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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

Switching,explosion,and chaos of multi-wavelength soliton states in ultrafast fiber lasers

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Science China(Physics,Mechanics & Astronomy) 2024年第7期67卷 82-90页

作者： zhi-zeng Si Yue-Yue Wang Chao-Qing Dai College of Optical Mechanical and Electrical EngineeringZhejiang A&F UniversityLin’an 311300China

Because of the complexity and difficulty of realizing a multi-wavelength soliton state,reports on its internal dynamic characteristics are scarce.In this study,the switching and periodic soliton explosion processes of the multi-wavelength soliton state in a negative dispersion passively mode-locked fiber laser are realized.The generation of the multi-wavelength soliton state undergoes the process of noise,oscillation,and stable mode-locking,and the splitting and annihilation of solitons with different group velocities directly impact the generation and disappearance of three wavelengths.Positive and negative dispersion lead to different group velocities of solitons.The presence and displacement of solitons with different group velocities cause soliton collisions,which lead to soliton explosions.A soliton experiences relative phase oscillation,chaos,and oscillation,as well as convergence and separation before and after an explosion.With an increase in parameters related to pump power,single-soliton oscillation,multi-wavelength solitons,and chaos are found in experiments and simulations,proving the relevance and reliability between simulation and experimental results.This work promotes the dynamical study of multi-soliton collisions in nonlinear science and the development of chaos theory in multi-comb lasers.

关键词： multi-wavelength fiber laser soliton explosion chaos state switching real-time dynamics

Flexible tuning of multifocal holographic imaging based on electronically controlled metasurfaces

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Photonics Research 2024年第1期12卷 61-69页

作者： OWEN zeng CHENXIA LI BO FANG zhi HONG XUFENG JING Institute of Optoelectronic Technology China Jiliang UniversityHangzhou 310018China Centre for THz Research China Jiliang UniversityHangzhou 310018China College of Metrology&Measurement Engineering China Jiliang UniversityHangzhou 310018China

Programmable hyper-coded holography has the advantage of being programmable as well as being flexibly modifiable.Digitally coded metamaterials with excellent electromagnetic modulation capability and the ability to control the phase to modulate the spatial radiation field through external excitation in the form of switching can be used to realize low-cost digital arrays.We design a 1-bit encoded programmable metasurface,which is electrically connected to control the PIN diode in the switching state and to switch the condition of each metasurface cell between“0”and“1.”Using the designed programmable metasurface,we can randomly encode the cell structure to realize single-focus focusing,multi-focusing,and simple holographic letter imaging.Based on the nonlinear holographic model,we employ the Gerchberg-Saxton improvement algorithm to modulate the energy distribution at the focus by adjusting the phase distribution.Importantly,we introduce the Fourier convolution principle to regulate the holographic imaging focus flexibly.

关键词： holographic letter excitation

Research on Risk Identification and Industrial Governance of Digital Education Products Based on Data Annotation Technology

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China Communications 2024年第3期21卷 273-282页

作者： Tong Lili zeng Jia Di ying Wang Nan Faculty of Education Beijing Normal University Beijing 100875China China Unicom Beijing 102211China

The social transformation brought aboutby digital technology is deeply impacting various industries.Digital education products, with core technologiessuch as 5G, AI, IoT (Internet of Things),etc., are continuously penetrating areas such as teaching,management, and evaluation. Apps, miniprograms,and emerging large-scale models are providingexcellent knowledge performance and flexiblecross-media output. However, they also exposerisks such as content discrimination and algorithmcommercialization. This paper conducts anevidence-based analysis of digital education productrisks from four dimensions: “digital resourcesinformationdissemination-algorithm design-cognitiveassessment”. It breaks through corresponding identificationtechnologies and, relying on the diverse characteristicsof governance systems, explores governancestrategies for digital education products from the threedomains of “regulators-developers-users”.

