Co2+ to Al3+ Substitution Induced Dual-Site Synergistic Catalysis to Friedel-Crafts Alkylation Reactions.

The dual-site synergistic effect in heterogeneous catalysis is quite interesting, and also complex because at least two substrate molecules are adsorbed or activated on the catalyst surface, which apparently needs two spatially separated and functionally independent active sites. It would become more difficult when the substrate molecules are large ones. The replacement of Al3+ in Al4 B6 O15 lattice with Co2+ leads to the formation of unsaturated Co2+ (4-fold coordination) along with oxygen vacancies (Ov ). The former one behaves as a medium-strength Lewis acid site, and can adsorb and activate molecules with a nitro group (e. g., ß-nitrostyrene). The latter one can adsorb and activate oxygen species, which further activates the indole derivatives. Next, the spatially separated dual sites on the catalyst surface can synergistically and efficiently catalyze their Friedel-Crafts alkylation reactions under mild conditions. The high durability can be proved by the as-maintained high yields, that is, 98, 93, 96, 92 and 90 % for 5 runs, respectively. The reaction kinetics obey the second-order characteristic. Annealing under hydrogen condition can further generate more surficial Ov , leading to an improvement to the catalytic activity. A simple and probably routine aliovalent doping endows such a complex synergistic catalysis involving two large substrate molecules, providing an inspired perspective of developing dual-site catalysts.

Structural Diversity and Incompatibility Induced Complex Phase Formation Behavior in the Stuffed Tridymites Ca1-xSrxGa2O4.

Stuffed tridymites AM2O4 composed of a condensed MO4-tetrahedra-based framework have been widely investigated due to their structural diversity and rich physical properties. Herein, the strategy of stuffing mixed Ca2+ and Sr2+ cations into the [Ga2O4]2- framework in (Ca1-xSrx)Ga2O4 (CSGO, 0 ≤ x ≤ 1) is utilized to manipulate the phase formation behavior with different structure types at particular annealing temperatures. Five derivatives, including α- and ß-CaGa2O4, ß- and γ-SrGa2O4, and new CSGO-type structures, were observed. The distinctive feature of the CSGO-structure is the coexistence of UUDDUD- and UDUDUD-type six-membered rings, where U (up) and D (down) denote the orientations of GaO4-tetrahedra with respect to the plane grids, in a ratio of 2:1. Single-phase α-Ca1-xSrxGa2O4 (x < 0.2) and γ-Ca1-xSrxGa2O4 (x > 0.67) could be obtained at low temperatures. Biphasic regions, including α-Ca1-xSrxGa2O4/CSGO (0.2 ≤ x ≤ 0.67), γ-Ca1-xSrxGa2O4/CSGO (0.67 < x ≤ 0.8), and ß-Ca1-xSrxGa2O4/CSGO (0.8 < x < 1), were observed at the intermediate temperature region and evolve irreversibly into the CSGO single-phase region upon elevating the temperature. Moreover, the structure-property relationship of the new CSGO-phase was further studied by doping coordination-sensitive Bi3+ activators to advance the development and applications of stuffed tridymites.

Substitution-Induced Structure Evolution and Zn2+/Ga3+ Ordering in "114" Oxides MAZn2Ga2O7 ( M = Ca2+, Sr2+; A = Sr2+, Ba2+).

The "114" oxides LnBa(Co/Fe)4O7+δ represent a new family of materials that exhibits intriguing physical properties, including geometrically frustrated magnetism, oxygen storage, and magnetoelectric couplings. Various chemical substitutions have been conducted to modify their crystal and magnetic structures as well as physical properties. However, the principles beneath the substitution-induced structural evolution and charge/cationic ordering have not yet been understood. Thus, in this contribution, two complete solid solutions of MAZn2Ga2O7 ( M = Ca2+, Sr2+; A = Sr2+, Ba2+) were designed, synthesized, and characterized by Rietveld refinements based on high-resolution X-ray diffraction (XRD) and neutron diffraction (ND) data. The structure symmetry of MAZn2Ga2O7 is determined by the cationic size mismatch between M and A cations that can be defined by the tolerance factor t, i.e., symmetry transitions from P63 mc ( t > 0.87) to P31 c (0.87 > t > 0.75) and to Pna21 ( t < 0.75) were observed for MAZn2Ga2O7, associated with the rotation of T1O4 tetrahedra in the triangular layers. The Zn2+/Ga3+ ordering at T sites is also a consequence of the increase or decrease of the average sizes of M and A cations. A small concentration of interstitial oxygen ions can be obtained in Sr2Zn2- xGa2+ xO7+ x/2 ( x = 0.1, 0.2); however, no oxygen ionic conduction was observed at high temperatures, indicating the migration ability of the interstitial oxygen was very limited.

