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Therapeutic genome editing of an aberrant splice site inβ-thalassemia by CRISPR/Cas9 with multiple sgRNAs

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Genes & Diseases 2024年第1期11卷 15-18页

作者： fei yang Shuqian Xu Chao Huang Zhiqiang Shao Yuefen Hu yang yang Yongrong Lai Qing Ke Dan Liang Yuxuan Wu Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Obstetrics and Gynecology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract(Anhui Medical University) HefeiAnhui 230032China Department of Hematology Qilu HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250012China BRLMedicine Inc. Shanghai 201108China Department of Hematology The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxi 530000China Department of Neurology The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China

Genetic mutations cause aberrant splicing,one of the important molecular mechanisms in human diseases.Ivs2-654,a mutation causing aberrant splicing ofβ-globin premRNA and contributing toβ-globin deficiency,is one of the most common diseases in Southeast Asia and China."In our previous work,we found a TTTV protospacer adjacent motif(PAM)by the Cas12a system and the editing efficiency of Ivs2-654 C>T achieving 76.7%.

关键词： CRISPR/Cas9 China thalassemia

Muscle strength and non-alcoholic fatty liver disease/metabolicassociated fatty liver disease

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World Journal of Gastroenterology 2024年第7期30卷 636-643页

作者： Xuan-Yu Hao Kai Zhang Xing-Yong Huang fei yang Si-Yu Sun Department of Gastroenterology Endoscopic CenterShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina Department of Gastroenterology Endoscopic CenterEngineering Research Center of Ministry of Education for Minimally Invasive Gastrointestinal Endoscopic TechniquesShengjing Hospital of China Medical UniversityShenyang 110004Liaoning ProvinceChina

This editorial comments on an article published in a recent issue of World Journal of Gastroenterology,entitled“Association of low muscle strength with metabolic dysfunction-associated fatty liver disease:A nationwide study”.We focused on the association between muscle strength and the incidence of non-alcoholic fatty liver disease(NAFLD)and metabolic-associated fatty liver disease(MAFLD),as well as the mechanisms underlying the correlation and related clinical applications.NAFLD,which is now redefined as MAFLD,is one of the most common chronic liver diseases globally with an increasing prevalence and is characterized by malnutrition,which may contribute to decreased muscle strength.Reduction of muscle strength reportedly has a pathogenesis similar to that of NAFLD/MAFLD,including insulin resistance,inflammation,sedentary behavior,as well as insufficient vitamin D.Multiple studies have focused on the relationship between sarcopenia or muscle strength and NAFLD.However,studies investigating the relationship between muscle strength and MAFLD are limited.Owing to the shortage of specific medications for NAFLD/MAFLD treatment,early detection is essential.Furthermore,the relationship between muscle strength and NAFLD/MAFLD suggests that improvements in muscle strength may have an impact on disease prevention and may provide novel insights into treatments including dietary therapy,as well as tailored physical activity.

关键词： Muscle strength Non-alcoholic fatty liver disease Metabolic-associated fatty liver disease Sarcopenia Insulin resistance Inflammation

Energy evolution and structural health monitoring of coal under different failure modes:An experimental study

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International Journal of Minerals,Metallurgy and Materials 2024年第5期31卷 917-928页

作者： Yarong Xue Xueqiu He Dazhao Song Zhenlei Li Majid Khan Taoping Zhong fei yang School of Civil and Resources Engineering University of Science and Technology BeijingBeijing 100083China Zhong-an Academy of Safety Engineering Beijing 100083China

Structural instability in underground engineering,especially in coal-rock structures,poses significant safety risks.Thus,the development of an accurate monitoring method for the health of coal-rock bodies is crucial.The focus of this work is on understanding energy evolution patterns in coal-rock bodies under complex conditions by using shear,splitting,and uniaxial compression tests.We examine the changes in energy parameters during various loading stages and the effects of various failure modes,resulting in an innovative energy dissipation-based health evaluation technique for coal.Key results show that coal bodies go through transitions between strain hardening and softening mechanisms during loading,indicated by fluctuations in elastic energy and dissipation energy density.For tensile failure,the energy profile of coal shows a pattern of “high dissipation and low accumulation” before peak stress.On the other hand,shear failure is described by “high accumulation and low dissipation” in energy trends.Different failure modes correlate with an accelerated increase in the dissipation energy before destabilization,and a significant positive correlation is present between the energy dissipation rate and the stress state of the coal samples.A novel mathematical and statistical approach is developed,establishing a dissipation energy anomaly index,W,which categorizes the structural health of coal into different danger levels.This method provides a quantitative standard for early warning systems and is adaptable for monitoring structural health in complex underground engineering environments,contributing to the development of structural health monitoring technology.

