Brain-X最新文献

{"title":"Waking up neural stem cells through inhibition of mitochondrial pyruvate import","authors":"Yajiao Shi,&nbsp;You Wan,&nbsp;Jie Zheng","doi":"10.1002/brx2.13","DOIUrl":"https://doi.org/10.1002/brx2.13","url":null,"abstract":"<p>Neurogenesis declines sharply in adulthood, partly because neural stem and progenitor cells (NSPCs) increasingly return to a dormant state as they age. However, innate NSPC pools are preserved in specific brain regions throughout an individual's lifetime. Petrelli et al.<span>¹</span> recently reported that inhibiting mitochondrial pyruvate import stimulated NSPCs to transition from a quiescent state to an active state, thereby promoting neurogenesis in both young and middle-aged mice. These findings indicate a novel approach for pro-neurogenic treatments.</p><p>Most neurogenesis in the brain is completed during embryonic development, with only small pools of NSPCs remaining to generate new neurons postnatally. These NSPCs are primarily found in the hippocampal dentate gyrus and the subventricular zone. This biological process, particularly adult hippocampal neurogenesis (AHN), plays a crucial role in specific functions such as pattern separation, learning and memory, and emotional regulation. The pool of NSPCs in the adult brain gradually diminishes but is maintained at a certain level throughout life due to the self-renewal of neural stem cells during symmetric cell division.</p><p>However, the extent of AHN declines much more sharply compared with the age-dependent depletion of the NSC pool. One of the most significant causes for this decline is the increasing rate at which NSCs in the adult brain transition from an active to a dormant state, remaining quiescent and refusing to proliferate to initiate neurogenesis. Thus, activating these dormant quiescent NSCs is pivotal for restoring neurogenesis.</p><p>The mitochondrial pyruvate carrier (MPC) on the inner mitochondrial membrane is responsible for transporting the glycolytic end-product pyruvate from the cytosol into the mitochondria, thereby linking glycolysis to the tricarboxylic acid cycle and oxidative phosphorylation. Given that glycolysis plays a critical role in determining the activity state of NSCs, Petrelli et al.<span>¹</span> recently found that MPC expression was highest in quiescent NSPCs, as opposed to those that were active or proliferating.</p><p>Moreover, both pharmacological blockage of MPC in vitro using the specific membrane-penetrating inhibitor UK5099 and selective deletion of the <i>Mpc1</i> gene in NSPCs led to the proliferation of these quiescent NSPCs. Subsequently, the authors aimed to investigate the underlying metabolic mechanism. They ruled out the contribution of lactate elevation resulting from MPC loss-of-function as neither lactate supplementation nor downregulation affected the proliferation of NSPCs.</p><p>Instead, they discovered that the elevated intracellular aspartate, presumed to be due to the upregulation of glutamic-oxaloacetic transaminase activity or enhanced mitochondrial aspartate import, played a significant role in activating quiescent NSPCs. In contrast to quiescent NSPCs, inhibiting MPCs did not affect the proliferat","PeriodicalId":94303,"journal":{"name":"Brain-X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brx2.13","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50147946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel mechanism of DNA repair in neurons opens promising avenues for combatting neurodegenerative diseases and brain aging","authors":"Conglin Wang,&nbsp;Xintong Ge,&nbsp;Wenqiang Xin,&nbsp;Ping Lei","doi":"10.1002/brx2.9","DOIUrl":"https://doi.org/10.1002/brx2.9","url":null,"abstract":"<p>A recent study, titled “A NPAS4-NuA4 Complex Couples Synaptic Activity to DNA Repair,” reveals an exciting new mechanism by which neurons maintain genomic stability in response to external stimuli. Published in Nature on February 23, 2023,<span>¹</span> this paper provides valuable insights into the molecular mechanisms underlying neurodegenerative diseases and brain aging that pave the way for the development of new therapeutic strategies. This commentary reviews the research findings and their potential for future applications.</p><p>The brain is a highly dynamic and plastic organ that relies on neurons to modify their gene expression under a variety of pathophysiological conditions. Excessive or prolonged neuronal response to external stimuli can lead to DNA damage and genomic instability, thereby being harmful to the brain. Cumulative DNA damage in the neuronal genome is also a hallmark of neurodegeneration and brain aging. Until recently, the molecular mechanism by which neurons repair DNA and maintain genomic stability in response to external stimuli remained unclear.</p><p>Neuronal PAS Domain Protein 4 (NPAS4) is an activity-induced transcription factor that is selectively expressed in neurons following membrane depolarization and subsequent calcium signaling. Through a series of biochemical and genomic experiments on mice, the researchers first determined that NPAS4 exists as part of a 21-protein complex called NPAS4-NuA4. They then measured DNA damage using γH2AX ChIP-seq, sBLISS-seq, END-seq and SAR-seq, which indicated that NPAS4 preferentially binds to active DNA breaking-induced sites in neurons. These advanced techniques can be used to analyze the binding sites of transcription factors,<span>²</span> provide whole-genome maps with DNA double-strand breaks,<span>³</span> monitor DNA terminal excision,<span>⁴</span> and localize DNA repair synthesis in vivo and in various cell types.