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Trilogy of drug repurposing for developing cancer and chemotherapy-induced heart failure co-therapy agent

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Acta Pharmaceutica Sinica B 2024年第2期14卷 729-750页

作者： xin Chen Xianggang Mu Lele Ding Xi Wang Fei Mao Jinlian Wei Qian liu Yixiang Xu Shuaishuai Ni lijun Jia jian li State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell MetabolismFrontiers Science Center for Materiobiology and Dynamic ChemistryShanghai Key Laboratory of New Drug DesignSchool of PharmacyEast China University of Science and TechnologyShanghai 200237China Cancer Institute Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China College of Pharmacy Jinan UniversityGuangzhou 510632China

Chemotherapy-induced complications,particularly lethal cardiovascular diseases,pose significant challenges for cancer *** intertwined adverse effects,brought by cancer and its complication,further complicate anticancer therapy and lead to diminished clinical *** supplementation of cardioprotective agents falls short in addressing these *** bifunctional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events *** repurposing was naturally endowed with co-therapeutic potential of two indications,implying a unique chance in the development of bi-functional ***,we further proposed a novel“trilogy of drug repurposing”strategy that comprises function-based,targetfocused,and scaffold-driven repurposing approaches,aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional *** function-based repurposing,a cardioprotective agent,carvedilol(CAR),was identified as a potential neddylation inhibitor to suppress lung cancer *** target-focused SAR studies and scaffold-driven drug design,we synthesized 44 CAR derivatives to achieve a balance between anticancer and ***,optimal derivative 43 displayed promising bi-functional effects,especially in various self-established heart failure mice models with and without ***,the present study validated the practicability of the“trilogy of drug repurposing”strategy in the development of bi-functional cotherapy agents.

关键词： Anticancer Heartfailure Complication Drug repurposing Bi-functional drug

TOPK Inhibition Enhances the Sensitivity of Colorectal Cancer Cells to Radiotherapy by Reducing the DNA Damage Response

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Current Medical Science 2024年第3期44卷 545-553页

作者： Shi-gui PANG xin ZHANG Zhao-xin li li-fei HE Feng CHEN Ming-long liu Ying-ze HUANG jian-mei MO Kong-lan LUO Juan-juan XIAO Feng ZHU Department of Oncology The Affiliated Hospital of Guilin Medical UniversityGuilin541001China Cancer Research Institute The Affiliated Hospital of Guilin Medical UniversityGuilin541001China Translational Medical Center Huaihe HospitalHenan UniversityKaifeng475000China Guangxi Key Laboratory of Molecular Medicine in liver Injury and Repair The Affiliated Hospital of Guilin Medical UniversityGuilin541001China

Objective Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase(TOPK)was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung ***,the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer(CRC)cells is *** study aimed to evaluate the radiosensitization of TOPK knockdown in CRC *** The expression of TOPK was detected in CRC tissues by immunohistochemistry,and the effect of TOPK knockdown was detected in CRC cells by Western ***-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC ***,proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after *** damage was detected by the comet *** in the DNA damage response signaling pathway were analyzed by Western blotting,and apoptosis was detected by flow *** The expression of TOPK was significantly greater in CRC tissues at grades 2–4 than in those at grade *** irradiation,CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins,including phospho-cyclin-dependent kinase 1(p-CDK1),phospho-ataxia telangiectasia-mutated(p-ATM),poly ADP-ribose polymerase(PARP),and meiotic recombination 11 homolog 1(MRE11).Conclusions TOPK was overexpressed in patients with moderately to poorly differentiated ***,TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.

