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Gene therapy for monogenic disorders: challenges, strategies, and perspectives

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Journal of Genetics and Genomics 2024年第2期51卷 133-143页

作者： Yi zhang Zhi-ying Wu Department of Medical Genetics and Center for Rare Diseases Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of Medical Neurobiology of Zhejiang Province HangzhouZhejiang 310009China

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.

关键词： Gene therapy Monogenic diseases Geneediting Genedelivery Challenges

Identification and functional characterization of female antennae-biased odorant receptor 23 involved in acetophenone detection of the Indian meal moth Plodia interpunctella

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Insect Science 2024年第1期31卷 59-78页

作者： Qi Chen Xiaoyan Zhu Guoqing kang Qiling Yu Qingxin Liu Lin Du Yi Yang Xinyu He ying Zhao Junjie zhang ying Hu Bingzhong Ren Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization School of Life SciencesNortheast Normal UniversityChangchunChina Key Laboratory of Vegetation Ecology Ministry of EducationNortheast Normal UniversityChangchunChina Jilin Provincial Engineering Laboratory of Avian Ecology and Conservation Genetics Northeast Normal UniversityChangchunChina Engineering Research Center of Natural Enemies Institute of Biological ControlJilin Agricultural UniversityChangchunChina

The Indian meal moth,Plodia interpunctella(Lepidoptera:Pyralidae),a globally distributed storage pest,relies on odors that are emitted from stored foods to select a suitable substrate for oviposition.However,the molecular mechanism underlying the chemical communication between P.interpunctella and its host remains elusive.In this study,130 chemosensory genes were identified from the transcriptomes of 7 P.interpunctella tissues,and the quantitative expression levels of all 56 P.interpunctella odorant receptor genes(PintORs)were validated using real-time quantitative polymerase chain reaction.The functional characteristics of 5 PintORs with female antennae-biased expression were investigated using 2-electrode voltage clamp recordings in Xenopus laevis oocytes.PintOR23 was found to be specifically tuned to acetophenone.Acetophenone could elicit a significant electrophysiological response and only attracted mated females when compared with males and virgin females.In addition,molecular docking predicted that the hydrogen bonding sites,TRP-335 and ALA-167,might play key roles in the binding of PintOR23 to acetophenone.Our study provides valuable insights into the olfactory mechanism of oviposition substrate detection and localization in P.interpunctella and points toward the possibility of developing eco-friendly odorant agents to control pests of stored products.

关键词： acetophenone docking EAG odorant receptor Plodia interpunctella TEVC

Classification of knowledge graph completeness measurement techniques

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Journal of Systems Engineering and Electronics 2024年第1期35卷 154-162页

作者： zhang ying XIAO Gang Institute of Systems Engineering Academy of Military SciencesBeijing 100107China

At present,although knowledge graphs have been widely used in various fields such as recommendation systems,question and answer systems,and intelligent search,there are always quality problems such as knowledge omissions and errors.Quality assessment and control,as an important means to ensure the quality of knowledge,can make the applications based on knowledge graphs more complete and more accurate by reasonably assessing the knowledge graphs and fixing and improving the quality problems at the same time.Therefore,as an indispensable part of the knowledge graph construction process,the results of quality assessment and control determine the usefulness of the knowledge graph.Among them,the assessment and enhancement of completeness,as an important part of the assessment and control phase,determine whether the knowledge graph can fully reflect objective phenomena and reveal potential connections among entities.In this paper,we review specific techniques of completeness assessment and classify completeness assessment techniques in terms of closed world assumptions,open world assumptions,and partial completeness assumptions.The purpose of this paper is to further promote the development of knowledge graph quality control and to lay the foundation for subsequent research on the completeness assessment of knowledge graphs by reviewing and classifying completeness assessment techniques.

关键词： quality assessment completeness assessment closed world assumptions open world assumption partial completeness assumption

Deep Guided Attention Network for Joint Denoising and Demosaicing in Real Image

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Chinese Journal of Electronics 2024年第1期33卷 303-312页

作者： Tao zhang ying FU Jun zhang School of Computer Science and Technology Beijing Institute of Technology Advanced Reasearch Institute of Multidisciplinary Science Beijing Institute of Technology

