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Chinese Chemical Letters 2025年第1期36卷 248-252页

作者： Meng Shan Yongmei Yu Mengli Sun Shuping Yang Mengqi Wang Bo Zhu Junbiao Chang State Key laboratory of Antiviral drugs Pingyuan LaboratoryNMPA Key Laboratory for Research and Evaluation of Innovative DrugSchool of Chemistry and Chemical EngineeringHenan Normal UniversityXinxiang 453007China

Herein,we report the dynamic kinetic resolution asymmetric acylation ofγ-hydroxy-γ-perfluoroalkyl butenolides/phthalides catalyzed by amino acid-derived bifunctional organocatalysts,and a series of ketals were obtained in high yields(up to 95%)and excellent enantioselectivities(up to 99%).In terms of synthetic utility,the reaction can be performed on a gram scale,and the product can be converted into potential biological nucleoside analog.

关键词： Bifunctional organocatalyst Dynamic kinetic resolution Hemiketal Chiral ketals Hydrogen bonding

Enhanced oral drug delivery by mimicking natural amino acid and oligopeptide absorption route

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Nano research 2025年第2期18卷 525-540页

作者： Ruinan Wu Xiaoxing Fan Licheng Wu Liyun Xing Jinxia Kong Zhou Zhou Jingyuan Wen Lian Li Yuan Huang Key laboratory of drug-Targeting and drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China School of Pharmacy Faculty of Medical and Health SciencesUniversity of AucklandAuckland 1023New Zealand

Oral delivery of protein and peptide drugs presents considerable challenges due to their susceptibility to digestive enzymes in gastrointestinal(Gl)tract and low efficiency of transepithelial ***,inspired by efficient absorption of protein-based nutrients,we constructed several kinds of oral drug delivery systems by mimicking natural amino acid and oligopeptide absorption *** kinds of amino acids and two kinds of oligopeptides were chosen as targeting ligands to mediate transportation of orally administered nanoparticles(NPs).Liraglutide(Lira),a kind of glucagon like peptide-1(GLP-1)receptor agonist,was used as model *** functionalized NPs could protect Lira from enzymatic degradation in Gl ***,compared with amino acid-modified NPs,oligopeptide-modified NPs exhibited greater transepithelial transport efficiency and were primarily absorbed in the proximal small intestine due to the high expression and transportation mediated by proton coupled oligopeptide transporter 1(PEPT1).These Lira-loaded NPs could effectively control the blood glucose level,reduce plasma lipid level,and repair tissue damage on type 2 diabetic mice and even showed comparable hypoglycemic effects of subcutaneous injection(s.c.)free *** study demonstrates the potential of mimicking natural oligopeptide absorption route to enhance oral delivery of protein and peptide drugs.

关键词： oral drug delivery amino acid absorption route oligopeptide absorption route liraglutide

Curvularin derivatives from hydrothermal vent sediment fungus Penicillium ***-50 guided by molecular networking and their antiinflammatory activity

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Chinese Journal of Natural Medicines 2025年第1期23卷 119-128页

作者： Chunxue Yu Zixuan Xia Zhipeng Xu Xiyang Tang Wenjuan Ding Jihua Wei Danmei Tian Bin Wu Jinshan Tang Institute of Traditional Chinese Medicine and Natural Products College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China Jinan University School of Traditional Chinese Materia Medica Shenyang Pharmaceutical University Ocean College Zhejiang UniversityZhoushan Campus

Guided by molecular networking, nine novel curvularin derivatives（1-9） and 16 known analogs（10-25） were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance（NMR） spectroscopy, X-ray diffraction, electronic circular dichroism（ECD） calculations,13C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide（LPS）-induced nitric oxide（NO）production in murine macrophage RAW264.7 cells, with IC50values ranging from 0.44 to 4.40μmol·L-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase（i NOS）, cyclooxygenase-2（COX-2）, NLR family pyrin domain-containing protein 3（NLRP3）, and nuclear factor kappa-B（NF-κB）. Additional studies demonstrated that the novel compound 7 possessed potent antiinflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.

关键词： Anti-inflammatory activity Curvularin derivatives Molecular networking Penicillium sp. HL-50

I_(2)-DMSO mediated tetra-functionalization of enaminones for the construction of novel furo[2,3:4,5]pyrimido[1,2-b]indazole skeletons via in situ capture of ketenimine cations

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Chinese Chemical Letters 2025年第1期36卷 277-282页

作者： You Zhou Li-Sheng Wang Shuang-Gui Lei Bo-Cheng Tang Zhi-Cheng Yu Xing Li Yan-Dong Wu Kai-Lu Zheng An-Xin Wu National Key laboratory of Green Pesticide International Joint Research Center for Intelligent Biosensor Technology and HealthCollege of ChemistryCentral China Normal UniversityWuhan 430079China Guangdong Provincial Key laboratory of research and Development of Natural drugs The First Dongguan Affiliated HospitalSchool of PharmacyGuangdong Medical UniversityDongguan 523808China State Key laboratory of Chemical Biology and drug Discovery Department of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHong Kong SAR 999077China

