Doping strategies for inorganic lead-free halide perovskite solar cells: progress and challenges.

In recent years, remarkable advancements have been achieved in the field of halide perovskite solar cells (PSCs). However, the commercialization of PSCs has been impeded by challenges such as Pb leakage and the instability of hybrid organic-inorganic perovskites (HOIPs). Hence, the future lies in the development of environmentally friendly inorganic lead-free halide perovskites (LFHPs) based on elements like Sn, Ge, Bi, Sb, and Cu, which show great promise for photovoltaic applications. However, LFHP photovoltaic cells still face challenges such as low efficiency, poor film quality, and stability in comparison to HOIPs. These limitations significantly hinder their further development. To address these issues, element doping strategies, including cationic and anionic doping, as well as the use of additives, are frequently employed. These strategies aim to improve film quality, passivate defects, reduce the band gap, and enhance device performance and stability. In this paper, we aim to provide a comprehensive review of the recent research progress in doping strategies for LFHPs.

A simple strategy to obtain graphitic carbon nitride modified TiO2layer for efficient perovskite solar cells.

The power conversion efficiency (PCE) of perovskite solar cells (PSCs) can be improved through the concurrent strategies of enhancing charge transfer and passivating defects. Graphite carbon nitride (g-C3N4) has been demonstrated as a promising modifier for optimizing energy level alignment and reducing defect density in PSCs. However, its preparation process can be complicated. A simple one-step calcination approach was used in this study to prepare g-C3N4-modified TiO2via the incorporation of urea into the TiO2precursor. This modification simultaneously tunes the energy level alignment and passivates interface defects. The comprehensive research confirms that the addition of moderate amounts of g-C3N4to TiO2results in an ideal alignment of energy levels with perovskite, thereby enhancing the ability to separate and transfer charges. Additionally, the g-C3N4-modified perovskite films exhibit an increase in grain size and crystallinity, which reduces intrinsic defects density and extends charge recombination time. Therefore, the g-C3N4-modified PSC achieves a champion PCE of 20.00%, higher than that of the control PSC (17.15%). Our study provides a systematic comprehension of the interfacial engineering strategy and offers new insights into the development of high-performance PSCs.

Advances in chloride additives for high-efficiency perovskite solar cells: multiple points of view.

Chloride (Cl) additives are rather effective in improving the performance of perovskite solar cells (PSCs) through the modulation of crystallization process and surface morphology. After incorporating Cl-containing additives, the optoelectrical properties of perovskite films, such as the electron/hole diffusion length and carrier lifetime, are greatly enhanced. However, only a trace amount of Cl has been identified in the resultant perovskite film, and the mechanism of efficiency improvement induced by Cl remains unclear. In this review, we discuss organic and inorganic Cl additives systematically from the perspective of their solubility, volatility, cation size and chemical groups. In addition, the roles of residual Cl anions and cations are analyzed in detail. Finally, some valuable future perspectives of Cl additives are proposed.

Unraveling the dynamic behaviors of BF4-based ionic liquids at the SnO2/FAPbI3 interface using ab initio molecular dynamics simulations.

Ab initio molecular dynamics simulations are performed to unravel the complex dynamic behaviors of BF4-based ionic liquids (ILs) at the SnO2/FAPbI3 interface. Specifically, the BMIM+BF4- IL not only eliminates the density of states induced by oxygen vacancies in SnO2, but also significantly increases the iodine ion migration energy barrier in FAPbI3.

Novel Bifunctional Affibody Molecules with Specific Binding to Both EBV LMP1 and LMP2 for Targeted Therapy of Nasopharyngeal Carcinoma.