Denoising(DN) and demosaicing(DM) are the first crucial stages in the image signal processing pipeline. Recently, researches pay more attention to solve DN and DM in a joint manner, which is an extremely undetermined inverse problem. Existing deep learning methods learn the desired prior on synthetic dataset, which limits the generalization of learned network to the real world data. Moreover, existing methods mainly focus on the raw data property of high green information sampling rate for DM, but occasionally exploit the high intensity and signalto-noise(SNR) of green channel. In this work, a deep guided attention network(DGAN) is presented for real image joint DN and DM(JDD), which considers both high SNR and high sampling rate of green information for DN and DM, respectively. To ease the training and fully exploit the data property of green channel, we first train DN and DM sub-networks sequentially and then learn them jointly, which can alleviate the error accumulation. Besides, in order to support the real image JDD, we collect paired raw clean RGB and noisy mosaic images to conduct a realistic dataset. The experimental results on real JDD dataset show the presented approach performs better than the state-of-the-art methods, in terms of both quantitative metrics and qualitative visualization.

关键词： Image denoising Image demosaicing Joint processing Guided attention Paired real dataset

The role of acute normovolemic hemodilution in reducing allogeneic blood transfusion in glioblastoma surgery:a case-control study

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Chinese Neurosurgical Journal 2024年第1期10卷 35-41页

作者： Ping Chen Xin‑Huang zhang ying Wang Xian‑Zhong Lin De‑Zhi kang Qing‑Song Lin Department of Anesthesiology The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005FujianChina Department of Neurosurgery The First Affiliated Hospital of Fujian Medical UniversityNo.20 Chazhong RdTaijiang DistrictFuzhou 350005FujianChina Department of Neurosurgery Binhai Branch of National Regional Medical CenterThe First Affiliated Hospital of Fujian Medical UniversityFuzhou 350209FujianChina Fujian Provincial Institutes of Brain Disorders and Brain Sciences The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005FujianChina Fujian Provincial Clinical Research Center for Neurological Diseases The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005FujianChina Fujian Provincial Key Laboratory of Precision Medicine for Cancer The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005FujianChina

Background Acute normovolemic hemodilution(ANH)was first introduced in glioblastoma surgery,and its role in reducing allogeneic blood transfusion was investigated in this study.Methods This study enrolled supratentorial glioblastoma patients who received total resection.In the ANH group,the patients were required to draw blood before the operation,and the blood will be transfused back to the patient during the operation.The association between ANH and clinical features was investigated.Results Sixty supratentorial glioblastoma patients were enrolled in this study,25 patients were allocated in the ANH group,and another 35 patients were included in the control group.ANH dramatically reduced the need for allogeneic blood transfusion(3[12%]vs 12[34.3%],P=0.049),and the blood transfusion per total of patients was dramatically decreased by the application of ANH(0.40±1.15 units vs 1.06±1.59 units,P=0.069).Furthermore,ANH also markedly reduced the requirement of fresh frozen plasma(FFP)transfusion(2[8%]vs 11[31.4%],P=0.030)and the volume of FFP transfusion per total of patients(32.00±114.46 mL vs 115.71±181.00 mL,P=0.033).The complication rate was similar between the two groups.Conclusions ANH was a safe and effective blood conservation technique in glioblastoma surgery.

关键词： Glioblastoma Acute normovolemic hemodilution Surgery Blood transfusion

Tumor-associated telocytes

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Chinese Medical Journal 2024年第4期137卷 490-492页

作者： Jinqing zhang ying Xu Department of General Surgery Shandong Provincial Third HospitalShandong UniversityJinanShandong 250117China

To the Editor:It has been eighteen years since telocytes(TCs)were first categorized by Popescu et al^([1])in 2005.TCs were classified into interstitial cells of the Cajal(ICC)type based on their ultrastructure and immunohistochemical features,which are similar to mesenchymal cells.^([2])In the following ten years,TCs were found to have their own distinctive characteristics in terms of three-dimensional structure,immunological biomarkers,genomics,and multiple functions.Interestingly,TCs are definitely distinct from fibroblasts,mesenchymal stem cells,and endothelial cells in multiple organs of human beings and animals.^([3])

关键词： cytes organs definitely

Microstructure evolution and strengthening mechanism of high -performance powder metallurgy TA15 titanium alloy by hot rolling

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International Journal of Minerals,Metallurgy and Materials 2024年第6期31卷 1426-1436页

作者： ying Gao Ce zhang Jiazhen zhang Xin Lu Beijing Advanced Innovation Center for Materials Genome Engineering State Key Laboratory for Advanced Metals and MaterialsInstitute for Advanced Ma-terials and TechnologyUniversity of Science and Technology BeijingBeijing 100083China National Engineering Research Center for Advanced Rolling Technology National Engineering Research Center for Flat Rolling EquipmentInstitute of Engin-eering TechnologyUniversity of Science and Technology BeijingBeijing 100083China

