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Design and fabrication of r-hirudin loaded dissolving microneedle patch for minimally invasive and long-term treatment of thromboembolic disease

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Asian Journal of Pharmaceutical Sciences 2022年第2期17卷 284-297页

作者： Mengfang Wu Tian Xia Yaran Li Tianfa Wang Shijia Yang Jinchao Yu Qiaoyan Liang teng shen Min Yu Bing Zhao Key Laboratory of Metabolism and Molecular Medicine Ministry of EducationFudan UniversityShanghai 200032China The Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFudan UniversityShanghai 200032China Key Laboratory of Smart Drug Delivery Ministry of EducationDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 201203China

Cardiovascular disease is the leading cause of global mortality,with anticoagulant therapy being the main prevention and treatment strategy.Recombinant hirudin(r-hirudin)is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous(SC)and intravenous(IV)administration,but there is a risk of haemorrhage via SC and IV.Thus,microneedle(MN)provides painless and sanitary alternatives to syringes and oral administration.However,the current technological process for the micro mould is complicated and expensive.The micro mould obtained via three-dimensional(3D)printing is expected to save time and cost,as well as provide a diverse range of MNs.Therefore,we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch.The results show that r-hirudin-loaded and hyaluronic acid(HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models.These results indicate that based on 3D printing technology,MNs combined with r-hirudin are expected to achieve diverse customizableMNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease.

关键词： Anticoagulant r-hirudin Microneedle patch 3D printing technology

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Path Planning and Tracking Control for Parking via Soft Actor-Critic Under Non-Ideal Scenarios

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IEEE/CAA Journal of Automatica Sinica 2024年第1期11卷 181-195页

作者： Xiaolin Tang Yuyou Yang teng Liu Xianke Lin Kai Yang shen Li IEEE the College of Mechanical and Vehicle Engineering Chongqing UniversityChongqing 400044China the Clinical Research Center and Medical Pathology Center Chongqing University Three Gorges HospitalChongqing UniversityWanzhou 404000 the Department of Automotive and Mechatronics Engineering Ontario Tech UniversityOshawa ON LIG OC5Canada the School of Civil Engineering Tsinghua UniversityBeijing 100084China

Parking in a small parking lot within limited space poses a difficult task. It often leads to deviations between the final parking posture and the target posture. These deviations can lead to partial occupancy of adjacent parking lots, which poses a safety threat to vehicles parked in these parking lots. However, previous studies have not addressed this issue. In this paper, we aim to evaluate the impact of parking deviation of existing vehicles next to the target parking lot(PDEVNTPL) on the automatic ego vehicle(AEV) parking, in terms of safety, comfort, accuracy, and efficiency of parking. A segmented parking training framework(SPTF) based on soft actor-critic(SAC) is proposed to improve parking performance. In the proposed method, the SAC algorithm incorporates strategy entropy into the objective function, to enable the AEV to learn parking strategies based on a more comprehensive understanding of the environment. Additionally, the SPTF simplifies complex parking tasks to maintain the high performance of deep reinforcement learning(DRL). The experimental results reveal that the PDEVNTPL has a detrimental influence on the AEV parking in terms of safety, accuracy, and comfort, leading to reductions of more than 27%, 54%, and 26%respectively. However, the SAC-based SPTF effectively mitigates this impact, resulting in a considerable increase in the parking success rate from 71% to 93%. Furthermore, the heading angle deviation is significantly reduced from 2.25 degrees to 0.43degrees.

关键词： Automatic parking control strategy parking deviation(APS) soft actor-critic(SAC)

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NF-κB in biology and targeted therapy:new insights and translational implications

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1322-1358页

作者： Qing Guo Yizi Jin Xinyu Chen Xiaomin Ye Xin shen Mingxi Lin Cheng Zeng teng Zhou Jian Zhang Department of Medical Oncology Fudan University Shanghai Cancer CenterNo.270Dong'an RoadShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina State Key Laboratory of Oncogenes and Related Genes Renj-Med-X Stem Cell Research CenterShanghai Cancer Institute&Department of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127PR China Department of Cardiology the First Affiliated Hospital of Sun Yat-Sen University58 Zhongshan 2nd RoadGuangzhou 510080China Department of Neurology Rujin HospitalShanghai JiaoTong University Schoolof MedicineShanghaiChina

