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3'-Deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome

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Neural Regeneration Research 2024年第10期19卷 2270-2280页

作者： Yize Qi Yao Zhou Jiyang Li Fangyuan zhu Gengni guo Can Wang Man Yu Yijie Wang Tengfei Ma Shanwu Feng Li Zhou Institute for Stem Cell and Neural Regeneration and Key Laboratory of Cardiovascular&Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Anesthesiology The Second People’s Hospital of LianyungangLianyungangJiangsu ProvinceChina Department of Anesthesiology Women’s Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjingJiangsu ProvinceChina

Methamphetamine addiction is a brain disorder characterized by persistent drug-seeking behavior, which has been linked with aberrant synaptic plasticity. An increasing body of evidence suggests that aberrant synaptic plasticity is associated with the activation of the NOD-like receptor family pyrin domain containing-3(NLRP3) inflammasome. 3′-Deoxyadenosin, an active component of the Chinese fungus Cordyceps militaris, has strong anti-inflammatory effects. However, whether 3′-deoxyadenosin attenuates methamphetamine-induced aberrant synaptic plasticity via an NLRP3-mediated inflammatory mechanism remains unclear. We first observed that 3′-deoxyadenosin attenuated conditioned place preference scores in methamphetamine-treated mice and decreased the expression of c-fos in hippocampal neurons. Furthermore, we found that 3′-deoxyadenosin reduced the aberrant potentiation of glutamatergic transmission and restored the methamphetamine-induced impairment of synaptic plasticity. We also found that 3′-deoxyadenosin decreased the expression of NLRP3 and neuronal injury. Importantly, a direct NLRP3 deficiency reduced methamphetamine-induced seeking behavior, attenuated the impaired synaptic plasticity, and prevented neuronal damage. Finally, NLRP3 activation reversed the effect of 3′-deoxyadenosin on behavior and synaptic plasticity, suggesting that the anti-neuroinflammatory mechanism of 3′-deoxyadenosin on aberrant synaptic plasticity reduces methamphetamine-induced seeking behavior. Taken together, 3′-deoxyadenosin alleviates methamphetamine-induced aberrant synaptic plasticity and seeking behavior by inhibiting the NLRP3 inflammasome.

关键词： 3′-deoxyadenosin hippocampus long-term potentiation methamphetamine NOD-like receptor family pyrin domain containing-3(NLRP3)inflammasome synaptic plasticity

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Early systemic anticoagulation reduces hospital readmission in acute necrotizing pancreatitis patients:A retrospective cohort study

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 77-82页

作者： Wen-Jian Mao Jing Zhou guo-Fu Zhang Fa-Xi Chen Jing-zhu Zhang Bai-Qiang Li Lu Ke Wei-Qin Li Department of Critical Care Medicine Jinling HospitalNanjing Medical UniversityNanjing 210002China Department of Critical Care Medicine Jinling HospitalMedical School of Nanjing UniversityNanjing 210002China National Institute of Healthcare Data Science Nanjing UniversityNanjing 210010China

Background:Early systemic anticoagulation(SAC)is a common practice in acute necrotizing pancreatitis(ANP),and its impact on in-hospital clinical outcomes had been assessed.However,whether it affects long-term outcomes is unknown.This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients.Methods:During January 2013 and December 2018,ANP patients admitted within 7 days from the onset of abdominal pain were screened.The primary outcome was 90-day readmission after discharge.Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission.Results:A total of 241 ANP patients were enrolled,of whom 143 received early SAC during their hospitalization and 98 did not.Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis(SVT)[risk ratio(RR)=0.40,95%CI:0.26-0.60,P<0.01]and lower 90-day readmission with an RR of 0.61(95%CI:0.41-0.91,P=0.02)than those who did not.For the quality of life,patients who received early SAC had a significantly higher score in the subscale of vitality(P=0.03)while the other subscales were all comparable between the two groups.Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57(95%CI:0.34-0.96,P=0.04).Mediation analysis showed that SVT mediated 37.0%of the early SAC-90-day readmission causality.Conclusions:The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients,and reduced SVT incidence might be the primary contributor.

