Annotation and evaluation of base editing outcomes in multiple cell types using CRISPRbase.

CRISPR-Cas base editing (BE) system is a powerful tool to expand the scope and efficiency of genome editing with single-nucleotide resolution. The editing efficiency, product purity, and off-target effect differ among various BE systems. Herein, we developed CRISPRbase (http://crisprbase.maolab.org), by integrating 1 252 935 records of base editing outcomes in more than 50 cell types from 17 species. CRISPRbase helps to evaluate the putative editing precision of different BE systems by integrating multiple annotations, functional predictions and a blasting system for single-guide RNA sequences. We systematically assessed the editing window, editing efficiency and product purity of various BE systems. Intensive efforts were focused on increasing the editing efficiency and product purity of base editors since the byproduct could be detrimental in certain applications. Remarkably, more than half of cancer-related off-target mutations were non-synonymous and extremely damaging to protein functions in most common tumor types. Luckily, most of these cancer-related mutations were passenger mutations (4840/5703, 84.87%) rather than cancer driver mutations (863/5703, 15.13%), indicating a weak effect of off-target mutations on carcinogenesis. In summary, CRISPRbase is a powerful and convenient tool to study the outcomes of different base editors and help researchers choose appropriate BE designs for functional studies.

Cu2+-Dominated Chirality Transfer from Chiral Molecules to Concave Chiral Au Nanoparticles.

Foreign ions as additives are of great significance for realizing excellent control over the morphology of noble metal nanostructures in the state-of-the-art seed-mediated growth method; however, they remain largely unexplored in chiral synthesis. Here, we report on a Cu2+-dominated chiral growth strategy that can direct the growth of concave chiral Au nanoparticles with C3-dominant chiral centers. The introduction of trace amounts of Cu2+ ions in the seed-mediated chiral growth process is found to dominate the chirality transfer from chiral molecules to chiral nanoparticles, leading to the formation of chiral nanoparticles with a concave VC geometry. Both experimental and theoretical results further demonstrate the correlation between the nanoparticle structure and optical chirality for the concave chiral nanoparticle. The Cu2+ ion is found to dominate the chiral growth by selectively activating the deposition of Au atoms along the [110] and [111] directions, facilitating the formation of the concave VC. We further demonstrate that the Cu2+-dominated chiral growth strategy can be employed to generate a variety of concave chiral nanoparticles with enriched geometric chirality and desired chiroptical properties. Concave chiral nanoparticles also exhibit appealing catalytic activity and selectivity toward electrocatalytic oxidation of enantiomers in comparison to helicoidal nanoparticles. The ability to tune the geometric chirality in a controlled manner by simply manipulating the Cu2+ ions as additives opens up a promising strategy for creating chiral nanomaterials with increasing architectural diversity for chirality-dependent optical and catalytic applications.

Chiral Au-Pd Alloy Nanorods with Tunable Optical Chirality and Catalytically Active Surfaces.

Integrating the plasmonic chirality with excellent catalytic activities in plasmonic hybrid nanostructures provides a promising strategy to realize the chiral nanocatalysis toward many chemical reactions. However, the controllable synthesis of catalytically active chiral plasmonic nanoparticles with tailored geometries and compositions remains a significant challenge. Here it is demonstrated that chiral Au-Pd alloy nanorods with tunable optical chirality and catalytically active surfaces can be achieved by a seed-mediated coreduction growth method. Through manipulating the chiral inducers, Au nanorods selectively transform into two different intrinsically chiral Au-Pd alloy nanorods with distinct geometric chirality and tunable optical chirality. By further adjusting several key synthetic parameters, the optical chirality, composition, and geometry of the chiral Au-Pd nanorods are fine-tailored. More importantly, the chiral Au-Pd alloy nanorods exhibit appealing chiral catalytic activities as well as polarization-dependent plasmon-enhanced nanozyme catalytic activity, which has great potential for chiral nanocatalysis and plasmon-induced chiral photochemistry.

Tuning the Plexcitonic Optical Chirality Using Discrete Structurally Chiral Plasmonic Nanoparticles.

