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This study aims to explore the impact of dual learning on preschool teachers' thriving at work and creative performance, and whether preschool teachers' thriving at work acts as a mediating factor in the relationship between dual learning and teachers' creative work. The participants were preschool teachers from Taiwan. Convenience sampling was used, resulting in a sample size of 388 people. The study results found that preschool teachers' dual learning, which includes both exploitative and exploratory learning, can improve the novelty and usefulness of their work and creativity. Furthermore, the study found that preschool teachers' thriving at work mediates the relationship between dual learning and creativity. This study also discovered that dual learning should combine and complement both exploitative and exploratory learning to achieve balance and the most significant effect. Therefore, it is essential to first help preschool teachers engage in both exploitative and exploratory learning. Schools and kindergartens can also provide relevant courses to help teachers combine these two learning methods. By integrating and complementing their advantages and disadvantages, a balance in learning can be achieved, thereby promoting teachers' creativity in their work.

Individuals diagnosed with autism spectrum disorder (ASD) are more likely to have suicidal thoughts and behaviors. However, little research delineates the temporal and mechanistic associations between potential risk factors and suicidality in autistic individuals. We assessed 129 autistic and 121 age-matched and sex-assigned-at-birth-matched typically developing (TD) children and youth at baseline and follow-up. We evaluated internalizing/externalizing problems, bullying experiences, and three executive function tasks at a mean baseline age of 13.4 years (standard deviation: 4.2 years). After an average of 5.8 years (standard deviation: 1.7 years), we evaluated their suicidal thoughts and behaviors. The experiences of being bullied partially mediated the temporal relationship between pre-existing ASD and later-reported suicidal thoughts. Several cognitive flexibility and sustained attention indices mediated the temporal relationship between pre-existing ASD and later-reported suicidal thoughts. A multiple mediation model confirmed that bullying victimization and cognitive flexibility jointly mediated the temporal relationship between ASD and suicidal thoughts. Better cognitive flexibility and experiences of bullying victimization in autistic children/youth were both associated with higher risks of later-reported suicidal thoughts in adolescence/adulthood. School bullying-prevention programs and tailored clinical support for autistic youth with better cognitive flexibility are warranted for personalized suicide prevention for the autistic population.

Akin to the impact that digital microelectronics had on electronic devices for information technology, digital microfluidics (DMF) was anticipated to transform fluidic devices for lab-on-a-chip (LoC) applications. However, despite a wealth of research and publications, electrowetting-on-dielectric (EWOD) DMF has not achieved the anticipated wide adoption, and commercialization has been painfully slow. By identifying the technological and resource hurdles in developing DMF chip and control systems as the culprit, we envision democratizing DMF by building a standardized design and manufacturing platform. To achieve this vision, we introduce a proof-of-concept cloud platform that empowers any user to design, obtain, and operate DMF chips (https://edroplets.org). For chip design, we establish a web-based EWOD chip design platform with layout rules and automated wire routing. For chip manufacturing, we build a web-based EWOD chip manufacturing platform and fabricate four types of EWOD chips (i.e., glass, paper, PCB, and TFT) to demonstrate the foundry service workflow. For chip control, we introduce a compact EWOD control system along with web-based operating software. Although industrial fabrication services are beyond the scope of this work, we hope this perspective will inspire academic and commercial stakeholders to join the initiative toward a DMF ecosystem for the masses.

Field experiences provide opportunities for early childhood and early childhood special education (EC/ECSE) educators to implement effective practices in learning settings, and are, therefore, a vital part of EC/ECSE teacher preparation. In this article, we describe field placement models from four universities in the United States: The Bridge Project, Getting Started Early, Peer Coaching to Increase Naturalistic Developmental Behavioral Interventions, and University Supervisors Coaching Teacher Candidates: Supporting Young Bi/Multilingual Children with Disabilities. Although there is variety in the settings and effective practices supported through these field placements, performance feedback and collaboration are clear themes across models.

Lusheng is a traditional wind musical instrument cherished by various ethnic minorities in China. The objective of this study is to investigate the role of Lusheng Chinese musical instruments in promoting literacy through educational functions and transmission. Conducted in Guizhou Province, a region rich in ethnic diversity, this study employs qualitative methods and engages two key informants who are local artisans with interview and observation forms. The data analysis reveals multifaceted insights into Lusheng's transmission and promotion. Findings highlight the challenges posed by modernization to traditional craftsmanship, emphasizing the urgency of preserving Lusheng production skills. The inclusion of Lusheng in the National Intangible Cultural Heritage list and the establishment of educational programs in primary, and secondary schools, and universities underscore the government's commitment to safeguarding Lusheng culture. Moreover, the research underscores the transformative impact of modern media on Lusheng's dissemination, and cross-cultural engagement is recognized as vital for expanding its influence. Balancing tradition and innovation remains a challenge. The study suggests collaborative efforts among government, academia, and society to develop a comprehensive conservation strategy, ensuring the continued transmission and promotion of Lusheng culture.

This study aims to explore whether the creativity of university students in Higher Vocational Education in China can enhance their creative performance through autonomous motivation. The theoretical foundation of this study is interactionist model of creativity, the study employs structural equation modeling for analysis and validation. A survey assessing creativity, creative performance, and autonomous motivation was administered to students from higher vocational schools in China, yielding a valid sample of 392. The overall model results indicate that the creativity of vocational college students has a significant positive impact on creative performance, creativity positively predicted autonomous motivation, which enhanced creative performance. The autonomous motivation partially mediates the relationship between creativity and creative performance. The findings recommend that higher vocational institutions initiate creative activities to foster students' creativity and continuously bolster their autonomous motivation, thus enhancing the creative performance of future technical and skilled professionals -- vocational college students.

The study focuses on the preservation and transmission of Gannan Tea Picking Opera knowledge after the Cultural Revolution in 1949 using qualitative research methods such as interviews and observations with seven key informants. The following findings were obtained, which can be divided into three distinct periods: The tortuous development phase from 1949 to 1966 marked significant growth and development, with the establishment of specialized schools and the implementation of the "three reforms" contributing to knowledge transmission and preservation. The survival dilemma period from 1966 to 1976 during the Cultural Revolution imposed constraints on artistic expression, but the return of artists from rural areas and their role in recruiting apprentices supported the continuity of Gannan Tea Picking Opera. Finally, the Ganzhou Gannan Tea Picking Opera Troupe and educational institutions contributed to the revival of this traditional art form during the period of rebirth from 1976 to 2023. Retired artists continue to play a vital role in knowledge preservation and dissemination, reflecting the enduring resilience of Gannan Tea Picking Opera.