关键词： Anticoagulation Splanchnic venous thrombosis Acute necrotizing pancreatitis Readmission Long-term outcomes

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Eccrine porocarcinoma in the tempus of an elderly woman:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1523-1529页

作者： zhi-Wei Wu Wen-Jie zhu Shan Huang Qi Tan Cong You Dian-Gui Hu Long-Nian Li Department of Dermatology First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina Department of Laser and Cosmetic Dermatology Ganzhou Dermatology HospitalGanzhou 341000Jiangxi ProvinceChina Department of Dermatology Tongxiang Dermatology HospitalJiaxing 314000Zhejiang ProvinceChina Department of Infectious Diseases The Fifth people’s Hospital of GanzhouGanzhou 341000Jiangxi ProvinceChina

BACKGROUND Eccrine porocarcinoma(EPC)is a rare skin tumor that mainly affects the elderly population.Tumors often present with slow growth and a good prognosis.EPCs are usually distinguished from other skin tumors using histopathology and immunohistochemistry.However,surgical management alone may be inadequate if the tumor has metastasized.However,currently,surgical resection is the most commonly used treatment modality.CASE SUMMARY A seventy-four-year-old woman presented with a slow-growing nodule in her left temporal area,with no obvious itching or pain,for more than four months.Histopathological examination showed small columnar and short spindle-shaped cells;thus,basal cell carcinoma was suspected.However,immunohistochemical analysis revealed the expression of cytokeratin 5/6,p63 protein,p16 protein,and Ki-67 antigen(40%),and EPC was taken into consideration.The skin biopsy was repeated,and hematoxylin and eosin staining revealed ductal differentiation in some cells.Finally,the patient was diagnosed with EPC,and Mohs micrographic surgery was performed.We adapted follow-up visits in a year and not found any recurrence of nodules.CONCLUSION This case report emphasizes the diagnosis and differentiation of EPC.

关键词： Eccrine porocarcinoma Sweat gland carcinoma Histopathology Immunohistochemistry Prognosis Case report

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High-speed GeSn resonance cavity enhanced photodetectors for a 50 Gbps Si-based 2 μm band communication system

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Photonics Research 2024年第4期12卷 767-773页

作者： JINLAI CUI JUN ZHENG YUPENG zhu XIANGQUAN LIU YIYANG WU QINXING HUANG YAZHOU YANG zhiPENG LIU zhi LIU YUHUA ZUO BUWEN CHENG Key Laboratory of Optoelectronic Materials and Devices Institute of SemiconductorsChinese Academy of SciencesBeijing 100083China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China

Expanding the optical communication band is one of the most effective methods of overcoming the nonlinear Shannon capacity limit of single fiber.In this study,GeSn resonance cavity enhanced(RCE)photodetectors(PDs)with an active layer Sn component of 9%–10.8%were designed and fabricated on an SOI substrate.The GeSn RCE PDs present a responsivity of 0.49 A/W at 2μm and a 3-dB bandwidth of approximately 40 GHz at 2μm.Consequently,Si-based 2μm band optical communication with a transmission rate of 50 Gbps was demonstrated by using a GeSn RCE detector.This work demonstrates the considerable potential of the Si-based 2μm band photonics in future high-speed and high-capacity optical communication.

关键词： resonance system approximate

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Effect of alumina occurrence form on metallurgical properties of hematite and magnetite pellets

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Journal of Iron and Steel Research(International) 2024年第4期31卷 797-809页

作者： Jian Pan Chen-mei Tang Cong-cong Yang De-qing zhu Zheng-qi guo Wei-qun Huang School of Minerals Processing and Bioengineering Central South UniversityChangsha 410083HunanChina Exploration and Development of Geology and Mineral Resources Co. Ltd.Nanchang 330030JiangxiChina