关键词： energy dissipation structural health monitoring early warning coal-rock mechanics failure mode

CPT: a pre-trained unbalanced transformer for both Chinese language understanding and generation

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Science China(Information Sciences) 2024年第5期67卷 43-55页

作者： Yunfan SHAO Zhichao GENG Yitao LIU Junqi DAI Hang YAN fei yang Zhe LI Hujun BAO Xipeng QIU School of Computer Science Fudan University Shanghai Key Laboratory of Intelligent Information Processing Fudan University Zhejiang Lab

In this paper, we take the advantage of previous pre-trained models(PTMs) and propose a novel Chinese pre-trained unbalanced transformer(CPT). Different from previous Chinese PTMs, CPT is designed to utilize the shared knowledge between natural language understanding(NLU) and natural language generation(NLG) to boost the performance. CPT consists of three parts: a shared encoder, an understanding decoder, and a generation decoder. Two specific decoders with a shared encoder are pretrained with masked language modeling(MLM) and denoising auto-encoding(DAE) tasks, respectively.With the partially shared architecture and multi-task pre-training, CPT can(1) learn specific knowledge of both NLU or NLG tasks with two decoders and(2) be fine-tuned flexibly that fully exploits the potential of the model. Moreover, the unbalanced transformer saves the computational and storage cost, which makes CPT competitive and greatly accelerates the inference of text generation. Experimental results on a wide range of Chinese NLU and NLG tasks show the effectiveness of CPT.

关键词： pre-trained model transformer language model generation unified model

Efficient C-N coupling in electrocatalytic urea generation on copper carbonate hydroxide electrocatalysts

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Journal of Energy Chemistry 2024年第6期93卷 289-298,I0008页

作者： Yinuo Wang Yian Wang Qinglan Zhao Hongming Xu Shangqian Zhu fei yang Ernest P.Delmo Xiaoyi Qiu Chi Song Juhee Jang Tiehuai Li Ping Gao MDanny Gu Minhua Shao Advanced Materials Thrust The Hong Kong University of Science and Technology(Guangzhou)Guangzhou 511400GuangdongChina Department of Chemical and Biological Engineering The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Department of Materials Science and Engineering Southern University of Science and Technology of Chin11088 Xueyuan BoulevardShenzhen 518055GuangdongChina Energy Institute and Chinese National Engineering Research Center for Control&Treatment of Heavy Metal PollutionThe Hong Kong University of Science and TechnologyKowloonHong KongChina Department of Chemistry City University of Hong KongTat Chee AvenueKowloonHong KongChina

Urea generation through electrochemical CO_(2) and NO_(3)~-co-reduction reaction(CO_(2)NO_(3)RR)is still limited by either the low selectivity or yield rate of urea.Herein,we report copper carbonate hydroxide(Cu_2(OH)_2CO_(3))as an efficient CO_(2)NO_(3)RR electrocatalyst with an impressive urea Faradaic efficiency of45.2%±2.1%and a high yield rate of 1564.5±145.2μg h~(-1)mg_(cat)~(-1).More importantly,H_(2) evolution is fully inhibited on this electrocatalyst over a wide potential range between-0.3 and-0.8 V versus reversible hydrogen electrode.Our thermodynamic simulation reveals that the first C-N coupling follows a unique pathway on Cu_2(OH)_2CO_(3) by combining the two intermediates,~*COOH and~*NHO.This work demonstrates that high selectivity and yield rate of urea can be simultaneously achieved on simple Cu-based electrocatalysts in CO_(2)NO_(3)RR,and provide guidance for rational design of more advanced catalysts.

