Hepatocellular carcinoma (HCC) has high relapse and low 5-year survival rates. Single-cell profiling in relapsed HCC may aid in the design of effective anticancer therapies, including ...immunotherapies. We profiled the transcriptomes of ∼17,000 cells from 18 primary or early-relapse HCC cases. Early-relapse tumors have reduced levels of regulatory T cells, increased dendritic cells (DCs), and increased infiltrated CD8+ T cells, compared with primary tumors, in two independent cohorts. Remarkably, CD8+ T cells in recurrent tumors overexpressed KLRB1 (CD161) and displayed an innate-like low cytotoxic state, with low clonal expansion, unlike the classical exhausted state observed in primary HCC. The enrichment of these cells was associated with a worse prognosis. Differential gene expression and interaction analyses revealed potential immune evasion mechanisms in recurrent tumor cells that dampen DC antigen presentation and recruit innate-like CD8+ T cells. Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse.
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•ScRNA-seq reveals a distinct immune ecosystem in early-relapse HCC•Decreased Tregs, increased DCs, and CD8+ T cells were observed in early-relapse HCC•CD8+ T cells have an innate-like, low cytotoxic, and low clonal expansion phenotype•Recurrent malignant cells mediate the compromised antitumor immune response
Single-cell analysis of primary and relapsed hepatocellular carcinoma tumors from patients reveal innate-like CD8+ T cells with low cytotoxicity and clonal expansion in the latter that may explain the compromised antitumor immunity and poor prognosis associated with liver cancer.
Mitochondria lie at the heart of innate immunity, and aberrant mitochondrial activity contributes to immune activation and chronic inflammatory diseases, including liver cancers. Mitophagy is a ...selective process for removing dysfunctional mitochondria. The link between mitophagy and inflammation in tumorigenesis remains largely unexplored. We observed that FUN14 domain‐containing 1 (FUNDC1), a previously characterized mitophagy receptor, accumulates in most human hepatocellular carcinomas (HCCs), and we thus explored the role of FUNDC1‐mediated mitophagy in HCC initiation and progression in a mouse model in which HCC is induced by the chemical carcinogen, diethylnitrosamine (DEN). We showed that specific knockout of FUNDC1 in hepatocytes promotes the initiation and progression of DEN‐induced HCC, whereas FUNDC1 transgenic hepatocytes protect against development of HCC. Hepatocyte‐specific FUNDC1 ablation results in the accumulation of dysfunctional mitochondria and triggers a cascade of events involving inflammasome activation and hyperactivation of Janus kinase/signal transducer and activator of transcription signaling. Specifically, cytosolic mitochondrial DNA (mtDNA) release and caspase‐1 activation are increased in FUNDC1‐depleted hepatocytes. This subsequently results in the elevated release of proinflammatory cytokines, such as interleukin‐1β (IL1β) and hyperproliferation of hepatocytes. Conclusion: Our results suggest that FUNDC1 suppresses HCC initiation by reducing inflammasome activation and inflammatory responses in hepatocytes, whereas up‐regulation of FUNDC1 expression at the late stage of tumor development may benefit tumor growth. Our study thus describes a mechanistic link between mitophagic modulation of inflammatory response and tumorigenesis, and further implies that FUNDC1‐mediated mitophagy and its related inflammatory response may represent a therapeutic target for liver cancer.
Teacher noticing has become a prominent construct in research on teacher education and professional development; however, the current state of research is quite diverse, with different theoretical ...foundations and a variety of research designs. The study described in this paper provides a systematic review of the literature on teacher noticing published over the past two decades. Based on a full-text analysis of 182 articles published in renowned databases and peer-reviewed Englishscholarly journals, the study reveals the dominance of a cognitive-psychological perspective of teacher noticing, especially in combination with qualitative studies. Although teacher noticing has been described as a holistic concept in many earlier articles, more recent studies from the last decade tend to differentiate teacher noticing into different facets. Overall, qualitative studies with small sample sizes are prevalent, which allows for fine-grained analysis but limits the generalizability of findings. This study highlights the limitations of the current discussion, such as the prevalence of teacher noticing mainly in the field of mathematics education and the low representation of work from parts of the world other than North America and Europe. In addition, the studies under consideration in this literature review are examined in depth in terms of their findings on improving teachers’ noticing through interventions and on comparisons between experts and novices, which allows for a discussion of the implications of learning to notice for teacher education and professional development.