The Accelerate Cancer Education (ACE) summer research program at The University of Kansas Cancer Center (KUCC) is a six-week, cancer-focused, summer research experience for high school students from historically marginalized populations in the Kansas City metropolitan area. Cancer affects all populations and continues to be the second leading cause of death in the United States, and a large number of disparities impact racial and ethnic minorities, including increased cancer incidence and mortality. Critically, strategies to bolster diversity, equity, inclusion, and accessibility are needed to address persistent cancer disparities. The ACE program offers an educational opportunity for a population of students who otherwise would not have easy access onto a medical center campus to make connections with cancer physicians and researchers and provides a vital response to the need for a more diverse and expansive oncology workforce. Students grow their technical, social, and professional skills and develop self-efficacy and long-lasting connections that help them matriculate and persist through post-secondary education. Developed in 2018, the ACE program has trained 37 high school junior and senior students. This article describes the need for and how we successfully developed and implemented the ACE program.

Attention to the disconnection between culture and mathematics has been addressed then and now (Wilder (in: Graves et al., Proceedings of the international congress of mathematicians, American Mathematical Society, 1950; Liu in Taiwan Journal of Mathematics Education, 8:79-88, 2021b). Recently, studies, workshops, and contests about an approach to relating culture and mathematics, such as incorporating mathematics history or mathematics writings in class, have emerged. However, although the effectiveness of such an approach was proved, employing it as instruction was still significantly ignored, not to mention the approach to creating mathematics literary writings--the goal that the Mathematics-Literature Contest aimed to achieve. Additionally, no empirical studies have systematically assessed the contest, especially from the cultural perspective. Through teachers' and students' perceptions, this qualitative case study aims to examine the impact of mathematics literary writings on the development of mathematics teaching/learning and the mathematics culture represented in the contest. Ten teachers and 20 students were interviewed. Data were analyzed by following Yin's five phases (2016). The study visualizes an evolutionary model of the contest, signifying the development of mathematics culture simultaneously. Results demonstrated that the contest caused teachers and students, who constituted the internal force, to consolidate the mathematics culture, which was enriched by the external force--to reinterpret the connection between mathematics as well as culture and the reform of general education. The developed mathematics culture included elements other than mathematics, such as the Chinese writings and their interactions with mathematics and life experiences. The findings hold implications for mathematics and general education: An interdisciplinary curriculum design can help cultivate teachers' and students' intellectual acumen; higher education communities worldwide must follow the trend.

The integration of education and robotics has emerged as a crucial development in the technological landscape. This study focuses on the use of a robot teaching assistant to enhance the learning efficiency of 8th-grade students in hands-on STEM activities centered around the theme of "Smart City." It explores the impact of educational robots on students' learning outcomes and their development of hands-on skills through diverse learning methods. Conducted over 12 weeks with 103 participants, the study employed a quasi-experimental design. Students were split into two groups: The Experimental Group (EG), using the 6E model with robot teaching assistants, and the Control Group (CG), using only the 6E model. The analysis of covariance revealed that the EG exhibited superior performance in STEM knowledge, motivation, and hands-on skills compared to the CG. Further analysis indicated that learning motivation significantly influenced hands-on performance in the EG, particularly in high-scoring subgroups. The findings suggest that combining the 6E model with educational robots effectively enhances STEM learning and student engagement. Educational robots as teaching assistants not only aid in knowledge acquisition but also significantly boost students' motivation and hands-on skill development. This implies a promising direction for integrating advanced technology in educational practices to foster more effective learning environments.

Based on expectancy-value theory, this study adopted a person-centred approach to explore the heterogeneous profiles of secondary German and Taiwanese students' mathematical modelling task values, and examined the differences in their mathematical modelling performance, controlling for the variable of intra-mathematical knowledge among the heterogeneous profiles. Authors conducted a survey study of 452 ninth graders (201 German students and 251 Taiwanese students). The results showed that German and Taiwanese students respectively displayed three profiles of mathematical modelling task values: a) moderate utility and moderate interest/attainment, b) high utility but low interest/attainment, and c) low utility but high interest/attainment. Furthermore, different profiles of mathematical modelling task values showed significant differences in mathematical modelling performance for Taiwanese students but not for German students, even after removing the variable of intra-mathematical knowledge. This study advances the understanding of students' mathematical modelling task values and its relation with their mathematical modelling performance by the expectancy-value model of achievement motivation and person-centred analyses, and sheds light on the learning and teaching of mathematical modelling.

Due to core challenges in social communication experienced by many young children with autism, children on the spectrum who are also dual language learners (DLLs) may benefit from developmentally-appropriate language supports in school settings. The current study examined whether home language status moderated the effect of a play-based intervention, JASPER, delivered in the classroom, in children with autism. Fifty-nine preschool children with autism received JASPER over eight weeks. Children who received JASPER improved significantly more in their language skills from entry to exit than children in preschool as usual. Home language status moderated the effect of treatment on receptive language where children of diverse linguistic backgrounds made greater gains in receptive language.

Number sense is fundamental to the development of numerical problem-solving skills. In early childhood, children establish associations between non-symbolic (e.g., a set of dots) and symbolic (e.g., Arabic numerals) representations of quantity. The developmental estrangement theory proposes that the relationship between non-symbolic and symbolic representations of quantity evolves with age, with increased dissociation across development. Consistent with this theory, recent research suggests that cross-format neural representational similarity (NRS) between non-symbolic and symbolic quantities is correlated with arithmetic fluency in children but not in adolescents. However, it is not known if short-term training (STT) can induce similar changes as long-term development. In this study, children aged 7-10 years underwent a theoretically motivated 4-week number sense training. Using multivariate neural pattern analysis, we investigated whether short-term learning could modify the relation between cross-format NRS and arithmetic skills. Our results revealed a significant correlation between cross-format NRS and arithmetic fluency in distributed brain regions, including the parietal and prefrontal cortices, prior to training. However, this association was no longer observed after training, and multivariate predictive models confirmed these findings. Our findings provide evidence that intensive STT during early childhood can promote behavioral improvements and neural plasticity that resemble and recapitulate long-term neurodevelopmental changes that occur from childhood to adolescence. More generally, our study contributes to our understanding of the malleability of number sense and highlights the potential for targeted interventions to shape neurodevelopmental trajectories in early childhood.

