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Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H:quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase

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Chinese Journal of Natural Medicines 2024年第1期22卷 75-88页

作者： SONG Jiangzhou ZOU Guiqing ZHAO Zhou ZHU ya XUE Jiayu AO Lanjia sun Huiyong HAO Haiping ZHANG Bo XU Xiaowei State Key Laboratory of Natural Medicines Key Lab of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjing 210009China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

NAD(P)H:quinone oxidoreductase 1(NQO1)is a flavin protease highly expressed in various cancer ***1 catalyzes a futile redox cycle in substrates,leading to substantial reactive oxygen species(ROS)*** ROS generation results in extensive DNA damage and elevated poly(ADP-ribose)polymerase 1(PARP1)-mediated consumption of nicotinamide adenine dinucleotide(NAD^(+)),ultimately causing cell *** phosphoribosyltransferase(NAMPT),the rate-limiting enzyme in the NAD^(+)salvage synthesis pathway,emerges as a critical target in cancer *** concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+*** this study,we designed,synthesized,and assessed a novel series of proqodine A derivatives targeting both NQO1 and *** these,compound T8 demonstrated potent antitumor ***,T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and *** discovery offers a promising new molecular entity for advancing anticancer research.

关键词： NQO1 ROS NAMPT NAD^(+) T8

Protein succinylation,hepatic metabolism,and liver diseases

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World Journal of Hepatology 2024年第3期16卷 344-352页

作者： Shuang Liu Rui Li ya-Wen sun Hai Lin Hai-Fang Li College of Animal Science and Veterinary Medicine Shandong Agricultural UniversityTai’an 271018Shandong ProvinceChina College of Life Sciences Shandong Agricultural UniversityTai’an 271018Shandong ProvinceChina

Succinylation is a highly conserved post-translational modication that is processed via enzymatic and non-enzymatic *** exhibits strong effects on protein stability,enzyme activity,and transcriptional *** succinylation is extensively present in the liver,and increasing evidence has demonstrated that succinylation is closely related to hepatic *** instance,histone acetyltransferase 1 promotes liver glycolysis,and the sirtuin 5-induced desuccinylation is involved in the regulation of the hepatic urea cycle and lipid ***,the effects of succinylation on hepatic glucose,amino acid,and lipid metabolism under the action of various enzymes will be discussed in this *** addition,how succinylases regulate the progression of different liver diseases will be reviewed,including the desuccinylation activity of sirtuin 7,which is closely associated with fatty liver disease and hepatitis,and the actions of lysine acetyltransferase 2A and histone acetyltransferase 1 that act as succinyltransferases to regulate the succinylation of target genes that influence the development of hepatocellular *** view of the diversity and significance of protein succinylation,targeting the succinylation pathway may serve as an attractive direction for the treatment of liver diseases.

关键词： Protein succinylation Hepatic metabolism Fatty liver Hepatitis Hepatocellular carcinoma

Dynamic tracking of exsolved PdPt alloy/perovskite catalyst for efficient lean methane oxidation

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Chinese Chemical Letters 2024年第4期35卷 170-175页

作者： yanling yang Zhenfa Ding Huimin Wang Jianhui Li yanping Zheng Hongquan Guo Li Zhang bing yang Qingqing Gu Haifeng Xiong Yifei sun College of Energy Xiamen UniversityXiamen 361005China School of Environment and Civil Engineering Dongguan University of TechnologyDongguan 523808China Department of Chemistry College of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China State Key Laboratory of Physical Chemistry of Solid Surfaces College of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China CAS Key Laboratory of Science and Technology on Applied Catalysis Dalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361102China

