Versatile Structural Engineering of Metal-Organic Frameworks Enabling Switchable Catalytic Selectivity.

The structure engineering of metal-organic frameworks (MOFs) forms the cornerstone of their applications. Nonetheless, realizing the simultaneous versatile structure engineering of MOFs remains a significant challenge. Herein, a dynamically mediated synthesis strategy to simultaneously engineer the crystal structure, defect structure, and nanostructure of MOFs is proposed. These include amorphous Zr-ODB nanoparticles, crystalline Zr-ODB-hz (ODB = 4,4'-oxalyldibenzoate, hz = hydrazine) nanosheets, and defective d-Zr-ODB-hz nanosheets. Aberration-corrected scanning transmission electron microscopy combined with low-dose high-angle annular dark-field imaging technique vividly portrays these engineered structures. Concurrently, the introduced hydrazine moieties confer self-reduction properties to the respective MOF structures, allowing the in situ installation of catalytic Pd nanoparticles. Remarkably, in the hydrogenation of vanillin-like biomass derivatives, Pd/Zr-ODB-hz yields partially hydrogenated alcohols as the primary products, whereas Pd/d-Zr-ODB-hz exclusively produces fully hydrogenated alkanes. Density functional theory calculations, coupled with experimental evidence, uncover the catalytic selectivity switch triggered by the change in structure type. The proposed strategy of versatile structure engineering of MOFs introduces an innovative pathway for the development of high-performance MOF-based catalysts for various reactions.

Single Site Coordination Enabled Construction of Metal-Diketimine-Linked Covalent Organic Frameworks for Boosted Electrooxidation of Biomass Derivative.

Aromatic aldehydes are widely used for the construction of covalent organic frameworks (COFs). However, due to the high flexibility, high steric hindrance, and low reactivity, it remains challenging to synthesize COFs using ketones as building units, especially the highly flexible aliphatic ones. Here, the single nickel site coordination strategy is reported to lock the configurations of the highly flexible diketimine to transform discrete oligomers or amorphous polymers into highly crystalline nickel-diketimine-linked COFs (named as Ni-DKI-COFs). The strategy has been successfully extended to the synthesis of a series of Ni-DKI-COFs by the condensation of three flexible diketones with two tridentate amines. Thanks to the ABC stacking model with high amount and easily accessible single nickel (II) sites on their 1D channels, Ni-DKI-COFs are exploited as well-defined electrocatalyst platforms for efficiently electro-upgrading biomass-derived 5-Hydroxymethylfurfural (HMF) into value-added 2,5-furandicarboxylic acid (FDCA) with a 99.9% yield and a 99.5% faradaic efficiency as well as a high turnover frequency of 0.31 s-1 .

A modified cyanobacteria prediction model based on cellular automata model using N and P concentration reverse data: a case study in Taihu Lake.

The problem of algal bloom caused by eutrophication has attracted global attention. Many scholars have studied the problem associated with algae bloom, but few have carried out dynamic monitoring, instead focusing on the formation mechanism of cyanobacteria. For our study of the Taihu Lake in China, we used Moderate-Resolution Imaging Spectroradiometer (MODIS) and Landsat remote sensing image data from 2017 to establish a prediction model. First, we used MODIS data to retrieve the concentration of N, P, and chlorophyll a in water. Then, we applied the analytic hierarchy process (AHP) model to the inversion results to construct the diffusion potential index. Finally, we used C# to compile the cellular automata (CA) model. We found that the distribution of cyanobacteria predicted by our method was consistent with the algal bloom situation of Taihu Lake in 2017. The results showed that the method effectively predicts the dynamic transfer of cyanobacteria from outbreak to diffusion in a short period of time, which can help decision-makers monitor lake health.

Utility of comprehensive genomic profiling in directing treatment and improving patient outcomes in advanced non-small cell lung cancer.