关键词： T-lymphokine-activated killer cell-originated protein kinase colorectal cancer DNA damage response radiosensitivity

Modeling of LF refining process:a review

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Journal of Iron and Steel Research International 2024年第2期31卷 289-317页

作者： Zi-cheng xin jiang-shan Zhang Kai-xiang Peng Jun-guo Zhang Chun-hui Zhang Qing liu State Key Laboratory of Advanced Metallurgy University of Science and Technology BeijingBeijing100083China School of Automation and Electrical Engineering University of Science and Technology BeijingBeijing100083China Tangshan Branch Hebei Iron and Steel Co.Ltd.Tangshan063000HebeiChina xinjiang Bayi Iron and Steel Co. Ltd.Baosteel GroupWulumuqi830022XinjiangChina

With the increasing demand for energy conservation and emission reduction,more attentions have been paid to the intelligentization,greenization and low carbonization during the transformation and upgrading of steelmaking *** furnace(LF)refining is one of the key procedures in steelmaking process and has been widely used in steelmaking plants for its high equipment matching degree,low equipment investment and outstanding refining *** to the main tasks of LF refining process,the modeling methods of temperature prediction model,slag-making model,alloying model,argon blowing model and model of inclusions behavior were systematically reviewed,and the advantages and disadvantages of each modeling method were *** addition,the technical framework for the future has also been proposed based on existing works,including classification of raw materials,graphic representation of knowledge,introduction,upgradation and management of device/equipment,customization of steelmaking,modeling of refining process,synergy of models,intelligentization of decision-making,automation of control,and digitization of processes and operations,aiming to provide a reference for the modeling and intelligent development of LF refining process.

关键词： LF refining Temperature prediction Slag-making Alloying Argon blowing Inclusion behavior Modeling method

Impact of Annealing on the Melt Recrystallization of a-PDLA/α-PLLA Double-layered Films

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Chinese Journal of Polymer Science 2024年第2期42卷 230-238,I0009页

作者： Yun-Peng li Hao-Ran Shen Shao-Juan Wang Hao Zhang jian Hu Rui xin Xiao-li Sun Shou-Ke Yan Key Laboratory of Rubber-Plastics Ministry of Education/Shandong Provincial Key Laboratory of Rubber-plasticsQingdao University of Science&TechnologyQingdao266042China State Key Laboratory of Chemical Resource Engineering Beijing University of Chemical TechnologyBeijing100029China

Poly(lactic acid)(PLA) as a bio-based polymer with biodegradability and biocompatibility has attracted much attention. To manipulate its properties for different applications, regulation of crystal structure and crystalline morphology becomes an attractive research topic. In this work, the structure evolution of layered samples containing an amorphous poly(D-lactide)(PDLA) layer and a crystalline poly(L-lactide)(PLLA)layer with highly oriented edge-on α lamellar crystals after annealing at 150 ℃ or/and after melt-recrystallization has been studied by AFM, FTIR,and TEM combined with electron diffraction. The results demonstrate that melt recrystallization of the as-prepared sample leads to the formation of abundant randomly oriented PLA stereo-complex(PLA SC) crystals. Annealing at 150 ℃ results in the formation of a small amount of oriented PLA SC crystals at the interface. These PLA SC crystals show great impact on the recrystallization behavior of sample after melting at 190 ℃ and then crystallizing at 90 ℃. First, they impede the mutual diffusion of the overlying PDLA and underlying PLLA, and thus reduce their stereocomplexation ability as manifested by the decreased amount of PLA SC crystals. Second, they act as substrate to initiate the epitaxial crystallization of the overlying PDLA and underlying PLLA, which ensures the production of a highly oriented structure of PDLA and PLLA after melt recrystallization again.

关键词： Poly(L-lactide) Poly(D-lactide) Double layer Stereocomplex

Exact Convergence Rate of the Local limit Theorem for a Branching Random Walk in Zd with a Random Environment in Time

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Chinese Annals of Mathematics,Series B 2024年第5期45卷 805-822页

作者： jian-xin liu Zhi-qiang GAO School of Mathematical Sciences Beijing Normal University Laboratory of Mathematics and Complex Systems (Ministry of Education) School of Mathematical Sciences Beijing Normal University

Abstract Consider a branching random walk with a random environment in time in the d-dimensional integer *** branching mechanism is governed by a supercritical branching process,and the particles perform a lazy random walk with an independent,non-identical increment *** A?Zd,let Z_n（A） be the number of offsprings of generation n located in *** exact convergence rate of the local limit theorem for the counting measure Zn（·） is *** partially extends the previous results for a simple branching random walk derived by Gao （2017,*** Appl.）.

