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Role of 5-hydroxytryptamine type 3 receptors in the regulation of anxiety reactions

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 23-37页

作者： Yinan DU Zhiwei LI Yukui ZHAO Jing HAN Weiping HU Zhiqiang LIU MOE key laboratory of modern Teaching Technology Shaanxi Normal UniversityXi’an710062China

5-Hydroxytryptamine(5-HT)type 3 receptor(5-HT_(3)R)is the only type of ligand-gated ion channel in the 5-HT receptor family.Through the high permeability of Na+,K+,and Ca2+and activation of subsequent voltage-gated calcium channels(VGCCs),5-HT_(3)R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system(CNS).5-HT_(3)Rs are widely expressed in the medial prefrontal cortex(mPFC),amygdala(AMYG),hippocampus(HIP),periaqueductal gray(PAG),and other brain regions closely associated with anxiety reactions.They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions.5-HT_(3)Rs mediate the activation of the cholecystokinin(CCK)system in the AMYG,and theγ-aminobutyric acid(GABA)“disinhibition”mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons(IINs).In contrast,a 5-HT_(3)R-induced GABA“disinhibition”mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects.5-HT_(2)R-mediated regulation of anxiety reactions are also activated by 5-HT_(3)R-activated 5-HT release in the HIP and PAG.This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT_(3)Rs.However,given the circuit specific modulation of 5-HT_(3)Rs on emotion,systemic use of 5-HT_(3)R agonism or antagonism alone seems unlikely to remedy anxiety,which deeply hinders the current clinical application of 5-HT_(3)R drugs.Therefore,the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.

关键词： 5-Hydroxytryptamine type 3 receptor(5-HT_(3)R) Anxiety Medial prefrontal cortex Amygdala Hippocampus Periaqueductal gray

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Enhanced hepatic metabolic perturbation of polystyrene nanoplastics by UV irradiation-induced hydroxyl radical generation

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Journal of Environmental Sciences 2024年第8期142卷 259-268页

作者： Shiyu He Jingran Wang Lihong Zhou Zhen Mao Xiaodan Zhang Jin Cai Peili Huang School of Public Health and Beijing key laboratory of Environmental toxicology Capital Medical UniversityBeijing 100069China

The environmental behavior of and risks associated with nanoplastics(NPs)have attracted considerable attention.However,compared to pristine NPs,environmental factors such as ultraviolet(UV)irradiation that lead to changes in the toxicity of NPs have rarely been studied.We evaluated the changes in morphology and physicochemical properties of polystyrene(PS)NPs before and after UV irradiation,and compared their hepatotoxicity in mice.The results showed that UV irradiation caused particle size reduction and increased the carbonyl index(CI)and negative charge on the particle surface.UV-aged PS NPs(aPS NPs)could induce the generation of hydroxyl radicals(·OH),but also further promoted the generation of·OH in the Fenton reaction system.Hepatic pathological damage was more severe in mice exposed to aPS NPs,accompanied by a large number of vacuoles and hepatocyte balloon-like changes and more marked perturbations in blood glucose and serum lipoprotein,alanine aminotransferase and aspartate aminotransferase levels.In addition,exposure to PS NPs and aPS NPs,especially aPS NPs,triggered oxidative stress and significantly damaged the antioxidant capacity of mice liver.Compared with PS NPs,exposure to aPS NPs increased the number of altered metabolites in hepatic and corresponding metabolic pathways,especially glutathione metabolism.Our research suggests that UV irradiation can disrupt the redox balance in organisms by promoting the production of·OH,enhancing PS NPs-induced liver damage and metabolic disorders.This study will help us understand the health risks of NPs and to avoid underestimation of the risks of NPs in nature.

关键词： Polystyrene nanoplastics Ultraviolet-aged nanoplastics Metabolic pathway Metabolomics Hydroxyl radical

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Discontinuous phase diagram of amorphous carbons

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National Science Review 2024年第4期11卷 164-171页

作者： YinBo Zhu ZhouYu Fang ZhongTing Zhang HengAn Wu CAS key laboratory of Mechanical Behavior and Design of Materials Department of Modern MechanicsUniversity of Science and Technology of China State key laboratory of Nonlinear Mechanics Institute of Mechanics Chinese Academy of Sciences

