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Precise genome-editing in human diseases:mechanisms,strategies and applications

Signal Transduction and Targeted Therapy 2024年第3期9卷 1065-1085页

作者： Yanjiang Zheng Yifei Li Kaiyu Zhou Tiange Li Nathan j.VanDusen Yimin hua Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE Department of PediatricsWest China Second University HospitalSichuan UniversityChengduSichuan 610041China Department of Cardiovascular Surgery West China HospitalSichuan UniversityChengduSichuan 610041China Department of Pediatrics Herman B Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisIN 46202USA

Precise genome-editing platforms are versatile tools for generating specific,site-directed DNA insertions,deletions,and *** continuous enhancement of these tools has led to a revolution in the life sciences,which promises to deliver novel therapies for genetic *** genome-editing can be traced back to the 1950s with the discovery of DNA’s doublehelix and,after 70 years of development,has evolved from crude in vitro applications to a wide range of sophisticated capabilities,including in vivo ***,precise genome-editing faces constraints such as modest efficiency,delivery challenges,and off-target *** this review,we explore precise genome-editing,with a focus on introduction of the landmark events in its history,various platforms,delivery systems,and ***,we discuss the landmark events in the history of precise ***,we describe the current state of precise genome-editing strategies and explain how these techniques offer unprecedented precision and versatility for modifying the human ***,we introduce the current delivery systems used to deploy precise genome-editing components through DNA,RNA,and ***,we summarize the current applications of precise genome-editing in labeling endogenous genes,screening genetic variants,molecular recording,generating disease models,and gene therapy,including ex vivo therapy and in vivo therapy,and discuss potential future advances.

关键词： precise generating editing

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STCF conceptual design report (Volume 1): Physics & detector

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Frontiers of physics 2024年第1期19卷 1-154页