<span>⁵</span> Thus, they could contribute greatly to future research in neuroscience and other biomedical fields.</p><p>In addition, the NPAS4-NuA4 complex serves as a critical mediator in the mechanism underlying neurodegenerative diseases and aging in the brain. Activated in response to neuronal activity driven by changes in sensory experience, NPAS4-NuA4 binds to periodically damaged transcriptional regulatory elements and recruits DNA repair machinery to prevent age-dependent somatic mutation accumulation. Furthermore, impaired NPAS4-NuA4 leads to a range of cellular defects that result in a shortened lifespan, including dysregulation of neuronal activity-dependent transcriptional responses, loss of somatic inhibition of pyramidal neurons, impaired localization of protective repair machinery, and genomic instability.</p><p>One of the most exciting aspects of this study is its discovery of a link between damage and neuronal activity-dependent regulatory elements and neuronal dysfunction in neuro","PeriodicalId":94303,"journal":{"name":"Brain-X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brx2.9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50138113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D printing-based full-scale human brain for diverse applications","authors":"Weijian Hua,&nbsp;Cheng Zhang,&nbsp;Lily Raymond,&nbsp;Kellen Mitchell,&nbsp;Lai Wen,&nbsp;Ying Yang,&nbsp;Danyang Zhao,&nbsp;Shu Liu,&nbsp;Yifei Jin","doi":"10.1002/brx2.5","DOIUrl":"10.1002/brx2.5","url":null,"abstract":"<p>Surgery is the most frequent treatment for patients with brain tumors. The construction of full-scale human brain models, which is still challenging to realize via current manufacturing techniques, can effectively train surgeons before brain tumor surgeries. This paper aims to develop a set of three-dimensional (3D) printing approaches to fabricate customized full-scale human brain models for surgery training as well as specialized brain patches for wound healing after surgery. First, a brain patch designed to fit a wound's shape and size can be easily printed in and collected from a stimuli-responsive yield-stress support bath. Then, an inverse 3D printing strategy, called “peeling-boiled-eggs,” is proposed to fabricate full-scale human brain models. In this strategy, the contour layer of a brain model is printed using a sacrificial ink to envelop the target brain core within a photocurable yield-stress support bath. After crosslinking the contour layer, the as-printed model can be harvested from the bath to photo crosslink the brain core, which can be eventually released by liquefying the contour layer. Both the brain patch and full-scale human brain model are successfully printed to mimic the scenario of wound healing after removing a brain tumor, validating the effectiveness of the proposed 3D printing approaches.</p>","PeriodicalId":94303,"journal":{"name":"Brain-X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brx2.5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41224669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-hydroxybutyrate in the brain: Biosynthesis, function, and disease therapy","authors":"Bing-Long Wang,&nbsp;Jian-Fei Wu,&nbsp;Da Xiao,&nbsp;Bo Wu,&nbsp;Dai-Xu Wei","doi":"10.1002/brx2.6","DOIUrl":"https://doi.org/10.1002/brx2.6","url":null,"abstract":"<p>3-hydroxybutyrate (3HB), or BHB, is an anionic small molecule acid metabolite with a hydroxyl group. 3HB is the major ketone body that is distributed in the human brain and its primary energy source when glucose is absent. A better understanding of 3HB and how to adapt neuronal response mechanisms is expected to facilitate the development of new interventions to promote cognitive brain function and prevent neurodegenerative diseases. It provides important concepts for the clinical application of 3HB therapy. This review summarizes the distribution of 3HB in the brain, its properties, and its mechanism in brain and nerve regulation. We focus on 3HB biosynthesis in natural human cells and engineered bacteria via synthetic biology platforms and 3HB treatment in various brain and nerve diseases, including epilepsy, multiple sclerosis, stroke, Parkinson's disease, Alzheimer's disease, Huntington's disease, depressive disorder, and schizophrenia. Ultimately, this review explores the future development trend of 3HB as a potential small-molecule drug for brain and nerve diseases.