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975 result(s) for "Wei, Liwei"
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Alternative splicing in ovarian cancer
Ovarian cancer is the second leading cause of gynecologic cancer death worldwide, with only 20% of cases detected early due to its elusive nature, limiting successful treatment. Most deaths occur from the disease progressing to advanced stages. Despite advances in chemo- and immunotherapy, the 5-year survival remains below 50% due to high recurrence and chemoresistance. Therefore, leveraging new research perspectives to understand molecular signatures and identify novel therapeutic targets is crucial for improving the clinical outcomes of ovarian cancer. Alternative splicing, a fundamental mechanism of post-transcriptional gene regulation, significantly contributes to heightened genomic complexity and protein diversity. Increased awareness has emerged about the multifaceted roles of alternative splicing in ovarian cancer, including cell proliferation, metastasis, apoptosis, immune evasion, and chemoresistance. We begin with an overview of altered splicing machinery, highlighting increased expression of spliceosome components and associated splicing factors like BUD31, SF3B4, and CTNNBL1, and their relationships to ovarian cancer. Next, we summarize the impact of specific variants of CD44, ECM1, and KAI1 on tumorigenesis and drug resistance through diverse mechanisms. Recent genomic and bioinformatics advances have enhanced our understanding. By incorporating data from The Cancer Genome Atlas RNA-seq, along with clinical information, a series of prognostic models have been developed, which provided deeper insights into how the splicing influences prognosis, overall survival, the immune microenvironment, and drug sensitivity and resistance in ovarian cancer patients. Notably, novel splicing events, such as PIGV|1299|AP and FLT3LG|50,941|AP, have been identified in multiple prognostic models and are associated with poorer and improved prognosis, respectively. These novel splicing variants warrant further functional characterization to unlock the underlying molecular mechanisms. Additionally, experimental evidence has underscored the potential therapeutic utility of targeting alternative splicing events, exemplified by the observation that knockdown of splicing factor BUD31 or antisense oligonucleotide-induced BCL2L12 exon skipping promotes apoptosis of ovarian cancer cells. In clinical settings, bevacizumab, a humanized monoclonal antibody that specifically targets the VEGF-A isoform, has demonstrated beneficial effects in the treatment of patients with advanced epithelial ovarian cancer. In conclusion, this review constitutes the first comprehensive and detailed exposition of the intricate interplay between alternative splicing and ovarian cancer, underscoring the significance of alternative splicing events as pivotal determinants in cancer biology and as promising avenues for future diagnostic and therapeutic intervention.
Resveratrol protects osteocytes against oxidative stress in ovariectomized rats through AMPK/JNK1-dependent pathway leading to promotion of autophagy and inhibition of apoptosis
A large number of studies in recent years indicate that osteocytes are the orchestrators of bone remodeling by regulating both osteoblast and osteoclast activities. Oxidative stress-induced osteocyte apoptosis plays critical roles in the pathological processes of postmenopausal osteoporosis. Resveratrol is a natural polyphenolic compound that ameliorates postmenopausal osteoporosis. However, whether resveratrol regulates osteocyte apoptosis via autophagy remains largely unknown. The effects of resveratrol on regulating osteocyte apoptosis and autophagy were analyzed both in vivo and in vitro. In vitro, cultured MLO-Y4 cells were exposed to H2O2 with or without resveratrol. In vivo, an ovariectomy-induced osteoporosis model was constructed in rats with or without daily intraperitoneal injection of 10 mg/kg body weight resveratrol. It was found that resveratrol attenuated H2O2-induced apoptosis through activating autophagy in cultured MLO-Y4 cells, which was mediated by the dissociation of Beclin-1/Bcl-2 complex in AMPK/JNK1-dependent pathway, ultimately regulating osteocytes function. Furthermore, it was shown that resveratrol treatment reduced osteocytes oxidative stress, inhibited osteocytes apoptosis and promoted autophagy in ovariectomized rats. Our study suggests that resveratrol protects against oxidative stress by restoring osteocytes autophagy and alleviating apoptosis via AMPK/JNK1 activation, therefore dissociating Bcl-2 from Beclin-1.
