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The structure of Au10Ag17 nanocluster was determined by SC-XRD. Our work revealed that charge or energy transfer from metal kernel (M25) to shell (two surface motifs) can quench the emission.

Au4(PPh3)4I2, having a Au4 tetrahedral structure is the smallest multinuclear Au superatom with two free e− reported so far. Au4 exhibits higher selectivity for CO (>60%); while the HER dominates when the potential becomes more negative.

SummaryDuring embryogenesis, distinct cardiac cell types form, which shape the structural and functional properties of the heart. How their activity is coordinated is largely unknown. Here we show that Rnf20 is a multifaceted regulator of cardiac morphogenesis and function. On the one hand, Rnf20 controls extracellular matrix dynamics and endothelial-cardiomyocyte crosstalk essential for second heart field development. On the other hand, it safeguards endothelial cell identity and function by maintaining physiological angiocrine signaling and preventing endothelial-to-mesenchymal transition. Endothelial-specific deletion of Rnf20 led to ventricular septal defects, myocardial thinning and cardiac dysfunction as a result of aberrant signaling and excessive extracellular matrix deposition that induced precocious cardiomyocyte binucleation and irregular contractility. Furthermore, we uncovered upstream factors (e.g. Sox9) and multiple angiocrine and extracellular matrix molecules that alter cardiomyocyte functionality upon endothelial Rnf20 loss. In summary, our work identifies a novel, endothelial-specific role of Rnf20 in regulating cardiac morphogenesis and function.

In recent years, the continuous growth of economic strength has promoted people’s pursuit of culture, and the demand for cultural and creative products has increased year by year. Cultural and creative products are different from ordinary products. Ordinary products pursue functions, beauty and economic benefits, while cultural and creative products endow the concept of product culture. Cultural and creative products can represent culture, ideals, beliefs, etc. At present, China has entered a new era. China has made major achievements in various fields. These achievements are areas that are difficult for ordinary people to get involved. However, these achievements are really closely related to people’s lives. How to let people understand these deep-seated areas and how to link ordinary people with high-tech achievements are the issues that this article focuses on. This article first sorts out the propaganda paths of various scientific and technological achievements nowadays, then analyzes their existing problems, proposes a design strategy for cultural and creative products based on scientific and technological achievements, and finally completes the design of cultural and creative products: These scientific and technological achievements can be designed into simple and easy-to-understand patterns, and then applied to the design of cultural and creative products such as T-shirts, which will provide impetus to telling Chinese stories, enhancing cultural strength and national self-confidence.

Summary During development, cells respond rapidly to intra- and intercellular signals, which induce signaling cascades regulating the activity of transcription factors at the transcriptional and/or post-translational level. The transcription factor ISL1 plays a key role in second heart field development and cardiac differentiation, and its mRNA levels are tightly regulated during cardiogenesis. Here, we show that a BMP-p38 MAPK signaling axis controls ISL1 protein function at the post-translational level. BMP-mediated activation of p38 MAPK leads to ISL1 phosphorylation at S269 by p38, which prevents ISL1 degradation and ensures its transcriptional activity during cardiogenesis. Interfering with p38 MAPK signaling leads to the degradation of ISL1 by the proteasome, resulting in defects in cardiomyocyte differentiation and impaired zebrafish and mouse heart morphogenesis and function. Given the critical role of the tight control of ISL1 activity during cardiac lineage diversification, modulation of BMP4-p38 MAPK signaling could direct differentiation into specific cardiac cell subpopulations., Highlights • ISL1 is phosphorylated by p38 MAPK at serine 269 • A BMP4-p38 MAPK signaling axis controls ISL1 protein stability • Phosphorylation of ISL1 by p38 regulates its activity during cardiogenesis • p38 Inhibition in vivo results in ISL1 degradation and second heart field defects, In this article, Jing and colleagues describe a key role of BMP4-p38 MAPK signaling in controlling ISL1 protein stability and activity during cardiogenesis through p38-mediated ISL1 phosphorylation at S269. Interfering with p38 MAPK signaling leads to the degradation of ISL1 by the proteasome, resulting in defects in ISL1+ cardiac progenitor cell differentiation and impaired heart morphogenesis and function.

Grounded on personification storytelling, this intervention study introduced a science program including extensive astronomy concepts to 24 children (4–5 years). The storytelling attributes persona...