•Full text analysis of 182 articles on the topic of teacher noticing.•Dominance of qualitative studies on noticing as theoretical foundation.•Recent studies differentiate sub-facets of noticing.•Dominance of studies with small sample sizes, which limit the generalizability of findings.•Predominance of U.S. and European studies without consideration of cultural differences.•Improvement of teacher noticing through interventions.•Expert-novice differences in teacher noticing.
In this paper we examine the relationship between teachers' knowledge, beliefs and instructional practices based on a study with 495 Chinese pre-service mathematics teachers. The results indicate ...that Chinese pre-service mathematics teachers tend to hold mixed beliefs about the nature of mathematics, and a constructivist view about mathematics teaching and learning, and that they are inclined to report that their teaching is inquiry-oriented. Mathematical content knowledge (MCK) and mathematics pedagogical content knowledge (MPCK) were found not to correlate with the teachers' self-reported instructional practice, in contrast to pre-service mathematics teachers' beliefs, which showed a stronger association with their self-reported inquiry-oriented instructional practice. Moreover, pre-service teachers' dynamic beliefs about the nature of mathematics, and constructivist beliefs about mathematics teaching and learning, acted as mediators between pre-service mathematics teachers' MCK, MPCK and instructional practice respectively. Author abstract
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•Non-flammable electrolyte with TMP and F-EPE improves the safety of SIB.•TMP/F-EPE electrolyte stabilizes the interface of NFM cathode during all processes.•The cycling life of ...NFM/HC pouch cell increases by using TMP/F-EPE electrolyte.
Despite their beneficial effect on battery safety, non-flammable electrolytes often have an adverse side effect on the electrochemical performance of lithium and sodium ion batteries due to their poor compatibility with the electrodes. In this paper, we report a new non-flammable electrolyte consisting of trimethyl phosphate (TMP) and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (F-EPE) as non-flammable solvents and fluoroethylene carbonate (FEC) as additive with different concentration of Na salts, and a EC-DEC-FEC electrolyte was also prepared as baseline electrolyte. The flammability and non-flammability of the prepared electrolytes was tested. It is shown that the prepared electrolyte not only increases the capacity (129.9 vs. 122.5 mAh g−1 of baseline electrolyte) of NaNi1/3Fe1/3Mn1/3O2 (NFM) cathode but also stabilizes the cyclability (70.8% retention after 500 cycles) of NFM/HC (HC: hard carbon) pouch cells. The dissolution of pristine NaNi1/3Fe1/3Mn1/3O2 cathode material in different solvents and electrolytes, and the XPS patterns of the cycled NFM cathode in the prepared electrolytes were also studied to understand the capacity fading mechanism. These results indicate that this new non-flammable electrolyte holds great potential for application in rechargeable sodium-ion batteries.
Teacher noticing has become increasingly acknowledged as a fundamental aspect of teacher professional competence. Teacher education scholars have examined how the development of noticing might be ...supported both in initial teacher
education and in professional development. In mathematics teacher education, several studies have explored the use of video as a supporting tool for teacher noticing. It remains unclear how this body of work builds on the various
theoretical perspectives of noticing prevalent in the literature, thus broadening our understanding of noticing. Furthermore, the field has not examined systematically the extent to which research has leveraged the affordances of digital
video technologies, and whether scholars have employed different research methods to answer questions that are critical to teacher educators. This survey paper reviews studies published in the last two decades on programs centered on
mathematics teacher noticing that used video as a supporting tool for teacher learning. Thirty-five peer-reviewed papers written in English were identified and coded along three dimensions: (1) theoretical perspectives; (2) use of video
technologies; and (3) research questions and methods. This review summarizes important findings and highlights several directions for future research. Most studies involved pre-service teachers, and only a few centered on in-service
teachers. Developers of the large majority of programs took a cognitive psychological perspective and focused on the attending/perceiving and interpreting/reasoning facets of noticing. Few studies used video-based software and few
studies used grouping, and even fewer used randomized grouping. Evidence of program effects on responding and decision making, and on instructional practice, is limited and should be extended in the future. Author abstract
DNA damage repair (DDR) may affect tumorigenesis and therapeutic response in hepatocellular carcinoma (HCC). Long noncoding RNAs (LncRNAs) can regulate DDR and play a vital role in maintaining ...genomic stability in cancers. Here, we identified a DDR-related prognostic signature in HCC and explored its potential clinical value.
