The novel oncogenic factor TET3 combines with AHR to promote thyroid cancer lymphangiogenesis via the HIF-1α/VEGF signaling pathway.

BACKGROUND: Lymphangiogenesis has been reported to play crucial roles in the metastasis of thyroid cancer (THCA), but despite the significant research on lymphangiogenesis in THCA, the precise regulatory mechanism remains unclear. METHODS: Public databases including the Cancer Genome Atlas (TCGA), TIMER, and UALCAN were used to analyze and visualize the expression of TET3 and AHR in THCA, and the correlation between these molecules were used by TIMER. Additionally, RT-PCR and Western Blot were performed to determine the mRNA and protein expression of related proteins. Plate colony formation, wound healing, cell cycle, apoptosis, angiogenesis and transwell assay were used to examine the ability of proliferation, movement, lymphangiogenesis, migration and invasion of THCA cells. RESULTS: Analysis of the TCGA database revealed higher expression levels of TET3 and AHR in tumor tissue compared to normal tissue in THCA. Additionally, a strong correlation was observed between TET3 and AHR. UALCAN database demonstrated that high expression of TET3 and AHR was associated with advanced THCA TNM stages in THCA patients. Furthermore, TET3 activation accelerated THCA cell proliferation by inducing G2/M phase arrest and suppressing apoptosis, while AHR inactivation reduced THCA cell proliferation by decreasing G2/M phase arrest and promoting apoptosis in vitro. Notably, both TET3 and AHR significantly enhanced THCA cell lymphangiogenesis, migration and invasion. Moreover, TET3 activation and AHR inactivation regulated HIF-1α/VEGF signaling pathway, which ultimately, blocked the HIF-1α/VEGF in THCA cells and impaired their movement, migration and invasion abilities. CONCLUSIONS: The combined action of TET3 and AHR to promote lymphangiogenesis in THCA through the HIF-1α/VEGF signaling pathway, and targeting them might provide a potential treatment strategy for THCA.

Meta-Analysis of Effects of Early Palliative Care on Health-Related Outcomes Among Advanced Cancer Patients.

BACKGROUND: Early palliative care (PC) has received more attention for improving health-related outcomes for advanced cancer patients in recent years, but the results of previous studies are inconsistent. OBJECTIVES: This study aimed to use meta-analysis and trial sequence analysis to evaluate the effect of early PC on health-related outcomes of advanced cancer patients. METHODS: All English publications were searched in PubMed, Web of Science, Embase, and the Cochrane Library from inception to March 2023, with a restriction that the study type was a randomized controlled trial. RESULTS: The results showed that early PC positively affected quality of life, satisfaction with care, and symptom burden reduction. However, early PC had no significant effect on anxiety or survival. Trial sequence analysis results showed that the effect of early PC on the quality of life was stable. DISCUSSION: This systematic review suggested that early PC could positively affect health-related outcomes for advanced cancer patients. Early PC can be used widely in clinical settings to improve health-related outcomes of advanced cancer. However, because of the trial sequence analysis results, further well-designed, clinical, randomized controlled trials with larger sample sizes are necessary to draw definitive conclusions.

Effectiveness of Acceptance and Commitment Therapy for people with advanced cancer: A systematic review and meta-analysis of randomized controlled trials.