The first-ever synthesis of the unknown furo[2,3:4,5]pyrimido[1,2-b]indazole skeleton was demonstrated based on the undiscovered tetra-functionalization of enaminones,with simple substrates and reaction *** key to realizing this process lies in the multiple trapping of the in situ generated ketenimine cation by the 3-aminoindazole,which results in the formation of four new chemical bonds and two new rings in one ***,the products of this new reaction were found to exhibit aggregationinduced emission(AIE)without modification.

关键词： Unknown skeleton Tetra-functionalization Ketenimine cations Aggregation-induced emission

The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal Key laboratory of Biomarker and Translational research in Neurodegenerative Diseases BeijingChina Key laboratory for neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

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Neural Regeneration research 2025年第9期20卷 2706-2726页

作者： Biao Xiao Chaoyang Chu Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui Shan Shiyu Chen Liping Li Department of Physiology and Pharmacology Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Ningbo Key laboratory of Behavioral neuroscience Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Key laboratory of Addiction research of Zhejiang Province NingboZhejiang ProvinceChina

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's ***,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and ***,nonpharmacological interventions aimed at inducing adult neurogenesis are currently *** individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully *** this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 *** deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease ***,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus *** findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 ***,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice

关键词： acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites

Marine dispersion of Fukushima-derived radiocesium in the North Pacific and its implications

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Science China Earth Sciences 2025年第2期68卷 389-406页

作者： Tong ZHANG Xiaolin HOU Yukun FAN State Key laboratory of Loess and Quaternary Geology Shaanxi Key Laboratory of Accelerator Mass Spectrometry Technology and ApplicationXi’an AMS CenterInstitute of Earth EnvironmentChinese Academy of SciencesXi’an 710061China University of Chinese Academy of Sciences Beijing 100049China Xi’an Institute for innovative Earth Environment research Xi’an 710061China

A key scientific approach to addressing the environmental radiation risks from Fukushima nuclear contaminated water(FNCW) discharge into the ocean is understanding and predicting the marine dispersion of *** dispersion of radiocesium(CsF:134Cs,137Cs) from the Fukushima nuclear accident in the North Pacific and its marginal seas post-2011 was systematically summarized,focusing on pathways,vertical distribution changes,and transit *** research examined CsFdispersion through the Kuroshio Extension and denser central mode water(D-CMW) to the eastern North Pacific,as well as through subtropical mode water(STMW),lighter central mode water(L-CMW),and D-CMW to the subtropical western North Pacific,China Seas,and Sea of *** considered broader implications of CsFdispersion in light of ongoing FNCW *** this prolonged liquid discharge and Kuroshio Extension’s barrier effect,it is crucial to emphasize the role of CMW besides STMW in transporting FNCW to the subtropical western North Pacific and its marginal *** research should focus on the key mechanism and longitude range of CMW crossing the Kuroshio *** short-lived134Cs decays rapidly during the storage and dispersion of FNCW,long-lived135Cs and135Cs/137Cs ratios can serve as valuable tracers for detecting and quantifying ***,there is an urgent need for high-precision analysis of these key radionuclides and their characteristic *** promptly detect,assess,and respond to FNCW intrusion,continuous monitoring and identification of nuclear pollution sources in key ocean currents and straits are ***,interdisciplinary research integrating monitoring with marginal sea circulation dynamics and high-resolution numerical simulations should be a priority.

关键词： Fukushima nuclear accident Fukushima nuclear contaminated water Marine dispersion Mode water Kuroshio Extension

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NIR-Ⅱfluorescence lateral flow immunosensor based on efficient energy transfer probe for point-of-care testing of tumor biomarkers

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Chinese Chemical Letters 2025年第1期36卷 469-473页

作者： Zhaorui Song Qiulian Hao Bing Li Yuwei Yuan Shanshan Zhang Yongkuan Suo Hai-Hao Han Zhen Cheng Shandong laboratory of Yantai drug Discovery Bohai Rim Advanced Research Institute for Drug DiscoveryYantai 264117China State Key laboratory of drug research Molecular Imaging CenterShanghai Institute of Materia MedicaShanghai 201203China Institute of Molecular Medicine joint laboratory for Molecular Medicine Northeastern University Shenyang 110000China Pharmacy College Shandong First Medical University&Shandong Academy of Medical SciencesJi’nan 250117China University of Chinese Academy of Sciences Beijing 100049China