The short-range order and medium-range order of amorphous carbons demonstrated in experiments allow us to rethink whether there exist intrinsic properties hidden by atomic disordering. Here we presented six representative phases of amorphous carbons（0.1–3.4 g/cm3）, namely, disordered graphene network（DGN）, high-density amorphous carbon（HDAC）, amorphous diaphite（a-DG）, amorphous diamond（a-D）, paracrystalline diamond（p-D）, and nano-polycrystalline diamond（NPD）, respectively, classified by their topological features and microstructural characterizations that are comparable with experiments. To achieve a comprehensive physical landscape for amorphous carbons, a phase diagram was plotted in the sp3/sp2versus density plane, in which the counterintuitive discontinuity originates from the inherent difference in topological microstructures, further guiding us to discover a variety of phase transitions among different amorphous carbons. Intriguingly, the power law, log（sp3/sp2） ∝ ρn, hints at intrinsic topology and hidden order in amorphous carbons, providing an insightful perspective to reacquaint atomic disorder in non-crystalline carbons.

关键词： amorphous carbons disordered carbons phase diagram microstructural topology phase transition

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Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury

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Neural Regeneration Research 2024年第3期19卷 629-635页

作者： Jingzhou Liu Xin Xin Jiejie Sun Yueyue Fan Xun Zhou Wei Gong Meiyan Yang Zhiping Li Yuli Wang Yang Yang Chunsheng Gao State key laboratory of toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijingChina Academy of Medical Engineering and Translational Medicine Medical CollegeTianjin UniversityTianjinChina

Traumatic brain injury results in neuronal loss and glial scar formation.Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury.Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue.However,previous studies have reported inconsistent results.In this study,an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects.The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes.Moreover,neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury.In summary,this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.

关键词： AAV9P1 astrocytes astrocyte-to-neuron conversion GFAP promoter glial scar induced neurons neuronal reprogramming P1 peptide PTBP1 traumatic brain injury

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CoFe_(2)O_(4) decorated graphene/C_(18)-functionalized mesoporous silica nanocomposites prepared for magnetic enrichment and electrochemical detection of promethazine in beef

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Chinese Chemical Letters 2024年第3期35卷 208-213页

作者： Xingdong Yang Shi-Ming Ying Sen Zhang Jinxia Dai Wei Gao Tian-Qi Wang Jun-Qin Qiao Hong-Zhen Lian Li Mao State key laboratory of Analytical Chemistry for Life Science School of Chemistry&Chemical Engineering and Centre of Materials AnalysisNanjing UniversityNanjing 210023China Ministry of Education(MOE)key laboratory of modern toxicology School of Public HealthNanjing Medical UniversityNanjing 211166China

Promethazine(PHZ)is used as a sedative in veterinary medicine,and its residue can threaten the health of human.The electrochemical detection of PHZ is suitable method for application in the field.However,the traditional electroanalysis is difficult to perform directly in meat samples due to matrix interference.This work integrates magnetic solid-phase extraction and differential pulse voltammetry for highly sensitive and selective determination of PHZ in beef and beef liver for the first time.CoFe_(2)O_(4)/graphene coated with C_(18)-functionalized mesoporous silica(MG@mSiO_(2)-C_(18))is synthesized as dispersed magnetic adsorbent to extract PHZ.Magnetic glassy carbon electrode modified with nitrogen-doped hollow carbon microspheres(HCM)attracts the MG@mSiO_(2)-C_(18)with PHZ,and directly detects the PHZ without elution procedure.MG@mSiO_(2)-C_(18)can separate PHZ to avoid the interference of impurities on following detection,and also concentrate PHZ on magnetic electrode.Additionally,the electrode modification with HCM can amplify the electrochemical signal of PHZ.Finally,the integrated PHZ determination method exhibits a wide linear range from 0.08μmol/L to 300μmol/L with a low limit of detection of 9.8 nmol/L.The beef sample analysis presents excellent recovery,demonstrating that this protocol is promising for the rapid and onsite detection of PHZ in real meat samples。

关键词： Promethazine(PHZ) Drug residue Magnetic solid phase extraction Electrochemical detection Beef

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Improving error-correcting capability in DNA digital storage via soft-decision decoding

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National Science Review 2024年第2期11卷 135-144页

作者：丁璐璐伍世刚候志浩李阿伦许亚苹冯虎潘玮华阮珏 Shenzhen Branch Guangdong Laboratory of Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural Sciences Guangdong Provincial key laboratory of Plant Molecular Breeding State Key Laboratory for Conservation and Utilization of Subtropical Agro-BioresourcesSouth China Agricultural University

