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| 1 | Mesenteric lymph reperfusion may exacerbate brain injury in a rat model of superior mesenteric artery occlusion shock显示文摘BACKGROUND:The intestinal lymphatic pathway and intestinal ischemia/reperfusion are mainly involved in mesenteric lymph duct ligation or drainage;moreover,intervention by reducing the lymph liquid reflux might relieve lung and other organ dysfunction induced by intestinal ischemia/reperfusion;however,research addressing mesenteric lymph reperfusion (MLR) and brain injury has not yet to be reported.OBJECTIVE:To observe the effect of MLR on brain tissue in a rat model of superior mesenteric artery occlusion (SMAO) shock,and to explore the molecular mechanism of MLR.DESIGN,TIME AND SETTING:A randomized,controlled,animal experiment at a neuro-pathophysiology level was performed at the Institute of Microcirculation,Hebei North University;Department of Pathophysiology,Basic Medical College;Department of Pathology,the First Hospital of Hebei North University between December 2007 and March 2009.MATERIALS:Adenosine triphosphate (ATP) standard was provided by the National Institute for the Control of Pharmaceutical and Biological Products;lactic acid (LA),superoxide dismutase (SOD),malonaldehyde (MDA),nitrogen monoxidum (NO),nitric oxide synthase (NOS),myeloperoxidase (MPO) and ATPase assay kits were provided by Nanjing Jiancheng Bioengineering Institute,China.METHODS:A total of 24 male Wistar rats were randomly divided into four groups.In the sham-surgery group (n=6),both the mesenteric lymph duct and the superior mesenteric artery were not blocked;in the MLR group (n=6),the mesenteric lymph duct was occluded for 1 hour followed by 2-hour reperfusion;in the SMAO group (n=6),the superior mesenteric artery was occluded for 1 hour followed by 2-hour reperfusion;in the MLR + SMAO group (n=6),both the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour followed by 2-hour reperfusion.MAIN OUTCOME MEASURES:Mean arterial blood pressure prior to and following ischemia/reperfusion;brain tissue morphology levels of LA,MDA,SOD,NO,NOS,MPO,ATPase and ATP following reperfusion.RESULTS:MLR did not cause changes in mean arterial blood pressure,brain tissue morphology,LA,MDA,NO,ATP,SOD,NOS,MPO and ATPase.However,SMAO caused a rapid decrease and gradual increase of mean arterial blood pressure.Neuronal necrosis,degeneration and swelling were observed in brain tissue.Contents of MDA,NO,LA and ATP as well as activities of NOS and MPO were significantly increased (P < 0.05),but activities of SOD and Na+-K+-ATPase were significantly decreased (P < 0.05).MLR aggravated neuronal damage in a rat model of SMAO shock.Following MLR,mean arterial blood pressure was significantly decreased (P < 0.05),contents of MDA and NO as well as activities of NOS and MPO were significantly increased (P < 0.05),but activities of Ca2+-ATPase,Mg2+-ATPase and Ca2+-Mg2+-ATPase as well as ATP content were significantly decreased (P < 0.05).CONCLUSION:MLR aggravates brain injury in a rat model of SMAO shock,which correlates with oxygen-derived free radical injury,NO synthesis and release,sequestration of neutrophilic granulocytes,decreasing activity of cell membrane pumps and energy metabolism dysfunction.Pathogenesis of the intestinal lymphatic pathway should be thoroughly investigated to prevent ischemia/reperfusion injury. | Zigang Zhao Chunyu Niu Aimin Shang Jiaming Tian Rui Han Chunhui Zhang Yuping Zhang Jing Zhang | 2010 | Neural Regeneration Research2010，5，9： | 7 |
| 2 | Recent advances in high-loading catalysts for low-temperature fuel cells: From nanoparticle to single atom显示文摘Low-temperature fuel cells(LTFCs)are considered to be one of the most promising power sources for widespread application in sustainable and renew-able energy conversion technologies.Although remarkable advances have been made in the mass activity of catalysts,mass transport impedance needs to be urgently addressed at a well-designed membrane electrode assembly(MEA)scale.Increasing the loading of electrocatalysts is conducive to prepare thinner and more efficient MEAs owing to the resulting enhanced reactant permeability,better proton diffusion,and lower electrical resistance.Herein,recent progress in high-loading(≥40 wt.%)Pt nanoparticle catalysts(NPCs)and high-loading(≥2 wt.%)single-atom catalysts(SACs)for LTFC applications are reviewed.A summary of various synthetic approaches and support materials for high-loading Pt NPCs and SACs is systematically presented.The influences of high surface area and appropriate surface functionalization for Pt NPCs,as well as coordina-tion environment,spatial confinement effect,and strong metal-support interac-tions(SMSI)for SACs are highlighted.Additionally,this review presents some ideas regarding challenges and future opportunities of high-loading catalysts in the application of LTFCs. | Lixiao Shen Miao Ma Fengdi Tu Zigang Zhao Yunfei Xia Kokswee Goh Lei Zhao Zhenbo Wang Guangjie Shao | 2021 | SusMat2021，1，4： | 3 |