Constructing chiral plexcitonic systems with tunable plasmon-exciton coupling may advance the scientific exploitation of strong light-matter interactions. Because of their intriguing chiroptical properties, chiral plasmonic materials have shown promising applications in photonics, sensing, and biomedicine. However, the strong coupling of chiral plasmonic nanoparticles with excitons remains largely unexplored. Here we demonstrate the construction of a chiral plasmon-exciton system using chiral AuAg nanorods and J aggregates for tuning the plexcitonic optical chirality. Circular dichroism spectroscopy was employed to characterize chiral plasmon-exciton coupling, in which Rabi splitting and anticrossing behaviors were observed, whereas the extinction spectra exhibited less prominent phenomena. By controlling the number of molecular excitons and the energy detuning between plasmons and excitons, we have been able to fine-tune the plexcitonic optical chirality. The ability to fine-tune the plexcitonic optical chirality opens up unique opportunities for exploring chiral light-matter interactions and boosting the development of emerging chiroptical devices.

Site-Selective Chiral Growth of Anisotropic Au Triangular Nanoplates for Tuning the Optical Chirality.

Site-selective chiral growth of anisotropic nanoparticles is of great importance to realize the plasmonic nanostructures with delicate geometry and desired optical chirality; however, it remains largely unexplored. This work demonstrates a controlled site-selective chiral growth system based on the seed-mediated growth of anisotropic Au triangular nanoplates. The site-selective chiral growth involves two distinct underlying pathways, faceted growth and island growth, which are interswitchable upon maneuvering the interplay of chiral molecules, surfactants, and reducing agents. The pathway switch governs the geometric and chirality evolution of Au triangular nanoplates, giving rise to tailorable circular dichroism spectra. The ability to tune the optical chirality in a controlled manner by manipulating the site-selective chiral growth pathway opens up a promising strategy for exploiting chiral metamaterials with increasing architectural complexity in chiroptical applications.

A tRNAModification-based strategy for Identifying amiNo acid Overproducers (AMINO).

Amino acids have a multi-billion-dollar market with rising demand, prompting the development of high-performance microbial factories. However, a general screening strategy applicable to all proteinogenic and non-proteinogenic amino acids is still lacking. Modification of the critical structure of tRNA could decrease the aminoacylation level of tRNA catalyzed by aminoacyl-tRNA synthetases. Involved in a two-substrate sequential reaction, amino acids with increased concentration could elevate the reduced aminoacylation rate caused by specific tRNA modification. Here, we developed a selection system for overproducers of specific amino acids using corresponding engineered tRNAs and marker genes. As a proof-of-concept, overproducers of five amino acids such as L-tryptophan were screened out by growth-based and/or fluorescence-activated cell sorting (FACS)-based screening from random mutation libraries of Escherichia coli and Corynebacterium glutamicum, respectively. This study provided a universal strategy that could be applied to screen overproducers of proteinogenic and non-proteinogenic amino acids in amber-stop-codon-recoded or non-recoded hosts.

Strategies for improving the production of bio-based vanillin.

Vanillin (4-hydroxy-3-methoxybenzaldehyde) is one of the most popular flavors with wide applications in food, fragrance, and pharmaceutical industries. However, the high cost and limited yield of plant extraction failed to meet the vast market demand of natural vanillin. Vanillin biotechnology has emerged as a sustainable and cost-effective alternative to supply vanillin. In this review, we explored recent advances in vanillin biosynthesis and highlighted the potential of vanillin biotechnology. In particular, we addressed key challenges in using microorganisms and provided promising approaches for improving vanillin production with a special focus on chassis development, pathway construction and process optimization. Future directions of vanillin biosynthesis using inexpensive precursors are also thoroughly discussed.

Artificial intelligence (AI) versus expert: A comparison of left ventricular outflow tract velocity time integral (LVOT-VTI) assessment between ICU doctors and an AI tool.