Although identifying the referents of single words is often cited as a key challenge for getting word learning off the ground, it overlooks the fact that young learners consistently encounter words in the context of other words. How does this company help or hinder word learning? Prior investigations into early word learning from children's real-world language input have yielded conflicting results, with some influential findings suggesting an advantage for words that keep a diverse company of other words, and others suggesting the opposite. Here, we sought to triangulate the source of this conflict, comparing different measures of diversity and approaches to controlling for correlated effects of word frequency across multiple languages. The results were striking: while different diversity measures on their own yielded conflicting results, once nonlinear relationships with word frequency were controlled, we found convergent evidence that contextual consistency supports early word learning.

In the current article, we describe the development and validation of the Social Comparison Rumination Scale. This measured was developed as a supplement to existing social comparison measures and to enable us to determine its potential relevance to perfectionism and other personality constructs. The Social Comparison Rumination Scale (SCRS) is a six-item inventory assessing the extent to which an individual is cognitively preoccupied and thinking repetitively about social comparison outcomes and information. Three studies with five samples of university students are described. Psychometric analyses established the SCRS consists of one factor assessed with high internal consistency and the measure is reliable and valid. Analyses showed that elevated levels of social comparison rumination are associated with trait perfectionism, perfectionistic automatic thoughts, perfectionistic self-presentation, ruminative brooding, burnout, depression, and fear of negative evaluation. Links were also established between social comparison rumination and both narcissism and dispositional envy. Overall, our findings support the further use of the SCRS and highlight the tendency of many people to think in deleterious ways about social comparisons long after the actual comparisons have taken place. We discuss social comparison rumination within the context of concerns about excessive social media use and young people being exposed to seemingly perfect lives that became a vexing cognitive preoccupation.

Teaching elementary students how to read is undeniably crucial, yet a substantial number of children encounter difficulties despite early interventions. Cross-age tutoring, a pedagogical approach that pairs older students with younger peers, emerges as a cost-effective solution that brings academic and social benefits to both the tutor and the tutee. Consequently, cross-age tutoring programs are widely adopted globally. To maximize the effectiveness of cross-age tutoring, we offer five evidence-based recommendations tailored for its implementation. When integrated into the preparation and implementation steps, these recommendations hold the potential to significantly improve learning outcomes for both tutors and tutees.

This study aims to examine the relationship among motivation for joining an educational leadership training programme (MOT), perceived skills (PS), and perceived changes in transformational leadership (PCTFL) in educational leadership training. The study drew on survey data from 761 participants who were associated with a leadership development programme under an EU-China cooperation project. The conceptual model was tested by structural equation modelling (SEM) by the Mplus programme. MOT and PCTFL were measured, respectively, by second-order factor structure assessments due to their multi-dimensional nature. The findings of the study suggest that motivation positively influences perceived changes in transformational leadership, and this relationship is positively mediated by perceived skills as learning gains in educational leadership training. The study provides novel empirical evidence on motivation that leads to transformational leadership changes in leadership training programmes. Policymakers and other key stakeholders can use these findings to gain a deeper understanding of the success of projects and encourage academic members to participate in leadership training programmes to improve transformational leadership.

This study investigates how trust influences parents' satisfaction with parenting apps. The study demonstrates that social ties and perceived value act as mediators between trust and user satisfaction. A questionnaire was conducted in Taiwan to test parents' perceptions of parenting apps, focusing particularly on user satisfaction and related social factors. The survey examined four latent factors: trust, satisfaction, social ties, and perceived value. In order to evaluate the validity and reliability of the latent factors, partial least squares regression was used. The soundness of the measurement model was confirmed by the statistical results. The study also examined hypothesized relationships and multiple mediations to establish statistical significance. The multiple mediating analysis revealed a significant relationship between trust and satisfaction regarding parenting apps. Social ties and perceived value were identified as significant mediators in this relationship. Parents' satisfaction with parenting apps is influenced by their perceptions of the apps' trustworthiness. This is influenced by the apps' information about education and childcare, which helps people improve their parenting literacy and their ability to raise children. Parents' attitudes towards social ties and perceived value also enhance their satisfaction with parenting apps, encouraging their continued use. Working cooperatively and socializing via the apps helps to construct a mobile community that allows parents of young children to interact with each other and develop their parenting skills.

Educational chatbots are gaining momentum due to their distinctive affordances of interactivity, immediacy, ease of use, and individualized experience. However, a fairly limited body of literature discusses how a chatbot can facilitate collaborative learning among peers in extensive reading contexts to encourage more vibrant interactions supporting further interest development. Therefore, this research aimed to analyze the affordances and limitations of a chatbot to facilitate human-human interactions by incorporating the refined Academically Productive Talk framework for nurturing a learning community, forming accurate knowledge, fostering rigorous thinking, and encouraging affective responses for elementary school learners. Specifically, the purpose of the research was to observe the situational interest of the learners, their interaction patterns, and their social learning behaviors. This research developed a chatbot stored with 64 children's storybooks to initiate and facilitate peer dialogues. A group of 30 learners were paired up to conduct two chatbot-facilitated dialogic reading activities. A total of 30 discourse logs and students' feedback on a survey of situational interest were analyzed. The discourse analysis of this research supports the affordances of the chatbot acting as an effective dialogue initiator and discussion facilitator to support both human-chatbot and human-human social learning. The chatbot encourages a diverse interactive dialogic climate, and four interaction patterns were identified. The situational interest of the initial encounter with the chatbot was boosted; however, their interest was unable to be sustained. The implications for the affordances and limitations of educational chatbots are discussed.

Successful computer-based assessments for learning greatly rely on an effective learner modeling approach to analyze learner data and evaluate learner behaviors. In addition to explicit learning performance (i.e., product data), the process data logged by computer-based assessments provide a treasure trove of information about how learners solve assessment questions. Unfortunately, how to make the best use of both product and process data to sequentially model learning behaviors is still under investigation. This study proposes a novel deep learning-based approach for enhanced learner modeling that can sequentially predict learners' future learning performance (i.e., item responses) based on modeling their history learning behaviors. The evaluation results show that the proposed model outperforms another popular deep learning-based learner model, and process data learning of the model contributes to improved prediction performance. In addition, the model can be used to discover the mapping of items to skills from scratch without prior expert knowledge. Our study showcases how product and process data can be modelled under the same framework for enhanced learner modeling. It offers a novel approach for learning evaluation in the context of computer-based assessments.

