Rainfall is a common trigger for landslide reactivation,as it raises groundwater levels and reduces bedrock or soil shear resistance.This study focuses on the Kualiangzi landslide in the southern region of Sichuan Pro...Rainfall is a common trigger for landslide reactivation,as it raises groundwater levels and reduces bedrock or soil shear resistance.This study focuses on the Kualiangzi landslide in the southern region of Sichuan Province,China.Real-time monitoring of groundwater levels and rainfall from July 2013 to September 2016 is analyzed.Groundwater table increments,considering groundwater drainage rate,were calculated using the water-table fluctuation and master recession curve method and the response time of the groundwater table to rainfall events was estimated using the cross-correlation function.Results reveal that groundwater level declines from tension troughs to landslide fronts in the rainy season,with a significant positive correlation between the groundwater level in the tension trough and landslide surface displacement.Evaluated spring elevations for groundwater discharge range from 410 m to 440 m,which is in agreement with the actual spring elevations(390-423 m).Lag times of groundwater response to rainfall decreases with cumulative rainfall of the rainy periods.In the middle part of the landslide,two responses between rainfall and groundwater levels indicate two water movement pathways:Vertical cracks or fractures resulting from the slow landslide movement,and matrix pore space in unconsolidated sediment.Variations in peak values of the cross-correlation function suggest early dominance of the uniform matrix flow and later dominance of preferential flow during the rainy period.展开更多
Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,de...Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,debilitating motor and sensory deficits.There are currently no therapeutic strategies proven to enhance the regenerative process in humans.A clinical need exists for the development of technologies to promote nerve regeneration and improve functional outcomes.Recent advances in the fields of tissue engineering and nanotechnology have enabled biomaterial scaffolds to modulate the host response to tissue repair through tailored mechanical,chemical,and conductive cues.New bioengineered approaches have enabled targeted,sustained delivery of protein therapeutics with the capacity to unlock the clinical potential of a myriad of neurotrophic growth factors that have demonstrated promise in enhancing regenerative outcomes.As such,further exploration of combinatory strategies leveraging these technological advances may offer a pathway towards clinically translatable solutions to advance the care of patients with peripheral nerve injuries.This review first presents the various emerging bioengineering strategies that can be applied for the management of nerve gap injuries.We cover the rationale and limitations for their use as an alternative to autografts,focusing on the approaches to increase the number of regenerating axons crossing the repair site,and facilitating their growth towards the distal stump.We also discuss the emerging growth factor-based therapeutic strategies designed to improve functional outcomes in a multimodal fashion,by accelerating axonal growth,improving the distal regenerative environment,and preventing end-organs atrophy.展开更多
Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information,with its application to neuroscience termed neuroinformatics.Da...Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information,with its application to neuroscience termed neuroinformatics.Data mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms,which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative diseases.Importantly,integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain profile.In this review,we first summarize data mining studies utilizing datasets from the individual type of omics analysis,including epigenetics/epigenomics,transcriptomics,proteomics,metabolomics,lipidomics,and spatial omics,pertaining to Alzheimer's disease,Parkinson's disease,and multiple sclerosis.We then discuss multi-omics integration approaches,including independent biological integration and unsupervised integration methods,for more intuitive and informative interpretation of the biological data obtained across different omics layers.We further assess studies that integrate multi-omics in data mining which provide convoluted biological insights and offer proof-of-concept proposition towards systems bioinformatics in the reconstruction of brain networks.Finally,we recommend a combination of high dimensional bioinformatics analysis with experimental validation to achieve translational neuroscience applications including biomarker discovery,therapeutic development,and elucidation of disease mechanisms.We conclude by providing future perspectives and opportunities in applying integrative multi-omics and systems bioinformatics to achieve precision phenotyping of neurodegenerative diseases and towards personalized medicine.展开更多
Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment c...Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment can achieve partial or complete remission of the unresectable tumors to meet the criteria for R0 resection,thus enabling the patients to prolong their survival time and improve their quality of life.In gastric cancer,translational therapy has been tried and improved.At present,there are a large number of patients with locally advanced gastric cancer in China,and the selection of suitable patients for transla-tional therapy to prolong objective survival and improve survival quality is one of the hot spots in the field of gastric cancer research.展开更多
In order to solve the problem of weak stifness of the existing fully decoupled parallel mechanism, a new synthesis method of fully decoupled three translational (3T) parallel mechanisms (PMs) with closed-loop units an...In order to solve the problem of weak stifness of the existing fully decoupled parallel mechanism, a new synthesis method of fully decoupled three translational (3T) parallel mechanisms (PMs) with closed-loop units and high stifness is proposed based on screw theory. Firstly, a new criterion for the full decoupled of PMs is presented that the reciprocal product of the transmission wrench screw matrix and the output twist screw matrix of PMs is a diagonal matrix, and all elements on the main diagonal are nonzero constants. The forms of the transmission wrench screws are determined by the criterion. Secondly, the forms of the actuated and unactuated screws can be obtained according to their relationships with the transmission wrench screws. The basic decoupled limbs are generated by combination of the above actuated and unactuated screws. Finally, a closed-loop units construction method is investigated to apply the decoupled mechanisms in a better way on the high stifness occasion. The closed-loop units are constructed in the basic decoupled limbs to generate a high-stifness fully decoupled 3T PM. Kinematic and stifness analyses show that the Jacobian matrix is a diagonal matrix, and the stifness is obviously higher than that of the coupling mechanisms, which verifes the correctness of the proposed synthesis method. The mechanism synthesized by this method has a good application prospect in vehicle durability test platform.展开更多