Antibodies are considered highly specific therapeutic agents in cancer medicines, and numerous formats have been developed. Among them, bispecific antibodies (BsAbs) have gained a lot of attention as a next-generation strategy for cancer therapy. However, poor tumor penetration is a major challenge because of their large size and thus contributes to suboptimal responses within cancer cells. On the other hand, affibody molecules are a new class of engineered affinity proteins and have achieved several promising results with their applications in molecular imaging diagnostics and targeted tumor therapy. In this study, an alternative format for bispecific molecules was constructed and investigated, named ZLMP110-277 and ZLMP277-110, that targets Epstein-Barr virus latent membrane protein 1 (LMP1) and latent membrane protein 2 (LMP2). Surface plasmon resonance (SPR), indirect immunofluorescence assay, co-immunoprecipitation, and near-infrared (NIR) imaging clearly demonstrated that ZLMP110-277 and ZLMP277-110 have good binding affinity and specificity for both LMP1 and LMP2 in vitro and in vivo. Moreover, ZLMP110-277 and ZLMP277-110, especially ZLMP277-110, significantly reduced the cell viability of C666-1 and CNE-2Z as compared to their monospecific counterparts. ZLMP110-277 and ZLMP277-110 could inhibit phosphorylation of proteins modulated by the MEK/ERK/p90RSK signaling pathway, ultimately leading to suppression of oncogene nuclear translocations. Furthermore, ZLMP110-277 and ZLMP277-110 showed significant antitumor efficacy in nasopharyngeal carcinoma-bearing nude mice. Overall, our results demonstrated that ZLMP110-277 and ZLMP277-110, especially ZLMP277-110, are promising novel prognostic indicators for molecular imaging and targeted tumor therapy of EBV-associated nasopharyngeal carcinoma.

High-performance lead-free quaternary antiperovskite photovoltaic candidate Ca6N2AsSb.

Accurate many-body perturbation theory-based calculations were used to study the electronic and excitonic properties of lead-free quaternary antiperovskite Ca6N2AsSb; large quasiparticle band gap renormalization, strong optical absorption, and low exciton binding energy, as well as high efficiency of >32% with a thickness of 500 nm were predicted.

MRGPRX2 signaling involves the Lysyl-tRNA synthetase and MITF pathway.

MRGPRX2, a G-protein-coupled-seven transmembrane domain receptor, is mainly expressed in mast cells and neurons and is involved in skin immunity and pain. It is implicated in the pathophysiology of non-IgE-mediated immediate hypersensitivity and has been related to adverse drug reactions. Moreover, a role has been proposed in asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. Although it has a prominent role in disease, its signaling transduction is poorly understood. This study shows that MRGPRX2 activation with substance P increased Lysyl t-RNA synthetase (LysRS) translocation to the nucleus. LysRS is a moonlighting protein with a dual role in protein translation and IgE signaling in mast cells. Upon allergen- IgE-FcεRI crosslinking, LysRS is translocated to the nucleus and activates microphthalmia-associated transcription factor (MITF) activity. In this study, we found that MRGPRX2 triggering led to MITF phosphorylation and increased MITF activity. Therefore, overexpression of LysRS increased MITF activity after MRGPRX2 activation. MITF silencing reduced MRGPRX2-dependent calcium influx and mast cell degranulation. Furthermore, a MITF pathway inhibitor, ML329, impaired MITF expression, calcium influx, and mast cell degranulation. Moreover, drugs such as atracurium, vancomycin, and morphine, reported to induce MRGPRX2-dependent degranulation, increased MITF activity. Altogether, our data show that MRGPRX2 signaling enhances MITF activity, and its abrogation by silencing or inhibition resulted in defective MRGPRX2 degranulation. We conclude that MRGPRX2 signaling involves the LysRS and MITF pathway. Thus, MITF and MITF-dependent targets may be considered therapeutic approaches to treat pathologies where MRGPRX2 is implicated.

Effectiveness of Center of Pressure Trajectory as Anticipatory Postural Adjustment Measurement in Parkinson's Disease With Freezing of Gait History.