The effect of alumina occurrence form on the metallurgical properties of both hematite and magnetite pellets was investigated at the same Al_(2)O level of 2 wt.%,including reduction index(RI),low-temperature reduction disintegration index(RDI),reduction swelling index(RSI),and high-temperature softening-dripping performance.The mineralogy of fired pellets was also studied to reveal the influence of alumina occurrence form on the phase composition and microstructure.From the results,the alumina occurrence form presents tremendous impacts on the metallurgical perfor-mance of both magnetite and hematite pellets.Addition of all alumina occurrence forms contributes to inferior reducibility of pellets,especially in the case of gibbsite for magnetite pellets with a RI of 58.4%and kaolinite for hematite pellets with a RI of 56.8%.However,addition of all alumina occurrence forms improves the RDI of magnetite pellets,while there is no significant difference among various alumina occurrence forms.In contrast,alumina occurrence forms have little influence on the RDI of hematite pellets.The presence of free alumina,gibbsite,and kaolinite tends to improve the RSI of hematite and magnetite pellets,whereas hercynite gives the opposite trend with a RSI of 25.6%.For softening-dripping performance of magnetite pellets,all alumina occurrence forms contribute to narrower softening-melting interval.Meanwhile,alumina,gibbsite,and kaolinite give narrower softening-dripping interval,at 229,217,and 88℃,respectively,whereas addition of hercynite results in the largest melting range at 276℃ due to its high melting point.Regarding hematite pellets,free alumina,gibbsite,and hercynite tend to enlarge melting range,whereas kaolinite contributes to lower dripping temperature of 1148℃ and narrow softening-dripping interval of 88℃ due to the formation of a greater amount of slag phase at high temperatures.

关键词： Oxidized pellet Magnetite Hematite Alumina occurrence form Metallurgical performance Blast furnace

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A Fault-Tolerant Mobility-Aware Caching Method in Edge Computing

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Computer Modeling in Engineering & Sciences 2024年第7期140卷 907-927页

作者： Yong Ma Han Zhao Kunyin guo Yunni Xia Xu Wang Xianhua Niu Dongge zhu Yumin Dong School of Computer Information Engineering Jiangxi Normal UniversityNanchang330000China School of Digital Industry Jiangxi Normal UniversityShangrao334000China The College of Computer Science Chongqing UniversityChongqing400044China College of Mechanical and Vehicle Engineering Chongqing UniversityChongqing400030China School of Computer and Software Engineering Xihua UniversityChengdu610039China Electric Power Research Institute of State Grid Ningxia Electric Power Company Ltd. Yinchuan750002China College of Computer and Information Science Chongqing Normal UniversityChongqing401331China

Mobile Edge Computing(MEC)is a technology designed for the on-demand provisioning of computing and storage services,strategically positioned close to users.In the MEC environment,frequently accessed content can be deployed and cached on edge servers to optimize the efficiency of content delivery,ultimately enhancing the quality of the user experience.However,due to the typical placement of edge devices and nodes at the network’s periphery,these components may face various potential fault tolerance challenges,including network instability,device failures,and resource constraints.Considering the dynamic nature ofMEC,making high-quality content caching decisions for real-time mobile applications,especially those sensitive to latency,by effectively utilizing mobility information,continues to be a significant challenge.In response to this challenge,this paper introduces FT-MAACC,a mobility-aware caching solution grounded in multi-agent deep reinforcement learning and equipped with fault tolerance mechanisms.This approach comprehensively integrates content adaptivity algorithms to evaluate the priority of highly user-adaptive cached content.Furthermore,it relies on collaborative caching strategies based onmulti-agent deep reinforcement learningmodels and establishes a fault-tolerancemodel to ensure the system’s reliability,availability,and persistence.Empirical results unequivocally demonstrate that FTMAACC outperforms its peer methods in cache hit rates and transmission latency.