The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantati...The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantation is essentially necessary.The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world.Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise,with a main focus on the field of translational research and innovation.The papers that are part of this Special Issue“Translational Research and Innovation and the current status of Transplantation in Greece”have presented innovative and meaningful approaches in modern transplant research and practice.They provide us with a clear overview of the current landscape in transplantation,including liver transplantation in the context of a major pandemic,the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation,while at the same time explore more recent challenges,such as the issue of frailty in the transplant candidate and the changes brought by newer treatments,such as immunotherapy,in transplant oncology.Additionally,they offer us a glimpse of the effect that technological innovations,such as virtual reality,can have on transplantation,both in terms of clinical and educational aspects.Just as critical is the fact that this Special Issue emphasizes the multidisciplinary,collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering,advanced information technology and artificial intelligence.In this Special Issue,in addition to the clinical and research evolution of the field of transplantation,we are witnessing the importance of interdisciplinary collaboration in medicine.展开更多
Purpose: Despite many scientific advances, Regenerative Medicine is still in the preclinical stages in many areas. In this article, we intend to discuss the role of microsurgery in the bench-to-bedside transition of s...Purpose: Despite many scientific advances, Regenerative Medicine is still in the preclinical stages in many areas. In this article, we intend to discuss the role of microsurgery in the bench-to-bedside transition of such primary findings. Method: By searching the papers related to the history of Regenerative Medicine (RM) and the news of Tissue Engineering (TE) in orthopedics in Pubmed, Scopus, and Google Scholar databases, we accessed a complete archive of various topics related to this field. Result: We first assessed the history and achievements of regenerative medicine, then we realized the importance of translational medical sciences and the role of animal models in this incipient phenomenon. Finally, after mastering the capabilities of microsurgery and the useful contribution of this technique to the advancement of clinical applications of regenerative medicine in various branches such as skin, skeletal system, nerves, and blood vessels, we decided to express the gist of our studies through this article. Conclusion: Considering the widespread use of small animals in regenerative medicine projects and the inevitable role of microsurgery in performing the best intervention on these animal models, the significant progress of regenerative medicine clinical application requires special attention to microsurgery in associated research.展开更多
As the emergence of conversion to aspect of culture in the study of translation, the subjectivity of translator is widely discussed. Translator is inevitably influenced by his/her own language and system of culture in...As the emergence of conversion to aspect of culture in the study of translation, the subjectivity of translator is widely discussed. Translator is inevitably influenced by his/her own language and system of culture in the process of translation. In order to make readers understand what is translated, a translator needs to bring subjectivity into play to make translated text conform to custom of his/her own language and system of culture. The study of subjectivity is mainly concentrated on understanding of original text and recreating of art on the level of linguistics. This paper studies the problem of subjectivity in the process of translation from translational norms, subjectivity, aim and creativity.展开更多
目的作为一本新创的英文期刊,Journal of Translational Neuroscience杂志需要尽快提升其学术水平,扩大其社会影响力,以期能迅速在国际专业学术期刊界占有一席之地,通过约稿获得高质量的学术论文就显得至关重要。方法笔者从找准期刊学...目的作为一本新创的英文期刊,Journal of Translational Neuroscience杂志需要尽快提升其学术水平,扩大其社会影响力,以期能迅速在国际专业学术期刊界占有一席之地,通过约稿获得高质量的学术论文就显得至关重要。方法笔者从找准期刊学术定位、采取灵活多样的约稿方式、分析解决约稿过程中可能存在的问题以及如何做好约稿后续服务工作等几个方面入手,初浅分析探讨了关于期刊约稿的方式方法。结果通过期刊定位准确锁定目标作者群,依托自身优势资源,参与学术会议,通过编委约稿以及提供优质的后续服务等方法获得稳定的高质量作者群,从而获得持续的优秀稿源。结论拥有持续的高质量稿件是促使期刊进入良性循环的重要保障,通过约稿可以解决新创办的期刊无稿可用和缺少优秀稿件的难题,推动期刊走出困境,渐入正轨。展开更多
Spinal cord injury(SCI) leads to loss of motor and sensory function below the injury level and imposes a considerable burden on patients, families, and society. Repair of the injured spinal cord has been recognized as...Spinal cord injury(SCI) leads to loss of motor and sensory function below the injury level and imposes a considerable burden on patients, families, and society. Repair of the injured spinal cord has been recognized as a global medical challenge for many years.Significant progress has been made in research on the pathological mechanism of spinal cord injury. In particular, with the development of gene regulation, cell sequencing, and cell tracing technologies, in-depth explorations of the SCI microenvironment have become more feasible. However, translational studies related to repair of the injured spinal cord have not yielded significant results. This review summarizes the latest research progress on two aspects of SCI pathology: intraneuronal microenvironment imbalance and regenerative microenvironment imbalance. We also review repair strategies for the injured spinal cord based on microenvironment imbalance, including medications, cell transplantation, exosomes, tissue engineering, cell reprogramming, and rehabilitation. The current state of translational research on SCI and future directions are also discussed. The development of a combined, precise, and multitemporal strategy for repairing the injured spinal cord is a potential future direction.展开更多