BACKGROUND: With the identification of new targetable drivers and the recent emergence of novel targeted drugs, using comprehensive genomic profiling in lieu of the routine testing for classic drivers in the clinical care for advanced NSCLC has been increasingly advocated. However, the key assumption justifying this practice, that comprehensive genomic profiling could lead to effective anticancer therapies and improve patient outcomes, remains unproved. METHODS: Comprehensive genomic profiling was prospectively applied in 1564 advanced NSCLC patients to identify potentially actionable genomic alterations. Patients were assigned to genotype-matched targeted therapies or nonmatched therapies based on the profiling results. Its utility in directing treatments was determined by the proportion of patients receiving genotype-matched targeted therapies and the proportion of patients being enrolled into genotype-matched clinical trials. Its impacts on patient outcomes were assessed by comparing progression-free survival (PFS) and overall survival (OS) between patients who received a genotype-matched and nonmatched therapy. RESULTS: From October 2016 to October 2019, tumor genomic profiles were established in 1166 patients, leading to a matched targeted therapy in 37.7% (n = 440) and a genotype-matched trial enrollment in 20.9% of patients (n = 244). Potentially actionable alterations were detected in 781 patients (67.0%). For these patients, a genomic profiling-directed matched therapy significantly improved PFS (9.0 months vs 4.9 months, P < 0.001) and OS (3.9 years vs 2.5 years, P < 0.001) compared with a nonmatched therapy. Excluding patients with standard targeted therapies, genomic profiling led to a matched targeted therapy in 16.7% (n = 24) and a matched trial enrollment in 11.2% (n = 16) of patients. No PFS (4.7 months vs 4.6 months, P = 0.530) or OS (1.9 years vs 2.4 years, P = 0.238) benefit was observed with the use of genotype-matched targeted therapies in this population. CONCLUSIONS: Comprehensive genomic profiling is of clinical utility in assisting treatment selection, facilitating clinical trial enrollment, and improving patient outcomes in advanced NSCLC. However, for patients carrying alterations without standard-of-care targeted drugs, the interpretation of genomic profiling results should be careful given the low likelihood of benefit from the investigational or off-label use of targeted therapies in this population in the current treatment landscape. TRIAL REGISTRATION: ChiCTR1900027582 (retrospectively registered on 19 November 2019).

An Improved Character Recognition Framework for Containers Based on DETR Algorithm.

An improved DETR (detection with transformers) object detection framework is proposed to realize accurate detection and recognition of characters on shipping containers. ResneSt is used as a backbone network with split attention to extract features of different dimensions by multi-channel weight convolution operation, thus increasing the overall feature acquisition ability of the backbone. In addition, multi-scale location encoding is introduced on the basis of the original sinusoidal position encoding model, improving the sensitivity of input position information for the transformer structure. Compared with the original DETR framework, our model has higher confidence regarding accurate detection, with detection accuracy being improved by 2.6%. In a test of character detection and recognition with a self-built dataset, the overall accuracy can reach 98.6%, which meets the requirements of logistics information identification acquisition.

Multi-Directional Scene Text Detection Based on Improved YOLOv3.

To address the problem of low detection rate caused by the close alignment and multi-directional position of text words in practical application and the need to improve the detection speed of the algorithm, this paper proposes a multi-directional text detection algorithm based on improved YOLOv3, and applies it to natural text detection. To detect text in multiple directions, this paper introduces a method of box definition based on sliding vertices. Then, a new rotating box loss function MD-Closs based on CIOU is proposed to improve the detection accuracy. In addition, a step-by-step NMS method is used to further reduce the amount of calculation. Experimental results show that on the ICDAR 2015 data set, the accuracy rate is 86.2%, the recall rate is 81.9%, and the timeliness is 21.3 fps, which shows that the proposed algorithm has a good detection effect on text detection in natural scenes.

Acid/Base-Co-catalyzed Formal Baeyer-Villiger Oxidation Reaction of Ketones: Using Molecular Oxygen as the Oxidant.

A novel acid/base-co-catalyzed formal Baeyer-Villiger oxidation of various ketones using O2 as the sole oxidant under metal-free conditions has been developed for the first time. The reaction tolerates a wide range of ketones and anilines and provides a simple and efficient method for the construction of various amides and isoquinolin-1-ones from the reactions of ketones with anilines in a single step.

Thermally induced formal [4+2] cycloaddition of 3-aminocyclobutenones with electron-deficient alkynes: facile and efficient synthesis of 4-pyridones.

A thermally induced novel formal [4+2] cycloaddition of cyclobutenones with electron-deficient alkynes under metal-free conditions has been developed for the first time. The reaction can proceed in a highly regioselective manner and provides a straightforward and efficient method for the synthesis of 4-pyridone derivatives from readily available starting materials in a single step.

