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STING signaling in islet macrophages impairs insulin secretion in obesity

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science China(life sciences) 2024年第2期67卷 345-359页

作者： Ze Hong Saihua Chen Jing Sun Dan Cheng Hanli Guo Jiahao Mei Xiang Zhang Munire Maimaiti Haiping Hao Peng Cao Haiyang Hu Chen Wang School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Natural Medicines Department of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 211198China School of life sciences Westlake UniversityHangzhou 310012China

The innate immune regulator stimulator of interferon genes(STING)mediates self-DNA sensing and leads to the induction of type I interferons and inflammatory cytokines,which promotes the progression of various inflammatory and autoimmune *** immune system plays a critical role in regulating obesity-induced islet dysfunction,whereas the potential effect of STING signaling is not fully ***,we demonstrate that STING is mainly expressed and activated in islet macrophages upon high-fat diet(HFD)***^(-/-)alleviates HFD-induced islet inflammation by inhibiting the expression of pro-inflammatory cytokines and the infiltration of ***,palmitic acid incubation promotes mitochondrial DNA leakage into the cytosol and subsequently activates STING pathway in ***,STING activation in macrophages impairs glucose-stimulated insulin secretion by mediating the engulfment ofβcell insulin secretory *** inhibiting STING activation enhances insulin secretion to control ***,our results reveal a regulatory mechanism in controlling the islet inflammation and insulin secretion in dietinduced obesity and suggest that selective blocking of the STING activation may be a promising strategy for treating type 2 diabetes.

关键词： STING obesity type 2 diabetes insulin macrophages islet

NQO1 Mediates Lenvatinib Resistance by Regulating ROS-induced Apoptosis in Hepatocellular Carcinoma

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Current Medical science 2024年第1期44卷 168-179页

作者： Wei XUE Ting WANG Wen-jing TIAN Si-qi PANG Hua-feng ZHANG Wei-dong JIA department of General Surgery The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Health and Medicine Hefei Comprehensive National Science CenterHefei 230601China The Chinese Academy of sciences Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China

Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death *** a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients,and the underlying mechanism remains largely *** present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC,explore the potential molecular mechanism,and propose combinatorial therapeutic targets for HCC *** Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and ***-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant(LR)*** upregulated genes were analyzed by GO and KEGG ***,qPCR and Western blotting were employed to determine the relative gene expression ***,the intracellular reactive oxygen species(ROS)and apoptosis were detected by flow *** PLC-LR and Hep3B-LR were *** was a total of 116 significantly upregulated genes common to both LR cell *** GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities,and reactive oxygen species ***,NAD(P)H:quinone oxidoreductase 1(NQO1)was highly expressed in LR cells,and was involved in the lenvatinib *** high expression of NQO1 decreased the production of ROS induced by lenvatinib,and subsequently suppressed the *** combination of lenvatinib and NQO1 inhibitor,dicoumarol,reversed the resistance of LR *** The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels,thereby promoting lenvatinib resistance in HCC cells.

关键词： hepatocellular carcinoma lenvatinib resistance NAD(P)H quinone oxidoreductase 1 reactive oxygen species apoptosis dicoumarol

Experimental arena settings might lead to misinterpretation of movement properties

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Insect science 2024年第1期31卷 271-284页

作者： Inon Scharf Kimberley Hanna Daphna Gottlieb The George S.Wise Faculty of life sciences School of ZoologyTel Aviv UniversityTel AvivIsrael department of Food science Institute of Post-Harvest and Food ScienceVolcani CenterARORishon LeZionIsrael

Movement is an important animal behavior contributing to reproduction and *** movement is often examined in arenas or enclosures under laboratory *** used the red flour beetle(Tribolium castaneum)to examine here the effect of the arena size,shape,number of barriers,access to the arena's center,and illumination on six movement *** demonstrate great differences among *** example,the beetles moved over longer distances in clear arenas than in obstructed *** along the arena's perimeter was greater in smaller arenas than in larger *** was more directional in round arenas than in rectangular *** general,the beetles stopped moving closer to the perimeter and closer to corners(in the square and rectangular arenas)than expected by *** some cases,the arena properties interacted with the beetle sex to affect several movement *** these suggest that arena properties might also interact with experimental manipulations to affect the outcome of studies and lead to results specific to the arena *** other words,instead of examining animal movement,we in fact examine the animal interaction with the arena *** is therefore advised in interpreting the results of studies on movement in arenas under laboratory conditions and we recommend paying attention also to barriers or obstacles in field *** instance,movement along the arena's perimeter is often interpreted as centrophobism or thigmotaxis but the results here show that such movement is arena dependent.

