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Sedimentary Characteristics,Ages,and Environmental Significance of Gravel Deposits and Loess in shandong,Eastern China:Regional Response to Global Change Since the Last Glacial Period

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Acta Geologica Sinica(English Edition) 2024年第2期98卷 491-504页

作者： WANG Min KONG Fanbiao KONG Xianglun CHEN Haitao WANG Jiawei MIAO Xiaodong JIA Guangju HAN Mei XU Shujian Department of Geography and Tourism Qilu Normal UniversityJinan 250014China School of Geography and Environment Shandong Normal UniversityJinan 250014China shandong Provincial Key Laboratory of Water and Soil Conservation and Environmental Protection Linyi UniversitySchool of Resources and EnvironmentLinyiShandong 276005China College of Earth Science and Engineering Shandong University of Science and TechnologyQingdaoShandong 266590China

Investigation of rarely studied gravel layers found in the loess in shandong Province,eastern China,reveals the fabric characteristics of two gravel layers(G1,G2)and the sedimentary characteristics of loess at the typical and well-preserved Heiyu section(HY),where,to determine the paleoclimatic changes during Marine Isotope Stage *** stimulated luminescence dates of the HY formation range from 0.26±0.02 ka to 39.00±2.00 *** addition,the ages of G1 and G2 were estimated using the Bayesian model to be 39.60-40.50 and 29.00-29.50 ka.G1 and G2 are mainly composed of fine and medium gravel,both of which were subangular to subrounded limestone,with gravel directions to NE and *** average flow velocity,average depth,and flood peak flow of G1 are 1.10 m/s,0.49 m,and 37.04 m^(3)/s,respectively,calculated using the flow energy method,whereas those of G2 are 0.98 m/s,0.38 m,and 18.38 m^(3)/s,*** of climate proxy indices show that the sedimentary environment of the gravel and loess in HY might be a regional response to global change.

关键词： paleoenvironment geochronology gravel layer sedimentology Pleistocene shandong Province

DNA methylation drives a new path in gastric cancer early detection:Current impact and prospects

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Genes & Diseases 2024年第2期11卷 847-860页

作者： Xinhui Wang Yaqi Dong Hong Zhang Yinghui Zhao Tianshu Miao Ghazal Mohseni Lutao Du Chuanxin Wang Department of Clinical Laboratory The Second Hospital of Shandong UniversityJinanShandong 250033China Department of Clinical Laboratory Fuling HospitalChongqing UniversityChongqing 402774China Suzhou Research Institute of shandong University SuzhouJiangsu 215123China Department of Biochemistry and Molecular Biology Shandong University School of Basic Medical SciencesJinanShandong 250012China shandong Engineering & Technology Research Center for Tumor Marker Detection JinanShandong 250033China shandong Provincial Clinical Medicine Research Center for Clinical Laboratory JinanShandong 250033China

Gastric cancer(GC)is one of the most common and deadly cancers *** detection offers the best chance for curative treatment and reducing its ***,the optimal population-based early screening for GC remains *** DNA methylation occurs in the early stage of GC,exhibiting cancer-specific genetic and epigenetic changes,and can be detected in the media such as blood,gastric juice,and feces,constituting a valuable biomarker for cancer early ***,DNA methylation is a stable epigenetic alteration,and many innovative methods have been developed to quantify it rapidly and ***,large-scale clinical validation of DNA methylation serving as tumor biomarkers is still lacking,precluding their implementation in clinical *** conclusion,after a critical analysis of the recent existing literature,we summarized the evolving roles of DNA methylation during GC occurrence,expounded the newly discovered noninvasive DNA methylation biomarkers for early detection of GC,and discussed its challenges and prospects in clinical applications.

关键词： Biomarkers DNA methylation Early detection Gastric cancer Translation

Rearranged 19-nor-7,8-seco-labdane diterpenoids and Diels-Alder cycloadducts from the Chinese liverwort Pallavicinia ambigua:Structural elucidation,photoinduced rearrangement,and cytotoxic activity

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Chinese Chemical Letters 2024年第3期35卷 415-418页

作者： Chunyang Zhang Yuelan Li Zhaojun Chu Shuangzhi Yuan Yanan Qiao Jiaozhen Zhang Lin Li Yueqing Zhang Ruifeng Tian Yajie Tang Hongxiang Lou Department of Natural Products Chemistry Key Lab of Chemical Biology(MOE)School of Pharmaceutical SciencesShandong UniversityJi'nan 250012China State Key Laboratory of Microbial Technology Shandong UniversityQingdao 266237China

Two distinctive rearranged 19-nor-7,8-seco-labdane diterpenoids(1 and 2)with a novel tetracyclo[5.***.1.0^(2,5.)0^(4,10)]decane skeleton,a derivative of the open tetrahydrofuran ring(7),three dimeric compounds(8-10),and four revised homologs(3-6)were obtained from Chinese liverwort Pallavicinia *** structures were identified via combined analysis of their spectroscopic data,single-crystal X-ray diffraction patterns,and ECD *** light-driven conversion of compound 5 to compounds 1-4 demonstrated that photochemically induced postmodification involved in biosynthesis is an important way to diversify natural structures.A preliminary cytotoxicity assay revealed that compound 5 showed significant inhibition in the human prostate cancer(PC-3)cell line via an apoptotic pathway.