Performance analysis and kinematic design of the 3-PUU pure translational parallel mechanism with vertical guide-ways are investigated. Two novel performance indices, the critical slider stroke and the main section ar...Performance analysis and kinematic design of the 3-PUU pure translational parallel mechanism with vertical guide-ways are investigated. Two novel performance indices, the critical slider stroke and the main section area of workspace, are defined; The expressions of two other indices, i.e. the global dexterity and global force transfer ratio are revised based on the main section of workspace. Using these indices, performance changes versus the varieties of dimensional parameters of mechanism are investigated in detail and the graphic descriptions of change tendencies of the performance indices are illustrated. By means of these obtained graphic descriptions, kinematic parameters for the 3-PUU pure translational parallel mechanism with better characteristics can be directly acquired.展开更多
Light plays a critical role in plant growth and development,but the mechanisms through which light regulates fruit ripening and nutritional quality in horticultural crops remain largely unknown.Here,we found that ELON...Light plays a critical role in plant growth and development,but the mechanisms through which light regulates fruit ripening and nutritional quality in horticultural crops remain largely unknown.Here,we found that ELONGATED HYPOCOTYL 5(HY5),a master regulator in the light signaling pathway,is required for normal fruit ripening in tomato(Solanum lycopersicum).Loss of function of tomato HY5(SlHY5)impairs pigment accumulation and ethylene biosynthesis.Transcriptome profiling identified 2948 differentially expressed genes,which included 1424 downregulated and 1524 upregulated genes,in the Slhy5 mutants.In addition,genes involved in carotenoid and anthocyanin biosynthesis and ethylene signaling were revealed as direct targets of SlHY5 by chromatin immunoprecipitation.Surprisingly,the expression of a large proportion of genes encoding ribosomal proteins was downregulated in the Slhy5 mutants,and this downregulation pattern was accompanied by a decrease in the abundance of ribosomal proteins.Further analysis demonstrated that SlHY5 affected the translation efficiency of numerous ripening-related genes.These data indicate that SlHY5 regulates fruit ripening both at the transcriptional level by targeting specific molecular pathways and at the translational level by affecting the protein translation machinery.Our findings unravel the regulatory mechanisms of SlHY5 in controlling fruit ripening and nutritional quality and uncover the multifaceted regulation of gene expression by transcription factors.展开更多
Cinnamon, is an exotic spice and a major constituent of our food which is commonly used in different areas of the world for the treatment of various diseases (Kawatra et al., 2015). Besides 让s anti-inflammatory, anti...Cinnamon, is an exotic spice and a major constituent of our food which is commonly used in different areas of the world for the treatment of various diseases (Kawatra et al., 2015). Besides 让s anti-inflammatory, anti-diabetic and anti-cancer properties, cinnamon also exerts strong brain protective and pro-cogrdtive effects in various models of neurodegeneration (Kawatra et al., 2015;Kelestemur et al., 2016)(Figure 1).展开更多
Coupling is the significant characteristic of parallel mechanism,while it is just the coupling that brings about much difficulty for the configuration design,theoretical analysis and the development of the control sys...Coupling is the significant characteristic of parallel mechanism,while it is just the coupling that brings about much difficulty for the configuration design,theoretical analysis and the development of the control system of the parallel mechanism. And recently,the research on the decoupled parallel mechanism becomes one of the research hot points in the mechanism fields. In this paper,a type synthesis method for the translational decoupled parallel mechanism( TDPM) is proposed based on the screw theory. To achieve the decoupling characteristics of the translational parallel mechanism,the translational decoupled criterion for type synthesis of the branches are presented in this paper. According to this criterion and the realization conditions of rotational degree of freedom of the mechanism proposed former,a large number of branches for the TDPM are obtained. Taking the three degrees of freedom( DOFs) TDPM as an example,the process of type synthesis is discussed in detail. Using this proposed type synthesis method,a serial of translational decoupled parallel mechanisms, including but not limited to all the existing typical 3-DOF TDPMs, are obtained, which identifies the correctness and effective of the method. The contents of this paper provide a reference and possess significant theoretical meanings for the synthesis and development of the novel decoupled parallel mechanisms.展开更多
Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e....Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e.g.,the serotonin re-uptake inhibitors(SSRI),and are considered affected by Treatment-Resistant Depression(TRD).The neurobiology of this condition is presently unknown.Recent attempts of developing novel treatments for TRD have been driven by four major breakthroughs:(1)Increasing dopaminergic neurotransmission improves TRD symptoms;(2)Anhedonia occurs when central dopaminergic neurotransmission is low;(3)Enhanced neuroplasticity is critical for the action of antidepressants;(4)Ketamine shows antidepressant properties in TRD patients and triggers neuroplasticity in preclinical animal models.These breakthroughs are at the basis of a putative human translational cellular model for antidepressant agents that we are proposing in this article.The rationale is briefly described here.展开更多
Three-degree of freedom(3-DOF) translational parallel manipulators(TPMs) have been widely studied both in industry and academia in the past decades. However, most architectures of 3-DOF TPMs are created mainly on ...Three-degree of freedom(3-DOF) translational parallel manipulators(TPMs) have been widely studied both in industry and academia in the past decades. However, most architectures of 3-DOF TPMs are created mainly on designers' intuition, empirical knowledge, or associative reasoning and the topology synthesis researches of 3-DOF TPMs are still limited. In order to find out the atlas of designs for 3-DOF TPMs, a topology search is presented for enumeration of 3-DOF TPMs whose limbs can be modeled as 5-DOF serial chains. The proposed topology search of 3-DOF TPMs is aimed to overcome the sensitivities of the design solution of a 3-DOF TPM for a LARM leg mechanism in a biped robot. The topology search, which is based on the concept of generation and specialization in graph theory, is reported as a step-by-step procedure with desired specifications, principle and rules of generalization, design requirements and constraints, and algorithm of number synthesis. In order to obtain new feasible designs for a chosen example and to limit the search domain under general considerations, one topological generalized kinematic chain is chosen to be specialized. An atlas of new feasible designs is obtained and analyzed for a specific solution as leg mechanisms. The proposed methodology provides a topology search for 3-DOF TPMs for leg mechanisms, but it can be also expanded for other applications and tasks.展开更多
Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model...Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model with supports of genomic data is still lacking. Recent technological advances have enabled much needed genome-wide experiments. While putting the effect of codon optimality on debate, these studies have supplied mounting evidence suggesting a role of m RNA structure in the regulation of protein folding by modulating translational elongation rate. In conjunctions with previous theories, this mechanistic model of protein folding guided by m RNA structure shall expand our understandings of genetic information and offer new insights into various biomedical puzzles.展开更多
The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbe...The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3'UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3'UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3'UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3'UTR binding factors and approaches to improve them.展开更多
The structural evolution fromβ_(1)(Mg_(3)Ce)toβ(Mg_(12)Ce)precipitates,which takes place at the over-aged stage of binary Mg-Ce alloys,are investigated by high-angle annular dark-field scanning transmission electron...The structural evolution fromβ_(1)(Mg_(3)Ce)toβ(Mg_(12)Ce)precipitates,which takes place at the over-aged stage of binary Mg-Ce alloys,are investigated by high-angle annular dark-field scanning transmission electron microscopy.The structural transformation mainly occurs in the{111}_(β1)crystallographic planes,where the newly formedβlattices exhibit two categories of domain structures,namely rotational and translational domains.The rotational domain is composed of threeβdomains(β_(RA),β_(RB)andβ_(RC)),which are related by a 120°rotation with respect to each other around the 111_(β1)axis of theirβ_(1)parent phase.The{111}_(β1)crystallographic planes can provide four sets of sublattices with the same orientation for an initial nucleation ofβlattice.It leads to the formation of four translationalβdomains(β_(TA),β_(TB),β_(TC)andβ_(TD)),among which any two differ by a vector of 1/6112_(β1).We deduce theoretically that there exist twenty-fourβdomains during this transition.However,considering the interfacial misfit,only one-third of domains can grow up and eventually formsβribbon.Furthermore,a majority ofβribbons overlap partiallyβ_(1)plate,which is beneficial to relax interfacial strain amongβ,β_(1)andα-Mg matrix(α/β/β_(1)).The configuration of multipleβdomains can effectively regulate interfacial misfit ofα/βandβ/β_(1),which are responsible for enhancing the hardness and strength of Mg-Ce alloy.Additionally,this study aims to provide some clues to improve the over-aged performance of magnesium alloys by constructingβdomains and optimizing theα/β/β_(1)interface.展开更多
The past decade has witnessed an outstanding scientific production focused towards the possible clinical applications of mesenchymal stromal cells(MSCs) in autoimmune and chronic inflammatory diseases. This raised the...The past decade has witnessed an outstanding scientific production focused towards the possible clinical applications of mesenchymal stromal cells(MSCs) in autoimmune and chronic inflammatory diseases. This raised the need of novel standards to adequately address quality, efficacy and safety issues of this advanced therapy. The development of a streamlined regulation is currently hampered by the complexity of analyzing dynamic biological entities rather than chemicals. Although numerous pieces of evidence show efficacy in reducing intestinal inflammation, some inconsistencies between the mechanisms of action of rodent vs human MSCs suggest caution before assigning translational value to preclinical studies. Preliminary evidence from clinical trials showed efficacy of MSCs in the treatment of fistulizing Crohn's disease(CD), and preparations of heterologous MSCs for CD treatment are currently tested in ongoing clinical trials. However, safety issues, especially in longterm treatment, still require solid clinical data. In this regard, standardized guidelines for appropriate dosing and methods of infusion could enhance the likelihood to predict more accurately the number of responders and the duration of remission periods. In addition, elucidating MSC mechanisms of action could lead to novel and more reliable formulations such as those derived from the MSCs themselves(e.g., supernatants).展开更多
基金This research is part of the"Survey and warning zonation of huge geological hazards in Southwestern China"project(No.12120113010100)which is supported by the China Geological Survey,and the"Application of electrical resistivity tomography to evaluate the temporal and spatial variation in matric suction of landslide"project(No.41402268)+1 种基金which is supported by the National Natural Science Foundation of Chinathe State Key Laboratory of Geohazard Prevention and Geoenvironment Protection(Chengdu University of Technology)(No.2007DA810083)。
文摘Rainfall is a common trigger for landslide reactivation,as it raises groundwater levels and reduces bedrock or soil shear resistance.This study focuses on the Kualiangzi landslide in the southern region of Sichuan Province,China.Real-time monitoring of groundwater levels and rainfall from July 2013 to September 2016 is analyzed.Groundwater table increments,considering groundwater drainage rate,were calculated using the water-table fluctuation and master recession curve method and the response time of the groundwater table to rainfall events was estimated using the cross-correlation function.Results reveal that groundwater level declines from tension troughs to landslide fronts in the rainy season,with a significant positive correlation between the groundwater level in the tension trough and landslide surface displacement.Evaluated spring elevations for groundwater discharge range from 410 m to 440 m,which is in agreement with the actual spring elevations(390-423 m).Lag times of groundwater response to rainfall decreases with cumulative rainfall of the rainy periods.In the middle part of the landslide,two responses between rainfall and groundwater levels indicate two water movement pathways:Vertical cracks or fractures resulting from the slow landslide movement,and matrix pore space in unconsolidated sediment.Variations in peak values of the cross-correlation function suggest early dominance of the uniform matrix flow and later dominance of preferential flow during the rainy period.