关键词： 60F05 60G50 60J10 60J80 Branching random walk Exact convergence rate Local limit theorems Random environment

Depositional model of the Member Deng-2 marginal microbial mound-bank complex of the Dengying Formation in the southwestern Sichuan Basin, SW China: Implications for the Ediacaran microbial mound construction and hydrocarbon exploration

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Petroleum Science 2024年第2期21卷 806-822页

作者： Jin-Min Song xin Jin Zhong Luo Shu-Gen liu Shao-Bo liu xing-Zhi Ma Zhi-Wu li Xue-Song Lu ling-li Zhao Ke-Ran li Jia-xin Ren li-Zhou Tian Hao-Shuang Deng State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation Chengdu University of TechnologyChengdu610059SichuanChina PetroChina Research Institute of Petroleum Exploration and Development Beijing100083China Xihua University Chengdu610039SichuanChina

Recent advances in hydrocarbon exploration have been made in the Member Deng-2 marginal microbial mound-bank complex reservoirs of the Dengying Formation in the western Sichuan Basin, SW China,where the depositional process is regarded confusing. The microfacies, construction types, and depositional model of the Member Deng-2 marginal microbial mound-bank complex have been investigated using unmanned aerial vehicle photography, outcrop section investigation, thin section identification,and seismic reflections in the southwestern Sichuan Basin. The microbialite lithologic textures in this region include thrombolite, dendrolite, stromatolite, fenestral stromatolite, spongiostromata stone,oncolite, aggregated grainstone, and botryoidal grapestone. Based on the comprehensive analysis of“depositional fabrics-lithology-microfacies”, an association between a fore mound, mound framework,and back mound subfacies has been proposed based on water depth, current direction, energy level and lithologic assemblages. The microfacies of the mound base, mound core, mound flank, mound cap, and mound flat could be recognized among the mound framework subfacies. Two construction types of marginal microbial mound-bank complex have been determined based on deposition location, mound scale, migration direction, and sedimentary facies association. Type Jinkouhe microbial mound constructions(TJMMCs) develop along the windward margin owing to their proximity to the seaward subfacies fore mound, with a northeastwardly migrated microbial mound on top of the mud mound,exhibiting the characteristics of large-sized mounds and small-sized banks in the surrounding area. Type E'bian microbial mound constructions(TEMMCs) primarily occur on the leeward margin, resulting from the presence of onshore back mound subfacies, with the smaller southwestward migrated microbial mounds existing on a thicker microbial flat. The platform margin microbial mound depositional model can be correlated with certain late

关键词： Sichuan Basin The Member Deng-2 Marginal microbial mound-bank complex Depositional model Exploration implications

Yolk shell-structured pyrite-type cobalt sulfide grafted by nitrogen-doped carbon-needles with enhanced electrical conductivity for oxygen electrocatalysis

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Chinese Chemical Letters 2024年第7期35卷 212-217页

作者： Jiahao Xie Jin liu Bin liu xin Meng Zhuang Cai Xiaoqin Xu cheng Wang Shijie You Jinlong Zou Key Laboratory of Functional Inorganic Material Chemistry Ministry of Education of the People’s Republic of ChinaSchool of Chemistry and Materials ScienceHeilongjiang UniversityHarbin 150080China School of Chemical Engineering and light Industry Guangdong University of TechnologyGuangzhou 510006China State Key Laboratory of Urban Water Resource and Environment School of EnvironmentHarbin Institute of TechnologyHarbin 150090China