BACKGROUND: Evidence showed that patients with Parkinson's disease (PD) who have a history of freezing of gait (FOG) have hypometric anticipatory postural adjustment (APA) during gait initiation (GI) compared to PD without FOG. OBJECTIVES: This study aimed to test the feasibility of center of pressure (COP) displacement during GI as the measure of APA in PD with and without a history of FOG. METHODS: Patients with PD underwent COP trajectory measurements, including duration, length, velocity, and acceleration in different phases of APA (APA1, APA2a, APA2, and LOC), as well as evaluation of New Freezing of Gait Questionnaire (NFOG-Q), Tinetti balance and gait score, and Postural Instability and Gait Difficulty (PIGD) score in the on and off medication states. RESULTS: The duration (seconds) of APA2a, APA2b, and LOC were highest while velocity in mediolateral direction (X) (m/s), including APA1, APA2a, APA2b, and LOC showed lowest in PD with FOG. Velocity in the mediolateral direction in different phases of APA increased in patients with FOG after dopaminergic therapy. APA2a (seconds) and APA2b (X) (m/s) were significantly associated with NFOG-Q part II, APA2b (X) (m/s) was significantly associated with NFOG-Q part III, and APA2a (seconds) was significantly associated with Tinetti balance and gait and PIGD score. CONCLUSIONS: PD with FOG history showed a favorable response of APAs to dopaminergic replacement. The APA parameters by COP trajectory, especially lateral COP shift toward the stance foot (APA2b (X) (m/s) and APA2a (seconds)) are surrogate markers to assess PD with FOG history.

One-Step Gas-Solid-Phase Diffusion-Induced Elemental Reaction for Bandgap-Tunable CuaAgm1Bim2In/CuI Thin Film Solar Cells.

Lead-free inorganic copper-silver-bismuth-halide materials have attracted more and more attention due to their environmental friendliness, high element abundance, and low cost. Here, we developed a strategy of one-step gas-solid-phase diffusion-induced reaction to fabricate a series of bandgap-tunable CuaAgm1Bim2In/CuI bilayer films due to the atomic diffusion effect for the first time. By designing and regulating the sputtered Cu/Ag/Bi metal film thickness, the bandgap of CuaAgm1Bim2In could be reduced from 2.06 to 1.78 eV. Solar cells with the structure of FTO/TiO2/CuaAgm1Bim2In/CuI/carbon were constructed, yielding a champion power conversion efficiency of 2.76%, which is the highest reported for this class of materials owing to the bandgap reduction and the peculiar bilayer structure. The current work provides a practical path for developing the next generation of efficient, stable, and environmentally friendly photovoltaic materials.

MITF Downregulation Induces Death in Human Mast Cell Leukemia Cells and Impairs IgE-Dependent Degranulation.

Activating mutations in KIT (CD117) have been associated with several diseases, including gastrointestinal stromal tumors and mastocytosis. Rapidly progressing pathologies or drug resistance highlight the need for alternative treatment strategies. Previously, we reported that the adaptor molecule SH3 binding protein 2 (SH3BP2 or 3BP2) regulates KIT expression at the transcriptional level and microphthalmia-associated transcription factor (MITF) expression at the post-transcriptional level in human mast cells and gastrointestinal stromal tumor (GIST) cell lines. Lately, we have found that the SH3BP2 pathway regulates MITF through miR-1246 and miR-5100 in GIST. In this study, miR-1246 and miR-5100 were validated by qPCR in the SH3BP2-silenced human mast cell leukemia cell line (HMC-1). MiRNA overexpression reduces MITF and MITF-dependent target expression in HMC-1. The same pattern was observed after MITF silencing. In addition, MITF inhibitor ML329 treatment reduces MITF expression and affects the viability and cell cycle progression in HMC-1. We also examine whether MITF downregulation affected IgE-dependent mast cell degranulation. MiRNA overexpression, MITF silencing, and ML329 treatment reduced IgE-dependent degranulation in LAD2- and CD34+-derived mast cells. These findings suggest MITF may be a potential therapeutic target for allergic reactions and deregulated KIT mast-cell-mediated disorders.

HOTAIR modulates hepatocellular carcinoma progression by activating FUT8/core-fucosylated Hsp90/MUC1/STAT3 feedback loop via JAK1/STAT3 cascade.

