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Article ; Online: Unveiling NUSAP1 as a common gene signature linking chronic HBV infection and HBV-related HCC.

Meng, Jiao / Yang, Zhenkun / Jiang, Xinyi / Zou, Jian

Discover. Oncology

2024 Volume 15, Issue 1, Page(s) 61

Abstract: Background: Hepatitis B virus (HBV) is a significant contributor to the development of hepatocellular carcinoma (HCC). Chronic HBV infection (CHB) facilitates disease progression through various mechanisms. However, the specific factor responsible for ... ...

Abstract	Background: Hepatitis B virus (HBV) is a significant contributor to the development of hepatocellular carcinoma (HCC). Chronic HBV infection (CHB) facilitates disease progression through various mechanisms. However, the specific factor responsible for the progression of HBV infection to HCC remains unresolved. This study aims to identify the hub gene linking CHB and HBV-related HCC through bioinformatic analysis and experimental verification. Methods: Differentially expressed genes (DEGs) were identified in datasets encompassing CHB and HBV-HCC patients from the GEO database. Enriched pathways were derived from GO and KEGG analysis. Hub genes were screened by protein-protein interaction (PPI) analysis and different modules in Cytoscape software. The significance of the selected hub gene in prognosis was further assessed in validated datasets. The effects of hub genes on cell growth and apoptosis were further determined in functional experiments. Results: The study revealed upregulation of NUSAP1 in CHBs and HBV-HCCs. High expression of NUSAP1 served as an independent predictor for poor prognosis of liver cancers. Functional experiments demonstrated that NUSAP1 promotes cell growth, influences cell cycle process, and protects cells from apoptosis in HepG2.2.15 cells. Conclusion: NUSAP1 serves as a poor prognostic indicator for liver cancers, and potentially plays a crucial role in HBV-HCC progression by promoting proliferation and inhibiting apoptosis.
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ISSN	2730-6011
ISSN (online)	2730-6011
DOI	10.1007/s12672-024-00922-4
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Article ; Online: A new multi-scale backbone network for object detection based on asymmetric convolutions.

Ma, Xianghua / Yang, Zhenkun

Science progress

2021 Volume 104, Issue 2, Page(s) 368504211011343

Abstract: Real-time object detection on mobile platforms is a crucial but challenging computer vision task. However, it is widely recognized that although the lightweight object detectors have a high detection speed, the detection accuracy is relatively low. In ... ...

Abstract	Real-time object detection on mobile platforms is a crucial but challenging computer vision task. However, it is widely recognized that although the lightweight object detectors have a high detection speed, the detection accuracy is relatively low. In order to improve detecting accuracy, it is beneficial to extract complete multi-scale image features in visual cognitive tasks. Asymmetric convolutions have a useful quality, that is, they have different aspect ratios, which can be used to exact image features of objects, especially objects with multi-scale characteristics. In this paper, we exploit three different asymmetric convolutions in parallel and propose a new multi-scale asymmetric convolution unit, namely MAC block to enhance multi-scale representation ability of CNNs. In addition, MAC block can adaptively merge the features with different scales by allocating learnable weighted parameters to three different asymmetric convolution branches. The proposed MAC blocks can be inserted into the state-of-the-art backbone such as ResNet-50 to form a new multi-scale backbone network of object detectors. To evaluate the performance of MAC block, we conduct experiments on CIFAR-100, PASCAL VOC 2007, PASCAL VOC 2012 and MS COCO 2014 datasets. Experimental results show that the detection precision can be greatly improved while a fast detection speed is guaranteed as well.
MeSH term(s)	Neural Networks, Computer ; Records ; Volatile Organic Compounds
Chemical Substances	Volatile Organic Compounds
Language	English
Publishing date	2021-04-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	128412-5
ISSN	2047-7163 ; 0036-8504 ; 0302-1785
ISSN (online)	2047-7163
ISSN	0036-8504 ; 0302-1785
DOI	10.1177/00368504211011343
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Article ; Online: EBMGC-GNF: Efficient Balanced Multi-view Graph Clustering via Good Neighbor Fusion.