关键词： activity centrophobism correlated random walk laboratory experiments movement ecology wall-following behavior

Ethanol-assisted synthesis of a Ni single-atom catalyst with poriferous 3D framework for efficient cascade CO_(2)electroreduction

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Rare Metals 2024年第9期43卷 4612-4619页

作者： Feng Wu Shi-Qi Wang Sebastian Kunze Xiao-Ping Gao Pei-Qun Yin Yu-En Wu Division of life sciences and Medicine Department of EndocrinologySchool of Chemistry and Materials ScienceThe First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefei 230026China department of Chemistry Seoul National UniversitySeoul 08826South Korea School of Biomedical Engineering Anhui Medical UniversityHefei 230032China

The electroreduction of carbon dioxide to generate multicarbon products is significant for achieving a carbon-neutral ***,the selectivity for multi-carbon products faces several challenges,such as the intricate nature of the multistep hydrogenation processes,slow reaction kinetics and the bicarbonate precipitate issue caused by alkaline *** factors hinder the extensive utilization of this ***,we successfully developed and implemented a tandem electrolyzer cascade to separate and optimize the complex elementary reactions involved in the process of multi-carbon production.

关键词： reaction. synthesis catalyst

Shallow sub-lakes are essential for sustaining the successful wintering of waterbirds in Poyang Lake,China

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Avian Research 2024年第2期15卷 219-228页

作者： Mengjie Lu Zhen Zhang Peng Chen Changxin Xu Bin Gao Luzhang Ruan School of life sciences Nanchang UniversityNanchang330031China Jiangxi Province Key Laboratory of Watershed Ecosystem Change and Biodiversity Center for Watershed EcologyInstitute of Life Science and School of Life SciencesNanchang UniversityNanchang330031China

For migratory waterbirds,the quality of wintering habitat is related to spring migration and successful breeding in the next *** availability of food resources in the habitat is critical and varies within water *** the water-level fluctuations in Poyang Lake have been extremely variable interannually in recent years,the wintering waterbird populations have remained relatively ***,the mechanism of maintaining the stability is worth *** study aimed to compare the distribution of vegetation and herbivorous wa-terbirds in 2015-2016 and 2016-2017,focusing on three shallow sub-lakes and one main lake *** results showed that the emergence of tubers and the growth of Carex *** a continuous food supply and habitat for wintering waterbirds with a gradual decline in the water *** sub-lakes supported almost all of the tuber-eating waterbirds(1.42-1.62×10^(5))and most geese(1.34-1.53×10^(6)).However,the main lake area,covered with Persicaria hydropiper,did not provide adequate and accessible *** resulted in almost no distribution of tuber-eating waterbirds,with only a few geese congregating in early *** results demonstrated that the shallow sub-lakes under human control provided a different environment from the main lake and are key to sustaining the successful wintering of hundreds of thousands of migratory waterbirds in Poyang ***,we recommend refining the anthropogenic management of the shallow sub-lakes to regulate the water level to ensure the carrying capacity of Poyang Lake.

关键词： Anthropogenic management Carrying capacity Seasonal lake Water level Wintering habitat

High glucose reduces Nrf2-dependent cRAGE release and enhances inflammasome-dependent IL-1βproduction in monocytes:the modulatory effects of EGCG

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Food science and Human Wellness 2024年第3期13卷 1531-1542页

作者： Chi-Hao Wu Yin-Hsuan Chang Chin-Lin Hsu Sheng-Yi Chen Gow-Chin Yen Graduate Programs of Nutrition science School of Life ScienceTaiwan Normal UniversityTaipei 106209TaiwanChina department of Food science and Biotechnology Chung Hsing UniversityTaichung 40227TaiwanChina School of Nutrition Chung Shan Medical UniversityTaichung 40201TaiwanChina

Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human ***,the molecular mechanisms underlying sRAGE remain *** this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)*** modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also *** enhanced intracellular reactive oxygen species(ROS)generation and RAGE *** secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear ***,the HG effects were counteracted by siRAGE and exacerbated by *** immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this *** data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating *** HG conditions,the treatment of EGCG reduced ROS generation and RAGE ***-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 *** inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.