BACKGROUND: Glycosylation exhibits crucial effect on hepatocellular carcinoma (HCC) progression. Long non-coding RNAs (lncRNAs) are involved in multilevel regulation of gene transcription during tumor development. The purpose of this study is to clarify the potential mechanism that HOTAIR modulates hepatocellular carcinoma progression by activating FUT8/core-fucosylated Hsp90/MUC1/STAT3 feedback loop via JAK1/STAT3 cascade. METHODS: qRT-PCR was used to show the differential expression of genes. Functional experiments were used to measure the malignancy of HCC cells. ChIP and co-IP assays showed the directly interaction of the key molecules. Xenografts was conducted to show the in vivo effects. RESULTS: Upregulation of FUT8 showed closely correlation with HCC progression. Core-fucosylation of Hsp90 stabilized MUC1 binding to the downstream p-STAT3, which involved in the activation of JAK1/STAT3 cascade. STAT3 was identified as the regulator of FUT8 and MUC1 transcription, while FUT8 and MUC1 impacted STAT3 level both in nuclear and cytoplasm. HOTAIR recruited P300 to efficiently bind with STAT3. The transcript complex co-modulated the transcrption of FUT8 and MUC1. Moreover, highly HOTAIR expression also exhibited closely correlation with HCC progression. CONCLUSIONS: FUT8 triggered core-fucosylated-Hsp90/MUC1/P300-HOTAIR-STAT3 cascade via JAK1/STAT3 pathway, which exhibited as positive feedback loop during HCC progression.

Novel Affibody Molecules Specifically Bind to SARS-CoV-2 Spike Protein and Efficiently Neutralize Delta and Omicron Variants.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been an unprecedented public health disaster in human history, and its spike (S) protein is the major target for vaccines and antiviral drug development. Although widespread vaccination has been well established, the viral gene is prone to rapid mutation, resulting in multiple global spread waves. Therefore, specific antivirals are needed urgently, especially those against variants. In this study, the domain of the receptor binding motif (RBM) and fusion peptide (FP) (amino acids [aa] 436 to 829; denoted RBMFP) of the SARS-CoV-2 S protein was expressed as a recombinant RBMFP protein in Escherichia coli and identified as being immunogenic and antigenically active. Then, the RBMFP proteins were used for phage display to screen the novel affibody. After prokaryotic expression and selection, four novel affibody molecules (Z14, Z149, Z171, and Z327) were obtained. Through surface plasmon resonance (SPR) and pseudovirus neutralization assay, we showed that affibody molecules specifically bind to the RBMFP protein with high affinity and neutralize against SARS-CoV-2 pseudovirus infection. Especially, Z14 and Z171 displayed strong neutralizing activities against Delta and Omicron variants. Molecular docking predicted that affibody molecule interaction sites with RBM overlapped with ACE2. Thus, the novel affibody molecules could be further developed as specific neutralization agents against SARS-CoV-2 variants. IMPORTANCE SARS-CoV-2 and its variants are threatening the whole world. Although a full dose of vaccine injection showed great preventive effects and monoclonal antibody reagents have also been used for a specific treatment, the global pandemic persists. So, developing new vaccines and specific agents are needed urgently. In this work, we expressed the recombinant RBMFP protein as an antigen, identified its antigenicity, and used it as an antigen for affibody phage-display selection. After the prokaryotic expression, the specific affibody molecules were obtained and tested for pseudovirus neutralization. Results showed that the serum antibody induced by RBMFP neutralized Omicron variants. The screened affibody molecules specifically bound the RBMFP of SARS-CoV-2 with high affinity and neutralized the Delta and Omicron pseudovirus in vitro. So, the RBMFP induced serum provides neutralizing effects against pseudovirus in vitro, and the affibodies have the potential to be developed into specific prophylactic agents for SARS-CoV-2 and its variants.

Novel Ag-based thin film solar cells: concept, materials, and challenges.

Novel Ag-based thin film solar cells have attracted extensive attention in recent years in the photovoltaic (PV) field due to their outstanding properties like a high light absorption coefficient, low toxicity, abundance, and an appropriate band gap. The emerging Ag-based thin film materials such as Ag2S, AgBiS2, Ag3CuS2, AgInS2, AgBiSe2, Ag2ZnSnS4, Ag(In1-x,Gax)Se2, AgaBibIc, Cs2AgBiBr6, and Cu2AgBiI6 are becoming ideal materials for light absorbing layers in the new generation of PV devices. Although the efficiency of ATFSCs has improved significantly in recent years, it is much lower than those of other PV devices. The relatively low efficiency of ATFSCs is mainly caused by structural defects such as poor crystallinity, voids, and instability which occur during the preparation of light absorbing layers. This paper defines the concept and classification of Ag-based materials and introduces in detail a thin film preparation method by overcoming structural defects. Finally, the vision of achieving high-efficiency ATFSCs by improving structural defects is proposed.