PURPOSE: The application of point of care ultrasound (PoCUS) in medical education is a relatively new course. There are still great differences in the existence, quantity, provision, and depth of bedside ultrasound education. The left ventricular outflow tract velocity time integral (LVOT-VTI) has been successfully used in several studies as a parameter for hemodynamic management of critically ill patients, especially in the evaluation of fluid responsiveness. While LVOT-VTI has been broadly used, valuable applications using artificial intelligence (AI) in PoCUS is still limited. We aimed to identify the degree of correlation between auto LVOT-VTI and the manual LVOT-VTI acquired by PoCUS trained ICU doctors. METHODS: Among the 58 ICU doctors who attended PoCUS training from 1 September 2019 to 30 November 2020, 46 ICU doctors who trained for more than 3 months were enrolled. At the end of PoCUS training, each of the enrolled ICU doctors acquired echocardiography parameters of a new ICU patient in 2 h after new patient was admitted. One of the two bedside expert sonographers would take standard echocardiogram of new ICU patients within 24 h. For ICU doctors, manual LVOT-VTI was obtained for reference and auto LVOT-VTI was calculated instantly by using an AI software tool. Based on the image quality of the auto LVOT-VTI, ICU patients was separated into ideal group (n = 31) and average group (n = 15). RESULTS: Left ventricular end-diastolic dimension (LVEDd, p = 0.1028), left ventricular ejection fraction (LVEF, p = 0.3251), left atrial dimension (LA-d, p = 0.0962), left ventricular E/A ratio (p = 0.160), left ventricular wall motion (p = 0.317) and pericardial effusion (p = 1) had no significant difference between trained ICU doctors and expert sonographer. ICU patients in average group had greater sequential organ failure assessment (SOFA) score (7.33 ± 1.58 vs. 4.09 ± 0.57, p = 0.022) and lactic acid (3.67 ± 0.86 mmol/L vs. 1.46 ± 0.12 mmol/L, p = 0.0009) with greater value of LVEDd (51.93 ± 1.07 vs. 47.57 ± 0.89, p = 0.0053), LA-d (39.06 ± 1.47 vs. 35.22 ± 0.98, p = 0.0334) and percentage of decreased wall motion (p = 0.0166) than ideal group. There were no significant differences of δLVOT-VTI (|manual LVOT-VTI - auto LVOT-VTI|/manual VTI*100%) between the two groups (8.8% ± 1.3% vs. 10% ± 2%, p = 0.6517). Statistically, significant correlations between manual LVOT-VTI and auto LVOT-VTI were present in the ideal group (R2  = 0.815, p = 0.00) and average group (R2  = 0.741, p = 0.00). CONCLUSIONS: ICU doctors could achieve the satisfied level of expertise as expert sonographers after 3 months of PoCUS training. Nearly two thirds of the enrolled ICU doctors could obtain the ideal view and one third of them could acquire the average view. ICU patients with higher SOFA scores and lactic acid were less likely to acquire the ideal view. Manual and auto LVOT-VTI had statistically significant agreement in both ideal and average groups. Auto LVOT-VTI in ideal view was more relevant with the manual LVOT-VTI than the average view. AI might provide real-time guidance among novice operators who lack expertise to acquire the ideal standard view.

Why the parent's gaze is so powerful in organizing the infant's gaze: The relationship between parental referential cues and infant object looking.

Parental scaffolding such as looking at and showing objects has long been considered to be helpful for early attention and language development. However, relatively little is known about how parental social multimodal cues work alone or together in guiding an infant's attention toward the referent items. The present study aims to document the dynamics of social referential input during an interactive play session and specify the different types of social cues in directing infant attention. Forty-three parent-infant dyads (infants aged from 5.0 to 18.0 months) in the U.S. completed a short play session recorded by head-mounted camera with eye-trackers. The present findings suggest that joint attention between parent and infant toward the same referent item often co-occurred with other referential input. Infants were more likely to maintain sustained attention to an object under the circumstance that the parent looked at the same item and named it explicitly. This was not the case when parent object looking accompanied other utterances, like "Look!" or the child's name. The present study highlights the importance of multimodal referential input, which sets up enriched opportunities for children to become sensitive to social input and develop sustained attention for further learning.

Individualized Short-Term Electric Load Forecasting Using Data-Driven Meta-Heuristic Method Based on LSTM Network.