AIMS: To systematically review existing evidence and assess the effectiveness of Acceptance and Commitment Therapy for people with advanced cancer. DESIGN: Systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: Nine databases, including PubMed, Web of Science, Cochrane Library, Embase, CINAHL, PsycINFO, Chinese National Knowledge Infrastructure, VIP Database and Wanfang, were searched. The search covered the period between the inception of the selected databases and August 2022. REVIEW METHODS: Two authors independently examined eligible studies and appraised the methodological quality of the included studies by applying the criteria suggested by the Cochrane Effective Practice and Organization of Care followed by data abstraction. The Template for Intervention Description and Replication (TIDieR) checklist was used to identify intervention characteristics. Meta-analysis was performed using RevMan 5.4 software, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the certainty of evidence. RESULTS: Eight studies, involving 488 people with advanced cancer, were included. The results showed significant effects of Acceptance and Commitment Therapy on the improvement of quality of life and the alleviation of anxiety, depression, psychological distress and fatigue in people with advanced cancer. However, its effects in relieving psychological flexibility and pain were not statistically significant. The certainty of the evidence was low to moderate. CONCLUSION: People with advanced cancer can benefit from Acceptance and Commitment Therapy, which is conducive to improving their health outcomes. IMPACT: This review provides evidence about the effectiveness of Acceptance and Commitment Therapy in people with advanced cancer. Further well-designed studies with larger sample sizes are required. This review may help nurses and researchers to design and implement Acceptance and Commitment Therapy in clinical practice, thereby improving health outcomes in this population. PROSPERO REGISTRATION NUMBER: CRD42021244568.

The structure correspondence hypothesis predicts how word and sentence in language correlate with term and principle in mathematics.

The association between language and mathematics is an important debated topic. Here, we proposed a structure correspondence hypothesis to explain under what conditions language and mathematics are closely related. According to the hypothesis, there would be an association when they have equivalent structure. One hundred and fifty high school students were recruited to finish mathematical and language tests at the element level (i.e., geometric term processing and word analogy) and at the low-dimensional combination level (i.e., geometric principle processing and sentence completion) as well as the tests to measure cognitive covariates (general intelligence and spatial processing). After controlling for age, gender and cognitive covariates, geometric term processing and word analogy were closely correlated, and geometric principle processing and sentence completion were significantly correlated. No other correlations were found. The results support the structure correspondence hypothesis and provide a new perspective of structure of language and verbalized mathematics for the relation between language and mathematics.

Different cognitive mechanisms used for solving open and closed math problems.

Problem-solving skills are very important in our daily life. Almost all problem-solving studies have addressed the cognitive correlates of solving closed problems, but only limited studies have investigated the cognitive mechanisms of solving open problems. The current study aimed to systematically examine differences between the cognitive mechanisms used for solving open and closed problems. In total, the abilities of 142 high school students to solve open and closed problems were assessed, as were a series of general cognitive abilities as controlled variates. Analogical reasoning uniquely contributed to solving both open and closed math problems, after controlling for age, gender, and inductive reasoning. Reactive cognitive flexibility (measured using the Wisconsin card sorting test) and spatial working memory uniquely correlated only with solving open and closed math problems, respectively. These findings suggest that the cognitive processes used to solve open and closed math problems differ. Open and closed math problems appear to require more reactive cognitive flexibility for generation and more memory for retrieval, respectively.

The Glycine-Glucolipid of Alcanivorax borkumensis Is Resident to the Bacterial Cell Wall.