KCNJ2 Facilitates Clear Cell Renal Cell Carcinoma Progression and Glucose Metabolism
Background: Clear cell renal cell carcinoma (ccRCC) is marked by aggressive characteristics and a poor prognosis. The involvement of KCNJ2, an inward rectifying potassium channel, in the progression of ccRCC, along with its potential roles in immune modulation and metabolic pathways, remains unclear. Methods: The Cancer Genome Atlas (TCGA) database was utilized to analyze the gene expression, clinicopathological characteristics, and clinical relevance of KCNJ2. The prognostic value of KCNJ2 in ccRCC was evaluated with Kaplan–Meier survival analysis and receiver operating characteristic curve analyses. The TCGA‐KIRC dataset was utilized to analyze tumor microenvironment (TME), focusing on tumor‐infiltrating immune cells and immunomodulators. The biological functions of KCNJ2 were investigated in vitro using CCK‐8, flow cytometry, wound healing, transwell, qRT‐PCR, and Western blotting assays. Results: KCNJ2 expression was notably higher in ccRCC than in normal kidney tissues, with increased levels associated with advanced tumor stages. However, KCNJ2 did not exhibit obvious prognostic value. Coexpression analysis identified associations with genes implicated in energy metabolism. Analysis of the TME and immune profile indicated a link between KCNJ2 expression and immune cell infiltration, along with particular immune checkpoints. In vitro studies demonstrated that KCNJ2 overexpression enhanced cell proliferation, migration, invasion, glucose production, and ATP generation. Conclusion: KCNJ2 plays a crucial role in ccRCC progression through affecting glucose metabolism and immune responses. Our findings reveal the functional role of KCNJ2 in promoting tumor progression and metabolic reprogramming in ccRCC, highlighting its therapeutic potential as a novel target for ccRCC treatment. Further studies are essential to clarify the mechanisms by which KCNJ2 affects ccRCC biology and to evaluate its clinical relevance.
Performance Research and Formulation Optimization of High-Performance Local Insulation Spray Coating Materials
Bird pest control has become a major task for the operation and maintenance of distribution network lines. Epoxy resin that cures quickly at room temperature can be used to coat locations where birds frequently build their nests. However, epoxy resin has enormous internal stress and is brittle, so it is essential to toughen it. In this paper, for a room temperature curing system composed of polyurethane-modified epoxy resin and a polythiol curing agent, three kinds of particles, i.e., Al2O3, SiO2, and Mg(OH)2, were used to modify a polyurethane modified epoxy resin. Orthogonal experiments were designed to study the effects of different fillers on the comprehensive properties of polyurethane-modified epoxy resins. The experimental results showed that there were not only independent effects of different kinds if particles on the resin, but also synergistic effects of multiple particles. Nanoparticles can reduce the defects introduced by microparticles to a certain extent and improve the mechanical and electrical properties of the resin. The overall performance of the resin was optimized when the amounts of SiO2, Al2O3, and Mg(OH)2 were 1.7%, 2.5%, and 7%, respectively. The tensile strength of the resin was increased by 70%, the elongation at a break by 67.53%, and the breakdown strength by 20.31% compared with before the addition of filler. The microscopic morphology and thermal properties of the resin before and after the addition of filler were also studied. Adding fillers caused more cracks to absorb part of the energy when the resin matrix was stressed and increased the rigidity of the resin matrix and the resin’s glass transition temperature (Tg) by 13.48 °C. Still, the temperature corresponding to the maximum rate of weight loss (Tmax) remained unchanged.