作者： M.Achasov x.C.Ai L.P.An R.Aliberti Q.An x.Z.Bai Y.Bai O.Bakina A.Barnyakov V.Blinov V.Bobrovnikov D.Bodrov A.Bogomyagkov A.Bondar I.Boyko Z.H.Bu F.M.Cai H.Cai j.j.Cao Q.H.Cao x.Cao Z.Cao Q.Chang K.T.Chao D.Y.Chen H.Chen H.x.Chen j.F.Chen K.Chen L.L.Chen P.Chen S.L.Chen S.M.Chen S.Chen S.P.Chen W.Chen x.Chen x.F.Chen x.R.Chen Y.Chen Y.Q.Chen H.Y.Cheng j.Cheng S.Cheng T.g.Cheng j.P.Dai L.Y.Dai x.C.Dai D.Dedovich A.Denig I.Denisenko j.M.Dias D.Z.Ding L.Y.Dong W.H.Dong V.Druzhinin D.S.Du Y.j.Du Z.g.Du L.M.Duan D.Epifanov Y.L.Fan S.S.Fang Z.j.Fang g.Fedotovich C.Q.Feng x.Feng Y.T.Feng j.L.Fu j.gao Y.N.gao P.S.ge C.Q.geng L.S.geng A.gilman L.gong T.gong B.gou W.gradl j.L.gu A.guevara L.C.gui A.Q.guo F.K.guo j.C.guo j.guo Y.P.guo Z.H.guo A.guskov K.L.Han L.Han M.Han x.Q.Hao j.B.He S.Q.He x.g.He Y.L.He Z.B.He Z.x.Heng B.L.Hou T.j.Hou Y.R.Hou C.Y.Hu H.M.Hu K.Hu R.j.Hu W.H.Hu x.H.Hu Y.C.Hu j.hua g.S.huang j.S.huang M.huang Q.Y.huang W.Q.huang x.T.huang x.j.hua.g Y.B.huang Y.S.huang N.Hüsken V.Ivanov Q.P.ji j.j.jia S.jia Z.K.jia H.B.jiang j.jiang S.Z.jiang j.B.jiao Z.jiao H.j.jing x.L.Kang x.S.Kang B.C.Ke M.Kenzie A.Khoukaz I.Koop E.Kravchenko A.Kuzmin Y.Lei E.Levichev C.H.Li C.Li D.Y.Li F.Li g.Li g.Li H.B.Li H.Li H.N.Li H.j.Li H.L.Li j.M.Li j.Li L.Li L.Li L.Y.Li N.Li P.R.Li R.H.Li S.Li T.Li W.j.Li x.Li x.H.Li x.Q.Li x.H.Li Y.Li Y.Y.Li Z.j.Li H.Liang j.H.Liang Y.T.Liang g.R.Liao L.Z.Liao Y.Liao C.x.Lin D.x.Lin x.S.Lin B.j.Liu C.W.Liu D.Liu F.Liu g.M.Liu H.B.Liu j.Liu j.j.Liu j.B.Liu K.Liu K.Y.Liu K.Liu L.Liu Q.Liu S.B.Liu T.Liu x.Liu Y.W.Liu Y.Liu Y.L.Liu Z.Q.Liu Z.Y.Liu Z.W.Liu I.Logashenko Y.Long C.g.Lu j.x.Lu N.Lu Q.F.Lü Y.Lu Y.Lu Z.Lu P.Lukin F.j.Luo T.Luo x.F.Luo Y.H.Luo H.j.Lyu x.R.Lyu j.P.Ma P.Ma Y.Ma Y.M.Ma F.Maas S.Malde D.Matvienko Z.x.Meng R.Mitchell A.Nefediev Y.Nefedov S.L.Olsen Q.Ouyang P.Pakhlov g.Pakhlova x.Pan Y.Pan E.Passemar Y.P.Pei H.P.Peng L.Peng x.Y.Peng x.j.Peng K.Peters S.Pivovarov E.Pyata B.B.Qi Y.Q.Qi W.B.Qian Y.Qian C.F.Qiao j.j.Qin j.j.Qin L.Q.Qin x.S.Qin T.L.Qiu j.Rademacker C.F.Redmer H.Y.Sang Anhui University Hefei 230039China Beihang University Beijing 100191China Budker Institute of Nuclear Physics Novosibirsk 630090Russia CAS Key Laboratory of Theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China Cavendish Laboratory University of CambridgeJJ Thomson AveCambridge CB30HEUnited Kingdom Central China Normal University Wuhan 430079China Central South University Changsha 410083China China University of geosciences Wuhan 430074China China University of Mining and Technology Xuzhou 221116China École Polytechnique Fédérale de Lausanne(EPFL) LausanneSwitzerland Fudan University Shanghai 200433China goethe University Frankfurt D-60325 Frankfurt am MainGermany guangxi Normal University Guilin 541004China guangxi Uninversity Nanning 530004China Hangzhou Institute for Advanced Study UCASHangzhou 310024China Hebei Normal University Shijiazhuang 050024China Hebei University Baoding 071002China Hefei University of Technology Hefei 230601China Helmholtz Institute Mainz Staudinger Weg 18D-55099 MainzGermany Henan Normal University Xinxiang 453007China Henan University Kaifeng 475004China High Energy Physics Center Chung-Ang UniversitySeoul 06974Korea Higher School of Economy 11 Pokrovsky Bulvar Moscow 109028Russia huangshan University Huangshan 245000China Hubei University of Automotive Technology Shiyan 442002China Hunan Normal University Changsha 410081China Hunan University of Science and Technology Xiangtan 411201China Hunan University Changsha 410082China Indiana University BloomingtonIndiana 47405USA Inner Mongolia University Hohhot 010021China Institute of Advanced Science Facilities Shenzhen 518107China Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China Institute of Modern Physics Chinese Academy of SciencesLanzhou 730000China Institute of Physics Academia SinicaTaipeiTaiwan 11529China Institute of Theoretical Physics Chinese Academy of SciencesBeijing 100190China jilin University Changch

The superτ-charm facility(STCF)is an electron–positron collider proposed by the Chinese particle physics *** is designed to operate in a center-of-mass energy range from 2 to 7 geV with a peak luminosity of 0.5×10^(35) cm^(–2)·s^(–1) or *** STCF will produce a data sample about a factor of 100 larger than that of the presentτ-charm factory—the BEPCII,providing a unique platform for exploring the asymmetry of matter-antimatter(charge-parity violation),in-depth studies of the internal structure of hadrons and the nature of non-perturbative strong interactions,as well as searching for exotic hadrons and physics beyond the Standard *** STCF project in China is under development with an extensive R&D *** document presents the physics opportunities at the STCF,describes conceptual designs of the STCF detector system,and discusses future plans for detector R&D and physics case studies.