Wu, Danyang / Yang, Zhenkun / Lu, Jitao / Xu, Jin / Xu, Xiangmin / Nie, Feiping

IEEE transactions on pattern analysis and machine intelligence

2024 Volume PP

Abstract: Exploiting consistent structure from multiple graphs is vital for multi-view graph clustering. To achieve this goal, we propose an Efficient Balanced Multi-view Graph Clustering via Good Neighbor Fusion (EBMGC-GNF) model which comprehensively extracts ... ...

Abstract	Exploiting consistent structure from multiple graphs is vital for multi-view graph clustering. To achieve this goal, we propose an Efficient Balanced Multi-view Graph Clustering via Good Neighbor Fusion (EBMGC-GNF) model which comprehensively extracts credible consistent neighbor information from multiple views by designing a Cross-view Good Neighbors Voting module. Moreover, a novel balanced regularization term based on p-power function is introduced to adjust the balance property of clusters, which helps the model adapt to data with different distributions. To solve the optimization problem of EBMGC-GNF, we transform EBMGC-GNF into an efficient form with graph coarsening method and optimize it based on accelareted coordinate descent algorithm. In experiments, extensive results demonstrate that, in the majority of scenarios, our proposals outperform state-of-the-art methods in terms of both effectiveness and efficiency.
Language	English
Publishing date	2024-05-08
Publishing country	United States
Document type	Journal Article
ISSN	1939-3539
ISSN (online)	1939-3539
DOI	10.1109/TPAMI.2024.3398220
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Article ; Online: Pd-Catalyzed Ligand-Directed Divergent Cycloaddition of Cyclic 1-Azadienes with Oxo-1,4-dipoles.

Xie, Hongling / Chen, Lei / Han, Zhengyu / Yang, Zhenkun / Sun, Jianwei / Huang, Hai

Organic letters

2023 Volume 25, Issue 27, Page(s) 5011–5016

Abstract: Ligand-directed divergent synthesis (LDS) is an important synthetic tool for the preparation of structurally diverse organic molecules without tedious steps to modify substrates. Herein, we introduce the realization of 3,4-, 1,2-, and 1,4-cyclization of ... ...

Abstract	Ligand-directed divergent synthesis (LDS) is an important synthetic tool for the preparation of structurally diverse organic molecules without tedious steps to modify substrates. Herein, we introduce the realization of 3,4-, 1,2-, and 1,4-cyclization of benzo[
MeSH term(s)	Catalysis ; Cycloaddition Reaction ; Ligands ; Palladium ; Pyrans/chemistry ; Stereoisomerism
Chemical Substances	Ligands ; Palladium (5TWQ1V240M) ; Pyrans ; trimethylene carbonate (4316AQ174Q)
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Journal Article
ISSN	1523-7052
ISSN (online)	1523-7052
DOI	10.1021/acs.orglett.3c01646
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Article ; Online: Tandem Allylic Amination/oxa-Michael Addition of Vinyl Methylene Cyclic Carbonates via Palladium-Organo Relay Catalysis.

Yang, Zhenkun / Bao, Yu / Huang, Jiaxin / Han, Zhengyu / Sun, Jianwei / Huang, Hai

Organic letters

2023 Volume 25, Issue 30, Page(s) 5624–5629

Abstract: A tandem allylic amination/oxa-Michael addition of vinyl methylene cyclic carbonates (VMCCs) has been developed to construct heterocycles by single palladium catalysis or palladium-organo relay catalysis. In this process, the bisnucleophiles first ... ...