Short-term load forecasting is viewed as one promising technology for demand prediction under the most critical inputs for the promising arrangement of power plant units. Thus, it is imperative to present new incentive methods to motivate such power system operations for electricity management. This paper proposes an approach for short-term electric load forecasting using long short-term memory networks and an improved sine cosine algorithm called MetaREC. First, using long short-term memory networks for a special kind of recurrent neural network, the dispatching commands have the characteristics of storing and transmitting both long-term and short-term memories. Next, four important parameters are determined using the sine cosine algorithm base on a logistic chaos operator and multilevel modulation factor to overcome the inaccuracy of long short-term memory networks prediction, in terms of the manual selection of parameter values. Moreover, the performance of the MetaREC method outperforms others with regard to convergence accuracy and convergence speed on a variety of test functions. Finally, our analysis is extended to the scenario of the MetaREC_long short-term memory with back propagation neural network, long short-term memory networks with default parameters, long short-term memory networks with the conventional sine-cosine algorithm, and long short-term memory networks with whale optimization for power load forecasting on a real electric load dataset. Simulation results demonstrate that the multiple forecasts with MetaREC_long short-term memory can effectively incentivize the high accuracy and stability for short-term power load forecasting.

Carboxypeptidase A4 negatively correlates with p53 expression and regulates the stemness of breast cancer cells.

Background: Triple-negative breast cancer (TNBC) is an aggressive cancer subtype lacking effective treatment options, and p53 is the most frequently mutated or deleted gene. Carboxypeptidase A4 (CPA4) is an extracellular metallocarboxypeptidase, which was closely associated with aggressiveness. Although a recent study indicated that CPA4 could induce epithelial­mesenchymal transition in breast cancer cells, no studies investigated its stemness-related function and the correlation between CPA4 and p53 in TNBC. In this study, we aimed to investigate the CPA4 levels in breast cancer tissues and analyze its association with p53, and study its roles in cancer stemness maintenance. Methods: CPA4 mRNA level and its prognostic value were analyzed by using online database UALCAN (http://ualcan.path.uab.edu) and Kaplan-Meier plotter (www.kmplot.com), respectively. The expression of CPA4, p53 and ALDH1A1 in breast cancer and adjacent normal tissues were evaluated by IHC using the corresponding primary antibodies on a commercial tissue array (Shanghai Biochip Co., Ltd., Shanghai, China). siRNA knockdown was used to study the function of proliferation, colony formation assay and sphere formation in serum-free medium. Results: Analysis of the UALCAN datasets identified that CPA4 mRNA levels were elevated in TNBC, especially in the TP53-mutant subgroup. Furthermore, high levels of CPA4 mRNA were significantly associated with unfavourable overall survival OS in breast cancer patients. Immunohistochemistical analysis demonstrated that CPA4 levels were elevated in 32.1% of breast cancer samples (45/140), and the positive rates of ALDH1A1 and p53 in the breast cancer tissues were 25% (35/140) and 50% (70/140), respectively. Statistical analysis revealed high levels of CPA4 was significantly associated with TNBC phenotype. Correlation analysis indicated that CPA4 over-expression was positively associated with ALDH1A1 (P<0.01) and negatively correlated with p53 (P<0.05). In Kaplan-Meier survival analysis, either high CPA4 or ALDH1A1 levels was significantly correlated with poor survival in breast cancer patients. Functional studies demonstrated that down-regulation of CPA4 significantly inhibited TNBC cell proliferation, colony-formation assays in soft agar and sphere formation in serum-free medium. Conclusion: This study demonstrated for the first time that CPA4 was negatively correlates with p53 expression and inhibition of CPA4 could reduce the number of breast cancer cells with stemness property. It might be a potential target for the TNBC treatment.

A Novel Training and Collaboration Integrated Framework for Human-Agent Teleoperation.

Human operators have the trend of increasing physical and mental workloads when performing teleoperation tasks in uncertain and dynamic environments. In addition, their performances are influenced by subjective factors, potentially leading to operational errors or task failure. Although agent-based methods offer a promising solution to the above problems, the human experience and intelligence are necessary for teleoperation scenarios. In this paper, a truncated quantile critics reinforcement learning-based integrated framework is proposed for human-agent teleoperation that encompasses training, assessment and agent-based arbitration. The proposed framework allows for an expert training agent, a bilateral training and cooperation process to realize the co-optimization of agent and human. It can provide efficient and quantifiable training feedback. Experiments have been conducted to train subjects with the developed algorithm. The performances of human-human and human-agent cooperation modes are also compared. The results have shown that subjects can complete the tasks of reaching and picking and placing with the assistance of an agent in a shorter operational time, with a higher success rate and less workload than human-human cooperation.

