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Photodynamic eradication of intratumoral microbiota with bacteria-targeted micelles overcomes gemcitabine resistance of pancreatic cancer

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Aggregate 2024年第1期5卷 377-384页

作者： Renfa liu Huanyu Yang Shuai qu Peipei Yang xin zhi Yunxue Xu zhifei Dai Linxue Qian Department of Biomedical Engineering College of Future TechnologyNational Biomedical Imaging CenterPeking UniversityBeijingChina Department of Ultrasound Beijing Friendship HospitalCapital Medical UniversityBeijingChina

Increasing evidence suggests that intratumoral microbiota plays a pivotal role in tumor progression,immunosurveillance,metastasis,and ***,in pancreatic ductal adenocarcinoma,tumor-resident Gammaproteobacteria could transform the chemotherapeutic drug gemcitabine(Gem)into its inactive form,thus rendering chemotherapy ***,a strategy for selectively eradicating intratumoral bacteria was described for overcoming Gem resistance in a pancreatic cancer animal *** antimicrobial peptide was linked with photosensitizer through a poly(ethylene glycol)chain,which can self-assemble into micelles with a diameter of∼20 *** micelles could efficiently kill bacteria under light irradiation by inducing membrane depolarization,thereby inhibiting Gem *** a bacteria-resident pancreatic cancer animal model,the selective photodynamic eradication of intratumoral bacteria was demonstrated to efficiently reverse Gem *** research highlights antibacterial photodynamic therapy as a promising adjuvant strategy for cancer therapy by modulating intratumoral microbiota.

关键词： antimicrobial peptide gemcitabine resistance intratumoral microbiota pancreatic ductal adenocarcinoma photodynamic antibacterial therapy

A positive feedback inhibition of isocitrate dehydrogenase 3β on paired-box gene 6 promotes Alzheimer-like pathology

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2324-2340页

作者： xin Wang Qian liu Hai-tao Yu Jia-zhao Xie Jun-ning Zhao zhi-ting Fang Min qu Yao Zhang Ying Yang Jian-zhi Wang Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Fundamental Medicine Wuxi School of MedicineJiangnan UniversityWuxiJiangsu 214122China Hubei Provincial Key Laboratory for Applied Toxicology Hubei Provincial Center for Disease Control and PreventionHubei Provincial Academy of Preventive MedicineWuhan 430000China Endocrine Department of Liyuan Hospital Key Laboratory of Ministry of Education of China for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430077China Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226000China

Impaired brain glucose metabolism is an early indicator of Alzheimer’s disease(AD);however,the fundamental mechanism is *** this study,we found a substantial decline in isocitrate dehydrogenase 3β(IDH3β)levels,a critical tricarboxylic acid cycle enzyme,in AD patients and AD-transgenic mice’s *** investigations demonstrated that the knockdown of IDH3βinduced oxidation-phosphorylation uncoupling,leading to reduced energy metabolism and lactate *** resulting increased lactate,a source of lactyl,was found to promote histone lactylation,thereby enhancing the expression of paired-box gene 6(PAX6).As an inhibitory transcription factor of IDH3β,the elevated PAX6 in turn inhibited the expression of IDH3β,leading to tau hyperphosphorylation,synapse impairment,and learning and memory deficits resembling those seen in *** AD-transgenic mice,upregulating IDH3βand downregulating PAX6 were found to improve cognitive functioning and reverse AD-like ***,our data suggest that impaired oxidative phosphorylation accelerates AD progression via a positive feedback inhibition loop of IDH3β-lactate-PAX6-IDH3β.Breaking this loop by upregulating IDH3βor downregulating PAX6 attenuates AD neurodegeneration and cognitive impairments.

关键词： metabolism Alzheimer impaired

Controllable Ring-opening Polymerization ofδ-Valerolactone Catalyzed by quinolinyl-Urea/MTBD Systems

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Chinese Journal of Polymer Science 2024年第8期42卷 1103-1110页

作者： xin-Yu liu liang Zhu Su-Yun Jie bo-Geng Li State Key Laboratory of Chemical Engineering College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310058China

Due to their excellent biocompatibility and biodegradability,aliphatic polyesters are widely used in the biomedical,packaging and agricultural fields,which are usually accessed by the ring-opening polymerization(ROP)of lactones and the catalysts particularly play an important *** a series of quinolinyl-urea catalysts have been synthesized via the reaction between isocyanate and aminoquinoline with an amino group at different substitution positions and *** combination with 7-methyl-1,5,7-triazabicyclo[4,4,0]dec-5-ene(MTBD)as a cocatalyst and benzyl alcohol(BnOH)as an initiator,1-(3,5-bis(trifluoromethyl)phenyl)-3-(quinolin-3-yl)urea(3-qu)was observed to be most active for the ROP ofδ-valerolactone(δ-VL).The polymerization conditions were optimized by varying the type of organic base,catalyst concentration and reaction *** changing the ratio of[M]_0/[I],linear polyvalerolactones(PVLs)with different molecular weights and narrow molecular weight distribution were *** kinetic and chain extension experiments were carried out to prove the"living"/controllable *** the NMR experiments were used to support the proposal of possible mechanism.