Data of HCC samples were obtained from the Cancer Genome Atlas (TCGA), and a list of DDR-related genes was extracted from the Molecular Signatures database (MSigDB). A DDR-related lncRNAs signature associated to overall survival (OS) was constructed using the least absolute shrinkage and selection operator-cox regression, and was further validated by the Kaplan-Meier curve and receiver operating characteristic curve. A nomogram integrating other clinical risk factors was established. Moreover, the relationships between the signature with somatic mutation, immune landscape and drug sensitivity were explored.
The prognostic model of 5 DDR-related lncRNAs was constructed and classified patients into two risk groups at median cut-off. The low-risk group had a better OS, and the signature was an independent prognostic indicator in HCC. A nomogram of the signature combined with TNM stage was constructed. TP53 gene was more frequently mutated in the high-risk group. Marked differences in immune cells were observed, such as CD4 + T cells, NK cells and macrophages, between the two groups. Moreover, an increase in the expression of immune checkpoint molecules was found in the high-risk group. The low-risk group presented with a significantly higher response to sorafenib or cisplatin. Finally, potential value of this signature was validated in real-world HCC patients.
Our findings provided a promising insight into DDR-related lncRNAs in HCC and a personalized prediction tool for prognosis and therapeutic response.
This paper investigates the problem of robust fault-tolerant containment control for a class of multiagent systems in which multiple active leaders and linear heterogeneous follower subsystems with ...mismatched affine uncertainties and actuator faults are distributed on a communication network. It first introduces a group of distributed adaptive intermediate estimators, based on which each following agent can estimate the desired containment trajectory objective. Then, by utilizing adaptive parameter estimation approach and S-procedure technique, a decentralized fault-tolerant tracking control algorithm is designed to guarantee all practical states of followers asymptotically track the desired containment trajectory even in the case of actuator faults and heterogeneous affine uncertainties. Interestingly, the main advantage of proposed fault-tolerant containment strategy is that, not only the faulty information from follower subsystems cannot affect neighbor agents, but also both actuator faults and heterogeneous affine uncertainties can be compensated in local subsystem. Finally, a numerical example is given to illustrate the effectiveness of the designed containment control protocol.
The last decade has witnessed increasing interest in the study of teacher noticing in mathematics education research; however, little is known about the growth of teacher noticing and how it is ...influenced by teaching practice.
Departing from the expert-novice-paradigm, in this paper we address this research gap by a cross-sectional study that investigates how Chinese mathematics teachers' noticing is affected by their developmental stage, measured by the
length of their teaching experience. The study included 152 pre-service teachers at the end of their initial teacher education, 162 early career teachers with one to five years' teaching experience, and 123 experienced mathematics
teachers with more than 15 years' teaching experience, who participated in a video-based assessment of their noticing competency conceptualized by the sub-facets of perception, interpretation, and decision-making. Our findings indicate a
nearly linear growth in teacher noticing among Chinese mathematics teachers, with significant differences identified between pre-service and experienced teachers and only small differences between pre-service and early career teachers.
Analyses using the method of Differential Item Functioning (DIF) further suggest that pre-service and early career teachers demonstrated strengths in aspects more related to reform-oriented or Westernized approaches to mathematics
teaching, such as working with open-ended tasks, identifying characteristics of cooperative learning, and mathematical modeling tasks. By contrast, experienced teachers demonstrated strengths in perceiving students' thinking, evaluating
teachers' behavior, and analyzing students' mathematical thinking. Our findings further highlight that the three sub-facets of teacher noticing develop differently within the three participating groups of teachers. These findings suggest
that teaching experience acts as one influential factor in the development of teacher noticing in the Chinese context. Author abstract
Polymerization degree plays a vital role in material properties. Previous methodologies of molecular weight control generally cannot suppress or alleviate batch-to-batch variations in device ...performance, especially in polymer solar cells. Herein, we develop an in-situ photoluminescence system in tandem with a set of analysis and processing procedures to track and estimate the polymerization degree of organic photovoltaic materials. To support the development of this protocol, we introduce polymer acceptor PYT constructed by near-infrared Y-series small molecule acceptors via Stille polymerization, and shed light on the correlations between molecular weight, spectral parameters, and device efficiencies that enable the design of the optical setup and confirm its feasibility. The universality is verified in PYT derivatives with stereoregularity and fluoro-substitution as well as benzo1,2-b:4,5-b'dithiophene-based polymers. Overall, our result provides a tool to tailor suitable conjugated oligomers applied to polymer solar cells and other organic electronics for industrial scalability and desired cost reduction.
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