关键词： Copper carbonate hydroxide Co-reduction Urea generation C-N coupling DFT calculation

Lignin-reinforced PVDF electrolyte for dendrite-free quasi-solid-state Li metal battery

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Rare Metals 2024年第3期43卷 1006-1016页

作者： Xin-yang Chen Xue-Jie Gao Han-Yan Wu Yu-Long Liu Xiao-fei yang Run-Cang Sun Center for Lignocellulosic Chemistry and Biomaterials College of Light Industry and Chemical EngineeringDalian Polytechnic UniversityDalian116034China Division of Energy Storage Dalian National Laboratory for Clean EnergyDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian116023China School of Chemistry Northeast Normal UniversityChangchun130024China

Quasi-solid-state lithium metal batteries(QSSLMBs)assembled with polyvinylidene fluoride(PVDF)are a promising class of next-generation rechargeable batteries due to their safety,high energy density,and superior interfacial properties.However,PVDF has a series of inherent drawbacks such as low ionic conductivity,ease of crystallization,and hydrophobic character that leading to poor cell properties.To tackle these issues,a lignin-reinforced PVDF electrolyte is proposed in this work to solve these drawbacks of PVDF and enhance the comprehensive performance of QSSBs.The lithophilic polar groups of lignin can promote uniform deposition of Li on the electrodes.Cooperating with the improved mechanical properties can efficiently prevent Li dendrites penetration through the separator.In addition,more active sites provided by lignin can also enhance Li^(+)transport and lead to a faster electrochemical reaction kinetic.Benefitting from the ingenious design,Li symmetric cells with 5%lignin-PVDF quasi-solid-state electrolyte can operate for 900 h at a high current density/capacity of 5 mA·cm^(-2)/5 mAh·cm^(-2),while shortcircuiting occurs after 56 h for the counterpart(pure PVDF).Moreover,a full cell of Li/5%lignin-PVDF/LFP cell demonstrates a high capacity of 96.2 mAh·g^(-1)after 2000 cycles at 10 C.This work is expected to open up promising opportunities to develop other high-energy/power-density QSSLMBs.

关键词： Quasi-solid-state electrolyte Lignin PVDF Dendrite-free Li metal battery

Preoperative neutrophil-to-lymphocyte ratio predicts symptomatic anastomotic leakage in elderly colon cancer patients: Multicenter propensity score-matched analysis

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 438-450页

作者： Chao-yang Wang Xiao-Long Li Xiao-Long Ma Xiong-fei yang Yong-Yong Liu Yong-Jiang Yu Department of Clinical Medicine The First Clinical Medical College of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of Gastrointestinal Surgery First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina Department of Clinical Medicine Gansu University of Chinese MedicineLanzhou 730000Gansu ProvinceChina Department of Anorectology Gansu Provincial People’s HospitalLanzhou 730000Gansu ProvinceChina Department of General Surgery The Second Hospital Affiliated to Lanzhou UniversityLanzhou 730000Gansu ProvinceChina

BACKGROUND The neutrophil-to-lymphocyte ratio(NLR),a composite inflammatory biomarker,is associated with the prognosis in patients with colorectal tumors.However,whether the NLR can be used as a predictor of symptomatic postoperative ana-stomotic leakage(AL)in elderly patients with colon cancer is unclear.AIM To assess the role of the NLR in predicting the occurrence of symptomatic AL after surgery in elderly patients with colon cancer.METHODS Data from elderly colon cancer patients who underwent elective radical colectomy with anastomosis at three centers between 2018 and 2022 were retrospectively analyzed.Receiver operating characteristic curve analysis was performed to determine the best predictive cutoff value for the NLR.Twenty-two covariates were matched using a 1:1 propensity score matching method,and univariate and multivariate logistic regression analyses were used to determine risk factors for the development of postoperative AL.RESULTS Of the 577 patients included,36(6.2%)had symptomatic AL.The optimal cutoff value of the NLR for predicting AL was 2.66.After propensity score matching,the incidence of AL was significantly greater in the≥2.66 NLR subgroup than in the<2.66 NLR subgroup(11.5%vs 2.5%;P=0.012).Univariate logistic regression analysis revealed statistically significant correlations between blood transfusion intraoperatively and within 2 d postoper-atively,preoperative albumin concentration,preoperative prognostic nutritional index,and preoperative NLR and AL occurrence(P<0.05);multivariate logistic regression analysis revealed that an NLR≥2.66[odds ratio(OR)=5.51;95%confidence interval(CI):1.50-20.26;P=0.010]and blood transfusion intraoperatively and within 2 d postoperatively(OR=2.52;95%CI:0.88-7.25;P=0.049)were risk factors for the occurrence of symptomatic AL.CONCLUSION A preoperative NLR≥2.66 and blood transfusion intraoperatively and within 2 d postoperatively are associated with a higher incidence of postoperative symptomatic AL in elderly patients with colon cancer.The preoperative NLR