The antioxidant transcription factor NFE2L1 (also called Nrf1) acts as a core regulator of redox signaling and metabolism homeostasis, and thus, its dysfunction results in multiple systemic metabolic diseases. However, the molecular mechanism(s) by which NFE2L1 regulates glycose and lipid metabolism remains elusive. Here, we found that loss of NFE2L1 in human HepG2 cells led to a lethal phenotype upon glucose deprivation and NFE2L1 deficiency could affect the uptake of glucose. Further experiments revealed that glycosylation of NFE2L1 enabled it to sense the energy state. These results indicated that NFE2L1 can serve as a dual sensor and regulator of glucose homeostasis. The transcriptome, metabolome, and seahorse data further revealed that disruption of NFE2L1 could reprogram glucose metabolism to aggravate the Warburg effect in NFE2L1-silenced hepatoma cells, concomitant with mitochondrial damage. Co-expression and Co-immunoprecipitation experiments demonstrated that NFE2L1 could directly interact and inhibit AMPK. Collectively, NFE2L1 functioned as an energy sensor and negatively regulated AMPK signaling through directly interacting with AMPK. The novel NFE2L1/AMPK signaling pathway delineate the mechanism underlying of NFE2L1-related metabolic diseases and highlight the crosstalk between redox homeostasis and metabolism homeostasis.

NFE2L1 (also called Nrf1) acts a core regulator of redox signaling and metabolism homeostasis, and thus its dysfunction results in multiple systemic metabolic diseases. However, the molecular mechanism(s) by which NFE2L1 regulates glycose and lipid metabolism is still elusive. Here, we found that the loss of NFE2L1 in human HepG2 cells led to a lethal phenotype upon glucose deprivation. The uptake of glucose was also affected by NFE2L1 deficiency. Further experiments unveiled that although the glycosylation of NFE2L1 was monitored through the glycolysis pathway, it enabled to sense the energy state and directly interacted with AMPK. These indicate that NFE2L1 can serve as a dual sensor and regulator of glucose homeostasis. In-depth sights into transcriptome, metabolome and seahorse data further unraveled that glucose metabolism was reprogrammed by disruption of NFE2L1, so as to aggravate the Warburg effect in NFE2L1-silenced hepatoma cells, along with the mitochondrial damage observed under the electron microscope. Collectively, these demonstrate that disfunction of NFE2L1 triggers the uncontrollable signaling by AMPK towards glucose metabolism reprogramming in the liver cancer development.

Nrf1 and Nrf2, as two principal CNC-bZIP transcription factors, regulate similar but different targets involved in a variety of biological functions for maintaining cell homeostasis and organ integrity. Of note, the unique topobiological behavior of Nrf1 makes its functions more complicated than Nrf2, because it is allowed for alternatively transcribing and selectively splicing to yield multiple isoforms (e.g., TCF11, Nrf1α). In order to gain a better understanding of their similarities and differences in distinct regulatory profiles, all four distinct cell models for stably expressing TCF11, TCF11ΔN, Nrf1α or Nrf2 have been herein established by an Flp-In™ T-REx™-293 system and then identified by transcriptomic sequencing. Further analysis revealed that Nrf1α and TCF11 have similar yet different regulatory profiles, although both contribute basically to positive regulation of their co-targets, which are disparate from those regulated by Nrf2. Such disparity in those gene regulation by Nrf1 and Nrf2 was further corroborated by scrutinizing comprehensive functional annotation of their specific and/or common target genes. Conversely, the mutant TCF11ΔN, resulting from a deletion of the N-terminal amino acids 2-156 from TCF11, resembles Nrf2 with the largely consistent structure and function. Interestingly, our further experimental evidence demonstrates that TCF11 acts as a potent tumor-repressor relative to Nrf1α, albeit both isoforms possess a congruous capability to prevent malignant growth of tumor and upregulate those genes critical for improving the survival of patients with hepatocellular carcinoma.