关键词： digital education products industry governance risk identification

Micropulse transscleral laser therapy for secondary angle-closure glaucoma in nanophthalmos: a case report

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1381-1384页

作者： Ping Yu Bai-Yu Hu Yu He Lin Jing Han-ying Fan Jing Shu Liu-zhi zeng Chengdu First People’s Hospital Chengdu 610095Sichuan ProvinceChina Eye School of Chengdu University of TCM Chengdu 610075Sichuan ProvinceChina

Dear Editor,The choice of surgical intervention for nanophthalmos patients with secondary angle-closure glaucoma poses a challenging decision for ophthalmologists.Because nanophthalmos patients who have undergone filtration surgery or other intraocular procedures are more susceptible to severe complications,including choroidal effusion,malignant glaucoma,and explosive choroidal hemorrhage,all of which can lead to vision loss[1].This dilemma is particularly pronounced in patients with shorter axial lengths.Micropulse transscleral laser therapy(M-TLT),also known as micropulse transscleral cyclophotocoagulation(MP-TSCPC),is a nonincisional laser therapy surgery for glaucoma[2].In 2015,Golan and Kurtz[3]were the first to report four patients with secondary angle-closure glaucoma in nanophthalmos with axial lengths ranging between 17 and 19 mm(mean 18 mm)who were successfully treated with M-TLT,and choroidal detachment was observed in all patients(recovery spontaneously in two patients and recovery after systemic steroid treatment in the other two),of which two had a slight decrease in visual acuity.

关键词： glaucoma surgery closure

Predator-prey encounters:deciphering the robbery relationship between highwayman flies and their ant victims

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Integrative Zoology 2024年第2期19卷 253-261页

作者： ying ZHAO Yulong YU zhi CHEN ying LI Huidan TENG Guillaume CHOMICKI Chuntian ZHANG Gao CHEN Yunnan Key Laboratory for Integrative Conservation of Plant Species with Extremely Small Populations KunmingChina CAS Key Laboratory for Plant Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of SciencesKunmingChina College of Life Science Shenyang Normal UniversityShenyangChina School of Ecology and Environmental Science Yunnan UniversityKunmingChina University of Chinese Academy of Sciences BeijingChina Ecology and Evolutionary Biology School of BiosciencesAlfred Denny BuildingUniversity of SheffieldWestern BankSheffieldUK

Examples of predator–prey interactions in which flies rob ants are uncommon.To date,this behavior has only been recorded in the genus Bengalia Robineau-Desvoidy(Bengaliinae,Diptera,Calliphoridae).These predatory flies ambush ants,and rob them of the food or offspring that they are carrying.However,because of the rarity of this behavior,the reasons and consequences(evolutionary advantages)are unknown,and indeed,the behavior has been sometimes considered anecdotal.In this study,we employed field investigations and behavioral analyses to investigate whether the sex of the fly Bengalia varicolor,or the weight and quality of the food carried by Pheidole nodus ants influenced fly–ant interactions in their natural habitats.We show that food weight and quality influenced the behavior of B.varicolor independent of the fly’s sex.Robbing behavior by the flies was more successful when the food robbed was of high-quality and light in weight.Furthermore,the weight of the food robbed modulated the escape distance the flies could carry it.This then may affect the food quality and weight transported by the ants.This is a novel example of deciphering the relationship between highwayman flies and their ant victims.Given the widespread distribution of Bengalia flies,we suggest that such interspecific predator–prey encounters may shape the robbery interactions and the carrying behavior of further ant species in nature.