关键词： electron–positron collider tau-charm region high luminosity STCF detector conceptual design

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Precise determination of the pole position of the exotic Z_(c)(3900)

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Science China(Physics,Mechanics & Astronomy) 2024年第9期67卷 84-90页

作者： Yun-hua Chen Meng-Lin Du Feng-Kun guo School of Mathematics and Physics University of Science and Technology BeijingBeijing 100083China School of Physics University of Electronic Science and Technology of ChinaChengdu 611731China CAS Key Laboratory of Theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China School of Physical Sciences University of Chinese Academy of SciencesBeijing 100049China Peng huanwu Collaborative Center for Research and Education Beihang UniversityBeijing 100191China

We perform a unified description of the experimental data of the π^(+)π^(-)and j/ψπ^(±)invariant mass spectra for e^(+)e^(-)→j/ψπ^(+)π^(-)and the D^(0)D^(*-)mass spectrum for e^(+)e^(-)→D^(0)D^(*-)π^(+)at e^(+)e^(-)center-of-mass energies 4.23 and 4.26 *** analysis takes into account open-charm meson loops that contain triangle singularities,the j/ψπ-DD^(*)coupled-channel interaction respecting unitarity,and the strong ππ-KK final state interaction using dispersion *** analysis leads to a precise determination of the Z_(c)(3900)pole with the pole mass and width(3880.7±1.7_(stat)±22.4_(syst))MeV and(35.9±1.4_(stat)±15.3_(syst))MeV,respectively,and hints at that the DD^(*)molecular and non-molecular components are of similar importance in the Z_(c)(3900)formation.

关键词： exotic hadrons dispersion relations final state interaction triangle singularity

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Multifunctional phase change film with high recyclability, adjustable thermal responsiveness, and intrinsic self-healing ability for thermal energy storage

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journal of Energy Chemistry 2024年第10期97卷 216-227,I0005页

作者： Bo Yang xuelai Zhang jun ji Weisan hua Miaomiao jiang Institute of Cool Thermal Storage Technology Shanghai Maritime UniversityShanghai 201306China

Phase change materials(PCMs) present promising potential for guaranteeing safety in thermal management ***,most reported PCMs have a single application in energy storage for thermal management systems,which does not meet the growing demand for multi-functional *** this paper,the flexible material and hydrogen-bonding function are innovatively combined to design and prepare a novel multi-functional flexible phase change film(PPL).The 0.2PPL-2 film exhibits solid-solid phase change behavior with energy storage density of 131.8 j/g at the transition temperature of42.1℃,thermal cycling stability(500 cycles),wide-temperature range flexibility(0-60℃) and selfhealing ***,the PPL film can be recycled up to 98.5% by intrinsic ***,the PPL film can be tailored to the desired colors and configurations and can be cleverly assembled on several thermal management systems at ambient temperature through its flexibility combined with shape-memory *** interestingly,the transmittance of PPL will be altered when the ambient temperature changes(60℃),conveying a clear thermal ***,the thermal energy storage performance of the PPL film is successfully tested by human thermotherapy and electronic device temperature control *** proposed functional integration strategy provides innovative ideas to design PCMs for multifunctionality,and makes significant contributions in green chemistry,highefficiency thermal management,and energy sustainability.

关键词： Phase change film Multifunctional material Energy storage Self-healing Recyclability

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Species recognition and the divergences in the chemical and ultrasonic signals between two coexisting Rattus species

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Current Zoology 2024年第4期70卷 531-538页

作者： Wei-Chao Wang Zhi-Ming Li Yi Chen jin-hua Zhang jian-xu Zhang Yao-hua Zhang The State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAs Center for Excellence in Biotic Interactions University of Chinese Academy of SciencesBeijingChina

The ability to recognize and differentiate between conspecifics and heterospecifics as well as their signals is critical for the coexistence of closely related *** the genus Rattus,species are morphologically similar and multiple species often ***,we investigated the interspecific recognition and signal differentiation of two sympatric rat species,the brown rat(Rattus norvegicus,RN)and the Asian house rat(Rattus tanezumi,RT).In a two-way choice test,both RN and RT females showed a preference for conspecific male rats to heterospecific *** females showed a significant preference for accessible urine of males of same species to those of other species,but not for the inaccessi-ble *** the other hand,there were significant differences in the structural characteristics of the ultrasonic vocalization emitted by males of these two rat *** dodecyl sulphate-polyacrylamide gel electrophoresis(SDS-PAgE)and isoelectric focusing electrophoresis unveiled that major urinary proteins(MUPs)in voided urine were more highly expressed in RN males versus RT *** interspecific dif-ferences of urinary volatile compounds were also *** conclusion,female rats had the ability to distinguish between males of either species.