NF-κB signaling has been discovered for nearly 40 years.Initially,NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses.However,with extensive and in-depth investigations,researchers have discovered that its role can be expanded to a variety of signaling mechanisms,biological processes,human diseases,and treatment options.In this review,we first scrutinize the research process of NF-κB signaling,and summarize the composition,activation,and regulatory mechanism of NF-κB signaling.We investigate the interaction of NF-κB signaling with other important pathways,including PI3K/AKT,MAPK,JAK-STAT,TGF-β,Wnt,Notch,Hedgehog,and TLR signaling.The physiological and pathological states of NF-κB signaling,as well as its intricate involvement in inflammation,immune regulation,and tumor microenvironment,are also explicated.Additionally,we illustrate how NF-κB signaling is involved in a variety of human diseases,including cancers,inflammatory and autoimmune diseases,cardiovascular diseases,metabolic diseases,neurological diseases,and covID-19.Further,we discuss the therapeutic approaches targeting NF-κB signaling,including IKK inhibitors,monoclonal antibodies,proteasome inhibitors,nuclear translocation inhibitors,DNA binding inhibitors,TKls,non-coding RNAs,immunotherapy,and CAR-T.Finally,we provide an outlook for research in the field of NF-κB signaling.We hope to present a stereoscopic,comprehensive NF-κB signaling that will inform future research and clinical practice.

关键词： PI3K/AKT diseases involvement

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Research advance of Bacillus velezensis:bioinformatics,characteristics,and applications

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Food Science and Human Wellness 2024年第4期13卷 1756-1766页

作者： Ting Su Biao shen Xingjuan Hu Yue teng Peifang Weng Zufang Wu Lianliang Liu State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Key Laboratory of Animal Protein Deep Processing Technology of ZhejiangZhejiang-Malaysia Joint Research Laboratory for Agricultural Product Processing and NutritionSchool of Food and Pharmaceutical SciencesNingbo UniversityNingbo 315000China Zhoushan Customs District Zhoushan 316100China

Bacillus velezensis is a Gram-positive and spore-forming bacterium.It has potent antimicrobial properties that can be used to promote plant growth and as a pesticide by inhibiting pathogens.B.velezensis has the capability to generate a diverse range of enzymes that have potential applications in various fields,such as enzyme production,fermented food,degradation of pollutants,and bioenergy.In addition,B.velezensis is a promising probiotic.It possesses high bile-salt tolerance characteristics and has a high success rate of colonization in the intestinal mucosa.Besides,the strain can also regulate gut microbiota constitute by increasing the number of beneficial microorganisms and decreasing the number of pathogens.Furthermore,based on its special properties,including high-yield protease production and high salt-tolerance,B.velezensis shows potential for use in marine protein fermentation,opening up new avenues for the development of novel food products and bioactive peptides.In addition,B.velezensis can shorten the fermentation time as well as improve the nutritional value and flavor of fermented food.The safety of B.velezensis for food production was evaluated.This review provides valuable insights into the potential uses and benefits of B.velezensis,particularly in the context of fermented foods.

关键词： Bacillus velezensis Bioinformatics Properties Fermentation Bioactive peptides

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Functional divergences of natural variations of TaNAM-A1 in controlling leaf senescence during wheat grain filling

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Journal of Integrative Plant Biology 2024年第6期66卷 1242-1260页

作者： Longxi Zhou Guowei Chang Chuncai shen Wan teng Xue He Xueqiang Zhao Yanfu Jing Zhixiong Huang Yiping Tong Key Laboratory of Seed Innovation Institute of Genetics and Developmental SciencesChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China The Innovative Academy of Seed Design Chinese Academy of SciencesBeijing 100101China