The growing adoption of online platforms for educational goals has raised concerns among learners regarding online learning contexts. These platforms have been identified as productive mediums for learning English as a second language. However, learners consistently strive for enhanced platforms, and their perspectives may change when confronted with concerns about the platform's overall quality, specifically in relation to its reliability and privacy. Therefore, this study aims to evaluate the impact of platform quality, including features such as reliability, design, and security, in combination with learners' familiarity with these platforms. A quantitative research approach was utilized to accomplish this goal, which entailed circulating an online survey by 410 Chinese North East public and private university graduate and postgraduate students, which were analyzed using SmartPLS 4 software. The study's findings indicate that certain elements of website quality, such as design and privacy, do not significantly impact platform satisfaction. Learners generally prefer criteria other than design and privacy considerations when assessing language learning applications. While platform design, familiarity and satisfaction significantly impact intrinsic motivation towards English learning. These characteristics contribute to the creation of a conducive learning environment for learners, which in turn promotes motivation, engagement, and, eventually, the development of language competency. By implementing these strategies, managers can cultivate a more immersive, gratifying, and stimulating English language acquisition encounter on online platforms, resulting in heightened satisfaction and competence. Based on the study's findings, the study suggested platform executives investigate these indicators using learner feedback and appropriately modify the platform's services.

Over the past decade, increasingly more colleges and universities have had to address student-initiated demands following racist incidents that occur both locally and nationally. However, the demands to address unfair conditions on campus do not necessarily result in meaningful change. To better understand how student activism facilitates administrative actions that lead to change and the extent to which social media accentuates activism, we examined student-initiated efforts to increase "diversity" at Yale University. Our study combined more than 100 documents with 5 years of social media data to identify key patterns that significantly contributed toward facilitating institutional change. The findings show that to facilitate administrative actions, student activists grew their reach, reiterated their demands over time, and activated the individuals and groups peripheral to the original demands. Their combined efforts were accentuated by the use of social media, which served to make their activism even more consequential for mediating tangible and demonstrable change at the institutional level.

The role that symbols play in facilitating or hindering institutional transformation efforts on campuses is underexplored. Through this embedded, multiple case study, we examine interview data from 52 participants at four private postsecondary institutions to investigate how power dynamics influence symbols to advance or hinder these institutional agents' work in diversity, equity, and inclusion (DEI). The findings highlight the contested nature of symbols and symbolic acts, which include (a) a disproportionate emphasis on positional leaders as symbols of opportunity, (b) complicating the idea of diversity centers as symbols of commitment, and (c) struggles to engage frameworks and strategic plans as symbols of shared vision and ownership. Specifically, we attend to how power dynamics may play a role in who/what becomes a symbol, and how symbols are interpreted in contradictory ways by different campus constituents, which have implications for how institutions can unite campus efforts toward DEI. Together, these findings present the tensions that universities must contend with as they use symbols to encourage a collective effort to advance DEI.

The present study aims to translate the questionnaires of Parents' Attitudes toward Early Childhood Career Development (PAECCD) and Parents' Attitudes toward Vocational Education Implementation in Preschool Curriculum (PAVEIPC) into Chinese versions (PAECCD-C and PAVEIPC-C) and examines their reliability and validity through two studies. In Study 1, exploratory factor analyses (EFAs) were conducted to evaluate their factor structure among 232 Chinese preschoolers' parents. In Study 2, confirmatory factor analyses (CFAs) were conducted to confirm their factor structures among other 355 Chinese preschoolers' parents, supporting the superiority of the initial theoretical model. Multigroup CFA comparisons indicated the measurement invariance for fathers and mothers. The PAECCD-C and PAVEIPC-C had excellent reliability values from 0.82 to 0.92. This study added to the existing research literature by supporting the applicability of PAECCD and PAVEIPC among Chinese preschoolers' parents.

This study examined the impact of integrating virtual science inquiry activities with Predict-Observe-Explain (POE) teaching strategies on 5th graders' understanding of science concepts and epistemic beliefs in science. A cohort of 80 5th graders (mean age of 12 years old, 40 boys and 40 girls) from a public primary school in North China took part in the research. The data collected encompassed pre-test and post-test results on understanding of science concepts and epistemic beliefs, along with students' behavioral data during virtual science inquiry. The findings demonstrated that integrating virtual science inquiry activities with POE strategies increased students' understanding of science concepts and epistemic beliefs in science. Furthermore, notable differences were found in observation time and inquiry strategy between high and low achievers, while significant distinctions in page time allocation and page navigation behavior were evident between boys and girls. The results provided empirical support for enhancing the implementation of virtual science inquiry activities in primary school science learning.

This study surveyed 183 college and senior high school students' graph-interpretation competence in scientific and daily contexts. Specifically, whether students' graph interpretation in scientific and daily contexts differed across educational levels was investigated. Furthermore, the questions of whether students' graph interpretation competence in scientific contexts might predict their graph interpretation in daily contexts were explored. Other factors including age and gender were also considered and examined to discern significant factor(s) predicting graph interpretation competence in daily contexts. Results indicated that there were statistically significant differences across educational levels in terms of graph interpretation competence in both scientific and daily contexts. Furthermore, the students' graph interpretation competence was related between scientific and daily contexts. The important factors predicting students' graph interpretation in daily contexts include age and graph-interpretation in scientific literacy. Implications are discussed.

Since the last IAEA-FEC in 2021, significant progress on the development of long pulse steady state scenario and its related key physics and technologies have been achieved, including the reproducible 403 s long-pulse steady-state H-mode plasma with pure radio frequency (RF) power heating. A thousand-second time scale (∼1056 s) fully non-inductive plasma with high injected energy up to 1.73 GJ has also been achieved. The EAST operational regime of high βP has been significantly extended (H98y2 > 1.3, βP ∼ 4.0, βN ∼ 2.4 and ne/nGW ∼ 1.0) using RF and neutral beam injection (NBI). The full edge localized mode suppression using the n = 4 resonant magnetic perturbations has been achieved in ITER-like standard type-I ELMy H-mode plasmas with q95 ≈ 3.1 on EAST, extrapolating favorably to the ITER baseline scenario. The sustained large ELM control and stable partial detachment have been achieved with Ne seeding. The underlying physics of plasma-beta effect for error field penetration, where toroidal effect dominates, is disclosed by comparing the results in cylindrical theory and MARS-Q simulation in EAST. Breakdown and plasma initiation at low toroidal electric fields (