Chemical Substitution-Induced and Competitive Formation of 6H and 3C Perovskite Structures in Ba3-xSrxZnSb2O9: The Coexistence of Two Perovskites in 0.3 ≤ x ≤ 1.0.

6H and 3C perovskites are important prototype structures in materials science. We systemically studied the structural evolution induced by the Sr2+-to-Ba2+ substitution to the parent 6H perovskite Ba3ZnSb2O9. The 6H perovskite is only stable in the narrow range of x ≤ 0.2, which attributes to the impressibility of [Sb2O9]. The preference of 90° Sb-O-Sb connection and the strong Sb5+-Sb5+ electrostatic repulsion in [Sb2O9] are competitive factors to stabilize or destabilize the 6H structure when chemical pressure was introduced by Sr2+ incorporation. Therefore, in the following, a wide two-phase region containing 1:2 ordered 6H-Ba2.8Sr0.2ZnSb2O9 and rock-salt ordered 3C-Ba2SrZnSb2O9 was observed (0.3 ≤ x ≤ 1.0). In the final, the successive symmetry descending was established from cubic (Fm3̅m, 1.3 ≤ x ≤ 1.8) to tetragonal (I4/m, 2.0 ≤ x ≤ 2.4), and finally to monoclinic (I2/m, 2.6 ≤ x ≤ 3.0). Here we proved that the electronic configurations of B-site cations, with either empty, partially, or fully filled d-shell, would also affect the structure stabilization, through the orientation preference of the B-O covalent bonding. Our investigation gives a deeper understanding of the factors to the competitive formation of perovskite structures, facilitating the fine manipulation on their physical properties.

Y(1-x)Sc(x)BaZn3GaO7 (0 ≤ x ≤ 1): Structure Evolution by Sc-Doping and the First Example of Photocatalytic Water Reduction in "114" Oxides.

"114" oxides have shown intriguing physical properties while their performance in photocatalysis has not yet been reported probably due to the instability in aqueous solution. YBaZn3GaO7 is an exception, which is stable and indeed shows observable photocatalytic H2 evolution (∼2 µmol/h/g) in methanol aqueous solution under UV light. This activity was enhanced to 23.6 µmol/h/g by a full replacement of Y(3+) by Sc(3+). Optical absorption spectra and theoretical calculations show no significant difference upon Sc(3+)-doping. Instead, a systematic analysis of the structure evolution by Rietveld refinements for Y(1-x)Sc(x)BaZn3GaO7 (0 ≤ x ≤ 1) suggests that the increase of the catalytic activity is likely due to the decrease of the structural defects and thus the lower level of recombination rate of e(-) and h(+). In detail, Sc(3+) substitution leads to a shrinkage of YO6 octahedra, and successively the adjustment of the Zn(2+)/Ga(3+) occupancy behaviors in tetrahedra sites. The photocatalytic H2 evolution rate was further optimized to 118.2 µmol/h/g in methanol solution and 42.9 µmol/h/g in pure water for 1 wt % Pt-loaded ScBaZn3GaO7. Here, the relatively less investigated nonmagnetic "114" oxides were, for the first time, proved to be good candidates for photocatalytic water reduction.

ß-RE1-xBixB3O6 (RE = Sm, Eu, Gd, Tb, Dy, Ho, Er, Y): Bi(3+) Substitution Induced Formation of Metastable Rare Earth Borates at Ambient Pressure.