Supported Pd based catalysts are considered as the efficient candidates for low-carbon alkane oxidation for their outstanding capability to break C-H bond. Whereas, the irreversible deactivation of Pd based catalysts was still frequently observed. Herein, we reinforced the extruded Pd nanoparticles with quantitive Pt to assemble the evenly distributed Pd Pt nanoalloy onto ferrite perovskite(Pd Pt-LCF) matrix with strengthened robustness of metal/oxide support interface. We further co-achieved the enhanced performance, anti-overoxidation as well as resistance of vapor-poisoning in durability measurement. The operando X-ray photoelectron spectroscopy(O-XPS) combined with various morphology characterizations confirms that the accumulation of surface deep-oxidation species of Pd^(4+) is the culprit for fast activity loss in exsolved Pd system, especially at high temperature of 400 ℃. Conversely, it could be completely suppressed by in-situ alloying Pd with equal amount of Pt, which helps maintain the metastable Pd^(2+)/Pd shell and metallic solid-solution core structure. The density function theory(DFT) calculations further buttress that the dissociation of C–H was facilitated on alloy/perovskite interface which is, on the contrary, resistant toward O–H bond cleavage, as compared to Pd/perovskite. Our work suggests that the modification of exsolved metal/oxide catalytic interface could further enrich the toolkit of heterogeneous catalyst design.

关键词： Exsolution PdPt alloy Operando characterization Methane conversion Deep-oxidation

A viscoelastic nonlinear energy sink with an electromagnetic energy harvester:Narrow-band random response

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Chinese Physics B 2024年第7期33卷 147-156页

作者：廖志晶孙亚辉刘洋 School of Mathematics and Statistics Guangdong University of TechnologyGuangzhou 510520China Exeter Small-Scale Robotics Laboratory Engineering DepartmentUniversity of ExeterNorth Park RoadExeter EX44QFUK

Nonlinear energy sink is a passive energy absorption device that surpasses linear dampers, and has gained significant attention in various fields of vibration suppression. This is owing to its capacity to offer high vibration attenuation and robustness across a wide frequency spectrum. Energy harvester is a device employed to convert kinetic energy into usable electric energy. In this paper, we propose an electromagnetic energy harvester enhanced viscoelastic nonlinear energy sink(VNES) to achieve passive vibration suppression and energy harvesting simultaneously. A critical departure from prior studies is the investigation of the stochastic P-bifurcation of the electromechanically coupled VNES system under narrowband random excitation. Initially, approximate analytical solutions are derived using a combination of a multiple-scale method and a perturbation approach. The substantial agreement between theoretical analysis solutions and numerical solutions obtained from Monte Carlo simulation underscores the method's high degree of validity. Furthermore, the effects of system parameters on system responses are carefully examined. Additionally, we demonstrate that stochastic P-bifurcation can be induced by system parameters, which is further verified by the steady-state density functions of displacement. Lastly,we analyze the impacts of various parameters on the mean square current and the mean output power, which are crucial for selecting suitable parameters to enhance the energy harvesting performance.

关键词： nonlinear energy sink fractional-order damping multiple-scale method energy harvester

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Development of a clinical nomogram for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 396-408页

作者： bing Liu Yu-Jie Xu Feng-Ran Chu Guang sun Guo-Dong Zhao Sheng-Zhong Wang Department of Gastrointestinal Surgery Central South University Xiangya School of Medicine Affiliated Haikou HospitalHaikou 570208Hainan ProvinceChina Clinical College Hainan Medical UniversityHaikou 571199Hainan ProvinceChina

BACKGROUND The efficacy of neoadjuvant chemotherapy(NAC)in advanced gastric cancer(GC)is still a controversial *** To find factors associated with chemosensitivity to NAC treatment and to provide the optimal therapeutic strategies for GC patients receiving *** The clinical information was collected from 230 GC patients who received NAC treatment at the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2016 to December *** absolute shrinkage and selection operator logistic regression analysis was used to find the possible predictors.A nomogram model was employed to predict the response to *** In total 230 patients were finally included in this study,including 154 males(67.0%)and 76 females(33.0%).The mean age was(59.37±10.60)years,ranging from 24 years to 80 *** to the tumor regression grade standard,there were 95 cases in the obvious response group(grade 0 or grade 1)and 135 cases in the poor response group(grade 2 or grade 3).The obvious response rate was 41.3%.Least absolute shrinkage and selection operator analysis showed that four risk factors significantly related to the efficacy of NAC were tumor location(P<0.001),histological differentiation(P=0.001),clinical T stage(P=0.008),and carbohydrate antigen 724(P=0.008).The C-index for the prediction nomogram was *** calibration curve revealed that the predicted value exhibited good agreement with the actual *** curve analysis showed that the nomogram had a good value in clinical *** A nomogram combining tumor location,histological differentiation,clinical T stage,and carbohydrate antigen 724 showed satisfactory predictive power to the response of NAC and can be used by gastrointestinal surgeons to determine the optimal treatment strategies for advanced GC patients.