IntroductionIn academic breast surgery, ultrasound use tends to be limited to radiology departments, thus formal surgical resident training in breast ultrasound is sparse. Building on residents' ultrasound skills in our general surgery training program, we developed a novel curriculum to teach ultrasound-guided breast procedures (UGBPs), including core needle biopsy (CNB) and wire localization (WL). We hypothesized that learning UGBPs on cadavers would be preferred to learning with a breast phantom model using chicken breasts.MethodsResidents received a 1-h lecture on breast CNB and WL followed by a 1-h hands-on laboratory session. Olives stuffed with red pimentos were used to replicate breast masses and implanted in chicken breasts and the breasts of lightly embalmed and unembalmed female cadavers. All residents practiced UGBPs with a course instructor on both models. Residents completed anonymous prelaboratory and postlaboratory surveys utilizing five-point Likert scales.ResultsA total of 35 trainees participated in the didactics; all completed the prelaboratory survey and 28 completed the postlaboratory survey. Participant clinical year ranged from 1 to 6. Residents' confidence in describing and performing CNBs and WLs increased significantly on postlaboratory surveys, controlling for clinical year (P

Ferroelectric HfO2-based thin films have attracted much interest in the utilization of ferroelectricity at the nanoscale for next-generation electronic devices. However, the structural origin and stabilization mechanism of the ferroelectric phase are not understood because the film is typically nanocrystalline with active yet stochastic ferroelectric domains. Here, electron microscopy is used to map the in-plane domain network structures of epitaxially grown ferroelectric Y:HfO2 films in atomic resolution. The ferroelectricity is confirmed in free-standing Y:HfO2 films, allowing for investigating the structural origin for their ferroelectricity by 4D-STEM, high-resolution STEM, and iDPC-STEM. At the grain boundaries of -oriented Pca21 orthorhombic grains, a high-symmetry mixed-(R3m, Pnm21) phase is induced, exhibiting enhanced polarization due to in-plane compressive strain. Nanoscale Pca21 orthorhombic grains and their grain boundaries with mixed-(R3m, Pnm21) phases of higher symmetry cooperatively determine the ferroelectricity of the Y:HfO2 film. It is also found that such ferroelectric domain networks emerge when the film thickness is beyond a finite value. Furthermore, in-plane mapping of oxygen positions overlaid on ferroelectric domains discloses that polarization is suppressed at vertical domain walls, while it is active when domains are aligned horizontally with subangstrom domain walls. In addition, randomly distributed 180° charged domain walls are confined by spacer layers.

Isochoric (constant-volume or volumetrically confined) vitrification has shown potential as an alternative cryopreservation-by-vitrification technique, but the complex processes at play within the chamber are yet poorly characterized, and recent investigations have prompted significant debate around whether a truly isochoric vitrification process (in which the liquid remains completely confined by solid boundaries) is indeed feasible. Based on a recent thermomechanical simulation of a high-concentration Me2SO solution, Solanki and Rabin (Cryobiology, 2023, 111, 9-15.) argue that isochoric vitrification is not feasible, because differential thermal contraction of the solution and container will necessarily drive generation of a cavity, corrupting the rigid confinement of the liquid. Here, we provide direct experimental evidence to the contrary, demonstrating cavity-free isochoric vitrification of a ∼3.5 M vitrification solution by combined isochoric pressure measurement (IPM) and photon-counting x-ray computed tomography (PC-CT). We hypothesize that the absence of a cavity is due to the minimal thermal contraction of the solution, which we support with additional volumetric analysis of the PC-CT reconstructions. In total, this study provides experimental evidence both demonstrating the feasibility of isochoric vitrification and highlighting the potential of designing vitrification solutions that exhibit minimal thermal contraction.

This review provides a comprehensive overview of the progress in light-material interactions (LMIs), focusing on lasers and flash lights for energy conversion and storage applications. We discuss intricate LMI parameters such as light sources, interaction time, and fluence to elucidate their importance in material processing. In addition, this study covers various light-induced photothermal and photochemical processes ranging from melting, crystallization, and ablation to doping and synthesis, which are essential for developing energy materials and devices. Finally, we present extensive energy conversion and storage applications demonstrated by LMI technologies, including energy harvesters, sensors, capacitors, and batteries. Despite the several challenges associated with LMIs, such as complex mechanisms, and high-degrees of freedom, we believe that substantial contributions and potential for the commercialization of future energy systems can be achieved by advancing optical technologies through comprehensive academic research and multidisciplinary collaborations.

Stability issues in membrane-free coacervates have been addressed with coating strategies, but these approaches often compromise the permeability of the coacervate. Here we report a facile approach to maintain both stability and permeability using tannic acid and then demonstrate the value of this approach in enzyme-triggered drug release. First, we develop size-tunable coacervates via self-assembly of heparin glycosaminoglycan with tyrosine and arginine-based peptides. A thrombin-recognition site within the peptide building block results in heparin release upon thrombin proteolysis. Notably, polyphenols are integrated within the nano-coacervates to improve stability in biofluids. Phenolic crosslinking at the liquid-liquid interface enables nano-coacervates to maintain exceptional structural integrity across various environments. We discover a pivotal polyphenol threshold for preserving enzymatic activity alongside enhanced stability. The disassembly rate of the nano-coacervates increases as a function of thrombin activity, thus preventing a coagulation cascade. This polyphenol-based approach not only improves stability but also opens the way for applications in biomedicine, protease sensing, and bio-responsive drug delivery.

BACKGROUND AND AIMS: Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. METHODS: Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. RESULTS: The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. CONCLUSIONS: The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

Proper regulation of organelle dynamics and inter-organelle contacts is critical for cellular health and function. Both the endoplasmic reticulum (ER) and actin cytoskeleton are known to regulate organelle dynamics, but how, when, and where these two subcellular components are coordinated to control organelle dynamics remains unclear. Here, we show that ER-associated actin consistently marks mitochondrial, endosomal, and lysosomal fission sites. We also show that actin polymerization by the ER-anchored isoform of the formin protein INF2 is a key regulator of the morphology and mobility of these organelles. Together, our findings establish a mechanism by which INF2-mediated polymerization of ER-associated actin at ER-organelle contacts regulates organelle dynamics.