基金supported by The Plastic Surgery Foundation Research Pilot Grant,No.627383(to KAS).
文摘Peripheral nerve injuries remain a challenging problem in need of better treatment strategies.Despite best efforts at surgical reconstruction and postoperative rehabilitation,patients are often left with persistent,debilitating motor and sensory deficits.There are currently no therapeutic strategies proven to enhance the regenerative process in humans.A clinical need exists for the development of technologies to promote nerve regeneration and improve functional outcomes.Recent advances in the fields of tissue engineering and nanotechnology have enabled biomaterial scaffolds to modulate the host response to tissue repair through tailored mechanical,chemical,and conductive cues.New bioengineered approaches have enabled targeted,sustained delivery of protein therapeutics with the capacity to unlock the clinical potential of a myriad of neurotrophic growth factors that have demonstrated promise in enhancing regenerative outcomes.As such,further exploration of combinatory strategies leveraging these technological advances may offer a pathway towards clinically translatable solutions to advance the care of patients with peripheral nerve injuries.This review first presents the various emerging bioengineering strategies that can be applied for the management of nerve gap injuries.We cover the rationale and limitations for their use as an alternative to autografts,focusing on the approaches to increase the number of regenerating axons crossing the repair site,and facilitating their growth towards the distal stump.We also discuss the emerging growth factor-based therapeutic strategies designed to improve functional outcomes in a multimodal fashion,by accelerating axonal growth,improving the distal regenerative environment,and preventing end-organs atrophy.
基金supported by a Lee Kong Chian School of Medicine Dean’s Postdoctoral Fellowship(021207-00001)from Nanyang Technological University(NTU)Singapore and a Mistletoe Research Fellowship(022522-00001)from the Momental Foundation USA.Jialiu Zeng is supported by a Presidential Postdoctoral Fellowship(021229-00001)from NTU Singapore and an Open Fund Young Investigator Research Grant(OF-YIRG)(MOH-001147)from the National Medical Research Council(NMRC)SingaporeSu Bin Lim is supported by the National Research Foundation(NRF)of Korea(Grant Nos.:2020R1A6A1A03043539,2020M3A9D8037604,2022R1C1C1004756)a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(Grant No.:HR22C1734).
文摘Bioinformatic analysis of large and complex omics datasets has become increasingly useful in modern day biology by providing a great depth of information,with its application to neuroscience termed neuroinformatics.Data mining of omics datasets has enabled the generation of new hypotheses based on differentially regulated biological molecules associated with disease mechanisms,which can be tested experimentally for improved diagnostic and therapeutic targeting of neurodegenerative diseases.Importantly,integrating multi-omics data using a systems bioinformatics approach will advance the understanding of the layered and interactive network of biological regulation that exchanges systemic knowledge to facilitate the development of a comprehensive human brain profile.In this review,we first summarize data mining studies utilizing datasets from the individual type of omics analysis,including epigenetics/epigenomics,transcriptomics,proteomics,metabolomics,lipidomics,and spatial omics,pertaining to Alzheimer's disease,Parkinson's disease,and multiple sclerosis.We then discuss multi-omics integration approaches,including independent biological integration and unsupervised integration methods,for more intuitive and informative interpretation of the biological data obtained across different omics layers.We further assess studies that integrate multi-omics in data mining which provide convoluted biological insights and offer proof-of-concept proposition towards systems bioinformatics in the reconstruction of brain networks.Finally,we recommend a combination of high dimensional bioinformatics analysis with experimental validation to achieve translational neuroscience applications including biomarker discovery,therapeutic development,and elucidation of disease mechanisms.We conclude by providing future perspectives and opportunities in applying integrative multi-omics and systems bioinformatics to achieve precision phenotyping of neurodegenerative diseases and towards personalized medicine.
文摘Translational therapy refers to a combination of chemotherapy,radiotherapy,targeted therapy,and immunotherapy for patients with advanced gastric cancer who are initially unable to undergo R0 resection.This treatment can achieve partial or complete remission of the unresectable tumors to meet the criteria for R0 resection,thus enabling the patients to prolong their survival time and improve their quality of life.In gastric cancer,translational therapy has been tried and improved.At present,there are a large number of patients with locally advanced gastric cancer in China,and the selection of suitable patients for transla-tional therapy to prolong objective survival and improve survival quality is one of the hot spots in the field of gastric cancer research.
基金Supported by National Natural Science Foundation of China(Grant No.52275032)Key Project of Hebei Provincial Natural Science Foundation of China(Grant No.E2022203077)Hebei Provincial Key Research and Development Plan of China(Grant No.202230808010057).