Focusing on 84 Chinese–English dual language learners (DLLs) in U.S. preschool programs serving children from low-income backgrounds, this study investigated which aspects of the home language and literacy environment and which parenting styles may be related to these DLLs’ oral receptive and expressive language abilities in Chinese and English. Key findings were: (1) the frequency of parental book reading was associated with better expressive English in DLLs; (2) parental book reading (whether in English or in a combination of English and Chinese) was linked to better expressive English in DLLs; (3) DLLs whose parents read to them in Chinese (Chinese-dominant) and those whose parents read to them in both Chinese and English (bilingual language-dominant) achieved better receptive Chinese than those whose parents did not read to them at all; (4) DLLs whose parents used both English and Chinese (bilingual language-dominant) when conversing with them achieved better expressive English than those whose parents used exclusively Chinese (Chinese-dominant); and (5) authoritative parenting was associated with better receptive Chinese in DLLs. Interpretations of the findings were discussed in the context of bilingualism.

Our previous work revealed that Nrf1α exerts a tumor-repressing effect because its genomic loss (to yield Nrf1α−/−) results in oncogenic activation of Nrf2 and target genes. Interestingly, β-catenin is concurrently activated by loss of Nrf1α in a way similar to β-catenin-driven liver tumor. However, a presumable relationship between Nrf1 and β-catenin is not yet established. Here, we demonstrate that Nrf1 enhanced ubiquitination of β-catenin for targeting proteasomal degradation. Conversely, knockdown of Nrf1 by its short hairpin RNA (shNrf1) caused accumulation of β-catenin so as to translocate the nucleus, allowing activation of a subset of Wnt/β-catenin signaling responsive genes, which leads to the epithelial-mesenchymal transition (EMT) and related cellular processes. Such silencing of Nrf1 resulted in malgrowth of human hepatocellular carcinoma, along with malignant invasion and metastasis to the lung and liver in xenograft model mice. Further transcriptomic sequencing unraveled significant differences in the expression of both Wnt/β-catenin-dependent and Wnt/β-catenin-independent responsive genes implicated in the cell process, shape, and behavior of the shNrf1-expressing tumor. Notably, we identified that β-catenin is not a target gene of Nrf1, but this CNC-bZIP factor contributes to differential or opposing expression of other critical genes, such as CDH1, Wnt5A, Wnt11A, FZD10, LEF1, TCF4, SMAD4, MMP9, PTEN, PI3K, JUN, and p53, each of which depends on the positioning of distinct cis-regulatory sequences (e.g., ARE and/or AP-1 binding sites) in the gene promoter contexts. In addition, altered expression profiles of some Wnt/β-catenin signaling proteins were context dependent, as accompanied by decreased abundances of Nrf1 in the clinic human hepatomas with distinct differentiation. Together, these results corroborate the rationale that Nrf1 acts as a bona fide dominant tumor repressor, by its intrinsic inhibition of Wnt/β-catenin signaling and relevant independent networks in cancer development and malignant progression.

This study aims to examine the mediating and moderating roles of self-concept and resilience in the relationship between teacher-child relationships and social withdrawal with a sample of 380 Chinese left-behind children in a rural region in Guangdong Province, China. They were measured by using Children's Social Behavioral Scale-Teacher Form, Devereux Early Childhood Assessment for Preschool (DECA-P2), Children’s Self-Concept Scale, and Student-Teacher Relationship Scale (STRS). The results indicated that: (1) Teacher-child relationships, resilience and self-concept are all negatively correlated to social withdrawal; (2) resilience plays a mediating role between the teacher-child relationships and social withdrawal; (3) self-concept moderates the effect of teacher-child relationships on resilience. This study would enhance the early childhood teachers’ understanding of the key factors that affect children’s social behaviours, and thus implement appropriate strategies for supporting left-behind children. It confirms the significant role of teachers in left-behind children’s development, which has implications for policymakers to prioritize teachers’ quality and training in rural preschools.

Metformin, as the first-line drug for the treatment of type 2 diabetes mellitus, has been shown to possess a capability to activate or inhibit the production of reactive oxygen species (ROS) in different ways. However, the detailed mechanisms of the opposite effect are poorly understood. Here we provide evidence that metformin induces accumulation of ROS by inhibiting the expression of a core antioxidant transcription factor nuclear factor erythroid 2 like 1 (NFE2L1/Nrf1) in human hepatocellular carcinoma HepG2 cells. In the present study, we originally found that the increased ROS induced by metformin was blunted in NFE2L1 knockdown cell line. Furtherly by examining the effects of metformin on endogenous and exogenous NFE2L1, we also found metformin could not only inhibit the transcription of NFE2L1 gene, but also promote the degradation of NFE2L1 protein at the post-transcriptional level, whereas this effect can be reversed by high glucose. The inhibitory effect of metformin on NFE2L1 was investigated to occur through the N-terminal domain (NTD) of NFE2L1 protein, and its downregulation by metformin was in an AMP-activated protein kinase (AMPK)-independent manner. But the activation of AMPK signaling pathway by metformin in NFE2L1 knockdown HepG2 cells is reversed, indicating that NFE2L1 may be an important regulator of AMPK signal. Altogether, this work provides a better understanding of the relationship between metformin and oxidative stress, and hence contributes to translational study of metformin through its hypoglycemic and tumor suppressive effects.