The marine bacterium Alcanivorax borkumensis produces a surface-active glycine-glucolipid during growth with long-chain alkanes. A high-performance liquid chromatography (HPLC) method was developed for absolute quantification. This method is based on the conversion of the glycine-glucolipid to phenacyl esters with subsequent measurement by HPLC with diode array detection (HPLC-DAD). Different molecular species were separated by HPLC and identified as glucosyl-tetra(3-hydroxy-acyl)-glycine with varying numbers of 3-hydroxy-decanoic acid or 3-hydroxy-octanoic acid groups via mass spectrometry. The growth rate of A. borkumensis cells with pyruvate as the sole carbon source was elevated compared to hexadecane as recorded by the increase in cell density as well as oxygen/carbon dioxide transfer rates. The amount of the glycine-glucolipid produced per cell during growth on hexadecane was higher compared with growth on pyruvate. The glycine-glucolipid from pyruvate-grown cells contained considerable amounts of 3-hydroxy-octanoic acid, in contrast to hexadecane-grown cells, which almost exclusively incorporated 3-hydroxy-decanoic acid into the glycine-glucolipid. The predominant proportion of the glycine-glucolipid was found in the cell pellet, while only minute amounts were present in the cell-free supernatant. The glycine-glucolipid isolated from the bacterial cell broth, cell pellet, or cell-free supernatant showed the same structure containing a glycine residue, in contrast to previous reports, which suggested that a glycine-free form of the glucolipid exists which is secreted into the supernatant. In conclusion, the glycine-glucolipid of A. borkumensis is resident to the cell wall and enables the bacterium to bind and solubilize alkanes at the lipid-water interface. IMPORTANCE Alcanivorax borkumensis is one of the most abundant marine bacteria found in areas of oil spills, where it degrades alkanes. The production of a glycine-glucolipid is considered an essential element for alkane degradation. We developed a quantitative method and determined the structure of the A. borkumensis glycine-glucolipid in different fractions of the cultures after growth in various media. Our results show that the amount of the glycine-glucolipid in the cells by far exceeds the amount measured in the supernatant, confirming the proposed cell wall localization. These results support the scenario that the surface hydrophobicity of A. borkumensis cells increases by producing the glycine-glucolipid, allowing the cells to attach to the alkane-water interface and form a biofilm. We found no evidence for a glycine-free form of the glucolipid.

Algebra dissociates from arithmetic in the brain semantic network.

BACKGROUND: Mathematical expressions mainly include arithmetic (such as 8 - (1 + 3)) and algebra (such as a - (b + c)). Previous studies have shown that both algebraic processing and arithmetic involved the bilateral parietal brain regions. Although previous studies have revealed that algebra was dissociated from arithmetic, the neural bases of the dissociation between algebraic processing and arithmetic is still unclear. The present study uses functional magnetic resonance imaging (fMRI) to identify the specific brain networks for algebraic and arithmetic processing. METHODS: Using fMRI, this study scanned 30 undergraduates and directly compared the brain activation during algebra and arithmetic. Brain activations, single-trial (item-wise) interindividual correlation and mean-trial interindividual correlation related to algebra processing were compared with those related to arithmetic. The functional connectivity was analyzed by a seed-based region of interest (ROI)-to-ROI analysis. RESULTS: Brain activation analyses showed that algebra elicited greater activation in the angular gyrus and arithmetic elicited greater activation in the bilateral supplementary motor area, left insula, and left inferior parietal lobule. Interindividual single-trial brain-behavior correlation revealed significant brain-behavior correlations in the semantic network, including the middle temporal gyri, inferior frontal gyri, dorsomedial prefrontal cortices, and left angular gyrus, for algebra. For arithmetic, the significant brain-behavior correlations were located in the phonological network, including the precentral gyrus and supplementary motor area, and in the visuospatial network, including the bilateral superior parietal lobules. For algebra, significant positive functional connectivity was observed between the visuospatial network and semantic network, whereas for arithmetic, significant positive functional connectivity was observed only between the visuospatial network and phonological network. CONCLUSION: These findings suggest that algebra relies on the semantic network and conversely, arithmetic relies on the phonological and visuospatial networks.

Transcriptomics and proteomics analysis to explore the mechanism of Yishen Tongluo formula repairing sperm DNA damage in rats.

The sperm DNA fragmentation index (DFI) is an objective indicator of male fertility. Currently, effective treatments for high sperm DFI are limited and traditional Chinese medicine (TCM) has certain advantages in this aspect. Yishen Tongluo formula (YSTL), a TCM formula, has been found to reduce DFI in patients. To better understand the mechanisms underlying its activity, we used transcriptomics and proteomics to analyse the potential target gene YSTL repairing tripterygium glycosides (TGs)-mediated sperm DNA damage in rats, followed by validation analyses using RT-qPCR and western blotting, which showed that relative to the control group, DFI was markedly elevated in the TGs group, but markedly lower in the YSTL group relative to the TGs group. KEGG pathway analysis of 119 differentially expressed genes and 158 DEPs identified using trend analysis revealed that they were enriched for apoptosis and base excision repair at the transcriptomic level and for microRNAs in cancer and complement and coagulation cascades at the proteomic level. Ttr and Pnpla2 were identified as potential target genes for YSTL. Our data show that YSTL can protect rat sperm DNA from TGs-induced damage, which may be related to apoptosis, DNA repair and other pathways, and the possible target genes are Ttr and Pnpla2.