Fluorescence lateral flow immunoassay(LFA)has emerged as a powerful tool for rapid screening of various biomarkers owing to its simplicity,sensitivity and *** is noteworthy that fluorescent probe mainly determines the analytical performance of *** to the emission and excitation wavelengths are located in the visible region,most fluorophores are inevitably subject to light scattering and background ***,we reported a novel LFA sensor based on the second near-infrared(NIR-Ⅱ)fluorescent probe with excellent anti-interference *** designed NIR-Ⅱprobe was the Nd^(3+)and Yb^(3+)doped rare earth nanoparticles(RENPs)by employing Nd^(3+)as energy donor and Yb^(3+)as energy acceptor,which of the donor-acceptor energy transfer(ET)efficiency reached up to 80.7%.Meanwhile,relying on the convenient and effective encapsulation strategy of poly(lactic-co-glycolic acid)(PLGA)microspheres to RENPs,the surface functionalized NIR-Ⅱprobe(RE@PLGA)was obtained for subsequent *** from the optical advantages of NIR-Ⅱprobe,this proposed NIR-ⅡLFA displayed a good linear relationship ranging from 7 ng/mL to 200 ng/mL for the detection ofα-fetoprotein(AFP),an important biomarker of hepatocellular carcinoma(HCC).The limit of detection(LOD)was determined as low as 3.0 ng/m L,which was of 8.3 times lower than clinical cutoff *** is promising that LFA sensor based on this efficient RENPs probe provides new opportunities for high sensitive detection of various biomarkers in biological samples.

关键词： Donor-acceptor energy transfer(ET) Lateral flow immunoassay(LFA) The second near-infrared(NIR-Ⅱ) fluorescence Rare-earth nanoparticles(RENPs) Poly(lactic acid-co-glycolic acid)(PLGA) Tumor biomarker

Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

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Neural Regeneration research 2025年第11期20卷 3193-3206页

作者： Ling-Xiao Yi Hui Ren Woon Genevieve Saw Li Zeng Eng King Tan Zhi Dong Zhou National neuroscience Institute Singapore Nanyang Technology University Singapore Department of Neurology Singapore General HospitalSingapore Signature research Program in neuroscience and Behavioral Disorders Duke-NUS Medical SchoolSingapore

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative *** the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and *** induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease *** current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem *** benefits of induced pluripotent stem cell-based research are *** dopaminergic neuron differentiation protocols from induced pluripotent stem cells are *** emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are ***,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

关键词： dopaminergic neurons induced pluripotent stem cells Parkinson's disease stem cell approaches

Impacts of emission reduction and meteorological conditions on air quality improvement from 2016 to 2020 in the Northeast Plain,China

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Journal of Environmental Sciences 2025年第5期151卷 484-496页

作者： Xueling Yang Qiyuan Wang Lang Liu Jie Tian Hailing Xie Luyao Wang Yue Cao Steven Sai Hang Ho Key laboratory of Aerosol Chemistry and Physics State Key Laboratory of Loess and Quaternary GeologyInstitute of Earth EnvironmentChinese Academy of SciencesXi’an 710061China Xi’an Institute for innovative Earth Environment research Xi’an 710061China National Observation and research Station of Regional Ecological Environment Change and Comprehensive Management in the Guanzhong Plain Xi’an 710061China College of Meteorology and Oceanography National University of Defense TechnologyChangsha 410073China Division of Atmospheric Sciences Desert Research InstituteRenoNV 89512USA

The Northeast Plain in China ranks among the top five regions that have been significantly impacted by haze *** effectively control pollution,it is crucial to accurately assess the effects of emission reduction *** this study,we analyzed surveillance data and found substantial decreases(ranging from 19.0%to 50.1%)in average annual mass concentrations of key pollutants(such as CO,SO_(2),NO_(2),and PM_(2.5))in the Northeast Plain from 2016 to *** precisely determine the contributions of meteorological conditions and emission reductions to the improvement of air quality in the Northeast Plain,we conducted three scenario *** comparing source emissions in December 2016 and 2020 using the WRF-Chem model(except for SO_(2)),we observed significant reductions of 21.3%,8.8%,and 9.8%in mass concentrations of PM_(2.5),NO_(2),and CO,respectively,from 2016 to *** highlights the essential role that meteorological conditions play in determining air quality in the Northeast ***,further reducing source emissions by 30%in December 2016 resulted in subsequent reductions of 25.3%,29.0%,4.5%,and 30.3%in mass concentrations of PM_(2.5),SO_(2),NO_(2),and CO,respectively,under the same meteorological ***,source emission reduction was effective for PM_(2.5),SO_(2),and CO,but not for NO_(2).The improvement in air quality in the Northeast Plain from 2016 to 2020 can be attributed to the combined effects of improved meteorological conditions and reduced pollution sources.

关键词： Air quality Emission reduction Meteorological conditions The Northeast Plain WRF-Chem