Our previous work revealed that Nrf1α exerts a tumor-repressing effect because its genomic loss (to yieldNrf1α−/−) results in oncogenic activation of Nrf2 and target genes. Interestingly, β-catenin is concurrently activated by loss of Nrf1α in a way similar to β-catenin-driven liver tumor. However, a presumable relationship between Nrf1 and β-catenin is not as yet established. Here, we demonstrate that Nrf1 enhanced ubiquitination of β-catenin for targeting to proteasomal degradation. Conversely, knockdown of Nrf1 by its short-hairpin RNA (shNrf1) caused accumulation of β-catenin so as to translocate the nucleus, allowing activation of a subset of Wnt–β-catenin signaling responsive genes, which leads to the epithelial-mesenchymal transition (EMT) and related cellular processes. Such silencing of Nrf1 resulted in malgrowth of human hepatocellular carcinoma, along with malignant invasion and metastasis to the lung and liver in xenograft model mice. Further transcriptomic sequencing unraveled significant differences in the expression of both Wnt/β-catenin-dependent and -independent responsive genes implicated in the cell process, shape and behavior of the shNrf1-expressing tumor. Notably, we identified that β-catenin is not a target gene of Nrf1, but this CNC-bZIP factor contributes to differential or opposing expression of other critical genes, such asCDH1, Wnt5A, Wnt11A, FZD10, LEF, TCF4, SMAD4, MMP9, PTEN, PI3K, JUN and p53, each of which depends on the positioning of distinctcis-regulatory sequences (e.g., ARE and/or AP-1 binding sites) in the gene promoter contexts. In addition, altered expression profiles of some Wnt–β-catenin signaling proteins were context-dependent, as accompanied by decreased abundances of Nrf1 in the clinic human hepatomas with distinct differentiation. Together, these results corroborate the rationale that Nrf1 acts as abona fidedominant tumor-repressor, by its intrinsic inhibition of Wnt–β-catenin signaling and relevant independent networks in cancer development and malignant progression.

International audience; Generation of widely differing and specialized cell types from a single totipotent zygote involves large-scale transcriptional changes and chromatin reorganization. Pioneer transcription factors play key roles in programming the epigenome and facilitating recruitment of additional regulatory factors during successive cell lineage specification and differentiation steps. Here we show that Isl1 acts as a pioneer factor driving cardiomyocyte lineage commitment by shaping the chromatin landscape of cardiac progenitor cells. Using an Isl1 hypomorphic mouse line which shows congenital heart defects, genome-wide profiling of Isl1 binding together with RNA- and ATAC-sequencing of cardiac progenitor cells and their derivatives, we uncover a regulatory network downstream of Isl1 that orchestrates cardiogenesis. Mechanistically, we show that Isl1 binds to compacted chromatin and works in concert with the Brg1-Baf60c-based SWI/SNF complex to promote permissive cardiac lineage-specific alterations in the chromatin landscape not only of genes with critical functions in cardiac progenitor cells, but also of cardiomyocyte structural genes that are highly expressed when Isl1 itself is no longer present. Thus, the Isl1/Brg1-Baf60c complex plays a crucial role in orchestrating proper cardiogenesis and in establishing epigenetic memory of cardiomyocyte fate commitment.