Leaf senescence is an essential physiological process related to grain yield potential and nutritional quality.Green leaf duration(GLD)after anthesis directly reflects the leaf senescence process and exhibits large genotypic differences in common wheat;however,the underlying gene regulatory mechanism is still lacking.Here,we identified TaNAM-A1 as the causal gene of the major loci q GLD-6A for GLD during grain filling by map-based cloning.Transgenic assays and TILLING mutant analyses demonstrated that TaNAM-A1 played a critical role in regulating leaf senescence,and also affected spike length and grain size.Furthermore,the functional divergences among the three haplotypes of TaNAM-A1 were systematically evaluated.Wheat varieties with TaNAM-A1d(containing two mutations in the coding DNA sequence of TaNAM-A1)exhibited a longer GLD and superior yield-related traits compared to those with the wild type TaNAM-A1a.All three haplotypes were functional in activating the expression of genes involved in macromolecule degradation and mineral nutrient remobilization,with TaNAM-A1a showing the strongest activity and TaNAM-A1d the weakest.TaNAM-A1 also modulated the expression of the senescencerelated transcription factors TaNAC-S-7A and TaNAC016-3A.TaNAC016-3A enhanced the transcriptional activation ability of TaNAM-A1a by protein–protein interaction,thereby promoting the senescence process.Our study offers new insights into the fine-tuning of the leaf functional period and grain yield formation for wheat breeding under various geographical climatic conditions.

关键词： allelic variation leaf senescence map-based cloning TaNAM-A1 transcription factor Triticum aestivum

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CoDetect: cooperative anomaly detection with privacy protection towards UAV swarm

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Science China(Information Sciences) 2024年第5期67卷 325-326页

作者： teng LI Weiguo LIN Ruichen MA Zhuo MA Yulong shen Jianfeng MA School of Cyber Engineering Xidian University School of Computer Science and Technology Xidian University

As mission scenarios grow more complex, the role of a single unmanned aerial vehicle(UAV) is limited. The UAV swarm,surpassing the single UAV, dynamically establishes temporary communication networks, ensuring high transmission rates and expansive communication coverage [1]. Unlike a single UAV, a swarm faces increased security risks, requiring specific capabilities.(1) Anomalies detection.

关键词： Unmanned aerial vehicles (UAV)

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Cell Wall Fixation,Translocation,and Vacuolar Detoxification of Cadmium Contribute to Differential Grain Cadmium Accumulation in Two Rice Cultivars

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Rice science 2024年第3期31卷 241-244,I0008-I0010页

作者： ZHU Xiaofang ZHAO Ling HUANG Jing HE Jiatong SONG Jiayin teng Ying shen Renfang State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil ScienceChinese Academy of ScienceNanjing 210008China State Key Laboratory of Subtropical Silviculture Zhejiang A&F UniversityHangzhou 311300China

Cadmium(Cd)toxicity in rice is a major concern for human health and the environment,as it can accumulate in rice grains when grown in Cd-contaminated soils.To mitigate the risk of Cd toxicity,it is crucial to cultivate rice varieties with low grain Cd accumulation.In the summers of 2021 and 2022,we conducted Cd analysis on two rice cultivars,Tianyouhuazhan(TYHZ)and Xiushui 14,grown in fields with varying Cd pollution levels.These cultivars were also subjected to hydroponic treatment with or without 1μmol/L Cd for 7 d to assess Cd accumulation,nitric oxide(NO)production。

关键词： cultivar soils pollution

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A novel mouse model of PEDF-associated serious liver inflammation,hepatic tumorigenesis and cardiovascular injury mimics human nonalcoholic steatohepatitis

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Genes & Diseases 2024年第1期11卷 11-14页

作者： Xinghui Li Haiping Wang Yandi Wu Li Zou Shijie Dengg Xintu Fu Tongsheng Huang Conghui shen teng Wu Weibin Cai Guangdong Engineering&Technology Research Center for Disease-Model Animals Laboratory Animal CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China Department of Biochemistry Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China School of Pharmacy Guangdong Pharmaceutical UniversityGuangzhouGuangdong 510006China Guangdong Provincial Key Laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107China

There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic metabolic disorders,hepatic steatosis,intense liver inflammation and fibrosis,liver tumorigenesis,and cardiovascularcomplications.i,2"Pigment"epitheliumderived factor(PEDF)is a lipid metabolism regulator with high expression in the liver,and its reduced expression in the liver is closely related to the development of nonalcoholic fatty liver disease(NAFLD).