关键词： Liverwort Pallavicinia ambigua 19-nor-7 8-seco-Labdan diterpenoid Photoinduced rearrangement Cytotoxic activity

Structure-based design and optimization lead to the identification of novel dihydrothiopyrano[3,2-d]pyrimidine derivatives as potent HIV-1 inhibitors against drug-resistant variants

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1257-1282页

作者： Zhao Wang Heng Zhang Zhen Gao Zihao Sang Erik De Clercq Christophe Pannecouque Dongwei Kang Peng Zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Rega Institute for Medical Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of shandong Province Jinan 250012China Suzhou Research Institute Shandong UniversitySuzhou 215123China

With our continuous endeavors in seeking potent anti-HIV-1 agents,we reported here the discovery,biological characterization,and druggability evaluation of a class of nonnucleoside reverse transcriptase *** fully explore the chemical space of the NNRTI-binding pocket,novel series of dihydrothiopyrano[3,2-d]pyrimidines were developed by employing the structure-based design *** of the derivatives were endowed with prominent antiviral activities against HIV-1 wild-type and resistant strains at nanomolar *** them,compound 23h featuring the aminopiperidine moiety was identified as the most potent inhibitor,with EC50values ranging from 3.43 to 21.4 nmol/***,for the challenging double-mutants F227L+V106A and K103N+Y181C,23h exhibited 2.3-to 14.5-fold more potent activity than the first-line drugs efavirenz and ***,the resistance profiles of 23h achieved remarkable improvement compared to efavirenz and *** binding target of 23h was further confirmed to be HIV-1 reverse *** modeling studies were also performed to elucidate the biological evaluation results and give guidance for the optimization ***,no apparent inhibition of the major CYP450 enzymes and hERG channel was observed for *** importantly,23h was characterized by good pharmacokinetic properties and excellent safety in ***,23h holds great promise as a potential candidate for its effective antiviral efficacy and favorable drug-like profiles.

关键词： HIV-1 Reverse transcriptase Dihydrothiopyrano[3,2-d]pyrimidine Antiviral agent

ZP2:the precision regulator of egg coat architecture during fertilization

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Science China(Life Sciences) 2024年第8期67卷 1779-1780页

作者： Yi Dong Shigang Zhao Han Zhao State Key Laboratory of Reproductive Medicine and Offspring Health Center for Reproductive MedicineInstitute of WomenChildren and Reproductive HealthShandong UniversityJinan 250012China

In a recent study published in Cell,(Nishio et al.,2024)elucidated the molecular regulatory mechanism through which organisms prevent *** process intricately involves conformational changes in the zona pellucida(ZP)*** authors present a fascinating mechanism whereby post-fertilization cleavage of the ZP subunit ZP2 triggers its oligomerization,leading to crosslinking of filaments to harden the egg coat and prevent *** also systematically analyzed the pattern of ZP filament assembly,which revealed that two protofilaments comprising type I(ZP3)and type II(ZP1/ZP2/ZP4)components interlock to form a left-handed double helix *** findings are immensely beneficial for understanding the specific role of the egg coat,providing a plethora of insights.

关键词： mechanism finding crosslinking

Electroencephalogram findings in 10 patients with post-stroke epilepsy:A retrospective study

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World Journal of Clinical Cases 2024年第2期12卷 249-255页

作者： Li-Min Wen Ran Li Yan-Ling Wang Qing-Xia Kong Min Xia Clinical Medicine College Jining Medical UniversityJining 272067Shandong ProvinceChina School of Basic Medical Sciences Shandong UniversityJinan 250012Shandong ProvinceChina Department of Neurology The Affiliated Hospital of Jining Medical UniversityJining 272007Shandong ProvinceChina

BACKGROUND Post-stroke epilepsy is a common and easily overlooked complication of acute cerebrovascular ***-term seizures can seriously affect the prognosis and quality of life of ***(EEG)is the simplest way to diagnose epilepsy,and plays an important role in predicting seizures and guiding *** To explore the EEG characteristics of patients with post-stroke epilepsy and improve the detection rate of inter-seizure epileptiform *** From January 2017 to June 2020,10 patients with post-stroke epilepsy in our hospital were *** clinical,imaging,and EEG characteristics were *** stroke location,seizure type,and ictal and interictal EEG manifestations of the patients with post-stroke epilepsy were then retrospectively *** In all 10 patients,epileptiform waves occurred in the side opposite to the stroke lesion during the interictal stage;these manifested as sharp wave,sharp-wave complex,or spike discharges in the anterior head lead of the side opposite to the *** In EEG,epileptiform waves can occur in the side opposite to the stroke lesion in patients with post-stroke epilepsy.