关键词： Advanced gastric cancer Predictor Neoadjuvant chemotherapy Nomogram Tumor regression grade

Preoperative prognostic nutritional index predicts long-term outcomes of patients with ampullary adenocarcinoma after curative pancreatoduodenectomy

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1291-1300页

作者： Chong-Yuan sun Xiao-Jie Zhang Zheng Li He Fei Ze-Feng Li Dong-bing Zhao Department of Pancreatic and Gastric Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND The prognostic nutritional index(PNI),a marker of immune-nutrition balance,has predictive value for the survival and prognosis of patients with various *** To explore the clinical significance of the preoperative PNI on the prognosis of ampullary adenocarcinoma(AC)patients who underwent curative *** The data concerning 233 patients diagnosed with ACs were extracted and analyzed at our institution from January 1998 to December *** patients were categorized into low and high PNI groups based on the cutoff value determined by receiver operating characteristic curve *** compared disease-free survival(DFS)and overall survival(OS)between these groups and assessed prognostic factors through univariate and multivariate *** The optimal cutoff value for the PNI was established at *** with a PNI≥45.3 were categorized into the PNI-high group,while those with a PNI<45.3 were assigned to the PNI-low *** within the PNI-low group tended to be of advanced age and exhibited higher levels of aspartate transaminase and total bilirubin and a lower creatinine level than were those in the PNI-high *** 5-year OS rates for patients with a PNI≥45.3 and a PNI<45.3 were 61.8%and 43.4%,respectively,while the 5-year DFS rates were 53.5%and 38.3%,*** in the PNI-low group had shorter OS(P=0.006)and DFS(P=0.012).In addition,multivariate analysis revealed that the PNI,pathological T stage and pathological N stage were found to be independent prognostic factors for both OS and *** The PNI is a straightforward and valuable marker for predicting long-term survival after *** PNI should be incorporated into the standard assessment of patients with AC.

关键词： Ampullary carcinoma Prognostic nutritional index Prognosis Pancreaticoduodenectomy

Grain boundary engineering for enhancing intergranular damage resistance of ferritic/martensitic steel P92

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Nuclear Science and Techniques 2024年第5期35卷 186-199页

作者： Lei Peng Shang-Ming Chen Jing-Yi Shi Yong-Jie sun Yi-Fei Liu Yin-Zhong Shen Hong-ya He Hui-Juan Wang Jie Tian State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026China School of Nuclear Science and Technology University of Science and Technology of ChinaHefei 230027China School of Materials Engineering Shanghai University of Engineering Science333 Long Teng RoadShanghai 201620China Experimental Center of Engineering and Material Science University of Science and Technology of ChinaHefei 230026China

Ferritic/martensitic(F/M)steel is widely used as a structural material in thermal and nuclear power ***,it is susceptible to intergranular damage,which is a critical issue,under service *** this study,to improve the resistance to intergranular damage of F/M steel,a thermomechanical process(TMP)was employed to achieve a grain boundary engineering(GBE)microstructure in F/M steel *** TMP,including cold-rolling thickness reduction of 6%,9%,and 12%,followed by austenitization at 1323 K for 40 min and tempering at 1053 K for 45 min,was applied to the as-received(AR)P92 *** prior austenite grain(PAG)size,prior austenite grain boundary character distribution(GBCD),and connectivity of prior austenite grain boundaries(PAGBs)were *** to the AR specimen,the PAG size did not change *** fraction of coincident site lattice boundaries(CSLBs,3≤Σ≤29)and Σ3^(n) boundaries along PAGBs decreased with increasing reduction ratio because the recrystallization fraction increased with increasing reduction *** PAGB connectivity of the 6%deformed specimen slightly deteriorated compared with that of the AR ***,potentiodynamic polarization studies revealed that the intergranular damage resistance of the studied steel could be improved by increasing the fraction of CSLBs along the PAGBs,indicating that the TMP,which involves low deformation,could enhance the intergranular damage resistance.