[Allergen Analysis of 4622 Children with Allergic Diseases in Shaanxi Province].

OBJECTIVE: To study the distributional characteristics of allergens in children with allergic diseases in Shaanxi province. METHODS: A total of 4 622 children diagnosed with allergic diseases in the Asthma Center, Department of Pediatrics, Xijing Hospital from March 2015 to February 2019 were selected. Serum allergen-specific immunoglobulin E (sIgE) of 19 common kinds of allergens were examined with enzyme-linked immunosorbent assay (ELISA). The children were divided into different groups according to sex, age and geographical regions, and the distributional characteristics of allergens of the different groups were compared. RESULTS: The overall positive rate for the 19 allergens of the 4 622 children was 62.8%. The ranking of the positive rates for individual allergens from high to low were as follows: 24.2% for milk, 18.0% for mold mix, 16.7% for dog dander, 16.4% for house dust mite, 11.7% for cat dander, 10.7% for cashew, 10.6% for weed pollen, 8.8% for egg white, 7.8% for house dust, 7.7% for tree pollen, 5.6% for amaranth, 4.9% for mulberry tree, 3.6% for mango, 3.2% for beef, 2.8% for cockroach, 2.1% for crab, 1.5% for shrimp, 0.8% for pineapple, and 0.3% for shellfish. Analysis based on sex showed that the allergen positive rates in boys were higher than those in girls. Analysis by age difference showed that generally the positive rates for inhaled allergens increased along with the increase in patient age, while the positive rates for ingested allergens decreased along with the increase in patient age. Analysis by geographical regions showed that the positive rate of house dust mite in the patients from the southern part of Shaanxi, the positive rate of weed pollen in the patients from the northern part of Shaanxi and the positive rates of milk and egg white in the patients from the central part of Shaanxi were higher than those in other areas. The cluster analysis and correlation analysis showed that the 19 allergens could be roughly divided into 4 categories. There were moderate correlations among tree pollen, mulberry tree and amaranth. There were moderate correlations among mulberry tree, mango and amaranth. There was moderate correlation between shrimp and crab, and there were mild or weak correlations among most of the other allergens. CONCLUSION: Among the 4 622 children with allergic diseases in Shaanxi Province who were treated in the Asthma Center, Department of Pediatrics, Xijing Hospital, male patients showed higher sensitivity to allergens. The positive rates of inhaled allergens increased, while the positive rates of ingested allergens decreased with increase in patient age. There were regional differences in the distribution of allergens. Some allergens were correlated with each other, which may be related to cross-reaction.

Concentration-Dependent Enhancing Effect of Dissolved Silicate on the Oxidative Degradation of Sulfamethazine by Zero-Valent Iron under Aerobic Conditions.