关键词： quinolinyl-urea Ring-opening polymerization PVL

Knockdown of fibrillin-1 suppresses retina-blood barrier dysfunction by inhibiting vascular endothelial apoptosis under diabetic conditions

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International Journal of Ophthalmology(English edition) 2024年第8期17卷 1403-1410页

作者： Yue Zhang Xiao-Jing liu xin-Ran Zhai Yao Yao Bin Shao Yu-Han Zhen xin Zhang Zhe Xiao Li-Fang Wang Ming-lian Zhang zhi-Min Chen Hebei Eye Hospital Provincial Key Laboratory of OphthalmologyHebei Provincial Clinical Research Center for Eye DiseasesXingtai 054001Hebei ProvinceChina Department of Ophthalmology Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina

AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic ***:Streptozotocin(STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy(DR)patients,and FBN1 expression was detected in retinas from STZ-diabetic mice and *** the Gene Expression Omnibus(GEO)database,the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR *** lentivirus to knock down FBN1 levels,vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay,fluorescein fundus angiography(FFA)and immunofluorescence labeled with tight junction marker in *** glucose-induced monkey retinal vascular endothelial cells(RF/6A)were used to investigate effects of FBN1 on the cells in *** vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance(TEER)assay and flow cytometry,***:FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients(GSE60436 datasets)using RNA-seq ***,knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA *** of tight junction markers in STZ-DR mouse retinas were lower than those in the control group,and knocking down of FBN1 increased the tight junction *** vitro,30 mmol/L glucose could significantly inhibit viability of RF/6A cells,and FBN1 mRNA expression was increased under 30 mmol/L glucose ***-regulation of FBN1 reduced high glucose(HG)-stimulated retinal microvascular endothelial cell permeability,increased TEER,and inhibited RF/6A cell apoptosis in ***:The expression level of FBN1 increases in reti

关键词： diabetic retinopathy fibrillin-1 retinablood barrier vascular leakage vascular permeability apoptosis retinal vascular endothelial cells

Pan-cancer immunogenic death analysis identifies key roles of CXCR3 and CCL18 in hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 568-570页

作者： Jia Guo xin Sun Guowei Pan Ce Li xin He Xiaofang Che Zan Teng Xiujuan qu Yunpeng liu bowen Yang Department of Medical Oncology Provincial Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning ProvinceLiaoning Provincial Clinical Research Center for CancerClinical Cancer Research Center of ShenyangThe First Hospital of China Medical UniversityShenyangLiaoning 110001China Research Center for Universal Health School of Public HealthChina Medical UniversityShenyangLiaoning 110122China

Immunogenic death is a form of programmed cell death that is common in the development and progression of ***,its impact on tumor progression differs depending on the location of the ***,it also plays an important role in antitumor immunity because the process of immunogenic death can release substances that activate immunity.1 Therefore,in this study,the key mechanism of mediating immunogenic death in hepatocellular carcinoma(HCC)was found from the excavation of the immunogenic death characteristics of pan-cancer and the in-depth investigation of its effects on different tumor types(Fig.1A).

关键词： death CXCR3 immunity

Correction:A positive feedback inhibition of isocitrate dehydrogenase 3β on paired-box gene 6 promotes Alzheimerlike pathology

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3537-3540页

作者： xin Wang Qian liu Hai-tao Yu Jia-zhao Xie Jun-ning Zhao zhi-ting Fang Min qu Yao Zhang Ying Yang Jian-zhi Wang Department of Pathophysiology School of Basic Medicine Key Laboratory of Education Ministry of China/Hubei Province for Neurological Disorders Tongji Medical College Huazhong University of Science and Technology Wuhan China Department of Fundamental Medicine Wuxi School of Medicine Jiangnan University Wuxi Jiangsu 214122 China Co-innovation Center of Neuroregeneration Nantong University Nantong 226000 China Hubei Provincial Key Laboratory for Applied Toxicology Hubei Provincial Center for Disease Control and Prevention Hubei Provincial Academy of Preventive Medicine Wuhan 430000 China Endocrine Department of Liyuan Hospital Key Laboratory of Ministry of Education of China for Neurological Disorders Tongji Medical College Huazhong University of Science and Technology Wuhan 430077 China

After online publication of the article',the authors noticed that,owing to authors'oversight in layer placement within the illustration,Golgi staining images representing both the 5xFAD group and,the 5xFAD+IDH3β_grou... 详细信息

关键词： illustration representing noticed

Discovery and characterization of novel potent non-covalent small molecule inhibitors targeting papain-like protease from SARS-CoV-2