关键词： Post-stroke epilepsy Electroencephalogram Seizure Stroke Slow wave

Chemical components in cultivated Cordyceps sinensis and their effects on fibrosis

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Chinese Herbal Medicines 2024年第1期16卷 162-167页

作者： Zhonghua Dong Xiao Sun Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalShandong Engineering and Technology Research Center for Pediatric Drug DevelopmentShandong Medicine and Health Key Laboratory of Clinical PharmacyJinan 250014China Department of Emergency Medicine Qilu Hospital of Shandong UniversityJinan 250012China shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityChest Pain CenterQilu Hospital of Shandong UniversityJinan 250012China Key Laboratory of Emergency and Critical Care Medicine of shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineShandong Key Laboratory:Magnetic Field-free Medicine&Functional ImagingQilu Hospital of Shandong UniversityJinan 250012China NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug Qilu Hospital of Shandong UniversityJinan 250012China

Objective:Cultivated Cordyceps sinensis powder has been used as clinical drug and healthy food to nourish the lung and kidney,which solves the problem of serious shortage of wild *** study aims to explore the chemical components and compared their anti-fibrotic effects in cultivated ***:Nucleosides,sterols and polysaccharides were separated and purified from cultivated ***,and analyzed by high performance liquid chromatography,gas chromatography-mass spectrometry and chemical chromogenic methods,*** high glucose-induced rat mesangial cell models,fibronectin and type 1 collagen were used as evaluation ***:There were 10 kinds of nucleosides and one sterol in cultivated *** contents of nucleosides,sterols and polysaccharides in the cultivated *** were close to 2%,0.55%and 4.4%,***,nucleoside,sterol and polysaccharide components exhibited varying degrees of antifibrotic *** nucleoside components and sterol components inhibited the expression of extracellular matrix more effectively in the three main ***:Cultivated *** remains the similar compounds with the wild ***,and nucleosides and sterols may be the main active substances that contribute to its anti-fibrotic *** project of this study may provide valuable information on further optimization of more effective remedies with few side effects based on cultivated ***.

关键词： anti-fibrotic effects cultivated Cordyceps sinensis ergosterol nucleosides polysaccharides

Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors

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Acta Pharmaceutica Sinica B 2024年第1期14卷 87-109页

作者： Letian Song Shenghua Gao Bing Ye Mianling Yang Yusen Cheng Dongwei Kang Fan Yi Jin-Peng Sun Luis Menéndez-Arias Johan Neyts Xinyong Liu Peng Zhan Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Shenzhen Research Institute of shandong University Shenzhen 518057China The Key Laboratory of Infection and Immunity of shandong Province Department of PharmacologySchool of Basic Medical SciencesShandong UniversityJinan 250012China Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Centro de Biologı´a Molecular“Severo Ochoa”(Consejo Superior de Investigaciones Cientı´ficas&Autonomous University of Madrid) Madrid 28049Spain KU Leuven Department of Microbiology and ImmunologyRega Institute for Medical ResearchLaboratory of Virology and ChemotherapyLeuven 3000Belgium

The main protease(M^(pro))of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life *** covalent M^(pro)inhibitor nirmatrelvir(in combination with ritonavir,a pharmacokinetic enhancer)and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic *** antiviral drugs are needed to fight the pandemic,while non-covalent M^(pro)inhibitors could be promising alternatives due to their high selectivity and favorable *** non-covalent M^(pro)inhibitors with desirable properties have been developed based on available crystal structures of M^(pro).In this article,we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^(pro)inhibitors,followed by a general overview and critical analysis of the available *** viewpoints and insights into current strategies for the development of non-covalent M^(pro)inhibitors are also discussed.

关键词： COVID-19 SARS-CoV-2 Main protease Non-covalent inhibitors Medicinal chemistry strategies

The Combined Effects of High Temperatures and Ozone Pollution on Medical Emergency Calls—Jinan City,shandong Province,China,2013–2019

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China CDC weekly 2024年第2期6卷 30-35,I0001-I0007页

作者： Huiyun Chang Chong Liu Xingyi Geng Xiumiao Peng Ke Huang Liheng Wang Liangliang Cui Department of Scientific Research and Education Jinan Municipal Center for Disease Control and PreventionJinan Municipal Center for Disease Control and Prevention Affiliated to Shandong UniversityJinan CityShandong ProvinceChina Jinan Health Well Development Center Jinan CityShandong ProvinceChina Department of Environmental Health Jinan Municipal Center for Disease Control and PreventionJinan CityShandong ProvinceChina Department of Emergency Jinan Medical Emergency CenterJinan CityShandong ProvinceChina

What is already known about this topic?Studies have extensively documented the separate and independent effects of extreme temperature and ozone on morbidity and mortality associated with respiratory and circulatory *** is added by this report?The study revealed a significant association between elevated temperature,ozone pollution,and the combined effect of high temperature and ozone pollution with an increased risk of all-cause medical emergency calls(MECs)and MECs specifically related to neurological *** are the implications for public health practice?Interventional measures should be implemented to mitigate exposure to high temperatures and ozone ***,during the warm season,it is crucial for relevant authorities to focus on disseminating scientific information regarding the health impacts of elevated temperatures and ozone ***,timely public health advisories should be issued to alert the public effectively.

关键词： ozone elevated pollution