High School Students’ Epistemic Cognition and Argumentation Practices during Small-Group Quality Talk Discussions in Science
For high school students to develop scientific understanding and reasoning, it is essential that they engage in epistemic cognition and scientific argumentation. In the current study, we used the AIR model (i.e., Aims and values, epistemic Ideals, and Reliable processes) to examine high school students’ epistemic cognition and argumentation as evidenced in collaborative discourse in a science classroom. Specifically, we employed a qualitative case study approach to focus on four small-group discussions about scientific phenomena during the Quality Talk Science intervention (QTS), where students regularly received explicit instruction on asking authentic questions and engaging in argumentation. In total, five categories of epistemic ideals and five categories of reliable processes were identified. Students demonstrated more instances of normative epistemic ideals and argumentative responses in the discussions after they received a revised scientific model for discussion and explicit instruction on argumentation. Concomitantly, there were fewer instances of students making decisions based on process of elimination to determine a correct scientific claim. With respect to the relationship of epistemic cognition to authentic questioning and argumentation, the use of epistemic ideals seemed to be associated with the initiation of authentic questions and students’ argumentation appeared to involve the use of epistemic ideals.
Quality Talk: Developing Students' Discourse to Promote High-level Comprehension
Students often struggle to comprehend complex text. In response, we conducted an initial, year-long study of Quality Talk, a teacher-facilitated, small-group discussion approach designed to enhance students' basic and high-level comprehension, in two fourth-grade classrooms. Specifically, teachers delivered instructional mini-lessons on discourse elements (e.g., questioning or argumentation) and conducted weekly text-based discussions in their language arts classes. Analysis of the videorecorded discussions showed decreases in teacher-initiated discourse elements, indicating a release of responsibility to students, whereas students' discourse reflected increased critical-analytic thinking (e.g., elaborated explanations or exploratory talk). Importantly, statistically and practically significant increases were evidenced on written measures of students' basic and high-level comprehension, indicating the promise of small-group discourse as a way to foster individual student learning outcomes.
Electrical Tree Characteristics of Bisphenol A Epoxy Resin/Maleopimaric Anhydride Curing System
Epoxy resin insulation materials are mainly derived from petrochemical materials which have the disadvantages of resource consumption and environmental pollution. In order to cure bisphenol A epoxy resin, a maleopimaric anhydride (MPA) curing agent was prepared from rosin, a renewable resource, and blended with a petroleum-based curing agent (methylhexahy-drophthalic anhydride). The influence of maleopimaric anhydride content on the initiation and growth characteristics of electrical trees was studied and analyzed in this paper using molecular dynamics simulation (MD) and electrical tree tests at an 18-kilovolt power frequency voltage. When the MPA content used was ≤10%, the free volume percentage of the curing system increased with MPA content, and thus the initiation voltage became lower; when the MPA content was ≥20%, the hydrogenated phenanthrene ring structure content increased significantly with increasing MPA content, and the rigidity of the curing system increased significantly; thus, the initiation voltage gradually increased. MPA4 had an 11.11% higher initiation voltage than the petroleum-based control group. The effect of the polar rigid structure within the curing system significantly inhibited the growth rate and length of electrical trees as MPA content increased. Electrical trees developed into light-colored, thin, and narrow dendritic structures when the MPA content reached 40%. The results show that curing epoxy resin with the rosin-based curing agent maleopimaric anhydride (MPA), in place of a petroleum-based curing agent, can produce environmentally friendly resins with excellent electrical tree resistance and potential application prospects.
HOW CAN TEACHERS FACILITATE PRODUCTIVE SMALL-GROUP TALK?
Small-group discussions in which teachers and students interact with text are common in language arts classrooms. As documented in the extant literature, teacher discourse moves affect how the discussion unfolds and the resulting quality of the talk. What is not present in the literature is a unified lexicon or taxonomy for defining and classifying the various kinds of discourse moves teachers routinely enact during small-group discussions to promote comprehension. As such, the purpose of the present review is (a) to synthesize research on teacher discourse moves across the various discussion approaches that aim to promote high-level comprehension and (b) to forward an integrated taxonomy of teacher discourse moves. The taxonomy was developed and iteratively refined through card-sorting activities and used as a coding rubric for classroom discussions. This integrated taxonomy is a noteworthy advancement for practitioners to facilitate their classroom discussions and for researchers studying the effects of small-group discussions.