Liver-specific knockout of Nrf1 in the mouse leads to spontaneous development of non- alcoholic steatohepatitis with dyslipidemia, and then its deterioration results in hepatoma, but the underlying mechanism remains elusive to date. A similar pathological model is reconstructed here by using human Nrf1&alpha, specific knockout cell lines. Our evidence has demonstrated that a marked increase of the inflammation marker COX2 definitely occurs in Nrf1&alpha, &minus, /&minus, cells. Loss of Nrf1&alpha, leads to hyperactivation of Nrf2, which results from substantial decreases in Keap1, PTEN and most of 26S proteasomal subunits in Nrf1&alpha, cells. Further investigation of xenograft model mice showed that malignant growth of Nrf1&alpha, derived tumors is almost abolished by silencing of Nrf2, while Nrf1&alpha, +/+-tumor is markedly repressed by an inactive mutant (i.e., Nrf2&minus, &Delta, TA), but largely unaffected by a priori constitutive activator (i.e., caNrf2&Delta, N). Mechanistic studies, combined with transcriptomic sequencing, unraveled a panoramic view of opposing and unifying inter-regulatory cross-talks between Nrf1&alpha, and Nrf2 at different layers of the endogenous regulatory networks from multiple signaling towards differential expression profiling of target genes. Collectively, Nrf1&alpha, manifests a dominant tumor-suppressive effect by confining Nrf2 oncogenicity. Though as a tumor promoter, Nrf2 can also, in turn, directly activate the transcriptional expression of Nrf1 to form a negative feedback loop. In view of such mutual inter-regulation by between Nrf1&alpha, and Nrf2, it should thus be taken severe cautions to interpret the experimental results from loss of Nrf1&alpha, Nrf2 or both.

Previous research mainly with monolingual children shows a positive relationship between English skills and emotion regulation. No study to date has examined if or how learning of grammatical morphemes might be associated with emotion regulation among bilingual preschoolers. This study examined how Mandarin-English bilingual preschoolers performed on three grammatical morphemes of plurals, past tense, present tense and whether the performance on the three morphemes was associated with emotion regulation. An elicitation task was used to assess proficiency in the three morphemes, and the Emotion Regulation Checklist (ERC) and the Disappointing Gift task were used to assess emotion regulation. The results indicate that Mandarin-English bilingual preschoolers had difficulties with all the three morphemes but they had a higher proficiency level on plurals than on past and present tense. Their proficiency in past and present tense was positively correlated with emotion regulation as measured by the ERC.

According to the United Nations (2014), 3.2 percent of the world population – 232 million people – were international migrants in 2013. English-speaking countries US, UK, Canada and Australia are within the top ten migrant receiving countries. Asians and Latinos are the two largest migrant groups to these countries (Bhui, McKenzie, & Rasul, 2007; Wong, 2000). The primary focus of this review is on children from Asia-Pacific contexts, but it also considers the broader research literature investigating children from Latino background for the purpose of informing future research. Despite large-scale Asian and Latino migration into English-speaking countries, research on these populations has just begun (Cheah & Leung, 2011). To date, most research with immigrant children has focused on their academic performance, but research on immigrant children’s development of social competence is limited (Halle et al., 2014; Marks, Patton, & Coll, 2010; Sam, 2006). Having a good understanding of immigrant children’s development of social competence is not only theoretically interesting but valuable for educational practices since it provides educators with valuable information which will impact on learning. However, advancement in theory and practice is constrained because prior studies either under-sampled immigrant children or prevented them from full participation due to lack of

This study investigated whether host and heritage cultural orientations were associated with Chinese preschoolers’ social competence and whether such associations varied across gender in Western contexts. Ninety-six Chinese-Australian children aged 36–69 months from 15 childcare centres in Sydney participated in the study. The General Ethnicity Questionnaires were modified to obtain a parent report of children's orientation to the host and heritage cultures. Social competence was assessed using teacher reports on the Behaviour Assessment System for Children-2 (BASC-2) with four composite scales: Externalising, Internalising, Behavioural Symptoms and Adaptive Skills. Host culture orientation was negatively associated with Internalising, Behavioural Symptoms and positively with Adaptive Skills in the overall sample. When analysed by gender, host cultural orientation was found to be positively associated with Adaptive Skills for boys and girls and negatively associated with Externalising and Behaviou...