Development, Reliability, and Validity of the Preschool Learning Skills Scale: A Tool for Early Identification of Preschoolers at Risk of Learning Disorder in Mainland China.

Background: Early identification of children at risk of learning disorders (LD) may mitigate the adverse effects of delayed intervention by guiding children to receive preventive services at an earlier age. However, there is no assessment tool for the early identification of children at risk of LD in Mainland China. Therefore, this study aimed to create a Chinese version of the Preschool Learning Skills Scale and investigate its validity and reliability. Methods: Firstly, a pilot scale was designed based on literature review and expert review. Secondly, a pre-survey of the pilot scale was conducted. In phase 3, a formal survey was carried out to test the reliability and validity of the scale by involving 2,677 preschool children from 7 kindergartens. Data were collected using a checklist for demographic characteristics, the preschool learning skills scale, the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P), and Conners' Rating Scales. Results: The final scale included 38 items under seven factors. The reliability and validity tests confirmed that the Cronbach's alpha, split-half reliability, and test-retest reliability coefficients of the scale were 0.946, 0.888, and 0.941, respectively. The Spearman correlations of factor-total score ranged from 0.685 to 0.876. The results of criterion-related validity showed a direct and significant association between the preschool learning skills scale with the BRIEF-P (r = 0.641, P < 0.001) and the cognitive problems factor of Conners' Rating Scales (r = 0.564, P < 0.001). The model had a good fit (χ 2 /df = 3.489, RMSEA = 0.047, RMR = 0.024, CFI = 0.912, TLI = 0.900, and IFI = 0.912). Multigroup confirmatory factor analysis supported the structural and measurement invariance on the preschool learning skills scale across gender and grade. Conclusions: The developed preschool learning skills scale has good reliability and validity, indicating that the scale can be used to identify preschool children at risk of LD and can be recommended for use in clinical research and practice.

Nucleocapsid protein of SARS-CoV-2 is a potential target for developing new generation of vaccine.

BACKGROUND: SARS-CoV-2 has spread worldwide causing more than 400 million people with virus infections since early 2020. Currently, the existing vaccines targeting the spike glycoprotein (S protein) of SARS-CoV-2 are facing great challenge from the infection of SARS-CoV-2 virus and its multiple S protein variants. Thus, we need to develop a new generation of vaccines to prevent infection of the SARS-CoV-2 variants. Compared with the S protein, the nucleocapsid protein (N protein) of SARS-CoV-2 is more conservative and less mutations, which also plays a vital role in viral infection. Therefore, the N protein may have the great potential for developing new vaccines. METHODS: The N protein of SARS-CoV-2 was recombinantly expressed and purified in Escherichia coli. Western Blot and ELISA assays were used to demonstrate the immunoreactivity of the recombinant N protein with the serum of 22 COVID-19 patients. We investigated further the response of the specific serum antibodies and cytokine production in BALB/c mice immunized with recombinant N protein by Western Blot and ELISA. RESULTS: The N protein had good immunoreactivity and the production of IgG antibody against N protein in COVID-19 patients was tightly correlated with disease severity. Furthermore, the N protein was used to immunize BALB/c mice to have elicited strong immune responses. Not only high levels of IgG antibody, but also cytokine-IFN-γ were produced in the N protein-immunized mice. Importantly, the N protein immunization induced a high level of IgM antibody produced in the mice. CONCLUSION: SARS-CoV-2 N protein shows a great big bundle of potentiality for developing a new generation of vaccines in fighting infection of SARS-CoV-2 and its variants.

The Traditional Uses, Phytochemistry, Pharmacokinetics, Pharmacology, Toxicity, and Applications of Corydalis saxicola Bunting: A Review.