Abstract	A tandem allylic amination/oxa-Michael addition of vinyl methylene cyclic carbonates (VMCCs) has been developed to construct heterocycles by single palladium catalysis or palladium-organo relay catalysis. In this process, the bisnucleophiles first underwent regioselective allylic amination, and then the second nucleophilic group further completed the hetero-Michael addition reaction to form a series of heterocycles. Among them, the chiral 3,4-dihydro-2
Language	English
Publishing date	2023-07-24
Publishing country	United States
Document type	Journal Article
ISSN	1523-7052
ISSN (online)	1523-7052
DOI	10.1021/acs.orglett.3c02014
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Article ; Online: p53/E2F7 axis promotes temozolomide chemoresistance in glioblastoma multiforme.

Meng, Jiao / Qian, Wei / Yang, Zhenkun / Gong, Lingli / Xu, Daxing / Huang, Hongbo / Jiang, Xinyi / Pu, Zhening / Yin, Ying / Zou, Jian

BMC cancer

2024 Volume 24, Issue 1, Page(s) 317

Abstract: Background: Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer, and chemoresistance poses a significant challenge to the survival and prognosis of GBM. Although numerous regulatory mechanisms that contribute to chemoresistance ... ...

Abstract	Background: Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer, and chemoresistance poses a significant challenge to the survival and prognosis of GBM. Although numerous regulatory mechanisms that contribute to chemoresistance have been identified, many questions remain unanswered. This study aims to identify the mechanism of temozolomide (TMZ) resistance in GBM. Methods: Bioinformatics and antibody-based protein detection were used to examine the expression of E2F7 in gliomas and its correlation with prognosis. Additionally, IC Results: Elevated levels of E2F7 were detected in GBM tissue and were correlated with a poor prognosis for patients. E2F7 was found to be upregulated in TMZ-R tumors, and its high levels were linked to increased chemotherapy resistance by limiting drug uptake and decreasing DNA damage. The expression of E2F7 was also found to be regulated by the activation of p53. Conclusions: The high expression of E2F7, regulated by activated p53, confers chemoresistance to GBM cells by inhibiting drug uptake and DNA damage. These findings highlight the significant connection between sustained p53 activation and GBM chemoresistance, offering the potential for new strategies to overcome this resistance.
MeSH term(s)	Humans ; Antineoplastic Agents, Alkylating/pharmacology ; Antineoplastic Agents, Alkylating/therapeutic use ; Brain Neoplasms/drug therapy ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics ; E2F7 Transcription Factor/metabolism ; Glioblastoma/drug therapy ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Prognosis ; Temozolomide/pharmacology ; Temozolomide/therapeutic use ; Tumor Suppressor Protein p53/genetics
Chemical Substances	Antineoplastic Agents, Alkylating ; E2F7 protein, human ; E2F7 Transcription Factor ; Temozolomide (YF1K15M17Y) ; Tumor Suppressor Protein p53 ; TP53 protein, human
Language	English
Publishing date	2024-03-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-024-12017-y
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Article: Identification of gene signatures and potential therapeutic targets for acquired chemotherapy resistance in gastric cancer patients.

Sun, Jie / Zhao, Jingjing / Yang, Zhenkun / Zhou, Zhiyi / Lu, Peihua

Journal of gastrointestinal oncology

2021 Volume 12, Issue 2, Page(s) 407–422

Abstract: Background: Gastric cancer (GC) is the most common type of gastrointestinal cancer, and has been studied extensively. However, resistance to chemotherapeutic agents has become a major problem, leading to treatment failure. This study aimed to ... ...