The formation and preservation of the active phase of the catalysts at the triple-phase interface during CO2 capture and reduction is essential for improving the conversion efficiency of CO2 electroreduction toward value-added chemicals and fuels under operational conditions. Designing such ideal catalysts that can mitigate parasitic hydrogen generation and prevent active phase degradation during the CO2 reduction reaction (CO2RR), however, remains a significant challenge. Herein, we developed an interfacial engineering strategy to build a new SnOx catalyst by invoking multiscale approaches. This catalyst features a hierarchically nanoporous structure coated with an organic F-monolayer that modifies the triple-phase interface in aqueous electrolytes, substantially reducing competing hydrogen generation (less than 5%) and enhancing CO2RR selectivity (∼90%). This rationally designed triple-phase interface overcomes the issue of limited CO2 solubility in aqueous electrolytes via proactive CO2 capture and reduction. Concurrently, we utilized pulsed square-wave potentials to dynamically recover the active phase for the CO2RR to regulate the production of C1 products such as formate and carbon monoxide (CO). This protocol ensures profoundly enhanced CO2RR selectivity (∼90%) compared with constant potential (∼70%) applied at -0.8 V (V vs RHE). We further achieved a mechanistic understanding of the CO2 capture and reduction processes under pulsed square-wave potentials via in situ Raman spectroscopy, thereby observing the potential-dependent intensity of Raman vibrational modes of the active phase and CO2RR intermediates. This work will inspire material design strategies by leveraging triple-phase interface engineering for emerging electrochemical processes, as technology moves toward electrification and decarbonization.

HER2, encoded by the ERBB2 gene, is an important druggable driver of human cancer gaining increasing importance as a therapeutic target in urothelial carcinoma (UC). The genomic underpinnings of HER2 overexpression in ERBB2 nonamplified UC are poorly defined. To address this knowledge gap, we investigated 172 UC tumors from patients treated at the University of California San Francisco, using immunohistochemistry and next-generation sequencing. We found that GATA3 and PPARG copy number gains individually predicted HER2 protein expression independently of ERBB2 amplification. To validate these findings, we interrogated the Memorial Sloan Kettering/The Cancer Genome Atlas (MSK/TCGA) dataset and found that GATA3 and PPARG copy number gains individually predicted ERBB2 mRNA expression independently of ERBB2 amplification. Our findings reveal a potential link between the luminal marker HER2 and the key transcription factors GATA3 and PPARG in UC and highlight the utility of examining GATA3 and PPARG copy number states to identify UC tumors that overexpress HER2 in the absence of ERBB2 amplification. In summary, we found that an increase in copy number of GATA3 and PPARG was independently associated with higher ERBB2 expression in patient samples of UC. This finding provides a potential explanation for HER2 overexpression in UC tumors without ERBB2 amplification and a way to identify these tumors for HER2-targeted therapies.

BACKGROUND AND AIMS: Extracellular vesicles (EVs) secreted by cardiosphere-derived cells exert immunomodulatory effects through the transmission of small non-coding RNAs. METHODS: The mechanism and role of yREX3, a small Y RNA abundant in EVs in myocardial injury, was investigated. RESULTS: yREX3 attenuates cardiac ischaemic injury by selective DNA methylation. Synthetic yREX3 encapsulated in lipid nanoparticles triggers broad transcriptomic changes in macrophages, localizes to the nucleus, and mediates epigenetic silencing of protein interacting with C kinase-1 (Pick1) through methylation of upstream CpG sites. Moreover, yREX3 interacts with polypyrimidine tract binding protein 3 (PTBP3) to methylate the Pick1 gene locus in a DNA methyltransferase-dependent manner. Suppression of Pick1 in macrophages potentiates Smad3 signalling and enhances efferocytosis, minimizing heart necrosis in rats with myocardial infarction. Adoptive transfer of Pick1-deficient macrophages recapitulates the cardioprotective effects of yREX3 in vivo. CONCLUSIONS: These findings highlight the role of a small Y RNA mined from EVs with a novel gene-methylating mechanism.

The interplay of topology, magnetism, and correlations gives rise to intriguing phases of matter. In this study, through state-of-the-art angle-resolved photoemission spectroscopy, density functional theory, and dynamical mean-field theory calculations, we visualize a fourfold degenerate Dirac nodal line at the boundary of the bulk Brillouin zone in the antiferromagnet YMn2Ge2. We further demonstrate that this gapless, antiferromagnetic Dirac nodal line is enforced by the combination of magnetism, space-time inversion symmetry, and nonsymmorphic lattice symmetry. The corresponding drumhead surface states traverse the whole surface Brillouin zone. YMn2Ge2 thus serves as a platform to exhibit the interplay of multiple degenerate nodal physics and antiferromagnetism. Interestingly, the magnetic nodal line displays a d-orbital dependent renormalization along its trajectory in momentum space, thereby manifesting Hund's coupling. Our findings offer insights into the effect of electronic correlations on magnetic Dirac nodal lines, leading to an antiferromagnetic Hund nodal line.