关键词： inflammation PEDF hepatic

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Impact of short-term ambient air pollution exposure on the risk of severe COVID-19

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Journal of Environmental Sciences 2024年第1期135卷 610-618页

作者： Baihuan Feng Jiangshan Lian Fei Yu Dan Zhang Weizhen Chen QiWang Yifei shen Guoliang Xie Ruonan Wang Yun teng Bin Lou Shufa Zheng Yida Yang Yu Chen Department of Laboratory Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province Hangzhou 310000China Institute of Laboratory Medicine Zhejiang UniversityHangzhou 310000China Department of Infectious Diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China

Ecological studies suggested a link between air pollution and severe COVID-19 outcomes,while studies accounting for individual-level characteristics are limited.In the present study,we aimed to investigate the impact of short-term ambient air pollution exposure on disease severity among a cohort of 569 laboratory confirmed COVID-19 patients admitted to designated hospitals in Zhejiang province,China,from January 17 to March 3,2020,and elucidate the possible biological processes involved using transcriptomics.Compared with mild cases,severe cases had higher proportion of medical conditions as well as unfavorable results in most of the laboratory tests,and manifested higher air pollution exposure levels.Higher exposure to air pollutants was associated with increased risk of severe COVID-19 with odds ratio(OR)of 1.89(95%confidence interval(CI):1.01,3.53),2.35(95%CI:1.20,4.61),2.87(95%CI:1.68,4.91),and 2.01(95%CI:1.10,3.69)for PM_(2.5),PM_(10),NO_(2)and CO,respectively.OR for NO_(2)remained significant in two-pollutant models after adjusting for other pollutants.Transcriptional analysis showed 884 differentially expressed genes which mainly were enriched in virus clearance related biological processes between patients with high and low NO_(2)exposure levels,indicating that compromised immune response might be a potential underlying mechanistic pathway.These findings highlight the impact of shortterm air pollution exposure,particularly for NO_(2),on COVID-19 severity,and emphasize the significance in mitigating the COVID-19 burden of commitments to improve air quality.

关键词： Air pollution COVID-19 Severity Transcriptomics Immune response

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General Psychiatry 2024年第1期37卷 73-82页

作者： Qian Lu Sisi Huang Tianjiao Zhang Jie Song Manyu Dong Yilun Qian Jing teng Tong Wang Chuan He Ying shen Department of Rehabilitation Medicine The Affiliated Jiangsu Shengze Hospital of Nanjing Medical UniversitySuzhouChina Rehabilitation Medicine Center The First Affiliated Hospital of Nanjing Medical UniversityNanjingChina

Background The neurophysiological differences in cortical plasticity and cholinergic system function due to ageing and their correlation with cognitive function remain poorly understood.Aims To reveal the differences in long-term potentiation(LTP)-like plasticity and short-latency afferent inhibition(SAl)between older and younger individuals,alongside their correlation with cognitive function using transcranial magnetic stimulation(TMS).Methods The cross-sectional study involved 31 younger adults aged 18-30 and 46 older adults aged 60-80.All participants underwent comprehensive cognitive assessments and a neurophysiological evaluation based on TMS.Cognitive function assessments included evaluations of global cognitive function,language,memory and executive function.The neurophysiological assessment included LTP-like plasticity and SAl.Results The findings of this study revealed a decline in LTP among the older adults compared with the younger adults(wald χ^(2)=3.98,p=0.046).Subgroup analysis further demonstrated a significant reduction in SAl level among individuals aged 70-80 years in comparison to both the younger adults(SAI(N20)):(t=-3.37,p=0.018);SAl(N20+4):(t=-3.13,p=0.038)and those aged 60-70(SAl(N20)):(t=3.26,p=0.025);SAl(N20+4):(t=-3.69,p=0.006).Conversely,there was no notable difference in SAl level between those aged 60-70 years and the younger group.Furthermore,after employing the Bonferroni correction,the correlation analysis revealed that only the positive correlation between LTP-like plasticity and language function(r=0.61,p<0.001)in the younger group remained statistically significant.Conclusions During the normal ageing process,a decline in synaptic plasticity may precede cholinergic system dysfunction.In individuals over 60 years of age,there is a reduction in LTP-like plasticity,while a decline in cholinergic system function is observed in those over 70.Thus,the cholinergic system may play a vital role in preventing cognitive decline during normal ageing.In younger individuals,LTP-like plasticit

关键词： function younger plasticity

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