关键词： Mobile edge networks mobility fault tolerance cooperative caching multi-agent deep reinforcement learning content prediction

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Machine learning solution for regional landslide susceptibility based on fault zone division strategy

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Journal of Mountain Science 2024年第5期21卷 1745-1760页

作者： WANG Yunhao WANG Luqi LIU Songlin SUN Weixin LIU Pengfei zhu Lin YANG Wenyu guo Tong School of Civil Engineering Chongqing UniversityChongqing 400045China Key Laboratory of New Technology for Construction of Cities in Mountain Area Chongqing UniversityMinistry of EducationChongqing 400045China National Joint Engineering Research Center of Geohazards Prevention in the Reservoir Areas Chongqing UniversityChongqing 400045China Institute of Geological Environment Monitoring Chongqing 401147China Chongqing 205 Geological Team Chongqing 401121China

Landslide susceptibility assessment is an essential tool for disaster prevention and management. In areas with multiple fault zones, the impact of fault zone on slope stability cannot be disregarded. This study performed qualitative analysis of fault zones and proposed a zoning method to assess the landslide susceptibility in Chengkou County, Chongqing Municipality, China. The region within a distance of 1 km from the faults was designated as sub-zone A, while the remaining area was labeled as sub-zone B. To accomplish the assessment, a dataset comprising 388 historical landslides and 388 non-landslide points was used to train the random forest model. 10-fold cross-validation was utilized to select the training and testing datasets for the model. The results of the models were analyzed and discussed, with a focus on model performance and prediction uncertainty. By implementing the proposed division strategy based on fault zone, the accuracy, precision, recall, F-score, and AUC of both two sub-zones surpassed those of the whole region. In comparison to the results obtained for the whole region, sub-zone B exhibited an increase in AUC by 6.15%, while sub-zone A demonstrated a corresponding increase of 1.66%. Moreover, the results of 100 random realizations indicated that the division strategy has little effect on the prediction uncertainty. This study introduces a novel approach to enhance the prediction accuracy of the landslide susceptibility mapping model in areas with multiple fault zones.

关键词： Landslide susceptibility mapping Fault division strategy Random forest GIS

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Single-cell mass spectrometry studies of drug metabolism heterogeneity and primary resistance to gefitinib in non-small cell lung cancer cells

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Chinese Chemical Letters 2024年第2期35卷 436-440页

作者： Guizhen zhu Yaoyao Zhao Wenmei Zhang Yuanyuan Wu Yuanxing Liu Guangsheng guo Xiayan Wang zhihong Liu Center of Excellence for Environmental Safety and Biological Effects Beijing Key Laboratory for Green Catalysis and SeparationDepartment of ChemistryBeijing University of TechnologyBeijing 100124China Minzu University of China Beijing 100081China Key Laboratory for the Synthesis and Application of Organic Functional Molecules College of Health Science and EngineeringHubei UniversityWuhan 430062China

Patients with epidermal growth factor receptor(EGFR)wild-type non-small cell lung cancer(NSCLC)often show primary resistance to gefitinib therapy.It is thus necessary to study the metabolism of gefitinib in NSCLC cells to comprehensively reveal the reasons for the primary resistance of tumors.Herein,we develop a platform for studying drug metabolism heterogeneity based on single-cell mass spectrometry(sDMH-scMS)by integrating living-cell electrolaunching ionization MS(ILCEI-MS)and high-performance liquid chromatography-MS(HPLC-MS)analysis,and the primary resistance of NSCLC cells to gefitinib was studied using this platform.The ILCEI-MS analysis showed that approximately 11.9%of NSCLC single cells contained the gefitinib metabolite M11;HPLC-MS detection diluted the intensity of M11 in subpopulations and concealed the heterogeneity of drug metabolism in tumor single cells.The intensity of gefitinib in EGFR wild-type A549 cells was markedly lower than in mutant PC9 cells,and the intensity of gefitinib metabolites was significantly higher than in PC9 cells,suggesting that the primary resistance of NSCLC cells is related to gefitinib metabolism.Moreover,the combination of gefitinib and the drug-metabolizing enzyme inhibitorα-naphthoflavone was shown to overcome the primary resistance of the NSCLC cells.Overall,the results of this study are expected to be applicable for clinical drug resistance diagnosis and treatment at the single-cell level.