关键词： Epigallocatechin gallate(EGCG) Inflammasome Nuclear factor erythroid 2-related factor 2(Nrf2) Receptor for advanced glycation end products(RAGE) Soluble RAGE(sRAGE)

Displacement-pressure biparametrically regulated softness sensory system for intraocular pressure monitoring

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National science Review 2024年第6期11卷 159-168页

作者： Yu Cheng Yifei Zhan Fangyi Guan Junli Shi Jingxiao Wang Yi Sun Muhammad Zubair Cunjiang Yu Chuan Fei Guo department of Materials science and Engineering Southern University of Science and Technology department of Engineering science and Mechanics Pennsylvania State University department of Biomedical Engineering Pennsylvania State University department of Materials science and Engineering Materials Research Institute Pennsylvania State University

High intraocular pressure(IOP) is one of the high-risk pathogenic factors of glaucoma. Existing methods of IOP measurement are based on the direct interaction with the cornea. Commercial ophthalmic tonometers based on snapshot measurements are expensive, bulky, and their operation requires trained *** contact lenses are easy to use, but they may block vision and cause infection. Here, we report a sensory system for IOP assessment that uses a soft indentor with two asymmetrically deployed iontronic flexible pressure sensors to interact with the eyelid-eyeball in an eye-closed situation. Inspired by human fingertip assessment of softness, the sensory system extracts displacement-pressure information for soft evaluation, achieving high accuracy IOP monitoring(>96%). We further design and custom-make a portable and wearable ophthalmic tonometer based on the sensory system and demonstrate its high efficacy in IOP screening. This sensory system paves a way towards cost-effective, robust, and reliable IOP monitoring.

关键词： intraocular pressure tonometer deep learning softness iontronic sensor

Cav3.2 channel regulates cerebral ischemia/reperfusion injury:a promising target for intervention

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Neural Regeneration Research 2024年第11期19卷 2480-2487页

作者： Feibiao Dai Chengyun Hu Xue Li Zhetao Zhang Hongtao Wang Wanjun Zhou Jiawu Wang Qingtian Geng Yongfei Dong Chaoliang Tang Graduate School Wannan Medical CollegeWuhuAnhui ProvinceChina department of Anesthesiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Core Facility Center for Medical sciences The First Affiliated Hospital of USTC(Anhui Provincial Hospital)HefeiAnhui ProvinceChina department of Pharmacy The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina department of Neurosurgery The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion *** calcium channels are involved in cerebral ischemia/reperfusion ***3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain ***,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains ***,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal *** results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal *** further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion ***3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion ***,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal *** the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion *** findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 *** from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

关键词： calcineurin Cav3.2 channel cerebral ischemia/reperfusion hippocampus hypoxia/reoxygenation inflammatory response nuclear factor of activated T cells 3 oxidative stress primary hippocampal neurons stroke

Development and validation of a nomogram model for predicting the risk of pre-hospital delay in patients with acute myocardial infarction

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World Journal of Cardiology 2024年第2期16卷 80-91页

作者： Jiao-Yu Cao Li-Xiang Zhang Xiao-Juan Zhou department of Cardiology The First Affiliated Hospital of USTCDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina

BACKGROUND Acute myocardial infarction(AMI)is a severe cardiovascular disease caused by the blockage of coronary arteries that leads to ischemic necrosis of the *** medical contact is critical for successful AMI treatment,and delays increase the risk of death for ***-hospital delay time(PDT)is a significant challenge for reducing treatment times,as identifying high-risk patients with AMI remains *** study aims to construct a risk prediction model to identify high-risk patients and develop targeted strategies for effective and prompt care,ultimately reducing PDT and improving treatment *** To construct a nomogram model for forecasting pre-hospital delay(PHD)likelihood in patients with AMI and to assess the precision of the nomogram model in predicting PHD *** A retrospective cohort design was employed to investigate predictive factors for PHD in patients with AMI diagnosed between January 2022 and September *** study included 252 patients,with 180 randomly assigned to the development group and the remaining 72 to the validation group in a 7:3 *** risk factors influencing PHD were identified in the development group,leading to the establishment of a nomogram model for predicting PHD in patients with *** model's predictive performance was evaluated using the receiver operating characteristic curve in both the development and validation *** Independent risk factors for PHD in patients with AMI included living alone,hyperlipidemia,age,diabetes mellitus,and digestive system diseases(P<0.05).A characteristic curve analysis indicated area under the receiver operating characteristic curve values of 0.787(95%confidence interval:0.716–0.858)and 0.770(95%confidence interval:0.660-0.879)in the development and validation groups,respectively,demonstrating the model's good discriminatory *** Hosmer–Lemeshow goodness-of-fit test revealed no statistically significant disparity between the an

关键词： Pre-hospital delay Acute myocardial infarction Risk prediction Nomogram