There emerge great interests in the syntheses of metastable polyborates; however, most are involved with the high-pressure technique. A facile method to synthesize metastable rare earth borates at ambient pressure is eagerly required for the large-scale production and property investigation. Here we demonstrate the critical role of Bi(3+) substitutions in the stabilization of metastable ß-REB3O6 (RE = Sm, Eu, Gd, Tb, Dy, Ho, Er, and Y) at ambient pressure, where the Bi(3+)-to-RE(3+) substitutions would efficiently reduce the synthetic temperatures to 735-820 °C, well below the upper limit of thermodynamically stable window (840-980 °C). Partial solid solutions of ß-RE1-xBixB3O6 were prepared, and the ranges of the solution were also studied experimentally. The thermal behaviors of ß-RE0.8Bi0.2B3O6 were investigated by differential thermal analyses and powder X-ray diffraction, and they were divided into two categories; that is, ß-RE0.8Bi0.2B3O6 (RE = Sm, Eu, Gd) transfers to α-RE0.8Bi0.2B3O6 with further increasing the temperature to 950 °C, while ß-RE0.8Bi0.2B3O6 (RE = Tb, Dy, Ho, Er, and Y) decomposes into hexagonal REBO3 and B2O3. In particular, the allowed concentration of Bi(3+) in ß-Gd1-xBixB3O6 was 0.10 ≤ x ≤ 0.25, and these samples show bright blue emissions under UV excitation, which suggests the high efficiency of light absorption and high potential as phosphors with further doping of other activators.

PKU-3: An HCl-Inclusive Aluminoborate for Strecker Reaction Solved by Combining RED and PXRD.

A novel microporous aluminoborate, denoted as PKU-3, was prepared by the boric acid flux method. The structure of PKU-3 was determined by combining the rotation electron diffraction and synchrotron powder X-ray diffraction data with well resolved ordered Cl(-) ions in the channel. Composition and crystal structure analysis showed that there are both proton and chlorine ions in the channels. Part of these protons and chlorine ions can be washed away by basic solutions to activate the open pores. The washed PKU-3 can be used as an efficient catalyst in the Strecker reaction with yields higher than 90%.

ZnGa(2-x)In(x)S4 (0 ≤ x ≤ 0.4) and Zn(1-2y)(CuGa)(y)Ga(1.7)In(0.3)S4 (0.1 ≤ y ≤ 0.2): optimize visible light photocatalytic H2 evolution by fine modulation of band structures.

Band structure engineering is an efficient technique to develop desired semiconductor photocatalysts, which was usually carried out through isovalent or aliovalent ionic substitutions. Starting from a UV-activated catalyst ZnGa2S4, we successfully exploited good visible light photocatalysts for H2 evolution by In(3+)-to-Ga(3+) and (Cu(+)/Ga(3+))-to-Zn(2+) substitutions. First, the bandgap of ZnGa2-xInxS4 (0 ≤ x ≤ 0.4) decreased from 3.36 to 3.04 eV by lowering the conduction band position. Second, Zn1-2y(CuGa)yGa1.7In0.3S4 (y = 0.1, 0.15, 0.2) provided a further and significant red-shift of the photon absorption to ∼500 nm by raising the valence band maximum and barely losing the overpotential to water reduction. Zn0.7Cu0.15Ga1.85In0.3S4 possessed the highest H2 evolution rate under pure visible light irradiation using S(2-) and SO3(2-) as sacrificial reagents (386 µmol/h/g for the noble-metal-free sample and 629 µmol/h/g for the one loaded with 0.5 wt % Ru), while the binary hosts ZnGa2S4 and ZnIn2S4 (synthesized using the same procedure) show 0 and 27.9 µmol/h/g, respectively. The optimal apparent quantum yield reached to 7.9% at 500 nm by tuning the composition to Zn0.6Cu0.2Ga1.9In0.3S4 (loaded with 0.5 wt % Ru).

Ga4B2O9: an efficient borate photocatalyst for overall water splitting without cocatalyst.