Lichen extracts regulate the expression of BMP7 via miR-194-5p targeting to decrease the risk atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF), the most common cardiac supraventricular arrhythmia, affects more than 5 million people worldwide. Increasing evidence has demonstrated that genetic factors play an important role in the pathogenesis of AF, and multiple genes responsible for AF have been identified. A better understanding of the genetic mechanism underlying AF would be expected to lead to more accurate risk stratification of AF and optimal clinical treatment strategies. METHODS: Immunofluorescence staining was performed to find the components which would have effects on the H9c2 cells development. The changes of BMP7 and miR-194-5p expressions were detected before and after Human Cardiac Myocytes (HCM) were treated with Lichen extraction. In order to confirm whether Lichen could increase the expression of BMP7 through inhibiting the expression of miR-194-5p, the mRNA levels of BMP7 and miR-194-5p were determined in HCM before and after the treatment of Lichen on the conditions that miR-194-5p was over-expressed or not. RESULTS: After 48 hours' treatment with 20 µg/mL Lichen extracts, the Collagen I expression level significantly decreased. The expressions of several genes in H9c2 cells could were changed after the treatment of Lichen extracts and some mRNA of them could also be targeted by miR-194-5p including BMP7. Lichen could depress the expression of miR-194-5p in HCM no matter miR-194-5p was overexpressed or not and correspondingly, the expression of BMP7 could be increased in both conditions. CONCLUSIONS: It is indicated that Lichen extracts could regulate the expression of atrial fibrillation-associated genes via miR-194-5a targeting.

Specific Inhibition of ß-Catenin in Jeko-1 Mantle Cell Lymphoma Cell Line Decreases Proliferation and Induces Apoptosis.

BACKGROUND: The canonical Wnt signaling pathway has been considered as a potent oncogenic signaling in the initiation and progression of hematological malignancies. As a key regulator of the Wnt signaling pathway, the role of ß-catenin in mantle cell lymphoma (MCL) pathogenesis and progression was investigated in this study. MATERIAL AND METHODS: A total of 30 MCL samples were collected from patients and were examined for the expression of ß-catenin and p-GSK3ß using immunohistochemical (IHC) staining. Further in vitro studies employed MTT and Western blot assays detecting proliferation and apoptosis-related proteins in MCL cell line Jeko-1, which were transfected with ß-catenin shRNA or specific inhibitor XAV939. RESULTS: Expression of ß-catenin and phosphorylated glycogen synthase kinase-3 beta (p-GSK3ß) in MCL was significantly higher than those in controlled samples. In vitro studies indicated that ß-catenin knockdown significantly inhibited cell proliferation and induced apoptosis in Jeko-1 cells. Furthermore, XAV939 induced apoptosis and growth arrest in Jeko-1 cells. Both inhibitory agents increased Bax and caspase 3 proteins, and decreased Bcl-2, c-Myc, and Cyclin D1 proteins. CONCLUSIONS: The specific inhibition of ß-catenin induces apoptosis and growth arrest, making it a potential therapeutic target against MCL.

[Expression Changes of ß-catenin and P-GSK-3ß in Patients with Mantle Cell Lymphoma].

OBJECTIVE: This study was purposed to detect the expressions of ß-catenin and P-GSK-3 ß in Wnt signaling pathway of patients with mantle cell lymphoma(MCL), and investigate its relationship with the pathogenesis of MCL. METHODS: The expression levels of ß -catenin protein and P-GSK-3 protein in mantle cell lymphoma and hyperplastic lymphadenitis were detected by using anti-ß-catenin, P-GSK-3ß polyclonal antibody and S-P staining technique. RESULTS: The abnormal expression of ß-catenin protein(73.33%) in mantle cell lymphoma group was significantly higher than that (6.7%) in reactive lymph node hyperplasia group (P<0.05); and the positive rate of P-GSK-3 ß(66.67%) in mantle cell lymphoma group was significantly higher than that (16.67%) in reactive hyperplasia of lymph node group (P<0.05). Spearman correlation analysis showed that there was obvious positive correlation (R=0.852, P<0.01). CONCLUSION: The abnormal high expressions of ß-catenin and P-GSK-3 ß protein have been confirmed to appeare in mantle cell lymphoma.

[Antiproliferative Effect of Specific Inhibitor XAV939 for ß-catenin on MCL Jeko-1 Cells].