Error-correcting codes(ECCs) employed in the state-of-the-art DNA digital storage(DDS) systems suffer from a trade-off between error-correcting capability and the proportion of redundancy. To address this issue, in this study, we introduce soft-decision decoding approach into DDS by proposing a DNA-specific error prediction model and a series of novel strategies. We demonstrate the effectiveness of our approach through a proof-of-concept DDS system based on Reed-Solomon(RS) code, named as Derrick. Derrick shows significant improvement in error-correcting capability without involving additional redundancy in both in vitro and in silico experiments, using various sequencing technologies such as Illumina, Pac Bio and Oxford Nanopore Technology(ONT). Notably, in vitro experiments using ONT sequencing at a depth of 7× reveal that Derrick, compared with the traditional hard-decision decoding strategy, doubles the error-correcting capability of RS code, decreases the proportion of matrices with decoding-failure by 229-fold, and amplifies the potential maximum storage volume by impressive 32 388-fold. Also, Derrick surpasses ‘state-of-the-art' DDS systems by comprehensively considering the information density and the minimum sequencing depth required for complete information recovery. Crucially, the soft-decision decoding strategy and key steps of Derrick are generalizable to other ECCs' decoding algorithms.

关键词： DNA digital storage (DDS) error-correcting code (ECC) soft-decision decoding error-correcting capability storage volume

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A mix & act liposomes of phospholipase A2-phosphatidylserine for acute brain detoxification by blood‒brain barrier selective-opening

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1827-1844页

作者： Zinan Zhang Wenbin Cao Huanchun Xing Shuai Guo Lijuan Huang Lin Wang Xin Sui Kui Lu Yuan Luo Yongan Wang Jun Yang State key laboratory of toxicology and Medical Countermeasures Beijing Institutes of Pharmacology and ToxicologyBeijing 100850China Tianjin University of Science and Technology Tianjin 300222China Hebei University of Science and Technology Shijiazhuang 050018China

In the treatment of central nervous system disease,the blood-brain barrier(BBB)is a major obstruction to drug delivery that must be overcome.In this study,we propose a brain-targeted delivery strat-egy based on selective opening of the BBB.This strategy allows some simple bare nanoparticles to enter the brain when mixed with special opening material;however,the BBB still maintains the ability to completely block molecules from passing through.Based on the screening of BBB opening and matrix delivery mate-rials,we determined that phospholipase A2-catalyzed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoserine li-posomes can efficiently carry drugs into the brain immediately.At an effective dose,this delivery system is safe,especially with its effect on the BBB being reversible.This mix&act delivery system has a simple structure and rapid preparation,making it a strong potential candidate for drug delivery across the BBB.

关键词： Liposomes Phospholipase A2 Phosphoserine Blood-brainbarrier Selectively open Mix&act

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Optimized Mask-RCNN model for particle chain segmentation based on improved online ferrograph sensor

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Friction 2024年第6期12卷 1194-1213页

作者： Shuo WANG Miao WAN Tonghai WU Zichen BAI Kunpeng WANG key laboratory of Education Ministry for modern Design and Rotor-Bearing System Xi’an Jiaotong UniversityXi’an 710049China

Ferrograph-based wear debris analysis(WDA)provides significant information for wear fault analysis of mechanical equipment.After decades of offline application,this conventional technology is being driven by the online ferrograph sensor for real-time wear state monitoring.However,online ferrography has been greatly limited by the low imaging quality and segmentation accuracy of particle chains when analyzing degraded lubricant oils in practical applications.To address this issue,an integrated optimization method is developed that focuses on two aspects:the structural re-design of the online ferrograph sensor and the intelligent segmentation of particle chains.For enhancing the imaging quality of wear particles,the magnetic pole of the online ferrograph sensor is optimized to enable the imaging system directly observe wear particles without penetrating oils.Furthermore,a light source simulation model is established based on the light intensity distribution theory,and the LED installation parameters are determined for particle illumination uniformity in the online ferrograph sensor.On this basis,a Mask-RCNN-based segmentation model of particle chains is constructed by specifically establishing the region of interest(ROI)generation layer and the ROI align layer for the irregular particle morphology.With these measures,a new online ferrograph sensor is designed to enhance the image acquisition and information extraction of wear particles.For verification,the developed sensor is tested to collect particle images from different degraded oils,and the images are further handled with the Mask-RCNN-based model for particle feature extraction.Experimental results reveal that the optimized online ferrography can capture clear particle images even in highly-degraded lubricant oils,and the illumination uniformity reaches 90%in its imaging field.Most importantly,the statistical accuracy of wear particles has been improved from 67.2%to 94.1%.

