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| 1 | Mitochondrial malic enzyme 2 promotes breast cancer metastasis via stabilizing HIF-1α under hypoxia显示文摘Objective: α-ketoglutarate(α-KG) is the substrate to hydroxylate collagen and hypoxia-inducible factor-1α(HIF-1α), which are important for cancer metastasis. Previous studies have shown that the upregulation of collagen prolyl 4-hydroxylase in breast cancer cells stabilizes the expression of HIF-1α by depleting α-KG levels. We hypothesized that mitochondrial malic enzyme 2(ME2) might also affect HIF-1α expression via modulating α-KG levels in breast cancer cells.Methods: We evaluated ME2 protein expression in 100 breast cancer patients using immunohistochemistry and correlated with clinicopathological indicators. The effect of ME2 knockout on cancer metastasis was evaluated using an orthotopic breast cancer model. The effect of ME2 knockout or knockdown on the levels of α-KG and HIF-1α proteins in breast cancer cell lines was determined both in vitro and in vivo.Results: ME2 was found to be upregulated in the human breast cancerous tissues compared with the matched precancerous tissues(P<0.001). The elevated expression of ME2 was associated with a poor prognosis(P=0.019).ME2 upregulation was also related to lymph node metastasis(P=0.016), pathological staging(P=0.033), and vascular cancer embolus(P=0.014). Also, ME2 knockout significantly inhibited lung metastasis in vivo. In the tumors formed by ME2 knockout cells, the levels of α-KG were significantly increased and collagen hydroxylation level did not change significantly but HIF-1α protein expression was significantly decreased, compared to the control samples. In cell culture, cells with ME2 knockout or knockdown demonstrated significantly higher α-KG levels but significantly lower HIF-1α protein expression than control cells under hypoxia. Exogenous malate and α-KG exerted similar effect on HIF-1α in breast cancer cells to ME2 knockout or knockdown. Additionally,treatment with malate significantly decreased 4 T1 breast cancer lung metastasis. ME2 expression was associated with HIF-1α levels in human breast cancer samples(P=0.008).Conclusions: Our results provide evidence that upregulation of ME2 is associated with a poor prognosis of breast cancer patients and propose a mechanistic understanding of a link between ME2 and breast cancer metastasis. | Duo You Danfeng Du Xueke Zhao Xinmin Li Minfeng Ying Xun Hu | 2021 | Chinese Journal of Cancer Research2021，33，3： | 3 |
| 2 | Evolution and protein interactions of AP2 proteins in Brassicaceae: Evidence linking development and environmental responses显示文摘Plants have evolved a large number of transcription factors(TF), which are enriched among duplicate genes,highlighting their roles in complex regulatory networks. The APETALA2/EREBP-like genes constitute a large plant TF family and participate in development and stress responses. To probe the conservation and divergence of AP2/EREBP genes,we analyzed the duplication patterns of this family in Brassicaceae and identified interacting proteins of representative Arabidopsis AP2/EREBP proteins. We found that many AP2/EREBP duplicates generated early in Brassicaceae history were quickly lost, but many others were retained in all tested Brassicaceae species, suggesting early functional divergence followed by persistent conservation. In addition,the sequences of the AP2 domain and exon numbers were highly conserved in rosids. Furthermore, we used 16 A.thaliana AP2/EREBP proteins as baits in yeast screens and identified 1,970 potential AP2/EREBP-interacting proteins,with a small subset of interactions verified in planta. Many AP2 genes also exhibit reduced expression in an antherdefective mutant, providing a possible link to developmental regulation. The putative AP2-interacting proteins participate in many functions in development and stress responses,including photomorphogenesis, flower development, pathogenesis, drought and cold responses, abscisic acid and auxin signaling. Our results present the AP2/EREBP evolution patterns in Brassicaceae, and support a proposed interaction network of AP2/EREBP proteins and their putative interacting proteins for further study. | Liping Zeng Yue Yin Chenjiang You Qianli Pan Duo Xu Taijie Jin Bailong Zhang Hong Ma | 2016 | Journal of Integrative Plant Biology2016，58，6： | 3 |