OBJECTIVE: To investigate the effect of short hairpin RNA (shRNA) and XAV939, a specific inhibitor for ß-catenin, on growth and apoptosis of mantle cell lymphoma(MCL) Jeko-1 cell line. METHODS: ß-catenin shRNA eukaryotic expression vector was transfected into Jeko-1 cells, the antiproliferative effect of shRNA on Jeko-1 cells was detected by RT-PCR and Western blot. The proliferation inhibitory rate of Jeko-1 cells treated by different doses of XAV939 was assayed by MTT method; the level of apoptosis of Jeko-1 cells was detected by flow cytometry; the expression levels of apoptosis-related protein BCL-2, BAX, CyclinD1, C-MYC and Caspase-3 in Jeko-1 cells were determined by Western blot. RESULTS: The expression of ß-catenin mRNA and growth of Jeko-1 cell line were inhibited by shRNA; after Jeko-1 cells treated with 0,2 and 8 µmol/L XAV939 for 48 hours, the cell proliferation rate decreased, while the cell apoptosis rate increased, the expressions of apoptosis-related protein BCL-2, CyclinD1 and C-MYC were down-regulated, on the contrary, the expression of BAX and caspase-3 were up-regulated. CONCLUSION: The specific inhibition of ß-catenin can inhibit Jeko-1 cell proliferation and promote the cell apoptosis.

EGF is required for cardiac differentiation of P19CL6 cells through interaction with GATA-4 in a time- and dose-dependent manner.

The regulation of cardiac differentiation is critical for maintaining normal cardiac development and function. The precise mechanisms whereby cardiac differentiation is regulated remain uncertain. Here, we have identified a GATA-4 target, EGF, which is essential for cardiogenesis and regulates cardiac differentiation in a dose- and time-dependent manner. Moreover, EGF demonstrates functional interaction with GATA-4 in inducing the cardiac differentiation of P19CL6 cells in a time- and dose-dependent manner. Biochemically, GATA-4 forms a complex with STAT3 to bind to the EGF promoter in response to EGF stimulation and cooperatively activate the EGF promoter. Functionally, the cooperation during EGF activation results in the subsequent activation of cyclin D1 expression, which partly accounts for the lack of additional induction of cardiac differentiation by the GATA-4/STAT3 complex. Thus, we propose a model in which the regulatory cascade of cardiac differentiation involves GATA-4, EGF, and cyclin D1.

Induction of the CLOCK gene by E2-ERα signaling promotes the proliferation of breast cancer cells.

Growing genetic and epidemiological evidence suggests a direct connection between the disruption of circadian rhythm and breast cancer. Moreover, the expression of several molecular components constituting the circadian clock machinery has been found to be modulated by estrogen-estrogen receptor α (E2-ERα) signaling in ERα-positive breast cancer cells. In this study, we investigated the regulation of CLOCK expression by ERα and its roles in cell proliferation. Immunohistochemical analysis of human breast tumor samples revealed high expression of CLOCK in ERα-positive breast tumor samples. Subsequent experiments using ERα-positive human breast cancer cell lines showed that both protein and mRNA levels of CLOCK were up-regulated by E2 and ERα. In these cells, E2 promoted the binding of ERα to the EREs (estrogen-response elements) of CLOCK promoter, thereby up-regulating the transcription of CLOCK. Knockdown of CLOCK attenuated cell proliferation in ERα-positive breast cancer cells. Taken together, these results demonstrated that CLOCK could be an important gene that mediates cell proliferation in breast cancer cells.

PTEN suppresses the oncogenic function of AIB1 through decreasing its protein stability via mechanism involving Fbw7 alpha.

BACKGROUND: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a phosphatase having both protein and lipid phosphatase activities, and is known to antagonize the phosphoinositide 3-kinase/AKT (PI3K/AKT) signaling pathway, resulting in tumor suppression. PTEN is also known to play a role in the regulation of numerous transcription factors. Amplified in breast cancer 1 (AIB1) is a transcriptional coactivator that mediates the transcriptional activities of nuclear receptors and other transcription factors. The present study investigated how PTEN may regulate AIB1, which is amplified and/or overexpressed in many human carcinomas, including breast cancers. RESULTS: PTEN interacted with AIB1 via its phophatase domain and regulated the transcriptional activity of AIB1 by enhancing the ubiquitin-mediated degradation of AIB1. This process did not appear to require the phosphatase activity of PTEN, but instead, involved the interaction between PTEN and F-box and WD repeat domain-containing 7 alpha (Fbw7α), the E3 ubiquitin ligase involved in the ubiquitination of AIB1. PTEN interacted with Fbw7α via its C2 domain, thereby acting as a bridge between AIB1 and Fbw7α, and this led to enhanced degradation of AIB1, which eventually accounted for its decreased transcriptional activity. At the cell level, knockdown of PTEN in MCF-7 cells promoted cell proliferation. However when AIB1 was also knocked down, knockdown of PTEN had no effect on cell proliferation. CONCLUSIONS: PTEN might act as a negative regulator of AIB1 whereby the association of PTEN with both AIB1 and Fbw7α could lead to the downregulation of AIB1 transcriptional activity, with the consequence of regulating the oncogenic function of AIB1.