Dissolved silicate, as a ubiquitous inorganic component in natural waters, is reported to depress the reactivity of zero-valent iron (ZVI) for reductive reactions under anoxic conditions, but it is unclear if the same inhibitory effect occurs for a ZVI/O2 system. In this study, the role of dissolved silicate for the reactivity of micron-sized ZVI (mZVI) was revisited under aerobic conditions, and different observations were found. Silicate had a volcano-type enhancing effect on the performance of the ZVI/O2 system for sulfamethazine (SMT) degradation. The results showed that, under a circum-neutral or alkaline pH condition (pH 6.0-9.0), the presence of dissolved silicate could significantly enhance the degradation of SMT because silicate coordinated with ferrous ions and further led to the generation of reactive oxygen species (ROS). This study suggests that silicate can act as both a ligand and corrosion inhibitor in a ZVI/O2 system: the coordination of silicate and ferrous iron accelerated the oxidative degradation of organic pollutants in an oxic aqueous solution, while the corrosion inhibitory effect of surface-bound silicate at higher concentrations may decrease the reactivity of the ZVI/O2 system, thereby offsetting the enhancing effect from the silicate-coordinated ferrous iron. This study not only redefines the role of naturally occurring silicate for a ZVI reaction system but also gives clues to develop high-efficiency ZVI/O2 technologies for water remediation.

Short-term numerosity training promotes symbolic arithmetic in children with developmental dyscalculia: The mediating role of visual form perception.

Studies have shown that numerosity-based arithmetic training can promote arithmetic learning in typically developing children as well as children with developmental dyscalculia (DD), but the cognitive mechanism underlying this training effect remains unclear. The main aim of the current study was to examine the role of visual form perception in arithmetic improvement through an 8-day numerosity training for DD children. Eighty DD children were selected from four Chinese primary schools. They were randomly divided into the intervention and control groups. The intervention group received training on an apple-collecting game, whereas the control group received an English dictation task. Children's cognitive and arithmetic performances were assessed before and after training. The results showed that the intervention group showed a significant improvement in arithmetic performance, approximate number system (ANS) acuity, and visual form perception, but not in spatial processing and sentence comprehension. The control group showed no significant improvement in any cognitive ability. Mediation analysis further showed that training-related improvement in arithmetic performance was fully mediated by the improvement in visual form perception. The results suggest that short-term numerosity training enhances the arithmetic performance of DD children by improving their visual form perception.

Electrogeneration of H2O2 utilizing anodic O2 on polytetrafluoroethylene-modified cathode in flow-through reactor.

Efficient electrogeneration of hydrogen peroxide (H2O2) is critical for treatment of refractory pollutants by the electro-Fenton process. An effective strategy is developed by combining a flow-through reactor with a poly- tetrafluoroethylene (PTFE)-modified graphite felt cathode. In this design, anodic oxygen is directly used for efficient H2O2 generation at the modified cathode. Experimental results show that the modified cathode with the optimum PTFE content can produce 29.6 mg/L of H2O2, which is 16 times higher than the unmodified graphite felt cathode for a flow rate of 3 mL/min. Maximum H2O2 production, up to 30.7 mg/L, was obtained under the following conditions: 120 mA, 3 mL/min, initial pH 13, no external aeration.

The semantic system is involved in mathematical problem solving.

Numerous studies have shown that the brain regions around bilateral intraparietal cortex are critical for number processing and arithmetical computation. However, the neural circuits for more advanced mathematics such as mathematical problem solving (with little routine arithmetical computation) remain unclear. Using functional magnetic resonance imaging (fMRI), this study (N = 24 undergraduate students) compared neural bases of mathematical problem solving (i.e., number series completion, mathematical word problem solving, and geometric problem solving) and arithmetical computation. Direct subject- and item-wise comparisons revealed that mathematical problem solving typically had greater activation than arithmetical computation in all 7 regions of the semantic system (which was based on a meta-analysis of 120 functional neuroimaging studies on semantic processing). Arithmetical computation typically had greater activation in the supplementary motor area and left precentral gyrus. The results suggest that the semantic system in the brain supports mathematical problem solving.

The neural circuits for arithmetic principles.