Abstract: —J. Blunden and T. Boyer In 2023, La Niña conditions that generally prevailed in the eastern Pacific Ocean from mid-2020 into early 2023 gave way to a strong El Niño by October. Atmospheric concentrations of Earth’s major greenhouse gases—carbon dioxide, methane, and nitrous oxide—all increased to record-high levels. The annual global average carbon dioxide concentration in the atmosphere rose to 419.3±0.1 ppm, which is 50% greater than the pre-industrial level. The growth from 2022 to 2023 was 2.8 ppm, the fourth highest in the record since the 1960s. The combined short-term effects of El Niño and the long-term effects of increasing levels of heat-trapping gases in the atmosphere contributed to new records for many essential climate variables reported here. The annual global temperature across land and oceans was the highest in records dating as far back as 1850, with the last seven months (June–December) having each been record warm. Over land, the globally averaged temperature was also record high. Dozens of countries reported record or near-record warmth for the year, including China and continental Europe as a whole (warmest on record), India and Russia (second warmest), and Canada (third warmest). Intense and widespread heatwaves were reported around the world. In Vietnam, an all-time national maximum temperature record of 44.2°C was observed at Tuong Duong on 7 May, surpassing the previous record of 43.4°C at Huong Khe on 20 April 2019. In Brazil, the air temperature reached 44.8°C in Araçuaí in Minas Gerais on 20 November, potentially a new national record and 12.8°C above normal. The effect of rising temperatures was apparent in the cryosphere, where snow cover extent by June 2023 was the smallest in the 56-year record for North America and seventh smallest for the Northern Hemisphere overall. Heatwaves contributed to the greatest average mass balance loss for Alpine glaciers around the world since the start of the record in 1970. Due to rapid volume loss beginning in 2021, St. Anna Glacier in Switzerland and Ice Worm Glacier in the United States disappeared completely. In August, as a direct result of glacial thinning over the past 20 years, a glacial lake on a tributary of the Mendenhall Glacier in Alaska burst through its ice dam and caused unprecedented flooding on Mendenhall River near Juneau. Across the Arctic, the annual surface air temperature was the fourth highest in the 124-year record, and summer (July–September) was record warm. Smaller-than-normal snow cover extent in May and June contributed to the third-highest average peak tundra greenness in the 24-year record. In September, Arctic minimum sea ice extent was the fifth smallest in the 45-year satellite record. The 17 lowest September extents have all occurred in the last 17 years. In Antarctica, temperatures for much of the year were up to 6°C above average over the Weddell Sea and along coastal Dronning Maud Land. The Antarctic Peninsula also experienced well-above-average temperatures during the 2022/23 melt season, which contributed to its fourth consecutive summer of above-average surface melt. On 21 February, Antarctic sea ice extent and sea ice area both reached all-time lows, surpassing records set just a year earlier. Over the course of the year, new daily record-low sea ice extents were set on 278 days. In some instances, these daily records were set by a large margin, for example, the extent on 6 July was 1.8 million km2 lower than the previous record low for that day. Across the global oceans, the annual sea surface temperature was the highest in the 170-year record, far surpassing the previous record of 2016 by 0.13°C. Daily and monthly records were set from March onward, including an historic-high daily global mean sea surface temperature of 18.99°C recorded on 22 August. Approximately 94% of the ocean surface experienced at least one marine heatwave in 2023, while 27% experienced at least one cold spell. Globally averaged ocean heat content from the surface to 2000-m depth was record high in 2023, increasing at a rate equivalent to ∼0.7 Watts per square meter of energy applied over Earth’s surface. Global mean sea level was also record high for the 12th consecutive year, reaching 101.4 mm above the 1993 average when satellite measurements began, an increase of 8.1±1.5 mm over 2022 and the third highest year-over-year increase in the record. A total of 82 named tropical storms were observed during the Northern and Southern Hemispheres’ storm seasons, below the 1991–2020 average of 87. Hurricane Otis became the strongest landfalling hurricane on record for the west coast of Mexico at 140 kt (72 m s−1), causing at least 52 fatalities and $12–16 billion U.S. dollars in damage. Freddy became the world’s longest-lived tropical cyclones on record, developing into a tropical cyclone on 6 February and finally dissipating on 12 March. Freddy crossed the full width of the Indian Ocean and made one landfall in Madagascar and two in Mozambique. In the Mediterranean Sea—outside of traditional tropical cyclone basins—heavy rains and flooding from Storm Daniel killed more than 4300 people and left more than 8000 missing in Libya. The record-warm temperatures in 2023 created conditions that helped intensify the hydrological cycle. Measurements of total-column water vapor in the atmosphere were the highest on record, while the fraction of cloud area in the sky was the lowest since records began in 1980. The annual global mean precipitation total over land surfaces for 2023 was among the lowest since 1979, but global one-day maximum totals were close to average, indicating an increase in rainfall intensity. In July, record-high areas of land across the globe (7.9%) experienced extreme drought, breaking the previous record of 6.2% in July 2022. Overall, 29.7% of land experienced moderate or worse categories of drought during the year, also a record. Mexico reported its driest (and hottest) year since the start of its record in 1950. In alignment with hot and prolonged dry conditions, Canada experienced its worst national wildfire season on record. Approximately 15 million hectares burned across the country, which was more than double the previous record from 1989. Smoke from the fires were transported far into the United States and even to western European countries. August to October 2023 was the driest three-month period in Australia in the 104-year record. Millions of hectares of bushfires burned for weeks in the Northern Territory. In South America, extreme drought developed in the latter half of the year through the Amazon basin. By the end of October, the Rio Negro at Manaus, a major tributary of the Amazon River, fell to its lowest water level since records began in 1902. The transition from La Niña to El Niño helped bring relief to the prolonged drought conditions in equatorial eastern Africa. However, El Niño along with positive Indian Ocean dipole conditions also contributed to excessive rainfall that resulted in devastating floods over southeastern Ethiopia, Somalia, and Kenya during October to December that displaced around 1.5 million people. On 5 September, the town of Zagora, Greece, broke a national record for highest daily rainfall (754 mm in 21 hours, after which the station ceased reporting) due to Storm Daniel; this one-day accumulation was close to Zagora’s normal annual total.

Rates of cannabis initiation among teenagers and young adults are increasing. Further, the use of various forms of cannabis (smoked or vaped) with nicotine (dual use) is increasingly common among young people. The health effects of dual use are lesser known, particularly in the context of high-potency cannabis products and across different routes of administration, which is ominous in terms of predicting future health outcomes. There is a long history of cannabis use being associated with decreased activity and increased snacking, both of which could portend an increased risk of metabolic and cardiovascular disease, particularly when these habits begin during formative years. However, modern forms of cannabis may not have these same effects. Here, we assess whether cannabis use alone and dual use of cannabis with nicotine impact dietary and exercise habits in young people. An anonymous, social media-based survey was designed based on the UC San Diego Inhalant Questionnaire and published diet and exercise questionnaires. A total of 457 surveys were completed. Young sole cannabis users represented 29% of responders, 16% were dual users of cannabis and nicotine, and 55% were non-users of either drug. Although the sole use of cannabis was not associated with dietary or activity differences relative to non-users, dual users of cannabis and nicotine reported higher consumption of unhealthy sugars. This novel finding of dual use being associated with increased sugar intake in young people raises concerns for an increased risk of metabolic syndrome and cardiovascular disease in this population.

