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Neural Regeneration Research 2024年第7期19卷 1433-1434页

作者： Camila M.Freria paul lu Department of Neurosciences University of CaliforniaSan DiegoLa JollaCAUSA Veterans Administration San Diego Healthcare System San DiegoCAUSA

Efforts to promote recovery of function after human spinal cord injury(SCI) will likely require interventions to rgeting the corticospinal tract(CST) motor system:the most important pathway for voluntary motor control in *** system has historically been the most refractory to regenerative efforts after *** "nonregeneration" of the CST changed when robust regeneration of the CST into spared tissue was demonstrated by the inactivation of phosphatase and tensin homolog and delivery of inosine.

关键词： cervical progenitor injury

Bridging the injured spinal cord with neural stem cells

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Neural Regeneration Research 2014年第3期9卷 229-231页

作者： Jennifer N. Dulin paul lu Department of Neurosciences University of California Veterans Administration Medical Center

Spinal cord injury （SCI） damages not only the gray matter neurons, but also the white matter axonal tracts that carry signals to and from the brain, re- suiting in permanent loss of function below injury. Neural stem cells （NSCs） have high therapeutic potential for reconstruction of the injured spinal cord since they can potentially fnrm neuronal relays to bridge functional con-nectivity between separated spinal cord segments. This requires host axonal regeneration into and connectivity with donor neurons, and axonal growth and connectivity of donor neurons to host central nervous system （CNS） circuitry. In this mini-review, we will discuss key studies that explore novel neuronal relay formation by grafting NSCs in models of SCI, with emphasis on long-distance axonal growth and connectivity of NSCs grafted into in-jured spinal cord.

关键词： NSCs cell Bridging the injured spinal cord with neural stem cells stem

Motor neuron replacement therapy for amyotrophic lateral sclerosis

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Neural Regeneration Research 2022年第8期17卷 1633-1639页

作者： Bochao Liu Mo Li Lingyan Zhang Zhiguo Chen paul lu Cell Therapy Center Beijing Institute of GeriatricsXuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric Diseasesand Key Laboratory of Neurodegenerative DiseasesMinistry of EducationBeijingChina Center of Neural Injury and Repair Beijing Institute for Brain DisordersBeijingChina Center of Parkinson’s Disease Beijing Institute for Brain DisordersBeijingChina iXCells Biotechnologies USA Inc.San DiegoCAUSA Amogene Biotech XiamenFujian ProvinceChina Veterans Administration San Diego Healthcare System San DiegoCAUSA Department of Neurosciences University of California-San DiegoLa JollaCAUSA

Amyotrophic lateral sclerosis is a motor neuron degenerative disease that is also known as Lou Gehrig’s disease in the United States,Charcot’s disease in France,and motor neuron disease in the *** loss of motor neurons causes muscle wasting,paralysis,and eventually death,which is commonly related to respiratory failure,within 3-5 years after onset of the *** there are a limited number of drugs approved for amyotrophic lateral sclerosis,they have had little success at treating the associated symptoms,and they cannot reverse the course of motor neuron ***,there is still a lack of effective treatment for this debilitating neurodegenerative *** cell therapy for amyotrophic lateral sclerosis is a very attractive strategy for both basic and clinical researchers,particularly as transplanted stem cells and stem cell-derived neural progenitor/precursor cells can protect endogenous motor neurons and directly replace the lost or dying motor *** cell therapies may also be able to re-establish the motor control of voluntary ***,we review the recent progress in the use of neural stem cells and neural progenitor cells for the treatment of amyotrophic lateral *** focus on MN progenitor cells derived from fetal central nervous system tissue,embryonic stem cells,and induced pluripotent stem *** our recent studies,we found that transplanted human induced pluripotent stem cell-derived motor neuron progenitors survive well,differentiate into motor neurons,and extend axons into the host white matter,not only in the rostrocaudal direction,but also along motor axon tracts towards the ventral roots in the immunodeficient rat spinal ***,the significant motor axonal extension after neural progenitor cell transplantation in amyotrophic lateral sclerosis models demonstrates that motor neuron replacement therapy could be a promising therapeutic strategy for amyotrophic lateral sclerosis,particularly as a variety