Pyrite-type sulfides(PTS)exhibit promising intrinsic activities for oxygen reduction and evolution reactions(ORR/OER).However,their poor electrical conductivities may limit the charge transfer rate to inevitably lower ***,yolk-shell structured cobalt-pyrite nanospheres(CoS_(2)YSS)are prepared and modified with amino groups as nucleation sites for coupling highly-conductive needle-like nitrogendoped carbon via a facile solvothermal method(CoS_(2)YSS@NC).The as-marked CoS_(2)YSS@NC-0.5 shows a gap between yolk and shell,and an obvious exterior layer of grafted NC,which can provide an integrated structure,an interior place,and three exposed surfaces on CoS_(2).CoS_(2)YSS@NC-0.5 reveals higher ORR activity(half-wave potential of 0.88 V)and methanol resistance than commercial Pt/*** to in-situ formation of highly-active CoOOH,CoS_(2)YSS@NC-0.5 shows a better overpotential(244 mV at 10 mA/cm^(2))and Tafel slope(135 mV/dec)than ***-air battery with CoS_(2)YSS@NC-0.5 air-cathode exhibits good open circuit potential(1.44 V),specific capacity(772.5 mAh/g)and cycling ***-like NC layer coated on the yolk-shell structure of CoS_(2)effectively lowers the charge transfer resistance to obtain extraordinary ORR/OER *** indicates that the integration of highly-conductive carbon onto pyritetype sulfides is an effective strategy to acquire durable bifunctional ORR/OER catalysts.

关键词： Cobalt sulfides Cycle stability Electrical conductivity Pyrite Yolk-shell structure

Spatial-Temporal Analysis of Drinking Water Type of Endemic Fluorosis—China,2009–2022

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China CDC weekly 2024年第2期6卷 25-29页

作者： lijun Zhao Zhe li Mang li Hongna Sun Wei Wei lin Gao Qiaoshi Zhao Yang liu Xiaohong Ji cheng.li jian Wang Yanhui Gao Junrui Pei Center for Endemic Disease Control Chinese Center for Disease Control and PreventionHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina Key Lab of Etiology and Epidemiology Education Bureau of Heilongjiang Province(23618504)Ministry of Health of PRHarbin Medical UniversityHarbin CityHeilongjiang ProvinceChina

What is already known about this topic?Endemic fluorosis,caused by high fluoride levels in drinking water,has been a significant health issue in rural areas of China for many *** is added by this report?There has been a notable decline in the detection rate of dental fluorosis in children aged 8–12 years in drinking water fluorosis areas across the country from 2009 to *** 14 provincial-level administrative divisions are classified as low-probability clusters,Tianjin remains classified as a high-probability *** are the implications for public health practice?The current policy for preventing and controlling endemic fluorosis in China needs *** than focusing solely on regions with high incidence,there should be a shift towards monitoring and early warning of fluoride ***,local containment measures should be intensified.

关键词： intensified Spatial fluoride

Super P and MoO_(2)/MoS_(2)co-doped gradient nanofiber membrane as multi-functional separator for lithium–sulfur batteries

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Rare Metals 2024年第9期43卷 4263-4273页

作者： xin liang Dong-Qing Zhao Qian-Qian Huang Sheng liang li-li Wang Lei Hu ling-li liu Kun-Hong Hu Chong-Hai Deng Sheng cheng Er-Tao Zhu Hua-Xia Deng School of Energy Materials and Chemical Engineering LIB Technology Center of Anhui ProvinceHefei UniversityHefei 230601China Instrumental Analysis Centre Hefei University of TechnologyHefei 230009China Hefei Youngy Energy Materials Co. Ltd.Hefei 230000China Department of Modern Mechanics University of Science and Technology of ChinaHefei 230026China

lithium-sulfur battery is one of the most promising battery systems for industrialization due to its high theoretical specific capacity and high energy ***,the"shuttle effect"has restrained the advancement of lithium-sulfur *** this work,a gradient-structured nanofiber membrane with pure gelatin on one side and Super P-MoO_(2)/MoS_(2)-gelatin on the other side was created using a multi-step electrostatic spinning technique,which was applied for multi-functional separator for lithium-sulfur *** pure gelatin layer facing the anode side primarily homogenizes the lithium flux,whereas the Super P-MoO_(2)/MoS_(2)-gelatin layer facing the cathode side primarily adsorbs polysulfides by physical and chemical adsorption and enhancing polysulfide conversion *** findings demonstrate that even after 150 cycles at 0.2C,the lithium-sulfur battery can still sustain a discharge-specific capacity of 572.3 mAh·g^(-1).When used with li||li symmetric batteries,it has a cycle life of more than 1200 *** commercialization of lithium-sulfur batteries is given a fresh idea by this straightforward preparation technique.

关键词： MoO_(2)/MoS_(2) Nanofiber Membrane li-S battery