Clinical characteristics and prognostic analysis of anti-gamma-aminobutyric acid-B (GABA-B) receptor encephalitis in Northeast China.

OBJECTIVE: To investigate the clinical characteristics and prognosis of anti-gamma-aminobutyric acid-B (GABA-B) receptor encephalitis. METHODS: This retrospective study enrolled nineteen patients with anti-GABA-B receptor encephalitis. Clinical manifestations, radiological and electroencephalogram features, treatment and outcomes were collected and analyzed. The neurological function was evaluated according to the modified Rankin Scale (mRS). RESULTS: There were eleven patients in the favorable-prognosis group (mRS ≤ 2) and eight patients in the poor-prognosis group (mRS > 2). In the favorable-prognosis group, clinical symptoms included memory deterioration (n = 10; 90.9%), epileptic seizures (n = 9; 81.8%), psychiatric disorders (n = 9; 81.8%), and conscious disturbance (n = 5; 45.5%); magnetic resonance imaging (MRI) indicated an involvement of the limbic system in three (27.3%) cases in this group. Lung cancer was detected in one patient (9.1%). After an average follow-up period of 11.7 months, four (36.4%) patients were cured, and seven (63.6%) patients showed significant improvements. In the poor-prognosis group, all patients presented with memory deterioration, epileptic seizures, psychiatric disorders, and conscious disturbance; five (62.5%) patients had convulsive status epilepticus, and five (62.5%) patients developed respiratory failure; MRI indicated an involvement of the limbic system in seven (87.5%) cases. Malignant tumors were detected in five (62.5%) patients. After an average follow-up period of 14.8 months, seven (87.5%) patients died and one (12.5%) patient remained dependent in daily life. CONCLUSIONS: The clinical manifestations of anti-GABA-B receptor encephalitis include epileptic seizures, cognitive impairment and psychiatric disorders. Patients with convulsive status epilepticus or respiratory failure have poor outcomes. In anti-GABA-B receptor encephalitis, limbic system involvement is associated with a poor prognosis in and radiological examinations can reflect disease progression. Early diagnosis and appropriate treatment should be highlighted.

Site-directed mutagenesis of coenzyme-independent carotenoid oxygenase CSO2 to enhance the enzymatic synthesis of vanillin.

Vanillin is a popular flavoring compound and an important food additive. Owing to the consumer preference for inexpensive natural aroma flavors, vanillin production through a biotechnological pathway has become of great interest and commercial value in recent years. In this study, an enzymatic synthetic system for vanillin using a coenzyme-independent decarboxylase (FDC) and oxygenase (CSO2) cascade was reconstituted and optimized. This system produces a slightly higher production yield (40.20%) than the largest yield reported for immobilized FDC and CSO2 (35.00%) with ferulic acid as a substrate. It was previously reported that the low catalytic activity and thermal instability of CSO2 restrict the overall productivity of vanillin. In present study, site-directed mutagenesis was applied to rate-limiting oxygenase CSO2 to generate positive mutants. The production yields of mutants A49P (58.44%) and Q390A (65.29%) were 1.45- and 1.62-fold that of CSO2 wild type, respectively. The potential mechanism for enhanced vanillin production using A49P involved increased thermostability and catalytic efficiency, while that using Q390A was probably associated with a better thermostable performance and increased catalytic efficiency resulting from a larger entrance channel.

Ameliorative effect of acetylshikonin on cigarette smoke-induced lung inflammation in mice.

Cigarette smoke exposure is the major cause of chronic obstructive pulmonary disease (COPD). Acetylshikonin was the active principle component of Purple Gromwell that show anti-oxidative and anti-inflammatory effect. However, no data are available to elucidate the protective effect of acetylshikonin on COPD. Acetylshikonin could attenuate smoke-induced lung pathological changes, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and monocyte chemoattractant protein 1 (MCP-1) productions, and tissue damages caused by oxidative stress. Furthermore, acetylshikonin was found to enhance the expression of Nrf2 and Nur77-mediated COX-2 in vivo and in vitro.