关键词： Asian house rats brown rats closely related species pheromones ultrasonic vocalization.

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Microphysical Insights into a Tornadic Supercell from Dual-Polarization Radar Observations in jiangsu, China on 14 May 2021

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journal of Meteorological Research 2024年第2期38卷 303-320页

作者： Chao YUAN Yang BAI Pengfei SUN hua BAI Lu xIA China Meteorological Administration Tornado Key Laboratory Foshan 528315 Institute of Atmospheric Environment China Meteorological AdministrationShenyang 110166 Panjin National Climate Observatory Panjin 124010 Yangzhou Meteorological Bureau of jiangsu Province Yangzhou 225100 Yichun Meteorological Bureau of Heilongjiang Province Yichun 153000

Tornadoes are incredibly powerful and destructive natural events,yet the microphysical characteristics of the parent storm and its effects on tornadogenesis remain *** study analyzed polarization radar data of a tornadic supercell that occurred in jiangsu Province of China on 14 May 2021,in comparison with another tornadic supercell and two non-tornadic supercells that occurred in the same region in *** two tornadic supercells exhibited lower differential reflectivity(ZDR)in the hook echo region compared with the non-tornadic supercells,indicating smaller median drop sizes.A distinct increase in ZDR from the melting of frozen hydrometeors,observed between2.5-and 4.0-km altitude in the non-tornadic storms,was absent in the tornadic *** non-tornadic supercells also displayed substantially higher specific differential phase(KDP)below the melting level,likely aroused from enhanced melting and *** findings suggest fundamental microphysical contrasts between tornadic and nontornadic ***,tornadic supercells have smaller droplets and may reduce melting in hook ***,greater separation between the ZDR arc and the KDP foot was observed during *** vertical gradient of KDP related to the cooling pool strength of the hook echo,regulating rear-flank downdraft *** the limited number of cases investigated,the findings of this study indicate that monitoring ZDR,KDP,and drop size distribution trends could assist with tornado prediction and warnings.

关键词： tornado polarimetric radar supercell hook echo drop size distribution

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Accurate characterization of bubble mixing uniformity in a circular region using computational geometric theory

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Particuology 2024年第3期86卷 149-159页

作者： Hui Sun jianxin xu Shibo Wang guangcheng Cai hua Wang Wuliang Yin State Key Laboratory ofComplex Nonferrous Metal Resources Clean Utilization Kunming University ofScience and TechnologyKunming650093China bFaulty of Metallurgical and Energy Engineering Kunming University ofScience and TechnologyKunming650093China Faculty of Science Kunming University ofScience and TechnologyKunming650500China Department of Elec.and Electronic Engineering.University of Manchester ManchesterM139PL UK

The present study proposes a novel method based on the geometric theory for measuring the distribution of bubble swarms in the circular region of a direct-contact heat *** was determined that the mixing is uniform when the average distance between the bubble swarms in the unit circular region is approximately 0.9054,which is the standard reference *** effect of sample size(i.e.,the number of bubbles)on mixing uniformity was investigated to determine the optimal sample *** was verified that the metric's accuracy and stability were higher with a sample size of ***,it was proposed to increase the sample size by filling irregular bubbles using a segmentation method,which enabled a further accurate assessment of the mixing *** mixing uniformity of bubble swarms in the circular region and its maximum internal connection with the square region was accurately *** was revealed that the relative average error increased by approximately 3.47% due to information *** proposed method was demonstrated to be rotationally *** present study provided novel insights into evaluating mixing uniformity,which would guide enhanced heat transfer and the effective evaluation of the spatiotemporal characteristics of transient mixing in circular regions or the cross-sections of chemical transport pipelines.

关键词： Direct-contact heat exchanger Circular region Bubble swarm Distribution uniformity AD-Circle method

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Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models

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World journal of gastroenterology 2024年第14期30卷 2038-2058页

作者： Pan Zheng xue-Yang Li xiao-Yu Yang huan Wang Ling Ding Cong He jian-hua Wan hua-jing Ke Nong-hua Lu Nian-Shuang Li Yin Zhu Department of gastroenterology Digestive Disease HospitalThe First Affiliated HospitalJiangxi Medical CollegeNanchang UniversityNanchang 330006Jiangxi ProvinceChina

BACKgROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ *** the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal *** this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP *** To investigate the shared molecular changes underlying the development of AP across varying severity *** AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6j-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce ***,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the gene Expression Omnibus(gEO)*** Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue *** with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS *** Encyclopedia of genes and genomes enrichment analysis and gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome *** significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal *** from the gEO database revealed that only MYD88 concurred in both mouse panc