Borates are well-known candidates for optical materials, but their potentials in photocatalysis are rarely studied. Ga(3+)-containing oxides or sulfides are good candidates for photocatalysis applications because the unoccupied 4s orbitals of Ga usually contribute to the bottom of the conducting band. It is therefore anticipated that Ga4B2O9 might be a promising photocatalyst because of its high Ga/B ratio and three-dimensional network. Various synthetic methods, including hydrothermal (HY), sol-gel (SG), and high-temperature solid-state reaction (HTSSR), were employed to prepare crystalline Ga4B2O9. The so-obtained HY-Ga4B2O9 are micrometer single crystals but do not show any UV-light activity unless modified by Pt loading. The problem is the fast recombination of photoexcitons. Interestingly, the samples obtained by SG and HTSSR methods both possess a fine micromorphology composed of well-crystalline nanometer strips. Therefore, the excited e(-) and h(+) can move to the surface easily. Both samples exhibit excellent intrinsic UV-light activities for pure water splitting without the assistance of any cocatalyst (47 and 118 µmol/h/g for H2 evolution and 22 and 58 µmol/h/g for O2 evolution, respectively), while there is no detectable activity for P25 (nanoparticles of TiO2 with a specific surface area of 69 m(2)/g) under the same conditions.

Open-framework gallium borate with boric and metaboric acid molecules inside structural channels showing photocatalysis to water splitting.

An open-framework gallium borate with intrinsic photocatalytic activities to water splitting has been discovered. Small inorganic molecules, H3BO3 and H3B3O6, are confined inside structural channels by multiple hydrogen bonds. It is the first example to experimentally show the structural template effect of boric acid in flux synthesis.

Systematic study of Cr3+ substitution into octahedra-based microporous aluminoborates.

Single crystals of pure aluminoborate PKU-1 (Al3B6O11(OH)5·nH2O) were obtained, and the structure was redetermined by X-ray diffraction. There are three independent Al atoms in the R3 structure model, and Al3 locates in a quite distorted octahedral environment, which was evidenced by (27)Al NMR results. This distortion of Al3O6 octahedra release the strong static stress of the main framework and leads to a symmetry lowering from the previously reported R3 to the presently reported R3. We applied a pretreatment to prepare Al(3+)/Cr(3+) aqueous solutions; as a consecquence, a very high Cr(3+)-to-Al(3+) substitution content (∼50 atom %) in PKU-1 can be achieved, which is far more than enough for catalytic purposes. Additionally, the preference for Cr(3+) substitution at the Al1 and Al2 sites was observed in the Rietveld refinements of the powder X-ray data of PKU-1:0.32Cr(3+). We also systematically investigated the thermal behaviors of PKU-1:xCr(3+) (0 ≤ x ≤ 0.50) by thermogravimetric-differential scanning calorimetry, in situ high-temperature XRD in vacuum, and postannealing experiments in furnace. The main framework of Cr(3+)-substituted PKU-1 could be partially retained at 1100 °C in vacuum. When 0.04 ≤ x ≤ 0.20, PKU-1:xCr(3+) transferred to the PKU-5:xCr(3+) (Al4B6O15:xCr(3+)) structure at ∼750 °C by a 5 h annealing in air. Further elevating the temperature led to a decomposition into the mullite phase, Al4B2O9:xCr(3+). For x > 0.20 in PKU-1:xCr(3+), the heat treatment led to a composite of Cr(3+)-substituted PKU-5 and Cr2O3, so the doping upper limit of Cr(3+) in PKU-5 structure is around 20 atom %.

From Lewis Acid to Lewis Base by La3+-to-Y3+ Substitution in α-YB5O9: Local Structure Modification Induced Lewis Basicity.

Different from the common perspective of average structure, we propose that the locally elongated metal-oxygen bonds induced by La3+-to-Y3+ substitution to a Lewis acid α-YB5O9 generate medium-strength basic sites. Experimentally, NH3- and CO2-TPD experiments prove that the La3+ doping of α-Y1-xLaxB5O9 (0 ≤ x ≤ 0.24) results in the emergence of new medium-strength basic sites and the increasing La3+ concentration modifies the number, not the strength, of the acidic and basic sites. The catalytic IPA conversion exhibits a reversal of the product selectivity, i.e., from 93% of propylene for α-YB5O9 to ∼90% of acetone for α-Y0.76La0.24B5O9, which means the La3+ doping gradually turns the solid from a Lewis acid to a Lewis base. Besides, α-Y0.76RE0.24B5O9 (RE = Ce, Eu, Gd, Tm) compounds were prepared to consolidate the above conjecture, where the acetone selectivity exhibits a linear dependence on the ionic radius (or electronegativity). This work suggests that the substitution-induced local structure change deserves more attention.