| 3 | Two-Phased Method for Detecting Evasive Network Attack Channels显示文摘With the rapid developments of information technology,various industries become much more dependent on networks.Driven by economic interests and the game between countries reflected by growing cyberspace confrontations,evasive network attacks on information infrastructures with high-tech,high concealment and longterm sustainability become severe threats to national security.In this paper,we propose a novel two-phased method for the detection of evasive network attacks which exploit or pretend to be common legal encryption services in order to escape security inspection.Malicious communications which camouflage themselves as legal encryption application are identified in the SSL'session structure verification phase firstly,and then by serverside X.509 certificate based anomaly detection,suspicious attack behaviors are further distinguished effectively.Experiment results show that our method is very useful for detecting the network activities of certain unknown threats or new malwares.Besides,the proposed method can be applied to other similar services easily. | CAO Zigang XIONG Gang ZHAO Yong GUO Li FANG Binxing | 2014 | China Communications2014，11，8： | 2 |
| 4 | Postconditioning of stellate ganglion block improves intestinal barrier function by inhibiting autophagy in conscious rats following hemorrhagic shock and resuscitation显示文摘To the Editor:Hemorrhagic shock is a critical pathological process characterized by microcirculation dysfunction and hypoperfusion,with severe consequences of cell damage and organ dysfunction.Intestinal barrier dysfunction is a critical link of distant organ injury caused by hemorrhagic shock.Prophylactic treatment with stellate ganglion block(SGB)significantly reduces hemorrhagic shock-induced intestinal barrier damage. | Zhonghua Li Wendi Wang Qi Sun Tingjiao Suo Jiayi Zhai Huibo Du Zhen’ao Zhao Fulong Li Chunyu Niu Zigang Zhao | 2022 | Chinese Medical Journal2022，，8： | 2 |
| 5 | Influence of mesenteric lymph reperfusion on neurotransmitter expression in brain tissue of a superior mesenteric artery occlusion shock rat model显示文摘BACKGROUND: Previous studies have shown that mesenteric lymph reperfusion (MLR) exacerbates brain injury in a rat model of superior mesenteric artery occlusion (SMAO) shock. However, little is known about the influence of MLR on neurotransmitter expression in brain tissue. OBJECTIVE: To observe the effect of MLR on brain tissue injury by measuring monoamine and cholinergic neurotransmitter levels. DESIGN, TIME AND SETTING: A randomized, controlled, animal experiment was performed at the Institute of Microcirculation, Hebei North University, China; Research Room of Microcirculation and Laboratory of Biochemistry, Department of Pathophysiology, Basic Medical College, Hebei North University between December 2007 and March 2009. MATERIALS: Choline acetyltransferase (ChAT) and acetylcholine esterase (AChE) kits were provided by Nanjing Jiancheng Bioengineering Institute, China; dopamine (DA) and noradrenalin (NE) standards were provided by the National Institute for the Control of Pharmaceutical and Biological Products; HP1100 chromatograph of liquid was provided by Agilent, USA. METHODS: A total of 24 male, Wistar rats were randomly assigned to 4 groups: sham-surgery, MLR, SMAO, and MLR + SMAO groups, with 6 rats in each group. In the MLR or SMAO groups, the mesenteric lymph duct or superior mesenteric artery was blocked for 1 hour. In the MLR + SMAO group, the mesenteric lymph duct and superior mesenteric artery were occluded for 1 hour, followed by 2-hour reperfusion. ChAT and AChE levels were measured using the synthesized and hydrolyzed acetylcholine method, respectively. Liquid chromatography was employed to quantitatively analyze DA and NE levels, using relative retention time and the external standard method. MAIN OUTCOME MEASURES: ChAT, AChE, DA, and