VP2 proteins, were constructed using the AdEasy system. The F and VP2 genes of the recombinant adenoviruses could be transcribed and expressed normally in HEK293A cells as verified by RT-PCR and Western blot. The three recombinant viruses were shown to have similar growth kinetics as rAd5-EGFP. Compared with the PBS and rAd5-EGFP groups, SPF chickens immunized with recombinant adenoviruses produced higher antibody levels, more significant lymphocyte proliferation, and significantly higher CD4+/CD3+ and CD8+/CD3+ cells in peripheral blood. The survival rate of SPF chickens immunized with rAd5-F and rAd5-VP2-F2A-F after the challenge with DHN3 was 100%, and 86% of SPF chickens showed no viral shedding at 7 dpc. The survival rate of SPF chickens immunized with rAd5-VP2 and rAd5-VP2-F2A-F after the challenge with BC6/85 was 86%. rAd5-VP2 and rAd5-VP2-F2A-F significantly inhibited bursal atrophy and pathological changes compared to the rAd5-EGFP and PBS groups. This study provides evidence that these recombinant adenoviruses have the potential to be developed into safe and effective vaccine candidates for the prevention and control of ND and IBD. [ABSTRACT FROM AUTHOR]