A Lewis acid-base paired InBO3 catalyst: synthesis and high selectivity for isopropanol dehydrogenation.

Whilst metal borates are well known as optical materials, their potential in solid catalysis has been less investigated. The calcite structured InBO3 was selected as the target borate and was prepared using a solvothermal method. High-resolution transmission electron microscopy and powder X-ray diffraction prove that the material has a nanoparticle morphology with an average size ∼50 nm and high crystallinity. Intrinsic surface oxygen vacancies, which are beneficial to catalysis, were detected using X-ray photoelectron spectroscopy. Lewis acidity and basicity were both observed using NH3-/CO2-temperature-programmed desorption experiments, and the total acid and base amounts were found to be 46.6 and 123.8 µmol g-1, respectively. Catalytic dehydration and dehydrogenation reactions for isopropanol at elevated temperatures were conducted in a fixed bed reactor to evaluate the catalytic performance of InBO3. InBO3 exhibits a high conversion rate (>90.5%) and, most importantly, a high dehydrogenation selectivity (acetone selectivity >92.5%), whilst the optimal acetone yield achieved was 121.3 mmol h-1 g-1cat at 350 °C. This study on InBO3 strongly suggests that metal borates have promising applications in heterogeneous catalysis.

Development of a Rare Earth Nanoprobe Enables In Vivo Real-Time Detection of Sentinel Lymph Node Metastasis of Breast Cancer Using NIR-IIb Imaging.

Sentinel lymph node (SLN) biopsy plays a critical role in axillary staging of breast cancer. However, traditional SLN mapping does not accurately discern the presence or absence of metastatic disease. Detection of SLN metastasis largely hinges on examination of frozen sections or paraffin-embedded tissues post-SLN biopsy. To improve detection of SLN metastasis, we developed a second near-infrared (NIR-II) in vivo fluorescence imaging system, pairing erbium-based rare-earth nanoparticles (ErNP) with bright down-conversion fluorescence at 1,556 nm. To visualize SLNs bearing breast cancer, ErNPs were modified by balixafortide (ErNPs@POL6326), a peptide antagonist of the chemokine receptor CXCR4. The ErNPs@POL6326 probes readily drained into SLNs when delivered subcutaneously, entering metastatic breast tumor cells specifically via CXCR4-mediated endocytosis. NIR fluorescence signals increased significantly in tumor-positive versus tumor-negative SLNs, enabling accurate determination of SLN breast cancer metastasis. In a syngeneic mouse mammary tumor model and a human breast cancer xenograft model, sensitivity for SLN metastasis detection was 92.86% and 93.33%, respectively, and specificity was 96.15% and 96.08%, respectively. Of note, the probes accurately detected both macrometastases and micrometastases in SLNs. These results overall underscore the potential of ErNPs@POL6326 for real-time visualization of SLNs and in vivo screening for SLN metastasis. SIGNIFICANCE: NIR-IIb imaging of a rare-earth nanoprobe that is specifically taken up by breast cancer cells can accurately detect breast cancer macrometastases and micrometastases in sentinel lymph nodes.

Novel Self-Assembled Multifunctional Nanoprobes for Second-Near-Infrared-Fluorescence-Image-Guided Breast Cancer Surgery and Enhanced Radiotherapy Efficacy.

Breast-conserving surgery (BCS) is the predominant treatment approach for initial breast cancer. However, due to a lack of effective methods evaluating BCS margins, local recurrence caused by positive margins remains an issue. Accordingly, radiation therapy (RT) is a common modality in patients with advanced breast cancer. However, while RT also protects normal tissue and enhances tumor bed doses to improve therapeutic effects, current radiosensitizers cannot meet these urgent clinical needs. To address this, a novel self-assembled multifunctional nanoprobe (NP) gadolinium (Gd)-diethylenetriaminepentaacetic acid-human serum albumin (HSA)@indocyanine green-Bevacizumab (NPs-Bev) is synthesized to improve the efficacy of fluorescence-image-guided BCS and RT. Fluorescence image guidance of the second near infrared NP improves complete resection in tumor-bearing mice and accurately discriminates between benign and malignant mammary tissue in transgenic mice. Moreover, targeting tumors with NPs induces more reactive oxygen species under X-ray radiation therapy, which not only increases RT sensitivity, but also reduces tumor progression in mice. Interestingly, self-assembled NPs-Bev using HSA, the magnetic resonance contrast agent and Bevacizumab-targeting vascular growth factor A, which are clinically safe reagents, are safe in vitro and in vivo. Therefore, the novel self-assembled NPs provide a solid precision therapy platform to treat breast cancer.