| 3 | Computation of an Emptiable Minimal Siphon in a Subclass of Petri Nets Using Mixed-Integer Programming显示文摘Deadlock resolution strategies based on siphon control are widely investigated.Their computational efficiency largely depends on siphon computation.Mixed-integer programming(MIP)can be utilized for the computation of an emptiable siphon in a Petri net(PN).Based on it,deadlock resolution strategies can be designed without requiring complete siphon enumeration that has exponential complexity.Due to this reason,various MIP methods are proposed for various subclasses of PNs.This work proposes an innovative MIP method to compute an emptiable minimal siphon(EMS)for a subclass of PNs named S^(4)PR.In particular,many particular structural characteristics of EMS in S4 PR are formalized as constraints,which greatly reduces the solution space.Experimental results show that the proposed MIP method has higher computational efficiency.Furthermore,the proposed method allows one to determine the liveness of an ordinary S^(4)PR. | Shouguang Wang Wenli Duo Xin Guo Xiaoning Jiang Dan You Kamel Barkaoui MengChu Zhou | 2021 | IEEE/CAA Journal of Automatica Sinica2021，8，1： | 2 |
| 4 | Increased prognostic value of clinical–reproductive model in Chinese female patients with esophageal squamous cell carcinoma显示文摘BACKGROUND In China,it has been well recognized that some female patients with esophageal squamous cell carcinoma(ESCC)have different overall survival(OS)time,even with the same tumor-node-metastasis(TNM)stage,challenging the prognostic value of the TNM system alone.An effective predictive model is needed to accurately evaluate the prognosis of female ESCC patients.AIM To construct a novel prognostic model with clinical and reproductive data for Chinese female patients with ESCC,and to assess the incremental prognostic value of the full model compared with the clinical model and TNM stage.METHODS A new prognostic nomogram incorporating clinical and reproductive features was constructed based on univariatie and Cox proportional hazards survival analysis from a training cohort(n=175).The results were recognized using the internal(n=111)and independent external(n=85)validation cohorts.The capability of the clinical–reproductive model was evaluated by Harrell’s concordance index(C-index),Kaplan–Meier curve,time-dependent receiver operating characteristic(ROC),calibration curve and decision curve analysis.The correlations between estrogen response and immune-related pathways and some gene markers of immune cells were analyzed using the TIMER 2.0 database.RESULTS A clinical–reproductive model including incidence area,age,tumor differentiation,lymph node metastasis(N)stage,estrogen receptor alpha(ESR1)and beta(ESR2)expression,menopausal age,and pregnancy number was constructed to predict OS in female ESCC patients.Compared to the clinical model and TNM stage,the time-dependent ROC and C-index of the clinical–reproductive model showed a good discriminative ability for predicting 1-,3-,and 5-years OS in the primary training,internal and external validation sets.Based on the optimal cut-off value of total prognostic scores,patients were classified into high-and low-risk groups with significantly different OS.The estrogen response was significantly associated with p53 and apoptosis pathways in esophageal cancer.CONCLUSION The clinical–reproductive prognostic nomogram has an incremental prognostic value compared with the clinical model and TNM stage in predicting OS in Chinese female ESCC patients. | Dong-Yun Zhang Jian-Wei Ku Xue-Ke Zhao Hai-Yan Zhang Xin Song Hong-Fang Wu Zong-Min Fan Rui-Hua Xu Duo You Ran Wang Ruo-Xi Zhou Li-Dong Wang | 2022 | World Journal of Gastroenterology2022，28，13： | 1 |
| 5 | Serum phospholipid omega-3 polyunsaturated fatty acids and insulin resistance in type 2 diabetes mellitus and non-alcoholic fatty liver disease显示文摘 | Da-jun Lou Qi-qian Zhu Xu-wei Si Li-li Guan Qiao-ying You Zhong-ming Yu Ai-zhen Zhang Duo Li | 2014 | Journal of Diabetes and Its Complications2014，，： | 1 |