文摘In order to solve the problem of weak stifness of the existing fully decoupled parallel mechanism, a new synthesis method of fully decoupled three translational (3T) parallel mechanisms (PMs) with closed-loop units and high stifness is proposed based on screw theory. Firstly, a new criterion for the full decoupled of PMs is presented that the reciprocal product of the transmission wrench screw matrix and the output twist screw matrix of PMs is a diagonal matrix, and all elements on the main diagonal are nonzero constants. The forms of the transmission wrench screws are determined by the criterion. Secondly, the forms of the actuated and unactuated screws can be obtained according to their relationships with the transmission wrench screws. The basic decoupled limbs are generated by combination of the above actuated and unactuated screws. Finally, a closed-loop units construction method is investigated to apply the decoupled mechanisms in a better way on the high stifness occasion. The closed-loop units are constructed in the basic decoupled limbs to generate a high-stifness fully decoupled 3T PM. Kinematic and stifness analyses show that the Jacobian matrix is a diagonal matrix, and the stifness is obviously higher than that of the coupling mechanisms, which verifes the correctness of the proposed synthesis method. The mechanism synthesized by this method has a good application prospect in vehicle durability test platform.
文摘The continuous clinical and technological advances,together with the social,health and economic challenges that the global population faces,have created an environment where the evolution of the field of transplantation is essentially necessary.The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world.Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise,with a main focus on the field of translational research and innovation.The papers that are part of this Special Issue“Translational Research and Innovation and the current status of Transplantation in Greece”have presented innovative and meaningful approaches in modern transplant research and practice.They provide us with a clear overview of the current landscape in transplantation,including liver transplantation in the context of a major pandemic,the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation,while at the same time explore more recent challenges,such as the issue of frailty in the transplant candidate and the changes brought by newer treatments,such as immunotherapy,in transplant oncology.Additionally,they offer us a glimpse of the effect that technological innovations,such as virtual reality,can have on transplantation,both in terms of clinical and educational aspects.Just as critical is the fact that this Special Issue emphasizes the multidisciplinary,collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering,advanced information technology and artificial intelligence.In this Special Issue,in addition to the clinical and research evolution of the field of transplantation,we are witnessing the importance of interdisciplinary collaboration in medicine.
文摘Purpose: Despite many scientific advances, Regenerative Medicine is still in the preclinical stages in many areas. In this article, we intend to discuss the role of microsurgery in the bench-to-bedside transition of such primary findings. Method: By searching the papers related to the history of Regenerative Medicine (RM) and the news of Tissue Engineering (TE) in orthopedics in Pubmed, Scopus, and Google Scholar databases, we accessed a complete archive of various topics related to this field. Result: We first assessed the history and achievements of regenerative medicine, then we realized the importance of translational medical sciences and the role of animal models in this incipient phenomenon. Finally, after mastering the capabilities of microsurgery and the useful contribution of this technique to the advancement of clinical applications of regenerative medicine in various branches such as skin, skeletal system, nerves, and blood vessels, we decided to express the gist of our studies through this article. Conclusion: Considering the widespread use of small animals in regenerative medicine projects and the inevitable role of microsurgery in performing the best intervention on these animal models, the significant progress of regenerative medicine clinical application requires special attention to microsurgery in associated research.
文摘As the emergence of conversion to aspect of culture in the study of translation, the subjectivity of translator is widely discussed. Translator is inevitably influenced by his/her own language and system of culture in the process of translation. In order to make readers understand what is translated, a translator needs to bring subjectivity into play to make translated text conform to custom of his/her own language and system of culture. The study of subjectivity is mainly concentrated on understanding of original text and recreating of art on the level of linguistics. This paper studies the problem of subjectivity in the process of translation from translational norms, subjectivity, aim and creativity.
文摘目的作为一本新创的英文期刊,Journal of Translational Neuroscience杂志需要尽快提升其学术水平,扩大其社会影响力,以期能迅速在国际专业学术期刊界占有一席之地,通过约稿获得高质量的学术论文就显得至关重要。方法笔者从找准期刊学术定位、采取灵活多样的约稿方式、分析解决约稿过程中可能存在的问题以及如何做好约稿后续服务工作等几个方面入手,初浅分析探讨了关于期刊约稿的方式方法。结果通过期刊定位准确锁定目标作者群,依托自身优势资源,参与学术会议,通过编委约稿以及提供优质的后续服务等方法获得稳定的高质量作者群,从而获得持续的优秀稿源。结论拥有持续的高质量稿件是促使期刊进入良性循环的重要保障,通过约稿可以解决新创办的期刊无稿可用和缺少优秀稿件的难题,推动期刊走出困境,渐入正轨。
基金the National Key Research and Development Project of Stem Cell and Transformation Research(2019YFA0112100).
文摘Spinal cord injury(SCI) leads to loss of motor and sensory function below the injury level and imposes a considerable burden on patients, families, and society. Repair of the injured spinal cord has been recognized as a global medical challenge for many years.Significant progress has been made in research on the pathological mechanism of spinal cord injury. In particular, with the development of gene regulation, cell sequencing, and cell tracing technologies, in-depth explorations of the SCI microenvironment have become more feasible. However, translational studies related to repair of the injured spinal cord have not yielded significant results. This review summarizes the latest research progress on two aspects of SCI pathology: intraneuronal microenvironment imbalance and regenerative microenvironment imbalance. We also review repair strategies for the injured spinal cord based on microenvironment imbalance, including medications, cell transplantation, exosomes, tissue engineering, cell reprogramming, and rehabilitation. The current state of translational research on SCI and future directions are also discussed. The development of a combined, precise, and multitemporal strategy for repairing the injured spinal cord is a potential future direction.
基金This project is supported by National Natural Science Foundation of China (No.60275031)Municipal Key Lab Open Fund of Beijing, China (No.KP01-072200384).