Biomarker Genes Discovery of Alzheimer's Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia.

Microglia, the major immune cells in the brain, mediate neuroinflammation, increased oxidative stress, and impaired neurotransmission in Alzheimer's disease (AD), in which most AD risk genes are highly expressed. In microglia, due to the limitations of current single-omics data analysis, risk genes, the regulatory mechanisms, the mechanisms of action of immune responses and the exploration of drug targets for AD immunotherapy are still unclear. Therefore, we proposed a method to integrate multi-omics data based on the construction of gene regulatory networks (GRN), by combining weighted gene co-expression network analysis (WGCNA) with single-cell regulatory network inference and clustering (SCENIC). This enables snRNA-seq data and bulkRNA-seq data to obtain data on the deeper intermolecular regulatory relationships, related genes, and the molecular mechanisms of immune-cell action. In our approach, not only were central transcription factors (TF) STAT3, CEBPB, SPI1, and regulatory mechanisms identified more accurately than with single-omics but also immunotherapy targeting central TFs to drugs was found to be significantly different between patients. Thus, in addition to providing new insights into the potential regulatory mechanisms and pathogenic genes of AD microglia, this approach can assist clinicians in making the most rational treatment plans for patients with different risks; it also has significant implications for identifying AD immunotherapy targets and targeting microglia-associated immune drugs.

Integrative Analysis of the Expression Levels and Prognostic Values for NEK Family Members in Breast Cancer.

Background: In the latest rankings, breast cancer ranks first in incidence and fifth in mortality among female malignancies worldwide. Early diagnosis and treatment can improve the prognosis and prolong the survival of breast cancer (BC) patients. The NIMA-related kinase (NEK), a group of serine/threonine kinase, is a large and conserved gene family that includes NEK1-NEK11. The NEK plays a pivotal role in the cell cycle and microtubule formation. However, an integrative analysis of the effect and prognosis value of NEK family members on BC patients is still lacking. Methods: In this study, the expression profiles of NEK family members in BC and its subgroups were analyzed using UALCAN, GEPIA2, and Human Protein Atlas datasets. The prognostic values of NEK family members in BC were evaluated using the Kaplan-Meier plotter. Co-expression profiles and genetic alterations of NEK family members were analyzed using the cBioPortal database. The function and pathway enrichment analysis of the NEK family were performed using the WebGestalt database. The correlation analysis of the NEK family and immune cell infiltration in BC was conducted using the TIMER 2.0 database. Results: In this study, we compared and analyzed the prognosis values of the NEKs. We found that NEK9 was highly expressed in normal breast tissues than BC, and NEK2, NEK6, and NEK11 were significantly highly expressed in BC than adjacent normal tissues. Interestingly, the expression levels of NEK2, NEK6, and NEK10 were not only remarkably correlated with the tumor stage but also with the molecular subtype. Through multilevel research, we found that high expression levels of NEK1, NEK3, NEK8, NEK9, NEK10, and NEK11 suggested a better prognosis value in BC, while high expression levels of NEK2 and NEK6 suggested a poor prognosis value in BC. Conclusion: Our studies show the prognosis values of the NEKs in BC. Thus, we suggest that NEKs may be regarded as novel biomarkers for predicting potential prognosis values and potential therapeutic targets of BC patients.

Notch3 Transactivates Glycogen Synthase Kinase-3-Beta and Inhibits Epithelial-to-Mesenchymal Transition in Breast Cancer Cells.