关键词： wear particle analysis online ferrography particle image acquisition particle chain segmentation

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Design and fabrication of self-suspending aluminum-plastic/semiconductor photocatalyst devices for solar energy conversion

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Journal of Environmental Sciences 2024年第2期136卷 615-625页

作者： Zhi-Ang Zhao Jingyun Mao Chengjing Lu Shuangqiao Yang Qingrong Qian Qinghua Chen Hun Xue Xiaoli Sun Min-Quan Yang College of Environmental and Resource Sciences College of Carbon Neutral Modern IndustryFujian Key Laboratory of Pollution Control and Resource ReuseFujian Normal UniversityFuzhou 350007China State key laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan UniversityChengdu 610065China

The design and synthesis of self-suspending photocatalyst device with easy recyclability is important for practical application.Here,this work utilizes aluminum-plastic package waste as raw material to prepare an aluminum-plastic supported TiO_(2)(AP-TiO_(2))photocatalyst device through 3D printing design and surface deposition method.A series of characterizations were carried out to explore the structure,morphology and performance of the AP-TiO_(2)device.Under UV light illumination,the AP-TiO_(2)-50 efficiently degrade 93.6%tetracycline hydrochloride(THC)after 4 hr,which increases by 8.3%compared with that of TiO_(2)powder suspension system with the same catalyst amount.Based on it,AP-ZnO,AP-CdS,AP-g-C_3N_4and AP-Pt-TiO_(2)are also fabricated,and applied in photocatalytic degradation and hydrogen evolution,which all exhibit higher photoactivities than powder suspension systems.This work provides a new avenue for the fabrication of advanced recyclable photocatalyst device.Moreover,the work offers a novel sight for the high-value utilization of aluminum-plastic package waste,which has positive implications for environmental protection.

关键词： TiO_(2) Self-suspending Photocatalyst device Aluminum plastic

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Decabromodiphenyl ether induces the chromosome association disorders of spermatocytes and deformation failures of spermatids in mice

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Journal of Environmental Sciences 2024年第4期138卷 531-542页

作者： Jinglong Xue Xiangyang Li Yafei Chi Leqiang Gao Yue Zhang Yan Wang Moxuan Zhao Jialiu Wei Zhixiong Shi Xianqing Zhou Department of toxicology and Hygienic Chemistry School of Public HealthCapital Medical UniversityBeijing 100069China Beijing key laboratory of Environmental toxicology Capital Medical UniversityBeijing 100069China laboratory Animal Center Capital Medical UniversityBeijing 100069China key laboratory of Cardiovascular Epidemiology&Department of Epidemiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

The environmental presence of decabromodiphenyl ether(BDE-209),which is toxic to the male reproductive system,is widespread.The current study investigated its mechanism of toxicity in mice.The results showed,that BDE-209 induced DNA damage,decreased the expression of the promoter of meiosis spermatogenesis-and oogenesis-specific basic helix-loop-helix 1(Sohlh1),meiosis related-factors Lethal(3)malignant brain tumor like 2(L3MBTL2),PIWI-like protein 2(MILI),Cyclin-dependent kinase 2(CDK2),Cyclin A,synaptonemal complex protein 1(SYCP1)and synaptonemal complex protein 3(SYCP3),and caused spermatogenic cell apoptosis,resulting in a decrease in sperm quantity and quality.Furthermore,BDE-209 downregulated the levels of anaphase-promoting complex/cyclosome(APC/C),increased the expression of PIWI-like protein 1(MIWI)in the cytoplasm of elongating spermatids,and decreased the nuclear levels of RING finger protein 8(RNF8),ubiquitinated(ub)-H2A/ub-H2B,and Protamine 1(PRM1)/Protamine 2(PRM2),while increasing H2A/H2B nuclear levels in spermatids.The reproductive toxicity was persistent for 50 days following the withdrawal of BDE-209 exposure.The results suggested that BDE-209 inhibits the initiation of meiosis by decreasing the expression of Sohlh1.Furthermore,the reduced expression of L3MBTL2 inhibited the formation of chromosomal synaptonemal complexes by depressing the expression of meiosis regulators affecting the meiotic progression and also inhibited histone ubiquitination preventing the replacement of histones by protamines,by preventing RNF8 from entering nuclei,which affected the evolution of spermatids into mature sperm.

关键词： BDE-209 Meiosis L3MBTL2 Sperm RNF8 Histone ubiquitination

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