关键词： amyotrophic lateral sclerosis motor neuron replacement neural progenitor cells neural stem cells stem cells

Direct reprogramming of somatic cells into neural stem cells or neurons for neurological disorders

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Neural Regeneration Research 2016年第1期11卷 28-31页

作者： Shaoping Hou paul lu Spinal Cord Research Center Department of Neurobiology & Anatomy Drexel University College of Medicine Philadelphia PA USA Veterans Administration Medical Center San Diego CA USA Department of Neurosciences University of California at San Diego La Jolla CA USA

Direct reprogramming of somatic cells into neurons or neural stem cells is one of the most important frontier fields in current neuroscience research. Without undergoing the pluripotency stage, induced neurons or induced neural stem cells are a safer and timelier manner resource in comparison to those derived from induced pluripotent stem cells. In this prospective, we review the recent advances in generation of induced neurons and induced neural stem cells in vitro and in vivo and their potential treatments of neurological disorders.

关键词： neural cells induced neural stem cells induced neurons pluripotent stem cells neurological diseases

CRISPR/Cas9 mediated somatic gene therapy for insertional mutations:the vibrator mouse model

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Precision Clinical Medicine 2021年第3期4卷 168-175页

作者： Xin Fu Jie Zhu Yaou Duan paul lu Kang Zhang Spine Center Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Guangzhou Women and Children’s Medical Center Guangzhou Medical UniversityGuangzhou 510623China Department of Nanoengineering Chemical Engineering Programand Moores Cancer CenterUniversity of California at San DiegoLa JollaCA 92093USA VA-San Diego Healthcare System San DiegoCA 92161USA Department of Neurosciences University of California at San DiegoLa JollaCA 92093USA Center for Biomedicine and Innovations Faculty of MedicineMacao University of Science and TechnologyMacaoChina

Somatic gene therapy remains technically challenging,especially in the central nervous system(CNS).Efficiency of gene delivery,efficacy in recipient cells,and proportion of cells required for overall benefit are the key points needed to be considered in any therapeutic *** efforts have demonstrated the efficacy of RNA-guided nucleases such as CRISPR/Cas9 in correcting point mutations or removing dominant *** we used viral delivered Cas9 plasmid and two guide RNAs to remove a recessive insertional mutation,vibrator(vb),in the mouse *** vb mice expressed∼20%of normal levels of phosphatidylinositol transfer protein,α(PITPα)RNA and protein due to an endogenous retrovirus inserted in intron 4,resulting in early-onset tremor,degeneration of brainstem and spinal cord neurons,and juvenile *** in situ CRISPR/Cas9 viral treatment effectively delayed neurodegeneration,attenuated tremor,and bypassed juvenile *** studies demonstrate the potential of CRISPR/Cas9-mediated gene therapy for insertional mutations in the postnatal brain.

关键词： somatic gene editing neurodegenerative disease vibrator mouse model CRISPR/Cas9 Pitpna

Induced pluripotent stem cell-derived neural stem cell therapies for spinal cord injury

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Neural Regeneration Research 2015年第1期10卷 10-16页

作者： Corinne A.Lee-Kubli paul lu Department of Neurosciences University of California Veterans Administration Medical Center

The greatest challenge to successful treatment of spinal cord injury is the limited regenerative capacity of the central nervous system and its inability to replace lost neurons and severed axons following injury. Neural stem cell grafts derived from fetal central nervous system tissue or embryonic stem cells have shown therapeutic promise by differentiation into neurons and glia that have the potential to form functional neuronal relays across injured spinal cord segments. However, implementation of fetal-derived or embryonic stem cell-derived neural stem cell ther- apies for patients with spinal cord injury raises ethical concerns. Induced pluripotent stem cells can be generated from adult somatic cells and differentiated into neural stem cells suitable for therapeutic use, thereby providing an ethical source of implantable cells that can be made in an autologous fashion to avoid problems of immune rejection. This review discusses the therapeutic potential of human induced pluripotent stem cell-derived neural stem cell transplantation for treatment of spinal cord injury, as well as addressing potential mechanisms, future perspectives and challenges.