关键词： Single-cell mass spectrometry Drug metabolism Non-small cell lung cancer Gefitinib Primary resistance

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In vivo imaging reveals a synchronized correlation among neurotransmitter dynamics during propofol and sevoflurane anesthesia

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Zoological Research 2024年第3期45卷 679-690页

作者： Gao-Lin Qiu Li-Jun Peng Peng Wang zhi-Lai Yang Ji-Qian Zhang Hu Liu Xiao-Na zhu Jin Rao Xue-Sheng Liu Department of Anesthesiology First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China

General anesthesia is widely applied in clinical practice.However,the precise mechanism of loss of consciousness induced by general anesthetics remains unknown.Here,we measured the dynamics of five neurotransmitters,includingγ-aminobutyric acid,glutamate,norepinephrine,acetylcholine,and dopamine,in the medial prefrontal cortex and primary visual cortex of C57BL/6 mice through in vivo fiber photometry and genetically encoded neurotransmitter sensors under anesthesia to reveal the mechanism of general anesthesia from a neurotransmitter perspective.Results revealed that the concentrations of γ-aminobutyric acid,glutamate,norepinephrine,and acetylcholine increased in the cortex during propofol-induced loss of consciousness.Dopamine levels did not change following the hypnotic dose of propofol but increased significantly following surgical doses of propofol anesthesia.Notably,the concentrations of the five neurotransmitters generally decreased during sevoflurane-induced loss of consciousness.Furthermore,the neurotransmitter dynamic networks were not synchronized in the non-anesthesia groups but were highly synchronized in the anesthetic groups.These findings suggest that neurotransmitter dynamic network synchronization may cause anesthetic-induced loss of consciousness.

关键词： General anesthesia Loss of consciousness In vivo neurotransmitter imaging Medial prefrontal cortex Primary visual cortex

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Senktide blocks aberrant RTN3 interactome to retard memory decline and tau pathology in social isolated Alzheimer’s disease mice

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Protein & Cell 2024年第4期15卷 261-284页

作者： He-Zhou Huang Wen-Qing Ai Na Wei Ling-Shuang zhu zhi-Qiang Liu Chao-Wen Zhou Man-Fei Deng Wen-Tao Zhang Jia-Chen Zhang Chun-Qing Yang Ya-zhuo Hu zhi-Tao Han Hong-Hong Zhang Jian-Jun Jia Jing Wang Fang-Fang Liu Ke Li Qi Xu Mei Yuan Hengye Man Ziyuan guo Youming Lu Kai Shu Ling-Qiang zhu Dan Liu Department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Medical Genetics School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pathology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450002China Department of Pathology School of Basic MedicineZhengzhou UniversityZhengzhou 450002China The Second Affiliated Hospital Department of NeurologyHengyang Medical SchoolUniversity of South ChinaHengyang 421001China Beijing Key Laboratory of Aging and Geriatrics National Clinical Research Center for Geriatric DiseaseInstitute of GeriatricsChinese PLA General Hospital and Chinese PLA Medical AcademyBeijing 100853China Department of Neurosurgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Neurology Union HospitalHuazhong University of Science and TechnologyWuhan 430022China Department of Biology Boston UniversityBostonMA 02215USA Center for Stem Cell and Organoid Medicine(CuSTOM) Division of Developmental BiologyCincinnati Children’s Hospital Medical CenterCincinnatiOH 45229USA

Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family history.Although genome-wide association studies have identified associated risk genes and loci for LOAD,numerous studies suggest that many adverse environmental factors,such as social isolation,are associated with an increased risk of dementia.However,the underlying mechanisms of social isolation in AD progression remain elusive.In the current study,we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD mice.We also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus(DG)-enriched miRNAs,which simultaneously target reticulon 3(RTN3),an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons(MFBs)by recruiting multiple mitochondrial and vesicle-related proteins.Interestingly,the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation,which,in turn,further elevates RTN3 and forms a vicious cycle.Finally,using an artificial intelligence-assisted molecular docking approach,we determined that senktide,a selective agonist of neurokinin3 receptors(NK3R),could reduce the binding of RTN3 with its partners.Moreover,application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD mice.Taken together,our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.

关键词： Alzheimer’s disease memory impairment synaptic disorder tau pathology

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