关键词： Bengalia kleptoparasitism Pheidole predatory flies robbing

Microstructure and mechanical properties of Ti/Al/Ti clad plates prepared via powder-in-tube method

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Journal of Iron and Steel Research(International) 2024年第3期31卷 670-687页

作者： Xian-lei Hu Qin-cheng Xie Yi Yuan ying zhi State Key Laboratory of Rolling and Automation Northeastern UniversityShenyang 110819LiaoningChina Suzhou Dongbao Haixing Metal Material Technology Co. Ltd.Suzhou 215600JiangsuChina School of Material Science and Engineering Northeastern UniversityShenyang 110819LiaoningChina

The Ti/Al/Ti clad plates exhibit a broad spectrum of potential applications.However,the conventional techniques of hot-pressing composite and explosive composite are intricate and environmentally hazardous.A novel method was introduced for preparing clad plates,namely,the powder-in-tube method.This method involves a combination of cold rolling,annealing at a temperature of 550℃,and double rolling.The morphology of the intermetallic compound layer was analyzed through the utilization of interface stripping test,tensile test,and microscopic characterization.The interface morphology,interface bonding properties,tensile fracture structures,and properties of plates under the first and second rolling were compared,along with the effects of intermetallic compounds on the interface properties.The results indicate that the powder-in-tube method,when annealed at 550℃,can produce a composite plate featuring a complete and uniform Ti/Al interface.The obtained plate exhibits a peeling strength of 21.5 N/mm,tensile strength of 424 MPa,and elongation of 11.5%.Furthermore,a systematic analysis was conducted to determine the causes of performance degra-dation observed during annealing at temperatures of 600 and 650℃.

关键词： Powder-in-tube method-Ti/Al/Ti clad plate Annealing Cold rolling-Mechanical property

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma:A case report

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World Journal of Clinical Cases 2024年第15期12卷 2649-2654页

作者： Xin-Xin Luo Yu-Xuan Du Qi-Qing Zhang Lin Zhang Shu-ying zeng zhi-Hong Yu Peng Shen Zheng-Quan Feng The Second School of Clinical Medicine Zhejiang Chinese Medical UniversityHangzhou310053Zhejiang ProvinceChina Department of Oncology Tongde Hospital of Zhejiang ProvinceHangzhou 310012Zhejiang ProvinceChina Department of Medical Oncology The First Affiliated HospitalMedical College of Zhejiang UniversityHangzhou 310003Zhejiang ProvinceChina

BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.

关键词： Synchronous multiple primary carcinoma Esophageal squamous cell carcinoma Colon adenocarcinoma Cetuximab Chemotherapy Case report

Clinical observation of gastrointestinal function recovery in patients after hepatobiliary surgery

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 76-84页

作者： Hua-Jun zeng Jing-Jing Liu ying-Chun Yang Department of General Practice Nanyang First People's HospitalNanyang 473000Henan ProvinceChina Department of Anesthesiology Chinese People’s Armed Police Force Hospital of BeijingBeijing 100027China Department of Anesthesiology Beijing Fengtai HospitalBeijing 100071China

BACKGROUND The liver is an important metabolic and digestive organ in the human body,ca-pable of producing bile,clotting factors,and vitamins.AIM To investigate the recovery of gastrointestinal function in patients after hepato-biliary surgery and identify effective rehabilitation measures.METHODS A total of 200 patients who underwent hepatobiliary surgery in our hospital in 2022 were selected as the study subjects.They were divided into a control group and a study group based on the extent of the surgery,with 100 patients in each group.The control group received routine treatment,while the study group re-ceived targeted interventions,including early enteral nutrition support,drinking water before gas discharge,and large bowel enema,to promote postoperative gastrointestinal function recovery.The recovery of gastrointestinal function was compared between the two groups.RESULTS Compared with the control group,patients in the study group had better recovery of bowel sounds and less accumulation of fluids in the liver bed and gallbladder fossa(P<0.05).They also had shorter time to gas discharge and first meal(P<0.05),higher overall effective rate of gastrointestinal function recovery(P<0.05),and lower incidence of postoperative complications(P<0.05).CONCLUSION Targeted nursing interventions(early nutritional support,drinking water before gas discharge,and enema)can effectively promote gastrointestinal function recovery in patients undergoing hepatobiliary surgery and reduce the incidence of complications,which is worthy of promotion.

关键词： Liver and gallbladder patients Gastrointestinal function Postoperative recovery