Role of the Hydrophilic Latex Particle Surface in Water Diffusion into Films from Waterborne Polymer Colloids.

The diffusion mechanism and growth of large-scale domains during the immersion of latex films in water have been thoroughly investigated with scattering techniques in a combination with the gravimetric method. Latex dispersions for film formation studies had identical main monomer compositions and only differ in the hydrophilic comonomers that result in distinct "hairy" layer structures of the particles. The major effects of the presence and the structure of the surface layers were identified: (1) Introducing the hydrophilic surface layer in the binder structure results in a more uniform penetration of water and a reduction in the water domain growth. (2) The nature of the particle shell defines the rate of the formation of the first hydration layer and the beginning of the large cluster formation. Poly(acrylamide) in the particle shell promotes the formation of the homogeneously swollen film and slows down the development of water "pockets." Poly(acrylic acid) leads to a more heterogeneous material and accelerates water uptake and cluster growth. (3) The thickness of the particle hairy layer regulates the thickness of the interstitials in the dry film and the number of the chemical groups involved in H-bonding with water molecules without a cluster formation. The amount of water that was absorbed before large domains start evolving increased with the growth of the particle shell thickness.

Distinct biological characterization of the CD44 and CD90 phenotypes of cancer stem cells in gastric cancer cell lines.

Recent study implicates that gastric cancer stem cells (CSCs) are capable of generating multiple types of cells to promote tumor growth and heterogeneity important for the development of gastric cancer. However, knowledge is limited regarding the expression and characteristics of marker-positive gastric CSCs. Therefore, gastric CSCs from a series of human gastric cancer cell lines (SNU-5, SNU-16, BGC-823, PAMC-82, MKN-45, and NCI-N87) using four putative CSC surface markers (CD44, CD90, CD133, and epithelial-cell adhesion molecule) were investigated the underlying mechanisms regulating such subpopulations. Only SNU-5 and SNU-16 exhibited independent co-expression of CD44+ and CD90+, which exhibited spheroid-colony formation in vitro and tumor formation in immunodeficient mice. Functional studies revealed that CD44+ cells were more invasive compared with CD90+ cells, whereas CD90+ cells exhibited higher levels of proliferation than CD44+ cells. Furthermore, serial xenotransplantation in mice of CD44+/CD90+ cells derived from SNU-5 and SNU-16 revealed rapid growth of CD90+ cells in subcutaneous lesions and a high metastatic capacity of CD44+ cells in the lung. Mechanistic analyses revealed that CD44+ cells underwent epithelial-to-mesenchymal transition (EMT) following acquisition of mesenchymal features, whereas CD90+ cells enhanced the activation of retinoblastoma phosphorylation at Ser780 and oncogenic cell cycle regulators. The expression of CD44 and CD90 in gastric cancer tissues was associated with distant metastasis and the differentiation state of tumors. These results demonstrated that CD44 and CD90 are specific biomarkers capable of identifying and isolating metastatic and tumorigenic CSCs through their ability to regulate EMT and the cell cycle in gastric cancer cell lines.

MEOX1 Promotes Tumor Progression and Predicts Poor Prognosis in Human Non-Small-Cell Lung Cancer.