Background: Corydalis saxicola Bunting (CSB) is a perennial herb belonging to genus Corydalis (Papaveraceae), called "Yan-huang-lian" in the Chinese folk. Traditionally, it is used to treat acute conjunctivitis, corneal pannus, acute abdominal pain, hemorrhoidal bleeding, haematochezia, swelling, hepatitis, cirrhosis and liver cancer based on traditional Chinese medicine (TCM) concepts. Purpose: This review aims to summarize and analyze the pharmacokinetics, pharmacological and toxicological properties of CSB and its extracts; to highlight the relevance of modern pharmacology to traditional pharmacology; also to assess its therapeutic potential. Methods: CSB related literatures were searched and screened from databases including PubMed, Web of Science and CNKI. The selected literatures provided reliable source identification evidences. Results: In traditional medicine concepts, CSB has the effects of clearing away heat and detoxification, eliminating dampness, relieving pain, and stopping bleeding. Its modern pharmacology includes hepatoprotective, anticancer, anti-inflammatory, analgesic, antibacterial, anti-oxidative effects. Further, some pharmacological effects support its traditional uses. The CSB total alkaloids (CSBTA) are the main constituents isolated from this plant, and they exert the major of the pharmacological effects. Toxicological studies have shown that the toxicity of CSBTA is mild and reversible in rodents and beagle dogs. Conclusion: Although the present study summarizes the botany, phytochemistry, pharmacokinetics, pharmacology, toxicity, and applications of this plant, it is still necessary to systemically evaluate the chemistry, safety and parameters related to drug metabolism of the extracts or compounds from this plant before or in clinical trials in the future. Meanwhile, cancers and inflammatory-related diseases may be new research directions of this ethnomedicine.

Automated detection of lung cancer-caused metastasis by classifying scintigraphic images using convolutional neural network with residual connection and hybrid attention mechanism.

BACKGROUND: Whole-body bone scan is the widely used tool for surveying bone metastases caused by various primary solid tumors including lung cancer. Scintigraphic images are characterized by low specificity, bringing a significant challenge to manual analysis of images by nuclear medicine physicians. Convolutional neural network can be used to develop automated classification of images by automatically extracting hierarchal features and classifying high-level features into classes. RESULTS: Using convolutional neural network, a multi-class classification model has been developed to detect skeletal metastasis caused by lung cancer using clinical whole-body scintigraphic images. The proposed method consisted of image aggregation, hierarchal feature extraction, and high-level feature classification. Experimental evaluations on a set of clinical scintigraphic images have shown that the proposed multi-class classification network is workable for automated detection of lung cancer-caused metastasis, with achieving average scores of 0.7782, 0.7799, 0.7823, 0.7764, and 0.8364 for accuracy, precision, recall, F-1 score, and AUC value, respectively. CONCLUSIONS: The proposed multi-class classification model can not only predict whether an image contains lung cancer-caused metastasis, but also differentiate between subclasses of lung cancer (i.e., adenocarcinoma and non-adenocarcinoma). On the context of two-class (i.e., the metastatic and non-metastatic) classification, the proposed model obtained a higher score of 0.8310 for accuracy metric.

SARS-CoV-2 vaccine excipients polyethylene glycol and trometamol do not induce mast cell degranulation, in an in vitro model for non-IgE-mediated hypersensitivity.

The development of vaccines against SARS-CoV2 brought about several challenges, including the management of hypersensitivity reactions to these formulations. The search for underlying mechanisms involved in these adverse events initially focused on excipients which may trigger mast cell activation responses via non-IgE pathways: polyethylene glycol and trometamol. We sought to determine whether these components, in their pure form, were capable of stimulating mast cells directly. To test this hypothesis, we used an in vitro model for non-IgE-mediated activation that has previously shown degranulation responses induced via MRGPRX2 with known drug agonists of the receptor. Human LAD2 mast cells were incubated with different concentrations (1, 10, 50 mg/ml) of trometamol and of purified polyethylene glycol/Macrogol (molecular weights: 2,000, 3,350, 4,000, and 6,000). Mast cell degranulation was assessed using a beta-hexosaminidase read-out. Interestingly, degranulation responses for all reagents tested showed no significant differences from those obtained from the negative control (basal degranulation). Receptor-silencing assays were therefore not conducted. In summary, purified PEG and trometamol did not induce mast cell degranulation in this in vitro model for the study of non-IgE mechanisms of drug hypersensitivity, previously shown to be useful in the investigation of MRGPRX2 ligands. Studies using complete vaccine formulations, lipid conjugates, and receptor gene variants are needed to further clarify mechanisms of vaccine hypersensitivity.