关键词： transplantation axonal growth axonal regeneration neuroprotection remyelination differentiation neuronal relay human astrocytes neurons oligodendrocytes secondary degeneration

pH-Responsive Theranostic Colloidosome Drug Carriers Enable Real-Time Imaging of Targeted Thrombolytic Process with Near-Infrared-II for Deep Venous Thrombosis

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Research 2024年第3期2024卷 17-33页

作者： Yaxin Ye Zhechang Chen Shengzhang Zhang paul Slezak Fei lu Ruiqi Xie Dongwon Lee Guangqian Lan Enling Hu State Key Laboratory of Resource Insects College of SericultureTextile and Biomass SciencesSouthwest UniversityChongqing 400715China Department of Cardiovascular Medicine Yueqing People's Hospital.Wenzhou 325699China ludwig Boltzmann Institute for Traumatology AUVA Research Center1200 ViennaAustria Department of Bionanotechnology and Bioconvergence Engineering and Department of Polymer-Nano Science and Technology Jeonbuk National UniversityJeonjuChonbuk 54896Republic of Korea School of Fashion and Textiles The Hong Kong Polytechnic UniversityHong KongChina

Thrombosis can cause life-threatening disorders. Unfortunately, current therapeutic methods for thrombosis using injecting thrombolytic medicines systemically resulted in unexpected bleeding complications. Moreover, the absence of practical imaging tools for thrombi raised dangers of undertreatment and overtreatment. This study develops a theranostic drug carrier, Pkr(IR-Ca/Pda-uPA)-cRGD, that enables real-time monitoring of the targeted thrombolytic process of deep vein thrombosis (DVT). Pkr(IR-Ca/Pda-uPA)-cRGD, which is prepared from a Pickering-emulsion-like system, encapsulates both near-infrared-II (NIR-II) contrast agent (IR-1048 dye, loading capacity: 28%) and urokinase plasminogen activators (uPAs, encapsulation efficiency: 89%), pioneering the loading of multiple drugs with contrasting hydrophilicity into one single-drug carrier. Upon intravenous injection, Pkr(IR-Ca/Pda-uPA)-cRGD considerably targets to thrombi selectively (targeting rate: 91%) and disintegrates in response to acidic thrombi to release IR-1048 dye and uPA for imaging and thrombolysis, respectively. Investigations indicate that Pkr(IR-Ca/Pda-uPA)-cRGD enabled real-time visualization of targeted thrombolysis using NIR-II imaging in DVT models, in which thrombi were eliminated (120 min after drug injection) without bleeding complications. This may be the first study using convenient NIR-II imaging for real-time visualization of targeted thrombolysis. It represents the precision medicine that enables rapid response to acquire instantaneous medical images and make necessary real-time adjustments to diagnostic and therapeutic protocols during treatment.

关键词： Infrared enable eliminated

A new Late Miocene Hystrix(Hystricidae,Rodentia)from Turkey

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Integrative Zoology 2024年第3期19卷 548-563页

作者： Kazım HALAÇLAR Ayla SEVIM EROL Tolga KÖROG˘lu paul RUMMY Tao DENG Serdar MAYDA Natural History Application and Research Centre Ege UniversityTurkey Key Laboratory of Vertebrate Evolution and Human Origins Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijingPeople’s Republic of China Department of Anthropology Faculty of Languages and HistoryGeographyAnkara UniversityTurkey Department of Biology Faculty of SciencesEge UniversityTurkey

TheÇorakyerler fossil locality in Anatolia reveals unique faunal *** study introduces Hystrix kayae ***.,a new Late Miocene porcupine initially classified as Hystrix *** et al.,*** finding expands our knowledge of Late Miocene Anatolian porcupines,bringing the total number of known species to *** *** larger than Hystrix aryanensis and exhibits greater upper cheek tooth crown *** cheek tooth morphology differs from Hystrix depereti,and it possesses distinctive U-shaped choanae unlike Hystrix ***Çorakyerler locality may predate sites with *** and *** but aligns temporally with Hystrix parvae *** study enhances our understanding of Late Miocene porcupine diversity in Anatolia,emphasizing the importance ofÇorakyerler in unraveling the evolutionary history of these fascinating mammals.