Promoting English Language Proficiency through Quality Talk: An Intervention with Mandarin-Speaking Students
With the development of globalization, English proficiency has become increasingly important in education advancement and career promotion. However, the teaching and learning of English in mainland China mainly focuses on low-level English language skills and teacher-centered instruction where students have limited opportunities to engage in meaningful interactions using English. A pedagogical shift from a teacher-centered instruction to student-centered instruction is needed.To address this challenge, in the current study, I examined the effect of a text-based, small-group discussion approach called Quality Talk (QT) in promoting Mandarin-speaking students’ English language proficiency (i.e., listening, speaking, reading, and writing). Specifically, a treatment class of 42 students and a comparison class of 40 students from an eighth grade of a public middle school in North China participated in the study. The treatment class received a series of lessons on how to ask different types of authentic questions and how to answer questions using argumentation skills in their English class. Subsequently, they experienced five QT discussions in Chinese and five QT discussions in English. The comparison class received business-as-usual instruction, mostly in the form of whole-class lectures with teacher-initiated questions. Assessments on participants’ English language proficiency were developed by the researcher and administered pre- and post-intervention.The results of the English language proficiency assessments revealed that there was moderate reliability for all researcher-developed English proficiency assessments used in the current study. Second, QT intervention did not have a statistically significant effect on participants’ English listening, reading, and speaking after taking into account their pretest performance, prior knowledge, Chinese proficiency, and oral reading fluency. Yet, it did statistically significantly impact participants’ English written argumentation in terms of quantity and quality for those who were mid or high at pretest among all the participants. Third, participants’ journal writing based on discussed texts at three different timepoints during the intervention revealed that participants benefited from QT intervention and improved their written argumentation about discussed texts. Specifically, their literacy journal writing quantity and quality scores statistically significantly improved from Time Point 1 to Time Point 2. Further, QT students outperformed the comparison students at Time Point 2. Comparison students, however, did not statistically significantly enhance their written argumentation from Time Point 1 to Time Point 2.The present research is significant in that it demonstrated the generalization of QT intervention in a different population (i.e., Mandarin-speaking eighth-grade students) and in a different domain (i.e., English learning classroom). It is also practically significant in providing implications for recontextualizing QT intervention considering the characteristics of the according context.
Bolstering students’ written argumentation by refining an effective discourse intervention
Effective interventions are needed to bolster students’ argumentation capacities, an area in which they consistently struggle. Quality Talk (QT) is an approach to small-group classroom discussion shown to support students’ oral argumentation with preliminary evidence that it may also bolster students’ written argumentation. Teachers often must adapt interventions to their local context, balancing needed flexibility with sufficient adherence to fidelity to reach expected efficacy. The present study was conducted over one school year with two fifth-grade teachers and their 46 students. In Phase I, two participating teachers implemented a refined version of QT, and we examined the effects on students’oral and written argumentation performance. While typical gains in students’oral argumentation performance were evidenced, students’written argumentation did not improve to the degree expected, particularly in terms of performance with unfamiliar texts. In Phase II, both teachers reincorporated a component of QT (i. e., regular post-discussion written argumentation practice) they had adapted in Phase I, and one teacher added a new written argumentation scaffold designed to further bolster students’transfer from oral to written argumentation. By the end of the study, students from both classes evidenced growth in written argumentation, but the students from the class receiving the writing scaffold outperformed comparison class students with large effects. Findings underscore the importance of including regular post-discussion written argumentation practice and illustrate the added value of a new written argumentation scaffold, while also contributing to a better understanding of how to balance flexibility and fidelity for efficacious QT implementation.