LncRNA LEF1-AS1/LEF1/FUT8 Axis Mediates Colorectal Cancer Progression by Regulating α1, 6-Fucosylationvia Wnt/ß-Catenin Pathway.

BACKGROUND: Fucosylation alteration is involved in several steps of human cancer pathogenesis. Dysregulated long non-coding RNA (lncRNA) often leads to malignancy in colorectal cancer (CRC). METHODS: Differential levels of LEF1-AS1, LEF1 and FUT8 are analyzed by qRT-PCR and western blot. Chip, RIP, EMSA and luciferase reporter assay confirm the direct interaction among LEF1-AS1, MLL1, H3K4me3, LEF1 and FUT8. Functionally, CRC cell proliferation, migration and invasion are analyzed by CCK8 assay, colony formation assay, transwell assay and flow cytometry. The xenografts nude mice models, lung metastasis and liver metastasis are established to determine the effect of LEF1-AS1/LEF1/FUT8 axis on CRC progression in vivo. RESULTS: Here, we identify that LEF1-AS1 and LEF1 are higher in CRC tissues than that in adjacent tissues, as well as upregulated in CRC cell lines than that in normal colorectal cells. Altered levels of LEF1-AS1 modulate LEF1 expression, while altered LEF1 could not regulate LEF1-AS1. LEF1-AS1 recruits MLL1 to the promoter region of LEF1, induces H3K4me3 methylation modification and mediates LEF1 transcription. Furthermore, α1-6 fucosyltransferase FUT8 is overexpressed in CRC tissues and positively correlated to LEF1. FUT8 is a direct target of transcription factor LEF1, which regulates FUT8 level. Altered FUT8 also regulates the core fucosylation of CRC cells, and LEF1-AS1 mediates FUT8 level through activation of Wnt/ß-catenin/LEF1 pathway, thereby resulting in ß-catenin nuclear translocation. In addition, LEF1-AS1 mediates the proliferation, migration and invasion of CRC cells in vitro. LEF1-AS1 silence hinders the tumorigenesis, liver and lung metastasis of SW620 cells in vivo, while overexpressed FUT8 abolishes the suppressive impact of LEF1-AS1 repression on the biological behavior of SW620 cells. CONCLUSION: Our studies uncovered a novel mechanism for constitutive LEF1-AS1/LEF1/FUT8 axis in CRC progression by regulating α1, 6-fucosylation via Wnt/ß-catenin pathway, and consequently, as a potential therapeutic target in CRC.

Two-dimensional Bhattacharyya bound linear discriminant analysis with its applications.

The recently proposed L2-norm linear discriminant analysis criterion based on Bhattacharyya error bound estimation (L2BLDA) was an effective improvement over linear discriminant analysis (LDA) and was used to handle vector input samples. When faced with two-dimensional (2D) inputs, such as images, converting two-dimensional data to vectors, regardless of the inherent structure of the image, may result in some loss of useful information. In this paper, we propose a novel two-dimensional Bhattacharyya bound linear discriminant analysis (2DBLDA). 2DBLDA maximizes the matrix-based between-class distance, which is measured by the weighted pairwise distances of class means and minimizes the matrix-based within-class distance. The criterion of 2DBLDA is equivalent to optimizing the upper bound of the Bhattacharyya error. The weighting constant between the between-class and within-class terms is determined by the involved data that make the proposed 2DBLDA adaptive. The construction of 2DBLDA avoids the small sample size (SSS) problem, is robust, and can be solved through a simple standard eigenvalue decomposition problem. The experimental results on image recognition and face image reconstruction demonstrate the effectiveness of 2DBLDA.