SUMMARYLiver-specific knockout of Nrf1 in mice leads to non-alcoholic steatohepatitis with dyslipidemia, and its deterioration results in spontaneous hepatoma, but the underlying mechanism remains elusive. A similar pathological model is herein reconstructed by using human Nrf1α-specific knockout cell lines. We demonstrated that a marked increase of the inflammation marker COX2 in Nrf1α−/− cells. Loss of Nrf1α leads to hyperactivation of Nrf2, which results from substantial decreases in both Keap1 and PTEN in Nrf1α−/− cells. Further investigation of xenograft mice showed that malignant growth of Nrf1α−/−-derived tumor is almost abolished by silencing Nrf2, while Nrf1α+/+-tumor is markedly repressed by inactive Nrf2−/−ΔTA, but unaffected by a priori constitutive activator of caNrf2ΔN. Mechanistic studies unraveled there exist opposing and unifying inter-regulatory cross-talks between Nrf1 and Nrf2. Collectively, Nrf1α manifests a dominant tumor-suppressive effect by confining Nrf2 oncogenicity, while Nrf2 can directly activate the transcriptional expression of Nrf1 to form a negative feedback loop.HIGHLIGHTSOpposing and unifying inter-regulatory cross-talks between Nrf1α and Nrf2Malignant growth of Nrf1α−/−-derived tumor is prevented by silencing Nrf2Hyper-activation of Nrf2 by Nrf1α−/− results from decreased Keap1 and PTENNrf1α+/+-tumor is repressed by Nrf2−/−ΔTA, but unaltered by its active caNrf2ΔN

Research Findings: The main aim of this study was to examine whether language skills and emotion regulation are associated with social competence and whether the relationship between English skills and social competence is moderated by emotion regulation in Mandarin–English bilingual preschoolers. The language skills of 96 children ages 36–69 months from Australian child care centers were assessed using standardized English and Mandarin tests. Social competence was assessed using teacher reports on the Behavior Assessment System for Children–2 (BASC-2) with 4 composite scales: Externalizing, Internalizing, Behavioral Symptoms, and Adaptive Skills. Positive emotion regulation and emotion dysregulation were assessed using the disappointing gift task and teacher report on the Emotion Regulation Checklist. The results show that positive emotion regulation, emotion dysregulation, English skills, and Mandarin skills were associated with different composites of the BASC-2; the relationships between Engli...

This study aims to examine social competence of Chinese immigrant children and its associations with age, length of attendance in childcare, gender, generational status and proficiencies in English and Mandarin Chinese. One hundred Mandarin-speaking children aged three to five years from 15 childcare centres in Sydney were assessed by normed English and Mandarin tests. Childcare educators rated the children's social competence questionnaires. The results indicated that Chinese children performed well in social competence although the children aged three years had a higher anxiety level than the normative sample. Age, length of attendance in childcare, gender and generational status were associated with some subscales of the social competence measure. English level was associated negatively with hyperactivity, atypicality, withdrawal, somatisation and attention problems but positively with adaptability, social skills and functional communication. Mandarin level was associated positively with somatisation b...

The full-length Nrf1α is processed into distinct isoforms, which together regulate genes essential for maintaining cellular homeostasis and organ integrity and liver-specific loss of Nrf1 in mice results in spontaneous hepatoma. Herein, we report that the human constitutive Nrf1α, rather than smaller Nrf1β/γ, expression is attenuated or abolished in the case of low-differentiated high-metastatic hepatocellular carcinomas. Therefore, Nrf1α is of importance in the physio-pathological origin and development, but its specific pathobiological function(s) remains elusive. To address this, TALENs-directed knockout of Nrf1α, but not Nrf1β/γ, is created in the human hepatocellular carcinoma (HepG2) cells. The resulting Nrf1α−/− cells are elongated, with slender spindle-shapes and enlarged gaps between cells observed under scanning electron microscope. When compared with wild-type controls, the invasive and migratory abilities of Nrf1α−/− cells are increased significantly, along with the cell-cycle G2-M arrest and S-phase reduction, as accompanied by suppressed apoptosis. Despite a modest increase in the soft-agar colony formation of Nrf1α−/− cells, its loss-of-function markedly promotes malgrowth of the subcutaneous carcinoma xenograft in nude mice with hepatic metastasis. Together with molecular expression results, we thus suppose requirement of Nrf1α (and major derivates) for gene regulatory mechanisms repressing cancer cell process (e.g. EMT) and malignant behaviour (e.g. migration).