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3286-3290页

作者： Miao Zheng bo Feng Yumin Zhang xin liu NaZhao Hui liu Zichao Xu xinheng He zhiyan qu ShizhaoChen zhidong Jiang Xi Cheng Hong liu Yi Zang Linxiang Zhao Jie Zheng Leike Zhang Jia Li Yu Zhou Key Laboratory of Structure-Based Drugs Design&Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Sciences and Biopharmaceuticals Shenyang Pharmaceutical UniversityShenyang 110016China Shanghai Institute of Materia Medica Chinese Academy of SciencesShanghai 201203and University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Chemical Biology Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203and University of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China Lingang Laboratory Shanghai 200031China School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Hubei Jiangxia Laboratory Wuhan 430200China

To the Editor:The papain-like protease(PL^(pro)),as one of the most important proteases of SARS-CoV-2,has emerged as a highly promising target protein,its inhibitor probably holds dual potentials,namely blocking the cleavage of viral polyprotein and intercepting the deubiquitination and deISGylation functions to restore antiviral immunity1.

关键词： Non-covalent PL^(pro)inhibitors Antiviral activity Structural-based drug design Imidazo[4,5-b]pyridine scaffold

Hetero-phase zirconia encapsulated with Au nanoparticles for boosting electrocatalytic nitrogen reduction

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Chinese Chemical Letters 2024年第5期35卷 509-513页

作者： Xue xin Qiming qu Islam E.Khalil Yuting Huang Mo Wei Jie Chen Weina Zhang Fengwei Huo Wenjing liu Key Laboratory of Flexible Electronics(KLOFE)&Institute of Advanced Materials(IAM) Nanjing Tech UniversityNanjing 211816China

Electrocatalytic nitrogen reduction reaction(NRR)is considered as an attractive approach for ammonia synthesis under mild conditions.A bottleneck of NRR is the exploration of efficient catalysts for accelerating reaction kinetics,among which heterogeneous structures possessing distinct atomic arrangement could modify electronic structure,and therefore altering their NRR ***,we report a facile strategy for fabricating hetero-phase metal oxides derived from metal organic framework that are further integrated with Au nanoparticles as NRR *** phase composition of zirconia can be easily adjusted by simply changing the reaction temperature,where the monoclinic and tetragonal phases with the roughly close proportions have a distinct interface,leading to a strong interaction between Au and ZrO_(2).The enhanced interaction renders Au to be more electropositive and facilitates stronger binding to N_(2).As a result,a remarkable ammonia yield of 22.32μg h^(-1)mg_(cat.)^(-1) and a Faradaic efficiency of 31.92%can be achieved at low *** work is expected to pave the way for the design of heterogeneous structures and the exploration of hetero-phase nanostructures in boosting the electrocatalytic NRR.

关键词： Hetero-phase Metal-organic framework derivatives Zirconia Nitrogen reduction reaction Electrochemistry

Measurement of atmospheric non-reciprocity effects for satellite-based two-way time-frequency transfer

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Photonics Research 2024年第6期12卷 1274-1282页

作者： TING ZENG QI SHEN YUAN CAO JIAN-YU GUAN MENG-ZHE lian JIN-JIAN HAN LEI HOU JIAN LU xin-xin PENG MIN LI WEI-YUE liu JIN-CAI WU YONG WANG JUAN YIN JI-GANG REN HAI-FENG JIANG QIANG ZHANG CHENG-zhi PENG JIAN-WEI PAN Hefei National Research Center for Physical Sciences at the Microscale and School of Physical Sciences University of Science and Technology of ChinaHefei 230026China Shanghai Research Center for quantum Science and CAS Center for Excellence in quantum Information and quantum Physics University of Science and Technology of ChinaShanghai 201315China Hefei National Laboratory University of Science and Technology of ChinaHefei 230094China Faculty of Information Science and Engineering Ningbo UniversityNingbo 315211China Key Laboratory of Space Active Opto-Electronic Technology Shanghai Institute of Technical PhysicsChinese Academy of SciencesShanghai 200083China xinjiang Astronomical Observatory Chinese Academy of SciencesUrumqi 830011China

Future optical clock networks will require high-precision optical time-frequency transfer between satellites and ground ***,due to atmospheric turbulence,satellite motion and time delay between the satellite–ground transmission links will cause spatial and temporal variations,respectively,resulting in the breakdown of the time-of-flight reciprocity on which optical two-way time-frequency transfer is ***,we experimentally simulate the atmospheric effects by two-way spatio-temporally separated links between two stationary terminals located 113 km apart and measure the effects for optical two-way time-frequency *** experiment shows that the effect on the link instability is less than 2.3×10^(−19) at 10,000 *** indicates that when the link instability of satellite-ground optical time-frequency transfer is on the order of 10^(−19),it is not necessary to consider the atmospheric non-reciprocity effects.

关键词： breakdown transfer satellite