Abstract	Background: Gastric cancer (GC) is the most common type of gastrointestinal cancer, and has been studied extensively. However, resistance to chemotherapeutic agents has become a major problem, leading to treatment failure. This study aimed to investigate the molecular mechanisms mediating acquired resistance to cisplatin and fluorouracil (CF) combination-based chemotherapy in GC patients. Methods: The microarray datasets (GSE14209, GSE30070) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) using the limma package in R/Bioconductor. Possible targets of the DEMs were predicted using miRWalk, and the putative miRNA-mRNA regulatory network was constructed using Cytoscape software. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analyses were then conducted and visualized using the Search Tool for Retrieval of Interacting Genes (STRING) and Cytoscape. The prognostic value of hub genes was revealed by Kaplan-Meier Plotter. The causal relationships and interactions between proteins were displayed using DisNor. Finally, similarity analysis was conducted using the Connectivity Map (CMap) profiles to predict a group of small molecules in GC treatment. Results: A total of 394 DEGs and 31 DEMs were identified after analysis of pre- and post-treatment samples of clinical responders to CF therapy. TM9SF4, hsa-miR-185-5p, and hsa-miR-145-5p were found to be critical in the miRNA-mRNA regulatory network. The DEGs were found to be mainly enriched in the processes of ribonucleoprotein complex assembly, catalytic activity acting on RNA, mitochondrial matrix, and thermogenesis. The DEMs were predominantly found to be involved in single-stranded RNA binding and endoplasmic reticulum lumen. HDAC5, DDX17, ILF3, and SDHC were identified as hub genes in the PPI network. Of these, HDAC5, DDX17, and ILF3 were found to be closely related to the overall survival of GC patients. DisNor identified the first neighbors of the key genes. Furthermore, CMap profiles predicted a group of small molecules, including several histone deacetylase inhibitors (HDACIs), menadione, and mibefradil, which could serve as promising therapeutic agents to reverse acquired resistance to CF therapy. Conclusions: Our findings reveal new targets and alternative therapies to overcome the acquired resistance of GC patients to CF treatment.
Language	English
Publishing date	2021-05-12
Publishing country	China
Document type	Journal Article
ZDB-ID	2594644-4
ISSN	2219-679X ; 2078-6891
ISSN (online)	2219-679X
ISSN	2078-6891
DOI	10.21037/jgo-21-81
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Article ; Online: Construction of nine-membered N,N,O-heterocycles

Xie, Hongling / Yang, Zhenkun / Tang, Luning / Han, Zhengyu / Sun, Jianwei / Huang, Hai

Chemical communications (Cambridge, England)

2022 Volume 58, Issue 75, Page(s) 10560–10563

Abstract: A new approach for the synthesis of 9-membered N,N,O-heterocycles by Pd-catalyzed [6+3] dipolar cycloaddition ... ...

Abstract	A new approach for the synthesis of 9-membered N,N,O-heterocycles by Pd-catalyzed [6+3] dipolar cycloaddition of
MeSH term(s)	Catalysis ; Cycloaddition Reaction ; Palladium
Chemical Substances	Palladium (5TWQ1V240M)
Language	English
Publishing date	2022-09-20
Publishing country	England
Document type	Journal Article
ZDB-ID	1472881-3
ISSN	1364-548X ; 1359-7345 ; 0009-241X
ISSN (online)	1364-548X
ISSN	1359-7345 ; 0009-241X
DOI	10.1039/d2cc03666e
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Article ; Online: Construction of diverse polycyclic N-heterocycles

Yang, Zhenkun / Xie, Hongling / Tang, Luning / Sun, Jianwei / Han, Zhengyu / Huang, Hai

Chemical communications (Cambridge, England)

2022 Volume 58, Issue 95, Page(s) 13258–13261

Abstract: An efficient cascade approach for the construction of nitrogen-containing polycyclic compounds from amines tethered with an alkenyl (or alkynyl) group and divinyl carbonates is described. In the presence of Pd(0)-catalyst, an active zwitterionic ... ...