文摘Performance analysis and kinematic design of the 3-PUU pure translational parallel mechanism with vertical guide-ways are investigated. Two novel performance indices, the critical slider stroke and the main section area of workspace, are defined; The expressions of two other indices, i.e. the global dexterity and global force transfer ratio are revised based on the main section of workspace. Using these indices, performance changes versus the varieties of dimensional parameters of mechanism are investigated in detail and the graphic descriptions of change tendencies of the performance indices are illustrated. By means of these obtained graphic descriptions, kinematic parameters for the 3-PUU pure translational parallel mechanism with better characteristics can be directly acquired.
基金the National Natural Science Foundation of China(grant Nos.31801601,31925035,and 31871855)the China Postdoctoral Science Foundation(2018T110153)the Youth Innovation Promotion Association CAS(2019083).
文摘Light plays a critical role in plant growth and development,but the mechanisms through which light regulates fruit ripening and nutritional quality in horticultural crops remain largely unknown.Here,we found that ELONGATED HYPOCOTYL 5(HY5),a master regulator in the light signaling pathway,is required for normal fruit ripening in tomato(Solanum lycopersicum).Loss of function of tomato HY5(SlHY5)impairs pigment accumulation and ethylene biosynthesis.Transcriptome profiling identified 2948 differentially expressed genes,which included 1424 downregulated and 1524 upregulated genes,in the Slhy5 mutants.In addition,genes involved in carotenoid and anthocyanin biosynthesis and ethylene signaling were revealed as direct targets of SlHY5 by chromatin immunoprecipitation.Surprisingly,the expression of a large proportion of genes encoding ribosomal proteins was downregulated in the Slhy5 mutants,and this downregulation pattern was accompanied by a decrease in the abundance of ribosomal proteins.Further analysis demonstrated that SlHY5 affected the translation efficiency of numerous ripening-related genes.These data indicate that SlHY5 regulates fruit ripening both at the transcriptional level by targeting specific molecular pathways and at the translational level by affecting the protein translation machinery.Our findings unravel the regulatory mechanisms of SlHY5 in controlling fruit ripening and nutritional quality and uncover the multifaceted regulation of gene expression by transcription factors.
文摘Cinnamon, is an exotic spice and a major constituent of our food which is commonly used in different areas of the world for the treatment of various diseases (Kawatra et al., 2015). Besides 让s anti-inflammatory, anti-diabetic and anti-cancer properties, cinnamon also exerts strong brain protective and pro-cogrdtive effects in various models of neurodegeneration (Kawatra et al., 2015;Kelestemur et al., 2016)(Figure 1).
基金Sponsored by the National Natural Science Foundation of China(Grant No.51005195,51205339)
文摘Coupling is the significant characteristic of parallel mechanism,while it is just the coupling that brings about much difficulty for the configuration design,theoretical analysis and the development of the control system of the parallel mechanism. And recently,the research on the decoupled parallel mechanism becomes one of the research hot points in the mechanism fields. In this paper,a type synthesis method for the translational decoupled parallel mechanism( TDPM) is proposed based on the screw theory. To achieve the decoupling characteristics of the translational parallel mechanism,the translational decoupled criterion for type synthesis of the branches are presented in this paper. According to this criterion and the realization conditions of rotational degree of freedom of the mechanism proposed former,a large number of branches for the TDPM are obtained. Taking the three degrees of freedom( DOFs) TDPM as an example,the process of type synthesis is discussed in detail. Using this proposed type synthesis method,a serial of translational decoupled parallel mechanisms, including but not limited to all the existing typical 3-DOF TDPMs, are obtained, which identifies the correctness and effective of the method. The contents of this paper provide a reference and possess significant theoretical meanings for the synthesis and development of the novel decoupled parallel mechanisms.
基金funded by Ministry of Education,University and Research(MIUR)ex-60%research fund University of Brescia,Italy.Emilio Merlo Pich is employee of Takeda Pharmaceutical International AG
文摘Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e.g.,the serotonin re-uptake inhibitors(SSRI),and are considered affected by Treatment-Resistant Depression(TRD).The neurobiology of this condition is presently unknown.Recent attempts of developing novel treatments for TRD have been driven by four major breakthroughs:(1)Increasing dopaminergic neurotransmission improves TRD symptoms;(2)Anhedonia occurs when central dopaminergic neurotransmission is low;(3)Enhanced neuroplasticity is critical for the action of antidepressants;(4)Ketamine shows antidepressant properties in TRD patients and triggers neuroplasticity in preclinical animal models.These breakthroughs are at the basis of a putative human translational cellular model for antidepressant agents that we are proposing in this article.The rationale is briefly described here.
基金supported by the Chinese Scholarship Council(CSC)for his Ph D study and research at LARM in the University of Cassino and South Latium,Italy,during 2013-2015
文摘Three-degree of freedom(3-DOF) translational parallel manipulators(TPMs) have been widely studied both in industry and academia in the past decades. However, most architectures of 3-DOF TPMs are created mainly on designers' intuition, empirical knowledge, or associative reasoning and the topology synthesis researches of 3-DOF TPMs are still limited. In order to find out the atlas of designs for 3-DOF TPMs, a topology search is presented for enumeration of 3-DOF TPMs whose limbs can be modeled as 5-DOF serial chains. The proposed topology search of 3-DOF TPMs is aimed to overcome the sensitivities of the design solution of a 3-DOF TPM for a LARM leg mechanism in a biped robot. The topology search, which is based on the concept of generation and specialization in graph theory, is reported as a step-by-step procedure with desired specifications, principle and rules of generalization, design requirements and constraints, and algorithm of number synthesis. In order to obtain new feasible designs for a chosen example and to limit the search domain under general considerations, one topological generalized kinematic chain is chosen to be specialized. An atlas of new feasible designs is obtained and analyzed for a specific solution as leg mechanisms. The proposed methodology provides a topology search for 3-DOF TPMs for leg mechanisms, but it can be also expanded for other applications and tasks.