NE levels. RESULTS: AChE levels were significantly increased, but ChAT levels were significantly decreased in the MLR and MLR + SMAO groups following 2-hour reperfusion (P < 0.01). However, AChE activity in the MLR + SMAO group was greater than in the MLR group (P < 0.05). DA and NE levels were significantly decreased in the SMAO and MLR + SMAO groups (P < 0.01), while DA levels in the MLR + SMAO group were less than in the SMAO group (P < 0.05). CONCLUSION: MLR exacerbated brain injury in a rat model of SMAO shock, which correlated with the intestinal lymphatic pathway. MLR decreased DA levels, but increased AChE activity, in a rat model of SMAO shock. | Chunyu Niu Zigang Zhao Aimin Shang Jiaming Tian Chunhui Zhang Rui Han Yuping Zhang Jing Zhang | 2010 | Neural Regeneration Research2010，5，11： | 2 |
| 6 | Cannabinoid re- ceptor 2 is upregulated in melanoma显示文摘 | Zigang Zhao Jie Yang Hua Zhao | 2012 | Journal of Cancer Research and Therapeutics2012，84，： | 1 |
| 7 | Erianin suppresses constitutive activation of MAPK signaling pathway by inhibition of CRAF and MEK1/2显示文摘Constitutive activation of RAS-RAF-MEK-ERK signaling pathway(MAPK pathway)frequently occurs in many cancers harboring RAS or RAF oncogenic mutations.Because of the paradoxical activation induced by a single use of BRAF or MEK inhibitors,dual-target RAF and MEK treatment is thought to be a promising strategy.In this work,we evaluated erianin is a novel inhibitor of CRAF and MEK1/2 kinases,thus suppressing constitutive activation of the MAPK signaling pathway induced by BRAF V600E or RAS mutations.KinaseProfiler enzyme profiling,surface plasmon resonance(SPR),isothermal titration calorimetry(ITC),cellular thermal shift assay,computational docking,and molecular dynamics simulations were utilized to screen and identify erianin binding to CRAF and MEK1/2.Kinase assay,luminescent ADP detection assay,and enzyme kinetics assay were investigated to identify the efficiency of erianin in CRAF and MEK1/2 kinase activity.Notably,erianin suppressed BRAF V600E or RAS mutant melanoma and colorectal cancer cell by inhibiting MEK1/2 and CRAF but not BRAF kinase activity.Moreover,erianin attenuated melanoma and colorectal cancer in vivo.Overall,we provide a promising leading compound for BRAF V600E or RAS mutant melanoma and colorectal cancer through dual targeting of CRAF and MEK1/2. | Penglei Wang Xuechao Jia Bingbing Lu Han Huang Jialin Liu Xuejiao Liu Qiong Wu Yamei Hu Pan Li Huifang Wei Tingting Liu Dengyun Zhao Lingwei Zhang Xueli Tian Yanan Jiang Yan Qiao Wenna Nie Xinli Ma Ruihua Bai Cong Peng Zigang Dong Kangdong Liu | 2023 | Signal Transduction and Targeted Therapy2023，8，4： | 1 |
| 8 | Novel dual inhibitor for targeting PIM1 and FGFR1 kinases inhibits colorectal cancer growth in vitro and patient-derived xenografts in vivo显示文摘Colorectal cancer(CRC) is the second most common cause of cancer-related death in the world. The pro-viral integration site for Moloney murine leukemia virus 1(PIM1) is a proto-oncogene and belongs to the serine/threonine kinase family, which are involved in cell proliferation, migration,and apoptosis. Fibroblast growth factor receptor 1(FGFR1) is a tyrosine kinase that has been implicated in cell proliferation, differentiation and migration. Small molecule HCI-48 is a derivative of chalcone, a class of compounds known to possess anti-tumor, anti-inflammatory and antibacterial effects. However,the underlying mechanism of chalcones against colorectal cancer remains unclear. This study reports that HCI-48 mainly targets PIM1 and FGFR1 kinases, thereby eliciting antitumor effects on colorectal cancer growth in vitro and in vivo. HCI-48 inhibited the activity of both PIM1 and FGFR1 kinases in an ATPdependent manner, as revealed by computational docking models. Cell-based assays showed that HCI-48inhibited cell proliferation in CRC cells(HCT-15, DLD1, HCT-116 and SW620), and induced cell cycle arrest in the G2/M phase through modulation of cyclin A2. HCI-48 also induced cellular apoptosis, as evidenced by an increase in the expression of apoptosis biomarkers such as cleaved PARP, cleaved caspase 3 and cleaved caspase 7. Moreover, HCI-48 attenuated the activation of downstream components of the PIM1 and FGFR1 signaling pathways. Using patient-derived xenograft(PDX) murine tumor models,we found that treatment with HCI-48 diminished the PDX tumor growth of implanted CRC tissue expressing high protein levels of PIM1 and FGFR1. This study suggests that the inhibitory effect of HCI-48 on colorectal tumor growth is mainly mediated through the dual-targeting of PIM1 and FGFR1kinases. This work provides a theoretical basis for the future application of HCI-48 in the treatment of clinical CRC. | Fanxiang Yin Ran Zhao Dhilli Rao Gorja Xiaorong Fu Ning Lu Hai Huang Beibei Xu Hanyong Chen Jung-Hyun Shim Kangdong Liu Zhi Li Kyle Vaughn Laster Zigang Dong Mee-Hyun Lee | 2022 | Acta Pharmaceutica Sinica B2022，12，11： | 1 |