BACKGROUND: Deeper insights into ERBB2-driven cancers are essential to develop new treatment approaches for ERBB2+ breast cancers (BCs). We employed the Collaborative Cross (CC) mouse model to unearth genetic factors underpinning Erbb2-driven mammary tumour development and metastasis. METHODS: 732 F1 hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains were monitored for mammary tumour phenotypes. GWAS pinpointed SNPs that influence various tumour phenotypes. Multivariate analyses and models were used to construct the polygenic score and to develop a mouse tumour susceptibility gene signature (mTSGS), where the corresponding human ortholog was identified and designated as hTSGS. The importance and clinical value of hTSGS in human BC was evaluated using public datasets, encompassing TCGA, METABRIC, GSE96058, and I-SPY2 cohorts. The predictive power of mTSGS for response to chemotherapy was validated in vivo using genetically diverse MMTV-Erbb2 mice. FINDINGS: Distinct variances in tumour onset, multiplicity, and metastatic patterns were observed in F1-hybrid female mice between FVB/N MMTV-Erbb2 and 30 CC strains. Besides lung metastasis, liver and kidney metastases emerged in specific CC strains. GWAS identified specific SNPs significantly associated with tumour onset, multiplicity, lung metastasis, and liver metastasis. Multivariate analyses flagged SNPs in 20 genes (Stx6, Ramp1, Traf3ip1, Nckap5, Pfkfb2, Trmt1l, Rprd1b, Rer1, Sepsecs, Rhobtb1, Tsen15, Abcc3, Arid5b, Tnr, Dock2, Tti1, Fam81a, Oxr1, Plxna2, and Tbc1d31) independently tied to various tumour characteristics, designated as a mTSGS. hTSGS scores (hTSGSS) based on their transcriptional level showed prognostic values, superseding clinical factors and PAM50 subtype across multiple human BC cohorts, and predicted pathological complete response independent of and superior to MammaPrint score in I-SPY2 study. The power of mTSGS score for predicting chemotherapy response was further validated in an in vivo mouse MMTV-Erbb2 model, showing that, like findings in human patients, mouse tumours with low mTSGS scores were most likely to respond to treatment. INTERPRETATION: Our investigation has unveiled many new genes predisposing individuals to ERBB2-driven cancer. Translational findings indicate that hTSGS holds promise as a biomarker for refining treatment strategies for patients with BC. FUNDING: The U.S. Department of Defense (DoD) Breast Cancer Research Program (BCRP) (BC190820), United States; MCIN/AEI/10.13039/501100011039 (PID2020-118527RB-I00, PDC2021-121735-I00), the European Union Next Generation EU/PRTR, the Regional Government of Castile and León (CSI144P20), European Union.

The contrast between the disruption of genome topology after cohesin loss and the lack of downstream gene expression changes instigates intense debates regarding the structure-function relationship between genome and gene regulation. Here, by analyzing transcriptome and chromatin accessibility at the single-cell level, we discover that, instead of dictating population-wide gene expression levels, cohesin supplies a general function to neutralize stochastic coexpression tendencies of cis-linked genes in single cells. Notably, cohesin loss induces widespread gene coactivation and chromatin co-opening tens of million bases apart in cis. Spatial genome and protein imaging reveals that cohesin prevents gene co-bursting along the chromosome and blocks spatial mixing of transcriptional hubs. Single-molecule imaging shows that cohesin confines the exploration of diverse enhancer and core promoter binding transcriptional regulators. Together, these results support that cohesin arranges nuclear topology to control gene coexpression in single cells.

The performance of superconducting qubits is degraded by a poorly characterized set of energy sources breaking the Cooper pairs responsible for superconductivity, creating a condition often called quasiparticle poisoning. Both superconducting qubits and low threshold dark matter calorimeters have observed excess bursts of quasiparticles or phonons that decrease in rate with time. Here, we show that a silicon crystal glued to its holder exhibits a rate of low-energy phonon events that is more than two orders of magnitude larger than in a functionally identical crystal suspended from its holder in a low-stress state. The excess phonon event rate in the glued crystal decreases with time since cooldown, consistent with a source of phonon bursts which contributes to quasiparticle poisoning in quantum circuits and the low-energy events observed in cryogenic calorimeters. We argue that relaxation of thermally induced stress between the glue and crystal is the source of these events.

Over 80% of the patients with pancreatic ductal adenocarcinoma (PDAC) have cachexia/wasting syndrome. Cachexia is associated with reduced survival, decreased quality of life, and higher metastasis rates. Here, we demonstrate that fat loss is the earliest feature of PDAC-exosome-induced cachexia. MicroRNA sequencing of exosomal components from normal and cancer-derived exosomes revealed enrichment of miR-16-5p, miR-21-5p, miR-29a-3p, and miR-125b-5p in serum exosomes of mice harboring PDAC and patients with PDAC. Further, miR-16-5p and miR-29a-3p inhibited adipogenesis through decreasing Erlin2 and Cmpk1 expression which downregulates C/EBPβ and PPARγ. Synergistically, miR-29a-3p promotes lipolysis through increasing ATGL expression by suppressing MCT1 expression. Furthermore, PDAC-exosomes deprived of miR-16-5p and miR-29a-3p fail to induce fat loss. Hence, miR-16-5p and miR-29a-3p exosomal miRs are essential for PDAC-induced fat loss. Thus, we unravel that PDAC induces adipose atrophy via exosomal miRs. This knowledge may provide new diagnostic and therapeutic strategies for PDAC-induced cachexia.

Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments. Through prospective genomic profiling of 459 consecutive primary treatment-naïve IDH-wildtype glioblastomas in adults, we identified a unique subgroup (2%, 9/459) defined by somatic hypermutation and DNA replication repair deficiency due to biallelic inactivation of a canonical mismatch repair gene. The deleterious mutations in mismatch repair genes were often present in the germline in the heterozygous state with somatic inactivation of the remaining allele, consistent with glioblastomas arising due to underlying Lynch syndrome. A subset of tumors had accompanying proofreading domain mutations in the DNA polymerase POLE and resultant "ultrahypermutation". The median age at diagnosis was 50 years (range 27-78), compared with 63 years for the other 450 patients with conventional glioblastoma (p

Mycobacterium tuberculosis (Mtb) infects lung myeloid cells, but the specific Mtb-permissive cells and host mechanisms supporting Mtb persistence during chronic infection are incompletely characterized. We report that after the development of T cell responses, CD11clo monocyte-derived cells harbor more live Mtb than alveolar macrophages (AM), neutrophils, and CD11chi monocyte-derived cells. Transcriptomic and functional studies revealed that the lysosome pathway is underexpressed in this highly permissive subset, characterized by less lysosome content, acidification, and proteolytic activity than AM, along with less nuclear TFEB, a regulator of lysosome biogenesis. Mtb infection does not drive lysosome deficiency in CD11clo monocyte-derived cells but promotes recruitment of monocytes that develop into permissive lung cells, mediated by the Mtb ESX-1 secretion system. The c-Abl tyrosine kinase inhibitor nilotinib activates TFEB and enhances lysosome functions of macrophages in vitro and in vivo, improving control of Mtb infection. Our results suggest that Mtb exploits lysosome-poor lung cells for persistence and targeting lysosome biogenesis is a potential host-directed therapy for tuberculosis.

Pasteurella spp. can cause fatal zoonotic infections in humans (2,2). Pasteurella spp., which are nonmotile, facultatively anaerobic bacteria, form the oral and gastrointestinal flora of many animals including companion and [...]