关键词： Çorakyerler Hystrix Late Miocene paleobiogeography Turkey

AI for science: Predicting infectious diseases

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Journal of Safety Science and Resilience 2024年第2期5卷 130-146页

作者： Alexis Pengfei Zhao Shuangqi Li Zhidong Cao paul Jen-Hwa Hu Jiaojiao Wang Yue Xiang Da Xie Xi lu Institute of Automation Chinese Academy of SciencesUniversity of Chinese Academy of SciencesBejing 100090China Systems Engineering Cornll UniversityIthacaNY 14853USA David Eccles School of Business the University of UtahUtahUSA Collge of Electrical Engineering Sichuan UniversityChina Department of Electrical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Electrical Engineering Southeast UniversityNanjing 210096China

The global health landscape has been persistently challenged by the emergence and re-emergence of infectious *** epidemiological models,rooted in the early 2oth century,have provided foundational in-sights into disease ***,the intricate web of modern global interactions and the exponential growth of available data demand more advanced predictive *** is where AI for Science(AI4S)comes into play,offering a transformative approach by integrating artificial intelligence(Al)into infectious disease *** paper elucidates the pivotal role of AI4s in enhancing and,in some instances,superseding tradi-tional epidemiological *** harnessing AI's capabilities,AI4S facilitates real-time monitoring,sophisticated data integration,and predictive modeling with enhanced *** comparative analysis highlights the stark contrast between conventional models and the innovative strategies enabled by *** essence,Al4S represents a paradigm shift in infectious disease *** addresses the limitations of traditional models and paves the way for a more proactive and informed response to future *** we navigate the complexities of global health challenges,Al4S stands as a beacon,signifying the next phase of evolution in disease prediction,characterized by increased accuracy,adaptability,and efficiency.

关键词： AI for science(AI4S) Data integration Global healthchallenges Infectious disease prediction Predictive modeling Real-timemonitoring

A simple and efficient CRISPR/Cas9 system permits ultra-multiplex genome editing in plants

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The Crop Journal 2024年第2期12卷 569-582页

作者： Suting Wu Htin Kyaw Zhijun Tong Yirong Yang Zhiwei Wang Liying Zhang Lihua Deng Zhiguo Zhang Bingguang Xiao William paul Quick Tiegang lu Guoying Xiao Guannan Qin Xue'an Cui Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China Key Laboratory of Genetics Breeding and Multiple Utilization of CropsMinistry of EducationCollege of AgricultureFujian Agriculture and Forestry UniversityFuzhou 350002FujianChina Key Laboratory of Biological Breeding for Fujian and Taiwan Crops Ministry of Agriculture and Rural AffairsCollege of AgricultureFujian Agriculture and Forestry UniversityFuzhou 350002FujianChina Key Laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125HunanChina School of Biosciences The University of SheffieldFirth CourtWestern BankSheffield S102TNUK Key Laboratory of Tobacco Biotechnological Breeding National Tobacco Genetic Engineering Research CenterYunnan Academy of Tobacco Agricultural SciencesKunming 650021YunnanChina

The development and maturation of the CRISPR/Cas genome editing system provides a valuable tool for plant functional genomics and genetic *** available genome-editing tools have a limited number of targets,restricting their application in genetic *** this study,we developed a novel CRISPR/Cas9 plant ultra-multiplex genome editing system consisting of two template vectors,eight donor vectors,four destination vectors,and one primer-design software *** combining the advantages of Golden Gate cloning to assemble multiple repetitive fragments and Gateway recombination to assemble large fragments and by changing the structure of the amplicons used to assemble sg RNA expression cassettes,the plant ultra-multiplex genome editing system can assemble a single binary vector targeting more than 40 genomic loci.A rice knockout vector containing 49 sg RNA expression cassettes was assembled and a high co-editing efficiency was *** plant ultra-multiplex genome editing system advances synthetic biology and plant genetic engineering.

关键词： CRISPR/Cas9 Multiplex genome editing Assembly system Plant