| 9 | RIN1 exhibits oncogenic property to suppress apoptosis and its aberrant accumulation associates with poor prognosis in melanoma显示文摘 | Ping Fang Zigang Zhao Hongfang Tian Xin Zhang | 2012 | Tumor Biology2012，，5： | 1 |
| 10 | N-cap helix nucleation: methods and their applications显示文摘Recapitulation of well-defined α-helices could result in constrained peptide mimetics with preferable secondary structures and enhanced therapeutic properties for various purposes. Among the helix-stabilizing strategies, the nucleation strategies are able to maximize recognition specificity of the original sequence without compromising the molecular recognition surface. In this review,current methodologies of helix nucleation are introduced including their constructing strategies, structure features and proof of concept biological applications. | Dongyuan Wang Xuan Qin Hui Zhao Zigang Li | 2017 | Science China Chemistry2017，60，6： | 0 |
| 11 | Analysis of differentially expressed genes in Verruca vulgaris vs.adjacent normal skin by RNA-sequencing显示文摘Introduction:Verruca vulgaris is one of the most common low-risk HPV infections and is characterized by excessive proliferation of keratinocytes.Currently,very little genetic information is available regarding verruca vulgaris in the Chinese population.This study aimed to obtain comprehensive transcript information of verruca vulgaris by RNA sequencing.Methods:High-throughput sequencing was performed on three fresh verruca vulgaris samples and adjacent normal skin on the Illumina sequencing platform.The transcriptomes were analyzed using bioinformatics and the differentially expressed genes(DEGs)were verified by immunohistochemistry.Verruca vulgaris exhibited a unique molecular signature.Results:In total,1,643 DEGs were identified in verruca vulgaris compared to normal skin.The functions of the DEGs were studies by Gene Ontology(GO)enrichment,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,DEGs Reactome analysis,disease annotation function,and STRING protein-protein interaction(PPI)network analysis.The results revealed 595 GO terms associated with the cell cycle,signal transduction,immune system,signaling molecules,and interaction.The Reactome analysis revealed enrichment in reversible hydration of carbon dioxide and BMP signaling,while the disease annotation function revealed that the enriched DEGs are involved in keratosis disorders.The STRING PPI network showed that the edges with the highest density mainly included the 2′-5′oligoadenylate synthase(OAS)family-related proteins.Furthermore,the M-code analysis found ISG15,IRF7,and OASL were scored as significant modules and their high expression compared to the control was verified by immunohistochemistry.Conclusion:These findings contribute to the genetic information of verruca vulgaris in the Chinese population,revealing that interferon-stimulated genes may play essential roles in verruca vulgaris. | QINGQING GUO JIAYUE QI XIAOQIANG LIANG ZIGANG ZHAO JIA BAI FANG XIE CHENGXIN LI | 2023 | BIOCELL2023，47，11： | 0 |
| 12 | Development of a potent peptide inhibitor of estrogen receptor α显示文摘We have developed a facile N-terminus helix-nucleating strategy using an unnaturally tethered aspartic acid(TD strategy). Relatively weak nuclear translocation efficiency of TD PERM limits its further biological applications. A potent peptide inhibitor of estrogen receptor α(ER-α) with significantly increased cellular uptake and cellular distribution was developed by cell penetrating peptide attachment.The resulted peptide conjugate showed selective toxicity towards estrogen receptor positive cell lines and induced decreased transcription of estrogen receptor a downstream genes. | Xuan Qin Hui Zhao Yanhong Jiang Feng Yin Yuan Tian Mingsheng Xie Xiyang Ye Naihan Xu Zigang Li | 2018 | Chinese Chemical Letters2018，29，7： | 0 |