Arithmetic principles are the regularities underlying arithmetic computation. Little is known about how the brain supports the processing of arithmetic principles. The current fMRI study examined neural activation and functional connectivity during the processing of verbalized arithmetic principles, as compared to numerical computation and general language processing. As expected, arithmetic principles elicited stronger activation in bilateral horizontal intraparietal sulcus and right supramarginal gyrus than did language processing, and stronger activation in left middle temporal lobe and left orbital part of inferior frontal gyrus than did computation. In contrast, computation elicited greater activation in bilateral horizontal intraparietal sulcus (extending to posterior superior parietal lobule) than did either arithmetic principles or language processing. Functional connectivity analysis with the psychophysiological interaction approach (PPI) showed that left temporal-parietal (MTG-HIPS) connectivity was stronger during the processing of arithmetic principle and language than during computation, whereas parietal-occipital connectivities were stronger during computation than during the processing of arithmetic principles and language. Additionally, the left fronto-parietal (orbital IFG-HIPS) connectivity was stronger during the processing of arithmetic principles than during computation. The results suggest that verbalized arithmetic principles engage a neural network that overlaps but is distinct from the networks for computation and language processing.

Disilicate-Assisted Iron Electrolysis for Sequential Fenton-Oxidation and Coagulation of Aqueous Contaminants.

Sodium disilicate (SD), an inorganic and environmentally friendly ligand, is introduced into the conventional iron electrolysis system to achieve an oxidizing Fenton process to degrade organic pollutants. Electrolytic ferrous ions, which are complexed by the disilicate ions, can chemically reduce dioxygen molecules via consecutive reduction steps, producing H2O2 for the Fenton-oxidation of organics. At the near-neutral pH (from 6 to 8), the disilicate-Fe(II) complexes possess strong reducing capabilities; therefore, a near-neutral pH rather than an acid condition is preferable for the disilicate-assisted iron electrolysis (DAIE) process. Following the DAIE process, the different complexing capacities of disilicate for ferrous/ferric ions and calcium ions can be used to break the disilicate-iron complexes. The addition of CaO or CaCl2 can precipitate ferrous/ferric ions, disilicates and possibly heavy metals in the wastewater. Compared to previously reported organic and phosphorus ligands, SD is a low-cost inorganic agent that does not lead to secondary pollution, and would not compete with the target organic pollutants for •OH; therefore, it would greatly expand the application fields of the O2 activation process. The combination of DAIE and CaO treatments is envisioned to be a versatile and affordable method for treating wastewater with complicated pollutants (e.g., mixtures of biorefractory organics and heavy metals).

Examining the relationship between rapid automatized naming and arithmetic fluency in Chinese kindergarten children.

Rapid automatized naming (RAN) has been found to predict mathematics. However, the nature of their relationship remains unclear. Thus, the purpose of this study was twofold: (a) to examine how RAN (numeric and non-numeric) predicts a subdomain of mathematics (arithmetic fluency) and (b) to examine what processing skills may account for the RAN-arithmetic fluency relationship. A total of 160 third-year kindergarten Chinese children (83 boys and 77 girls, mean age=5.11years) were assessed on RAN (colors, objects, digits, and dice), nonverbal IQ, visual-verbal paired associate learning, phonological awareness, short-term memory, speed of processing, approximate number system acuity, and arithmetic fluency (addition and subtraction). The results indicated first that RAN was a significant correlate of arithmetic fluency and the correlations did not vary as a function of type of RAN or arithmetic fluency tasks. In addition, RAN continued to predict addition and subtraction fluency even after controlling for all other processing skills. Taken together, these findings challenge the existing theoretical accounts of the RAN-arithmetic fluency relationship and suggest that, similar to reading fluency, multiple processes underlie the RAN-arithmetic fluency relationship.

Dynamic mental number line in simple arithmetic.