关键词： Colon cancer Anastomotic leak Neutrophil-to-lymphocyte ratio Propensity score-matched

Dynamic manipulation of multimodal emission in Er3+-activated non-core-shell structure for optical thermometry and information security

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Rare Metals 2024年第4期43卷 1702-1712页

作者： Xuan Liu Zi-Xia Lin Yin-Biao Shi Xiao-Yan Wang Ming-Ye Ding Xiao-fei yang College of Science Nanjing Forestry University Testing Center Yangzhou University

Regulating luminescent dynamics of lanthanide-based luminescent materials via external stimuli is of great significance in the fields of optical thermometry and high-level anti-counterfeiting.However,it is still a huge challenge to realize multimodal emissions with tunable color outputs from a single activator in simple structures via smart dynamic control of photon transition processes.Herein,we present a mechanistic strategy to achieve multimodal luminescence of Er3+activators with color-switchable outputs in a non-core-shell host.Under the control of excitation dynamics(λex=980,808,1532,377 nm),the population among the intermediate en ergy levels of Er3+and the interaction between Er3+and Yb3+could be precisely modulated through energy transfer and migration processes,leading to the generation of colortunable multimodal luminescence upon diverse excitation modes（non-steady-state,single-/dual-wavelength steady,thermal activation）.Inspired by its special luminescent performance,the as-obtained material exhibits great potential in noncontact thermometry,multimodal anticounterfeiting,and high-capacity information encryption by performing a series of proof-of-concept experiments.Our findings might provide a conceptual model to modulate the luminescent dynamics in a simple-structured system for the generation of color-adjustable multimodal emissions,which is convenient for the development of advanced luminescent materials toward versatile cuttingedge applications.

关键词： Lanthanide ions Multimodal emission Upconversion Downshifting Anti-counterfeiting Luminescent thermometry

Optimized air-ground data fusion method for mine slope modeling

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Journal of Mountain Science 2024年第6期21卷 2130-2139页

作者： LIU Dan HUANG Man TAO Zhigang HONG Chenjie WU Yuewei FAN En yang fei State Key Laboratory for Tunnel Engineering China University of Mining and Technology(Beijing)Beijing 100083China Department of Civil Engineering Shaoxing UniversityShaoxing 312000China Department of Computer Science and Engineering Shaoxing UniversityShaoxing 312000China

Refined 3D modeling of mine slopes is pivotal for precise prediction of geological hazards.Aiming at the inadequacy of existing single modeling methods in comprehensively representing the overall and localized characteristics of mining slopes,this study introduces a new method that fuses model data from Unmanned aerial vehicles(UAV)tilt photogrammetry and 3D laser scanning through a data alignment algorithm based on control points.First,the mini batch K-Medoids algorithm is utilized to cluster the point cloud data from ground 3D laser scanning.Then,the elbow rule is applied to determine the optimal cluster number(K0),and the feature points are extracted.Next,the nearest neighbor point algorithm is employed to match the feature points obtained from UAV tilt photogrammetry,and the internal point coordinates are adjusted through the distanceweighted average to construct a 3D model.Finally,by integrating an engineering case study,the K0 value is determined to be 8,with a matching accuracy between the two model datasets ranging from 0.0669 to 1.0373 mm.Therefore,compared with the modeling method utilizing K-medoids clustering algorithm,the new modeling method significantly enhances the computational efficiency,the accuracy of selecting the optimal number of feature points in 3D laser scanning,and the precision of the 3D model derived from UAV tilt photogrammetry.This method provides a research foundation for constructing mine slope model.

关键词： Air-ground data fusion method Mini batch K-Medoids algorithm Ebow rule Optimal cluster number 3D laser scanning UAV tilt photogrammetry