This paper presents pilot research findings, applying quantitative and qualitative methods, on the effects of CET-4 upon English education at the tertiary level in China. The research uses questionnaires delivered to 35 teachers and 210 students and semi-structured interviews with 22 teachers and 30 students conducted in five sampled universities in the city of Tianjin. CET-4 is a high-stakes national English examination measuring college students' listening, reading, writing and translating skills. Findings suggest the examination has a questionable validity but strong influence upon learning and the development of classroom assessments. Students are encouraged to learn for the test by memorizing word lists and doing past and practice papers and it is hard for the learning results to extend to non-test contexts. Classroom assessments highly resemble the exam both in test tasks and techniques. CET-4 exerts varying degrees of effects upon teaching at different schools. The exam and its prior language exams may contribute to students' low proficiency of using English for real-life purposes. They may also be responsible for teachers' unwillingness and simplicity of teaching communication. To examine the exact validity of CET-4 and to gauge more accurately the exam's washback, it is recommended a further nationwide CET-4 study be conducted.

Although MHC-peptide binding is the most selective event in epitope presentation process, the protein fragments generated by proteasomal cleavage require to be recognized by transporter associated with antigen processing (TAP) and translocated from cytosol to endoplasmic reticulum before they can be loaded into the ligand-binding groove of MHC. In this article, we report the use of a new and powerful machine learning tool called Gaussian process (GP) to model the linear and nonlinear relationships between the sequence pattern and binding affinity of peptide to TAP, and to explain the physicochemical properties and structural implications underlying the specific recognition and association of peptide with TAP. The resulting statistics are compared systematically with those obtained by sophisticated PLS, ANN and SVM. Results show that: (i) Nonlinear methods such as the ANN and GP perform much better than the linear PLS. (ii) GP is capable of handling both linearity- and nonlinearity-hybrid relationship and thus exhibits a good performance relative to other two nonlinear methods. (iii) Investigation of the GP model shows that the P1, P2, P3 and P9 of peptide are the most important positions that dominate TAP-peptide recognition, P5 contributes slightly to the peptide binding, whereas P4, P6, P7 and P8 can only exert very limited potency on the binding. (iv) Diverse properties cast remarkable effects on the interaction between TAP and peptide. In particular, hydrophobility, electronic property and hydrogen bond contribute most significantly to the binding affinity of TAP-peptide association.

A new kind of amino acid descriptors we named integrated property scores (IP scores), were derived from 516 physico‐chemical properties using the classical principal component analysis technique, and employed to characterise the sequence pattern profile of 162 single-protonated tripeptides. Based upon the sophisticated partial least squares (PLS) regression coupled with genetic algorithm-variable selection, the resulting structural parameters of the characterisation were then used to develop several robust quantitative structure–spectrum relationship models with the ion mobility spectrometry collision cross sections of these peptides. The results for 94.1% samples in the data panel are satisfactorily accurate, compared to those experimentally measured. Subsequently, the predictive power and stability of the constructed models were analysed and tested in detail through both internal and external validations, with the correlation coefficients of fitting r 2, cross-validation q 2 and prediction of 0.978, 0.9...

N-doped CuCrO 2 thin films were prepared by using radio frequency magnetron sputtering technique. The XRD and XPS measurements were used to confirm the existence of the N acceptors in CuCrO 2 thin films. Hall measurements show the p-type conduction for all films. The electrical conductivity increases rapidly with the increase in N doping concentration, and the maximum of the electrical conductivity of 17 S cm −1 is achieved for the film deposited with 30 vol.% N 2 O, which is about three orders of magnitude higher than that of the undoped CuCrO 2 thin film. Upon increasing the doping concentrations the band gaps of N-doped CuCrO 2 thin films increase due to the Burstein–Moss shift.