基金supported by the start-up grant from“Top 100 Talents Program”of Sun Yat-sen University to JRY(50000-31131114)General Program of National Natural Science Foundation of China to JRY(31671320)
文摘Currently many facets of genetic information are illdefined. In particular, how protein folding is genetically regulated has been a long-standing issue for genetics and protein biology. And a generic mechanistic model with supports of genomic data is still lacking. Recent technological advances have enabled much needed genome-wide experiments. While putting the effect of codon optimality on debate, these studies have supplied mounting evidence suggesting a role of m RNA structure in the regulation of protein folding by modulating translational elongation rate. In conjunctions with previous theories, this mechanistic model of protein folding guided by m RNA structure shall expand our understandings of genetic information and offer new insights into various biomedical puzzles.
文摘The messenger RNA 3'-untranslated region(3'UTR)plays an important role in regulation of gene expres-sion on the posttranscriptional level. The 3'UTR con-trols gene expression via orchestrated interactionbetween the structural components of mRNAs(cis-ele-ment) and the specific trans-acting factors(RNA bind-ing proteins and non-coding RNAs). The crosstalk ofthese factors is based on the binding sequences and/or direct protein-protein interaction, or just functionalinteraction. Much new evidence that has accumulatedsupports the idea that several RNA binding factors canbind to common mRNA targets: to the non-overlappingbinding sites or to common sites in a competitive fash-ion. Various factors capable of binding to the sameRNA can cooperate or be antagonistic in their actions.The outcome of the collective function of all factorsbound to the same mRNA 3'UTR depends on manycircumstances, such as their expression levels, affinity to the binding sites, and localization in the cell, which can be controlled by various physiological conditions. Moreover, the functional and/or physical interactions of the factors binding to 3'UTR can change the character of their actions. These interactions vary during the cell cycle and in response to changing physiological condi-tions. Abnormal functioning of the factors can lead to disease. In this review we will discuss how alterations of these factors or their interaction can affect cancer development and promote or enhance the malignant phenotype of cancer cells. Understanding these altera-tions and their impact on 3'UTR-directed posttran-scriptional gene regulation will uncover promising new targets for therapeutic intervention and diagnostics. We will also discuss emerging new tools in cancer di-agnostics and therapy based on 3'UTR binding factors and approaches to improve them.
文摘The structural evolution fromβ_(1)(Mg_(3)Ce)toβ(Mg_(12)Ce)precipitates,which takes place at the over-aged stage of binary Mg-Ce alloys,are investigated by high-angle annular dark-field scanning transmission electron microscopy.The structural transformation mainly occurs in the{111}_(β1)crystallographic planes,where the newly formedβlattices exhibit two categories of domain structures,namely rotational and translational domains.The rotational domain is composed of threeβdomains(β_(RA),β_(RB)andβ_(RC)),which are related by a 120°rotation with respect to each other around the 111_(β1)axis of theirβ_(1)parent phase.The{111}_(β1)crystallographic planes can provide four sets of sublattices with the same orientation for an initial nucleation ofβlattice.It leads to the formation of four translationalβdomains(β_(TA),β_(TB),β_(TC)andβ_(TD)),among which any two differ by a vector of 1/6112_(β1).We deduce theoretically that there exist twenty-fourβdomains during this transition.However,considering the interfacial misfit,only one-third of domains can grow up and eventually formsβribbon.Furthermore,a majority ofβribbons overlap partiallyβ_(1)plate,which is beneficial to relax interfacial strain amongβ,β_(1)andα-Mg matrix(α/β/β_(1)).The configuration of multipleβdomains can effectively regulate interfacial misfit ofα/βandβ/β_(1),which are responsible for enhancing the hardness and strength of Mg-Ce alloy.Additionally,this study aims to provide some clues to improve the over-aged performance of magnesium alloys by constructingβdomains and optimizing theα/β/β_(1)interface.
文摘The past decade has witnessed an outstanding scientific production focused towards the possible clinical applications of mesenchymal stromal cells(MSCs) in autoimmune and chronic inflammatory diseases. This raised the need of novel standards to adequately address quality, efficacy and safety issues of this advanced therapy. The development of a streamlined regulation is currently hampered by the complexity of analyzing dynamic biological entities rather than chemicals. Although numerous pieces of evidence show efficacy in reducing intestinal inflammation, some inconsistencies between the mechanisms of action of rodent vs human MSCs suggest caution before assigning translational value to preclinical studies. Preliminary evidence from clinical trials showed efficacy of MSCs in the treatment of fistulizing Crohn's disease(CD), and preparations of heterologous MSCs for CD treatment are currently tested in ongoing clinical trials. However, safety issues, especially in longterm treatment, still require solid clinical data. In this regard, standardized guidelines for appropriate dosing and methods of infusion could enhance the likelihood to predict more accurately the number of responders and the duration of remission periods. In addition, elucidating MSC mechanisms of action could lead to novel and more reliable formulations such as those derived from the MSCs themselves(e.g., supernatants).