| 13 | A Proximity-Triggered Strategy toward Transferable Proteolysis Targeting Chimeras显示文摘Over the past 20 years,great efforts have been invested in developing site-specific approaches to protein modification to dissect protein functions directly and accurately.Here,we report a proximitytriggered group transfer strategy from a sulfonium warhead to a Cysteine(Cys)residue of the target protein.With a guiding ligand,cargoes could be transferred selectively from a sulfonium center onto the Cys residue in the vicinity of their binding interface.The successful thalidomide transfer of sulfonium 1-X could be applied intracellularly for epidermal growth factor receptor degradation,highlighting the potential of group transfer strategy as a suite of chemical biology studies,including cell imaging,protein profiling,and protein degradation by simply employing different transferrable groups. | Yuena Wang Rongtong Zhao Chuan Wan Wei Kang Rui Wang Chengyao Chiang Xiaochun Guo Qi Chang Zhanfeng Hou Yuxin Ye Qinhong Luo Ziyuan Zhou Jianbo Liu Shuiming Li Dongyuan Wang Feng Yin Zigang Li | 2023 | CCS Chemistry2023，5，6： | 0 |
| 14 | Repurposed benzydamine targeting CDK2 suppresses the growth of esophageal squamous cell carcinoma显示文摘Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway. | Yubing Zhou Xinyu He Yanan Jiang Zitong Wang Yin Yu Wenjie Wu Chenyang Zhang Jincheng Li Yaping Guo Xinhuan Chen Zhicai Liu Jimin Zhao Kangdong Liu Zigang Dong | 2023 | Frontiers of Medicine2023，17，2： | 0 |
| 15 | Reversibly switching the conformation of short peptide through in-tether chiral sulfonium auxiliary显示文摘A chirality induced helicity method has been developed to modulate the peptide's biophysical and biochemical properties. We report herein a novel approach for reversibly switching the conformation of short constraint a-helical peptides through alkylation of the in-tether thioether and dealkylation of the chiral sulfonium. This traceless redox sensitive tagging strategy broadened our scope of CIH(chirality induced helicity) strategy and provided a valuable approach to functionalize the peptide tether. | Xiaodong Shi Yixiang Jiang Dan Yang Hui Zhao Yuan Tian Zigang Li | 2018 | Chinese Chemical Letters2018，29，3： | 0 |
| 16 | Recent advances in chemical protein synthesis:method developments and biological applications显示文摘The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and versatility.Chemical protein synthesis,a powerful approach utilizing chemical reactions for the de novo construction of structurally accurate proteins,has emerged as a transformative tool for studying proteins and generating protein derivatives/mimics inaccessible by natural biological machinery,including post-translationally modified proteins,proteins comprised of unnatural amino acids,as well as mirror-image proteins.This review summarizes recent strides in synthetic method developments for chemical protein synthesis,including innovative techniques in solid-phase peptide synthesis,the challenges presented by difficult sequences in either synthesis or folding and the exploration of novel ligation reactions using both chemical and enzymatic methods.Furthermore,the review also delves into newly developed protocols for site-selective protein modifications and the generation of stapled or macrocyclized peptides/miniproteins,highlighting the power of chemical methods to make structurally diverse proteins.Recent applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further discussed.Together,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis. | Suwei Dong Ji-Shen Zheng Yiming Li Huan Wang Gong Chen Yongxiang Chen Gemin Fang Jun Guo Chunmao He Honggang Hu Xuechen Li Yanmei Li Zigang Li Man Pan Shan Tang Changlin Tian Ping Wang Bian Wu Chuanliu Wu Junfeng Zhao Lei Liu | 2024 | Science China Chemistry2024，67，4： | 0 |
| 17 | Acetylshikonin inhibits inflammatory responses and Papain-like protease activity in murine model of COVID-19显示文摘Dear Editor,The emerging severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variant Omicron has rapidly replaced the Delta variant and presents a huge challenge to public health and health care infrastructure.Cytokine-driven hyperinflammation is the leading cause of a series of COVID-19 clinical symptoms.1 Our research attempted to discover an anti-inflammatory or anti-viral small molecule agent capable of treating COVID-19 hyperinflammation. | Ning Lu Tingxuan Gu Xueli Tian Simin Zhao Guoguo Jin Fredimoses Mangaladoss Yan Qiao Kangdong Liu Ran Zhao Zigang Dong | 2022 | Signal Transduction and Targeted Therapy2022，7，11： | 0 |
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