Studies have found that spatial-numerical associations could extend to arithmetic. Addition leads to rightward shift in spatial attention while subtraction leads to leftward shift (e.g., Knops et al. 2009; McCrink et al. 2007; Pinhas & Fischer 2008), which is consistent with the hypothesis of static mental number line (MNL) for arithmetic. The current investigation tested the hypothesis of dynamic mental number line which was shaped by the relative magnitudes of two operands in simple arithmetic. Horizontal and vertical electrooculograms (HEOG and VEOG) during simple arithmetic were recorded. Results showed that the direction of eye movements was dependent on the relative magnitudes of two operands. Subtraction was associated with larger rightward eye movements than addition (Experiment 1), and smaller-operand-first addition (e.g., 2+9) was associated with larger rightward eye movement than larger-operand-first addition (e.g., 9+2) only when the difference of two operands was large (Experiment 2). The results suggest that the direction of the mental number line could be dynamic during simple arithmetic, and that the eyes move along the dynamic mental number line to search for solutions.

Iron electrolysis-assisted peroxymonosulfate chemical oxidation for the remediation of chlorophenol-contaminated groundwater.

BACKGROUND: Electrolysis with an iron anode is a novel way to provide ferrous activators for chemical oxidation. The objective of this study is to evaluate the performance of peroxymonosulfate (PMS) for chlorophenol destruction when compared with H2O2 and persulfate (PS), and to see whether the electrolysis mode facilitates the buildup of conditions that favor the activation of PMS and removal of chlorophenols. RESULTS: Ferrous species can effectively activate the PMS over a wide pH range. In comparison with H2O2 and PS, PMS is less sensitive to the solution's pH and possesses stronger oxidation capability at alkaline pHs. The optimal molar ratio of PMS to Fe(II) activator is 1:1 for the destruction of 2,4-dichlorophenol (2,4-DCP). The column experiments show that an acidic zone developed downstream from the anode is favorable to maintain ferrous ions and subsequent activation of PMS. The reactivity of the PMS can be manipulated by varying the electrical currents, and the process demonstrates effectiveness for treating organic contaminants. 2,4-DCP contaminated groundwater shows decreased biotoxicity after the chemical oxidation process without considering the residual PMS. CONCLUSIONS: Iron electrolysis-assisted peroxymonosulfate chemical oxidation can effectively treat the 2,4-dichlorophenol and mixtures of organic contaminants. This process can be engineered as an in situ chemical oxidation method for groundwater remediation.

Discovery of bis-aryl urea derivatives as potent and selective Limk inhibitors: Exploring Limk1 activity and Limk1/ROCK2 selectivity through a combined computational study.

Lim kinase (Limk), a proline/serine-rich sequence, can regulate the polymerization of the actin filaments by phosphorylating, and it is found to be highly involved in various human diseases. In this paper, 47 reported Limk1 inhibitors with bis-aryl urea scaffold were used to design potent and selective Limk inhibitors by computational approaches. Firstly, the structure-Limk1 activity relationship models (3D-QSAR) and structure-Limk1/ROCK2 selectivity relationship models (3D-QSSR) were developed and both 3D-QSAR and 3D-QSSR models showed good correlative and predictive abilities. Then, the molecular docking and molecular dynamics (MD) simulations were employed to validate the optimal docking conformation and explore the binding affinities. Finally, five new compounds were designed and all of them exhibited good Limk1 inhibition and Limk1/ROCK2 selectivity after synthesis and biological evaluation, which demonstrated that the obtained information from computational studies were valuable to guide Limk inhibitors' design.

Development of fraction concepts and procedures in U.S. and Chinese children.

We compared knowledge of fraction concepts and procedures among sixth and eighth graders in China and the United States. As anticipated, Chinese middle school children had higher knowledge of fraction concepts and procedures than U.S. children in the same grades, and the difference in procedural knowledge was much larger than the difference in conceptual knowledge. Of particular interest, national differences in knowledge of fraction concepts were fully mediated by differences in knowledge of fraction procedures, and differences between the knowledge of Chinese and U.S. children were most pronounced among the lowest achieving children within each country. Based on these and previous results, a theoretical model of the mutually facilitative interaction between conceptual and procedural knowledge of fractions is proposed and discussed.