The transcriptional activity of co-activator AIB1 is regulated by the SUMO E3 ligase PIAS1.

BACKGROUND INFORMATION: Amplified in breast cancer 1 (AIB1) is a transcriptional coactivator of nuclear receptors and other transcription factors. It is required for animal growth and reproductive development, and has also been implicated in breast carcinogenesis. Although AIB1 is known to be covalently modified by SUMO-1, which serves to regulate its stability and transcriptional activity, the exact SUMO E3 ligase involved in its sumoylation has not been determined. In order to resolve this question, we investigated the interaction between AIB1 and different members of PIAS proteins (all are SUMO E3 ligases) through immunoprecipiation. RESULTS: Among the five different PIAS proteins, only PIAS1 co-immunoprecipitated with AIB1 in extract prepared from breast cancer cells (MCF-7). Over-expression of PIAS1 together with AIB1 in MCF-7 cells led to increased sumoylation of AIB1, resulting in repression of its transcriptional activity. In contrast, the PIAS1 mutant (C350S) lacking E3 ligase activity appeared to have no effect on the sumoylation of AIB1. Through sumoylation of AIB1, PIAS1 also promoted the stability of AIB1 and attenuated its interaction with estrogen receptor α (ERα), resulting in repression of the transactivation activity of ERα. In addition, MCF-7 cells co-transfected with wild-type PIAS1 and AIB1 showed about 40% reduction in cell growth, while cells co-transfected with wild-type PIAS1 and mutant AIB1 resistant to sumoylation showed about 34% increase in cell growth compared to cells transformed with wild-type AIB1 only. CONCLUSIONS: Taken together, these results suggested that PIAS1 may play a crucial role in the regulation of AIB1 transcriptional activity through sumoylation.

[Study on aberration in histone methylation and acetylation in acute leukemia].

OBJECTIVE: To study the aberration in histone H3K4 and H3K9 methylation and H3 and H4 acetylation in human acute leukemia (AL) cells. METHODS: The histone H3K4 and H3K9 methylation and H3 and H4 acetylation were detected by Western blot in 34 AL patients and 13 controls (9 non leukemia patients, 4 healthy volunteers). RESULTS: The level of H3K4 methylation was significantly lower in 19 AL patients than in non leukemia (0.220 ± 0.096 vs 0.447 ± 0.186, P < 0.01), while the level of H3K9 methylation was significantly higher (0.409 ± 0.106 vs 0.168 ± 0.015, P < 0.01); Both level of histone H3 and H4 acetylation in 15 AL patients were significantly lower (H3: 0.128 ± 0.013 vs 0.386 ± 0.104, H4: 0.096 ± 0.008 vs 0.341 ± 0.096, respectively, both P < 0.01). CONCLUSION: Aberration of histone methylation and deficient histone acetylation in AL may represent the markers for an aberrant post-translational modification of histones and chromatin structure. It might be a potential epigenetic target for anti-leukemia agent.

Deficient histone acetylation in acute leukemia and the correction by an isothiocyanate.

OBJECTIVE: Since histone hypoacetylation due to excess histone deacetylases (HDACs) has been associated with transcriptional repression in leukemia, we aimed to determine deficient histone acetylation in patients with acute leukemia and the effect of its correction by an isothiocyanate. METHODS: The acetylation status of histones H3 and H4 in cells from patients with untreated acute leukemia was determined by Western blot. Deficient histone acetylation was analyzed in relation to the disease state. Bone marrow cells from 10 patients with acute myeloid leukemia (AML) were cultured in phenylhexyl isothiocyanate (PHI) to evaluate correction of the deficiency. RESULTS: Acetylation of histones H3 and H4 was virtually undetectable or significantly lower in acute leukemia. This deficiency was consistent among all the patients examined. Histone acetylation was up-regulated in the presence of PHI, revealing an excess of deacetylation activity in AML. PHI treatment induced apoptosis, indicating HDAC inhibition was able to correct the deficiency. CONCLUSIONS: Deficient histone acetylation may represent an aberration at the epigenetic level in acute leukemia. PHI might represent a target for correcting deficient acetylation, and potential epigenetic regulators for preventing the progression of leukemia.