关键词： Grain boundary engineering Ferritic/martensitic steel Prior austenite grain boundary character distribution Grain boundary connectivity Intergranular damage resistance

A novel profile modification HPF-Co gel satisfied with fractured low permeability reservoirs in high temperature and high salinity

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Petroleum Science 2024年第1期21卷 683-693页

作者： ya-Kai Li Ji-Rui Hou Wei-Peng Wu Ming Qu Tuo Liang Wei-Xin Zhong Yu-Chen Wen Hai-Tong sun Yi-Nuo Pan China University of Petroleum Beijing Beijing102249China PetroChina Tarim Oilfield Company Korla 841000XinjiangChina Key Laboratory of Improving Oil and Gas Recovery of Ministry of Education Northeast Petroleum University Daqing 163318HeilongjiangChina Xi'an Shiyou University Xi'an 710065ShaanxiChina Northwest Oilfield Company SINOPECUrumqi 830011XinjiangChina

Conformance control and water plugging are a widely used EOR method in mature ***,majority of conformance control and water plugging agents are unavoidable dehydrated situation in high-temperature and high-salinity low permeability ***,a novel conformance control system HPF-Co gel,based on high-temperature stabilizer(CoCl_(2)·H_(2)O,CCH)is *** HPF-Co bulk gel has better performances with high temperature(120℃)and high salinity(1×10^(5)mg/L).According to Sydansk coding system,the gel strength of HPF-Co with CCH is increased to code *** dehydration rate of HPF-Co gel is 32.0%after aging for 150 d at 120℃,showing excellent thermal *** rheological properties of HPF gel and HPF-Co gel are also *** results show that the storage modulus(G′)of HPF-Co gel is always greater than that of HPF *** effect of CCH on the microstructure of the gel is *** results show that the HPF-Co gel with CCH has a denser gel network,and the diameter of the three-dimensional network skeleton is 1.5-3.5μ*** 90 d of aging,HPF-Co gel still has a good three-dimensional *** spectroscopy results show that CCH forms coordination bonds with N and O atoms in the gel amide group,which can suppress the vibration of cross-linked sites and improve the stability at high *** core plugging test determines the optimized polymer gel injection strategy and injection velocity with HPF-Co bulk gel system,plugging rate exceeding 98%.Moreover,the results of subsequent waterflooding recovery can be improved by 17%.

关键词： Low permeability reservoir High-temperature resistant gel Complexation reaction Polymer gel injection strategy Plugging rate Enhanced oil recovery

Control of GaN inverted pyramids growth on c-plane patterned sapphire substrates

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Journal of Semiconductors 2024年第6期45卷 92-96页

作者： Luming Yu Xun Wang Zhibiao Hao Yi Luo Changzheng sun bing Xiong yanjun Han Jian Wang Hongtao Li Lin Gan Lai Wang Beijing National Research Center for Information Science and Technology Department of Electronic EngineeringTsinghua UniversityBei-jing 100084China Center for Flexible Electronics Technology Tsinghua UniversityBeijing 100084China

Growth of gallium nitride(GaN)inverted pyramids on c-plane sapphire substrates is benefit for fabricating novel devices as it forms the semipolar *** this work,GaN inverted pyramids are directly grown on c-plane patterned sapphire substrates(PSS)by metal organic vapor phase epitaxy(MOVPE).The influences of growth conditions on the surface morphol-ogy are experimentally studied and explained by Wulff *** competition of growth rate among{0001},{1011},and{1122}facets results in the various surface morphologies of GaN.A higher growth temperature of 985 ℃ and a lowerⅤ/Ⅲratio of 25 can expand the area of{}facets in GaN inverted *** the other hand,GaN inverted pyramids with almost pure{}facets are obtained by using a lower growth temperature of 930℃,a higherⅤ/Ⅲratio of 100,and PSS with pattern arrangement perpendicular to the substrate primary flat.

关键词： inverted pyramids GaN MOVPE crystal growth competition model