As a critical transformational process in the attributes of epithelial cells, epithelial-to-mesenchymal transition (EMT) is involved in tumor invasion, metastasis, and resistance to treatment, which contributes to the ultimate death of some patients with breast cancer. Glycogen synthase kinase-3-beta (GSK3ß) is thought to be an EMT suppressor that down-regulates the protein, snail, a zinc finger transcription inhibitor, and regulates E-cadherin expression and the Wnt signaling pathway. Our previous studies have shown that Notch3 also inhibits EMT in breast cancer. In mammary gland cells, GSK3ß physically bound and phosphorylated the intracellular domain of two Notch paralogs: N1ICD was positively regulated, but N2ICD was negatively regulated; however, the relationship between Notch3, GSK3ß, and EMT in breast cancer is still unclear and crosstalk between Notch3 and GSK3ß has not been widely investigated. In this study, we revealed that Notch3 was an essential antagonist of EMT in breast cancer cells by transcriptionally upregulating GSK3ß. In breast cancer, MCF-7 and MDA-MB-231 cell lines, the silencing of Notch3 reduced GSK3ß expression, which is sufficient to induce EMT. Conversely, ectopic Notch3 expression re-activated GSK3ß and E-cadherin. Mechanistically, Notch3 can bind to the GSK3ß promoter directly and activate GSK3ß transcription. In human breast cancer samples, Notch3 expression is positively associated with GSK3ß (r = 0.416, p = 0.001); moreover, high expressions of Notch3 and GSK3ß mRNA are correlated to better relapse-free survival in all breast cancer patients via analysis in "the Kaplan-Meier plotter" database. In summary, our preliminary results suggested that Notch3 might inhibit EMT by trans-activating GSK3ß in breast cancer cells. The suppression of Notch3 expression may contribute to EMT by transcriptionally downregulating GSK3ß in breast cancer.

SCMAG: A Semisupervised Single-Cell Clustering Method Based on Matrix Aggregation Graph Convolutional Neural Network.

Clustering analysis is one of the most important technologies for single-cell data mining. It is widely used in the division of different gene sequences, the identification of functional genes, and the detection of new cell types. Although the traditional unsupervised clustering method does not require label data, the distribution of the original data, the setting of hyperparameters, and other factors all affect the effectiveness of the clustering algorithm. While in some cases the type of some cells is known, it is hoped to achieve high accuracy if the prior information about those cells is utilized sufficiently. In this study, we propose SCMAG (a semisupervised single-cell clustering method based on a matrix aggregation graph convolutional neural network) that takes into full consideration the prior information for single-cell data. To evaluate the performance of the proposed semisupervised clustering method, we test on different single-cell datasets and compare with the current semisupervised clustering algorithm in recognizing cell types on various real scRNA-seq data; the results show that it is a more accurate and significant model.

The lncRNA SLCO4A1-AS1/miR-876-3p/RBBP6 axis regulates cell proliferation and apoptosis in acute lymphocytic leukemia via the JNK signaling pathway.

INTRODUCTION: Acute lymphocytic leukemia (ALL) is a hematologic malignancy caused by the clonal proliferation of immature lymphocytes. Long noncoding RNAs (lncRNAs) have been reported as critical regulators in several cancers, including ALL. LncRNA SLCO4A1 antisense RNA 1 (SLCO4A1-AS1) has been revealed to be implicated in tumorigenesis of several cancers. Our study focused on the role of SLCO4A1-AS1 in ALL. METHODS: RT-qPCR, Western blot analysis, CCK-8, EdU, and Flow cytometry analysis were used to explore the biological function of SLCO4A1-AS1 in ALL cellular processes. Luciferase reporter and RNA pull-down assays were applied to explore the mechanism of SLCO4A1-AS1 in ALL cells. RESULTS: SLCO4A1-AS1 was upregulated in ALL tissues and cell lines. We found that suppression of SLCO4A1-AS1 suppressed ALL cell proliferation and facilitated cell apoptosis. Our result confirmed that SLCO4A1-AS1 acted as a ceRNA by sponging microRNA 876-3p (miR-876-3p) to upregulate retinoblastoma binding protein 6 (RBBP6) expression in ALL cells. Moreover, SLCO4A1-AS1 activated the JNK signaling pathway by upregulating RBBP6. Rescue assays revealed that the activation of the JNK signaling or overexpression of RBBP6 revered the suppressive effect of SLCO4A1-AS1 knockdown on growth of ALL cells. CONCLUSION: SLCO4A1-AS1 promoted cell growth of ALL by the miR-876-3p/RBBP6 axis to activate the JNK signaling pathway.