Abstract	An efficient cascade approach for the construction of nitrogen-containing polycyclic compounds from amines tethered with an alkenyl (or alkynyl) group and divinyl carbonates is described. In the presence of Pd(0)-catalyst, an active zwitterionic allylpalladium species is generated and undergoes allylic amination with various amines followed by Diels-Alder reaction to form various polycyclic
MeSH term(s)	Amination ; Cycloaddition Reaction ; Molecular Structure ; Catalysis ; Amines
Chemical Substances	Amines
Language	English
Publishing date	2022-11-29
Publishing country	England
Document type	Journal Article
ZDB-ID	1472881-3
ISSN	1364-548X ; 1359-7345 ; 0009-241X
ISSN (online)	1364-548X
ISSN	1359-7345 ; 0009-241X
DOI	10.1039/d2cc05208c
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Article ; Online: Neovascularization directed by CAVIN1/CCBE1/VEGFC confers TMZ-resistance in glioblastoma.

Wang, Mei / Xia, Die / Xu, Daxing / Yin, Ying / Xu, Fei / Zhang, Bo / Li, Koukou / Yang, Zhenkun / Zou, Jian

Cancer letters

2023 Volume 582, Page(s) 216593

Abstract: Acquisition of resistance to temozolomide (TMZ) poses a significant challenge in glioblastoma (GBM) therapy. Neovascularization, a pivotal process in tumorigenesis and development, remains poorly understood in its contribution to chemoresistance in GBMs. ...

Abstract	Acquisition of resistance to temozolomide (TMZ) poses a significant challenge in glioblastoma (GBM) therapy. Neovascularization, a pivotal process in tumorigenesis and development, remains poorly understood in its contribution to chemoresistance in GBMs. This study unveils aberrant vascular networks within TMZ-resistant (TMZ-R) GBM tissues and identifies the extracellular matrix (ECM) protein CCBE1 as a potential mediator. Through in vivo and in vitro experiments involving gain and loss of function assessments, we demonstrate that high expression of CCBE1 promotes hyper-angiogenesis and orchestrates partial endothelial-to-mesenchymal transition (EndMT) in human microvascular endothelial cells (HCMEC/d3) within GBM. This is likely driven by VEGFC/Rho signaling. Intriguingly, CCBE1 overexpression substantially fails to promote tumor growth, but endows resistance to GBM cells in a vascular endothelial cell-dependent manner. Mechanically, the constitutive phosphorylation of SP1 at Ser101 drives the upregulation of CCBE1 transcription in TMZ resistant tumors, and the excretion of CCBE1 depends on caveolae associated protein 1 (CAVIN1) binding and assembling. Tumor cells derived CCBE1 promotes VEGFC maturation, activates VEGFR2/VEGFR3/Rho signaling in vascular endothelial cells, and ultimately results in hyper-angiogenesis in TMZ-R tumors. Collectively, the current study uncovers the cellular and molecular basis of abnormal angiogenesis in a chemo resistant microenvironment, implying that curbing CCBE1 is key to reversing TMZ resistance.
MeSH term(s)	Humans ; Temozolomide/pharmacology ; Temozolomide/therapeutic use ; Glioblastoma/drug therapy ; Glioblastoma/genetics ; Glioblastoma/metabolism ; Endothelial Cells/metabolism ; Drug Resistance, Neoplasm ; Signal Transduction ; Cell Line, Tumor ; Brain Neoplasms/drug therapy ; Brain Neoplasms/genetics ; Brain Neoplasms/metabolism ; Antineoplastic Agents, Alkylating/pharmacology ; Tumor Microenvironment ; Calcium-Binding Proteins/genetics ; Calcium-Binding Proteins/metabolism ; Tumor Suppressor Proteins/metabolism
Chemical Substances	Temozolomide (YF1K15M17Y) ; Antineoplastic Agents, Alkylating ; CCBE1 protein, human ; Calcium-Binding Proteins ; Tumor Suppressor Proteins
Language	English
Publishing date	2023-12-12
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	195674-7
ISSN	1872-7980 ; 0304-3835
ISSN (online)	1872-7980
ISSN	0304-3835
DOI	10.1016/j.canlet.2023.216593
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