| 6 | THE NONLINEAR CUSP-CATASTROPHE MODEL OF THE SEDIMENT TRANSPORT RATE显示文摘In the catastrophe theory of nonlinear science, the intensity of water flow Θ and the coefficient of non uniform sediment m are regarded as two bound variables, and the intensity of bed load transport Φ as the state variable in the motion of non uniform sediment in cusp catastrophe model. Based on the standard equation of the cusp catastrophe theory, the relation equation between the intensity of bed load transport Φ and the intensity of water flow Θ has been derived by used coordinate transform and topology transform. The equation of bed load transport rate was built on the cusp catastrophe theory of nonlinear science. The others are applied to verify this equation, that the results calculated by the cusp catastrophe equation agree well with the other equations. This indicates that the cusp catastrophe equation is reasonable, and the results fully reflect the characteristics of threshold motion and transport of non uniform sediment. The purpose of this paper is to explore the incipient motion and transport laws of non uniform sediment from the viewpoint of nonlinear science. | Yang Ju rui, Fang Duo, Cao Shu you, Liu Xing nian State Key Hydraulics Laboratory of High Speed Flows, Sichuan University, Chengdu 610065, China | 2002 | Journal of Hydrodynamics2002，14，3： | 0 |
| 7 | SYNTHESIS OF BENZO-15-CROWN-5 PHENOL-FORMALDEHYDE RESIN FOR LITHIUM ISOTOPE SEPARATION显示文摘SYNTHESISOFBENZO-15-CROWN-5PHENOL-FORMALDEHYDERESINFORLITHIUMISOTOPESEPARATION￥YOUHengSHI;QunYAN;DuoYuanWANG;XiaoZhiZHANG;Zho... | YOU Heng SHI Qun YAN Duo Yuan WANG Xiao Zhi ZHANG Zhong Guo DENG Hui Bao LU (Institute of Photographic Chemistry, Academia Sinica, Beijing, 100101)(China Institute of Atomic Energy, Beijing, 102413) | 1996 | Chinese Chemical Letters1996，7，3： | 0 |
| 8 | Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19显示文摘COVID-19 remains a serious emerging global health problem,and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity.Here,we present the oropharyngeal microbiota characteristics identified by shotgun metagenomic sequencing analyses of oropharynx swab specimens from 31 COVID-19 patients,29 influenza B patients,and 28 healthy controls.Our results revealed a distinct oropharyngeal microbiota composition in the COVID-19 patients,characterized by enrichment of opportunistic pathogens such as Veillonella and Megasphaera and depletion of Pseudopropionibacterium,Rothia,and Streptococcus.Based on the relative abundance of the oropharyngeal microbiome,we built a microbial classifier to distinguish COVID-19 patients from flu patients and healthy controls with an AUC of 0.889,in which Veillonella was identified as the most prominent biomarker for COVID-19 group.Several members of the genus Veillonella,especially Veillonella parvula which was highly enriched in the oropharynx of our COVID-19 patients,were also overrepresented in the BALF of COVID-19 patients,indicating that the oral cavity acts as a natural reservoir for pathogens to induce co-infections in the lungs of COVID-19 patients.We also found the increased ratios of Klebsiella sp.,Acinetobacter sp.,and Serratia sp.were correlated with both disease severity and elevated systemic inflammation markers(neutrophil-lymphocyte ratio,NLR),suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the inflammatory response.Moreover,the oropharyngeal microbiome of COVID-19 patients exhibited a significant enrichment in amino acid metabolism and xenobiotic biodegradation and metabolism.In addition,all 26 drug classes of antimicrobial resistance genes were detected in the COVID-19 group,and were significantly enriched in critical cases.In conclusion,we found that oropharyngeal microbiota alterations and functional differences were associated with COVID-19 severity. | Shengli Ma Fan Zhang Fengxia Zhou Hui Li Wenyu Ge Rui Gan Huan Nie Biao Li Yindong Wang Meng Wu Duo Li Dongmei Wang Zheng Wang Yuhong You Zhiwei Huang | 2021 | Signal Transduction and Targeted Therapy2021，6，6： | 0 |
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