关键词： Acute pancreatitis RNA-sequencing Experimental acute pancreatitis models Inflammatory Apoptosis TLR and NOD-like signaling pathways

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Enhancing energy storage density of poly(arylene ether nitrile)via incorporating modified barium titanate nanorods and hotstretching

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Nano Research 2024年第8期17卷 7574-7584页

作者： Zhengjiao Zhang Lingyun Zhou Lingling Wang Qingqing Hao xiufu hua Renbo Wei School of Chemical Engineering Northwest UniversityXi’an 710069China Yangtze Delta Region Institute Tsinghua UniversityJiaxing 314006China

Dielectric energy storage materials that are extensively employed in capacitors and other electronic devices have attracted increasing attentions amid the rapid progress of electronic ***,the commercialized polymeric and ceramic dielectric materials characterized by low energy storage density face numerous limitations in practical *** this study,we report the simultaneous enhancement of dielectric properties of poly(arylene ether nitrile)(PEN)through the incorporating of sulfonated PEN(SPEN)modified barium titanate nanorods(BTNR)(SPEN@BTNR)and *** is synthesized using a two-step hydrothermal method,aminated with KH550,and then reacted with SPEN to form the cladding-modified SPEN@*** to the intrinsic high permittivity of barium titanate(BT)and enhanced compatibility between SPEN@BTNR and PEN stemming from the cladding of SPEN,the dielectric constant and breakdown strength of SPEN@BTNR/PEN composite are as high as 14.0 at 103 Hz and 198.1 kV/mm at the doping amount of 15 wt.%,*** a result,the energy storage density of SPEN@BTNR/PEN is increased to 2.43 j/cm^(3),compared with that of 0.82 j/cm^(3)for *** addition,derived from the rearrangement of SPEN@BTNR and orientation of PEN after hot-stretching,the dielectric constant and breakdown strength of SPEN@BTNR/PEN with 15 wt.%fillers are further enhanced to 17.1 and 204.8 kV/mm,respectively,resulting in an energy storage density of 3.36 j/cm^(3).The boosting of energy storage density up to 310%provides a new idea for improving the performances of dielectric energy storage materials.

关键词： barium titanate nanorods poly(arylene ether nitrile) dielectric constant breakdown strength energy density

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Microstructural Evolutions and Mechanical Properties of Energetic Al_(1) (TiZrNbTaMoCr)_(15) High-Entropy Alloys

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Acta Metallurgica Sinica(English Letters) 2024年第4期37卷 620-632页

作者： xuan-Hong Cai Zhen-hua Wang Ben Niu jin-Feng Li Qing Wang Show authors Key Laboratory of Materials Modification By Laser Ion and Electron Beams(Ministry of Education)Engineering Research Center of High Entropy Alloy Materials(Liaoning Province)School of Materials Science and EngineeringDalian University of TechnologyDalian116024China Institute of Materials China Academy of Engineering PhysicsMianyang621908China

The present study focuses on investigating the microstructural evolutions and mechanical properties of energetic Al_(1)(TiZrNbTaMoCr)_(15) refractory high-entropy alloys with the different heat treatments at low Al content state. It is found that even with a reduction in the Al content, the strength of these alloys remains unaffected at room temperature and high temperature, while the plasticity improves significantly. In particular, the coherent BCC/B_(2) microstructure with needle-like B_(2) nanoprecipitates dispersed into the BCC matrix is formed in 873 K-aged Al_(1)Ti_(6)Zr_(2)Nb_(3)Ta_(3)Mo_(0.5)Cr_(0.5) alloy. Therefore, this alloy exhibits the highest compression yield strength (σ_(YS) = 1333 and 717 MPa) at room temperature and 1073 K, respectively. After 973 K-aged, the coherent BCC/B_(2) microstructure underwent destabilization, and the B_(2) phase transforms into the brittle Zr5Al3 phase which then coarsens and dominates the microstructure of S3-AlTa_(3) alloy after 1073 K-aged. Moreover, these current alloys exhibit exceptionally high theoretical exothermic enthalpy (ΔH), surpassing 11606 j·g^(−1), which highlights their significant potential as innovative high-performance energetic structural materials.

关键词： Refractory high-entropy alloy Coherent microstructure Mechanical property Exothermic enthalpy

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