Background: MEOX1 is a homeobox transcriptional factor, and plays essential roles in regulating somite development. Our previous study indicated that MEOX1 is a critical molecular target in mesenchymal-like cancer cells in PTEN-deficient Trastuzumab resistant breast cancer. Despite the potential implication of MEOX1 for the cancer progression, no previous studies examined its level and clinical significance in lung cancer tissues. In this study, we aimed to detect the MEOX1 expression and correlate its level with clinical outcome in non-small-cell lung cancer patients (NSCLC). Methods: MEOX1 gene expression in lung cancer was examined by using the Oncomine database. MEOX1 protein levels were evaluated by IHC using the corresponding primary antibody on two different commercial lung cancer tissue arrays. siRNA knockdown was used to elucidate the function of MEOX1. Results: Analysis of the Oncomine datasets identified that an elevation of MEOX1 in gene amplification in lung cancer tissues in comparison to normal lung tissues. Immunohistochemistical analysis demonstrated that MEOX1 was localized predominantly in the nucleus, and positive rate was 67.3% (111/165) in NSCLC samples. Statistical analysis revealed high levels of MEOX1 significantly correlated with Lymph Node Metastasis and Stage. Kaplan-Meier survival analysis showed that high levels of MEOX1 were significantly associated with unfavorable survival in NSCLC patients, and MEOX1 nucleus staining had worse survival, than did patients with overall expression in lung squamous cell carcinoma patients. Multivariate Cox's regression analysis found that MEOX1 was an independent poor prognostic predictor for patients with NSCLC. Silencing of MEOX1 by specific SiRNA significantly inhibited H460 and H1299 cell proliferation and sphere formation in serum-free medium. Conclusions: Our results firstly indentified that high levels of MEOX1 especially nuclear staining was an independent prognostic factor for NSCLC, and it served a essential roles in the regulation of cell proliferation and colony formation in vitro. It may represent a potential target for the NSCLC treatment.

Neuroemergentism: A Framework for Studying Cognition and the Brain.

There has been virtual explosion of studies published in cognitive neuroscience primarily due to increased accessibility to neuroimaging methods, which has led to different approaches in interpretation. This review seeks to synthesize both developmental approaches and more recent views that consider neuroimaging. The ways in which Neuronal Recycling, Neural Reuse, and Language as Shaped by the Brain perspectives seek to clarify the brain bases of cognition will be addressed. Neuroconstructivism as an additional explanatory framework which seeks to bind brain and cognition to development will also be presented. Despite sharing similar goals, the four approaches to understanding how the brain is related to cognition have generally been considered separately. However, we propose that all four perspectives argue for a form of Emergentism in which combinations of smaller elements can lead to a greater whole. This discussion seeks to provide a synthesis of these approaches that leads to the emergence of a theory itself. We term this new synthesis Neurocomputational Emergentism (or Neuromergentism for short).

CREB Protects against Temporal Lobe Epilepsy Associated with Cognitive Impairment by Controlling Oxidative Neuronal Damage.

BACKGROUND: Cognitive dysfunction as a common comorbidity of epilepsy often manifests as learning and memory impairments in patients with temporal lobe epilepsy (TLE). The pathogenetic molecular mechanisms underlying epilepsy-associated cognitive dysfunction are incompletely understood. We investigated the role of cAMP response element binding protein (CREB) and its downstream signaling pathways in the pathogenesis of cognitive impairment in mice with TLE. METHODS: Plasmid vectors of CREB-specific short-hairpin RNAs and CREB cDNA were prepared and transfected into primary neurons. Neuronal apoptosis and mitochondrial oxidative stress were assessed by flow cytometry. For in vivo studies, TLE in mice was induced by pilocarpine injection, and TLE-associated memory decline was evaluated using the Morris water maze after treatment with the CREB inhibitor 666-15, with or without the mitochondria-specific antioxidant MitoQ. CREB and its downstream mediators were examined by Western blotting analysis and quantitative reverse transcription polymerase chain reaction. RESULTS: CREB knockdown induced mitochondrial reactive oxygen species production and apoptosis in primary neurons whereas CREB overexpression brought the opposite effects. The TLE mice exhibited elevated oxidative stress and neuronal apoptosis with decreased expression of CREB and its downstream mediators including PKA, CaMKIV, arc, and c-fos. CREB inhibition exacerbated TLE-associated oxidative neuronal apoptosis and memory decline. MitoQ treatment restored the expression of CREB and its downstream mediators, and prevented TLE-associated oxidative neuronal damage and memory deficits aggravated by CREB inhibition. CONCLUSION: CREB plays a significant role in TLE-associated oxidative neuronal damage and memory impairment. This novel finding provides the evidence of the relationship between CREB and mitochondrial oxidative stress and cognitive dysfunction in epilepsy. Mitochondria-specific antioxidants such as MitoQ may alleviate TLE-associated cognitive dysfunction through activation of CREB and its downstream signaling pathways.