The C-terminal domain (CTD, aa 686–741) of nuclear factor-erythroid 2 p45-related factor 1 (Nrf1) shares 53% amino acid sequence identity with the equivalent Neh3 domain of Nrf2, a homologous transcription factor. The Neh3 positively regulates Nrf2, but whether the Neh3-like (Neh3L) CTD of Nrf1 has a similar role in regulating Nrf1-target gene expression is unknown. Herein, we report that CTD negatively regulates the full-length Nrf1 (i.e. 120-kDa glycoprotein and 95-kDa deglycoprotein) and its shorter isoform LCR-F1/Nrf1β (55-kDa). Attachment of its CTD-adjoining 112-aa to the C-terminus of Nrf2 yields the chimaeric Nrf2-C112Nrf1 factor with a markedly decreased activity. Live-cell imaging of GFP-CTD reveals that the extra-nuclear portion of the fusion protein is allowed to associate with the endoplasmic reticulum (ER) membrane through the amphipathic Neh3L region of Nrf1 and its basic c-tail. Thus removal of either the entire CTD or the essential Neh3L portion within CTD from Nrf1, LCR-F1/Nrf1β and Nrf2-C112Nrf1, results in an increase in their transcriptional ability to regulate antioxidant response element (ARE)-driven reporter genes. Further examinations unravel that two smaller isoforms, 36-kDa Nrf1γ and 25-kDa Nrf1δ, act as dominant-negative inhibitors to compete against Nrf1, LCR-F1/Nrf1β and Nrf2. Relative to Nrf1, LCR-F1/Nrf1β is a weak activator, that is positively regulated by its Asn/Ser/Thr-rich (NST) domain and acidic domain 2 (AD2). Like AD1 of Nrf1, both AD2 and NST domain of LCR-F1/Nrf1β fused within two different chimaeric contexts to yield Gal4D:Nrf1β607 and Nrf1β:C270Nrf2, positively regulate their transactivation activity of cognate Gal4- and Nrf2-target reporter genes. More importantly, differential expression of endogenous ARE-battery genes is attributable to up-regulation by Nrf1 and LCR-F1/Nrf1β and down-regulation by Nrf1γ and Nrf1δ.

Recent findings have demonstrated that the overexpression of lineage-specific transcription factors induces cell fate changes among diverse cell types. For example, neurons can be generated from mouse and human fibroblasts. It is well known that neurons are terminally differentiated cells that do not divide. Therefore, we consider how to induce glioma cells to become neurons by introducing transcription factors. Here, we describe the efficient generation of induced neuronal (iN) cells from glioma cells by the infection with three transcription factors: Ascl1, Brn2 and Ngn2 (ABN). iN cells expressed multiple neuronal markers and fired action potentials, similar to the properties of authentic neurons. Importantly, the proliferation of glioma cells following ABN overexpression was dramatically inhibited in both in vitro and in vivo experiments. In addition, iN cells that originated from human glioma cells did not continue to grow when they were sorted and cultured in vitro. The strategies by which glioma cells are induced to become neurons may be used to clinically study methods for inhibiting tumor growth.

The membrane-bound Nrf1 transcription factor regulates critical homeostatic and developmental genes. The conserved N-terminal homology box 1 (NHB1) sequence in Nrf1 targets the cap‘n’collar (CNC) basic basic-region leucine zipper (bZIP) factor to the endoplasmic reticulum (ER), but it is unknown how its activity is controlled topologically within membranes. Herein, we report a hitherto unknown mechanism by which the transactivation activity of Nrf1 is controlled through its membrane-topology. Thus after Nrf1 is anchored within ER membranes, its acidic transactivation domains (TADs), including the Asn/Ser/Thr-rich (NST) glycodomain situated between acidic domain 1 (AD1) and AD2, are transiently translocated into the lumen of the ER, where NST is glycosylated in the presence of glucose to yield an inactive 120-kDa Nrf1 glycoprotein. Subsequently, portions of the TADs partially repartition across membranes into the cyto/nucleoplasmic compartments, whereupon an active 95-kDa form of Nrf1 accumulates, a process that is more obvious in glucose-deprived cells and may involve deglycosylation. The repartitioning of Nrf1 out of membranes is monitored within this protein by its acidic-hydrophobic amphipathic glucose-responsive domains, particularly the Neh5L subdomain within AD1. Therefore, the membrane-topological organization of Nrf1 dictates its post-translational modifications (i.e. glycosylation, the putative deglycosylation and selective proteolysis), which together control its ability to transactivate target genes.

O-Linked N-acetylglucosamine transferase (OGT) was identified as an Nrf1-interacting protein. Herein, we show that Nrf1 enables interaction with OGT and their co-immunoprecipitates are O-GlcNAcylated by the enzyme. The putative O-GlcNAcylation negatively regulates Nrf1/TCF11 to reduce both its protein stability and transactivation activity of target gene expression. The turnover of Nrf1 is enhanced upon overexpression of OGT, which promotes ubiquitination of the CNC-bZIP protein. Furthermore, the serine/theorine-rich sequence of PEST2 degron within Nrf1 is identified to be involved in the protein O-GlcNAcylation by OGT. Overall, Nrf1 is negatively regulated by its O-GlcNAcylation status that depends on the glucose concentrations.