Hot deformation of sintered billets by powder metallurgy(PM)is an effective preparation technique for titanium alloys,which is more significant for high-alloying alloys.In this study,Ti–6.5Al–2Zr–Mo–V(TA15)titanium alloy plates were prepared by cold press-ing sintering combined with high-temperature hot rolling.The microstructure and mechanical properties under different process paramet-ers were investigated.Optical microscope,electron backscatter diffraction,and others were applied to characterize the microstructure evolution and mechanical properties strengthening mechanism.The results showed that the chemical compositions were uniformly dif-fused without segregation during sintering,and the closing of the matrix craters was accelerated by increasing the sintering temperature.The block was hot rolled at 1200℃ with an 80%reduction under only two passes without annealing.The strength and elongation of the plate at 20–25℃ after solution and aging were 1247 MPa and 14.0%,respectively,which were increased by 24.5%and 40.0%,respect-ively,compared with the as-sintered alloy at 1300℃.The microstructure was significantly refined by continuous dynamic recrystalliza-tion,which was completed by the rotation and dislocation absorption of the substructure surrounded by low-angle grain boundaries.After hot rolling combined with heat treatment,the strength and plasticity of PM-TA15 were significantly improved,which resulted from the dense,uniform,and fine recrystallization structure and the synergistic effect of multiple slip systems.

关键词： elemental powder powder metallurgy titanium alloy hot rolling strength and plasticity

Gabapentinoids for the treatment of stroke

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Neural Regeneration Research 2024年第7期19卷 1509-1516页

作者： ying zhang Chenyu zhang Xiaoli Yi Qi Wang Tiejun zhang Yuwen Li Department of Pharmacy West China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Neurosurgery West China HospitalSichuan UniversityChengduSichuan ProvinceChina

Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium channels.In this review,we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids.We systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro ke.This review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related diseases.Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke.Therefore,gabapentinoids have both opportunities and challenges in the treatment of stroke.

关键词： cortical spreading depolarization gabapentinoid intracerebral hemorrhage pain after stroke stroke subarachnoid hemorrhage

Compatibility evaluation between waterborne epoxy resin and SBR latex modified asphalt emulsion

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Journal of Traffic and Transportation Engineering(English Edition) 2024年第1期11卷 160-171页

作者： Jianhua Yang Zhengqi zhang ying Fang Key Laboratory for Special Area Highway Engineering of Ministry of Education Chang'an UniversityXi'an 710064China

Good compatibility between waterborne epoxy resin(WER)modifier and styrene-butadiene rubber(SBR)latex modified asphalt emulsion(SBRE)is an essential premise for good pavement performance of WER and SBR latex compositely modified asphalt emulsion(WSAE).This study aims to explore the compatibility between WER modifier and SBRE.To achieve the goal,several WER modifiers produced by two methods were first selected to modify SBRE,thus the WSAEs were prepared.Next,storage stability and workability of the WSAEs themselves,and high-temperature performance,rheological behavior and temperature sensitivity of their evaporated residues were compared and evaluated via performing a series of experiments,respectively,thus the WER modifier possessing an optimal modification effect was recommended.Results show that the storage stability of WSAEs is sensitive to the amount of WERs.The incorporation of 1%WERs by the mass of SBRE improves the storage stability of SBRE,while WERs that exceed 1%weaken its storage stability.When the WERs reach 3%and 4%,the 5 d storage stability of prepared WSAEs will be beyond the limitation of specification.Incorporating WERs into SBRE negatively affects the workability of SBRE,and the workability of WSAEs is adversely influenced by the WERs content and the storage time.To ensure the construction,the WSAEs with 3%and 4%WERs should not be stored for more than 36 h and 48 h,respectively.The WERs effectively improve the high-temperature performance of SBRE residue,especially the 3%WERs.Besides,the WERs notably enhance the rheological property and thermal stability of SBRE residue.In contrast,the WER modifier produced by chemically modified method has a smaller adverse impact on the storage stability and workability of WSAE,and a larger enhancement on the high-temperature performance,rheological property and thermal stability of SBRE residue,which is thus recommended to modify SBRE.

关键词： Waterborne epoxy resin SBR modified asphalt emulsion Workability Rheological property Temperature sensitivity Compatibility evaluation