</p>","PeriodicalId":94303,"journal":{"name":"Brain-X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brx2.6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50145576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleic acid delivery by ionizable nanocarriers for brain disease treatment","authors":"Ruru Xiong,&nbsp;Guixia Ling,&nbsp;Yuqi Zhang,&nbsp;Jibin Guan,&nbsp;Peng Zhang","doi":"10.1002/brx2.7","DOIUrl":"https://doi.org/10.1002/brx2.7","url":null,"abstract":"<p>The successful application of messenger RNA vaccines in the market has demonstrated the potential of gene therapy in treating various diseases, including infectious diseases, autoimmune disorders, brain diseases, and other cancers. However, gene therapy faces great challenges in treating brain diseases such as brain tumors, infections, and strokes because the limitations of the blood-brain barrier make it difficult for nucleic acid drugs to be delivered safely and effectively into the brain. Therefore, there is a high demand for carriers delivering nucleic acid drugs to the brain. Ionizable nanocarriers (INs) have great advantages in gene therapy due to their pH-responsive properties, which facilitate the safe and efficient delivery of targets, responsive release in the disease microenvironment, and the protection of nucleic acids from degradation. To better understand INs and their potential as therapeutic vectors for brain diseases, the present review describes their biological properties, recent progress in the field, and promising applications. In particular, the related prospects and challenges are discussed to promote the further development of INs.</p>","PeriodicalId":94303,"journal":{"name":"Brain-X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brx2.7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50144491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systolic pressure target after endovascular thrombectomy in acute large-vessel occlusion ischemic stroke patients: Comment on ENCHANTED2/MT","authors":"Yunpeng Yuan,&nbsp;Baozhu Wei,&nbsp;Wenyun Zhu,&nbsp;Yang Liu,&nbsp;Yingfeng Wan","doi":"10.1002/brx2.4","DOIUrl":"https://doi.org/10.1002/brx2.4","url":null,"abstract":"<p>Patients with large-vessel occlusion ischemic stroke continue to have high mortality and disability rates after mechanical thrombectomy with or without intravenous alteplase treatment. Elevated blood pressure during the perioperative period is associated with higher mortality and disability prevalence rates.<span>¹</span> Thus, lowering post-procedure systolic pressure is a potential approach to improving patients' outcomes. The guideline<span>²</span> recommends a systolic pressure of &lt;180 mmHg before and after mechanical thrombectomy without randomized clinical trial evidence.</p><p>Recently, Yang et al.<span>³</span> reported the results of the multicenter, open-label, blinded-endpoint, and randomized controlled trial ENCHANTED2/MT, which aimed to determine if a more aggressive blood pressure goal is beneficial in patients with acute ischemic stroke. Patients were required to have a diagnosis of large-vessel occlusion acute ischemic stroke and a successful endovascular thrombectomy procedure followed by hypertension (defined as ≥2 successive measurements of systolic blood pressure ≥140 mmHg for &gt;10 min). The randomization arms were &lt;120 mmHg versus 140–180 mmHg for 72 h, and the primary outcome was assessed by a shift analysis of the modified Rankin Scale at 90 days. The 821 patients who were prospectively enrolled between 2020 and 2022 were randomized, and the source populations were derived from 44 hospitals in China. The trial was suspended in June 2022 due to safety concerns after an independent data and safety monitoring board reviewed the data. Unexpectedly, the primary results were that the more intensive treatment group was more likely to have worse outcomes and higher early neurological deterioration and disability rates than the less intensive treatment group.</p><p>This study again proved the complex relationship between blood pressure and functional outcomes after acute large-vessel occlusion ischemic stroke.<span>¹</span> This is an important trial that was built on accumulating observational data in the field and provided randomized trial evidence that more intensive blood pressure lowering (&lt;120 mmHg) is not only neutral but harmful. In this regard, this study is of broad general interest to emergency departments and stroke centers, as blood pressure is a parameter that must be managed in all stroke patients' post-procedures.</p><p>However, several points need to be noted and comprehensively discussed before interpreting the results and applying them clinically. First, fig. 2 from the ENCHANTED2/MT trial paper<span>³</span> suggested that a systolic pressure of &lt;120 mmHg was only narrowly achieved in the more intensive treatment group during the first 3 days. Although current guidelines<span>²</span> recommend a blood pressure of &lt;180 mmHg, no optimal blood pressure target for patients with ischemic stroke who undergo mechanical thrombectomy h","PeriodicalId":94303,"journal":{"name":"Brain-X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brx2.4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50117446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhythmic calcium ion activity related to glioma growth reveals the mechanism of ion transmission","authors":"Geer Teng","doi":"10.1002/brx2.8","DOIUrl":"https://doi.org/10.1002/brx2.8","url":null,"abstract":"<p>Considering their substantial morbidity and mortality rates, tumors of the brain and central nervous system (CNS) are among the most fatal cancers.<span>¹</span> Among them, gliomas are the most common malignant forms of cancer. Regarding the growth mechanism of gliomas, the surrounding microenvironment and local network activity among tumor cells are key areas of interest. The oscillations of brain activity are also directly related to tumor growth and can be induced by external stimuli. Out of the relevant signals and biomarkers, calcium ion (Ca²⁺) channels and signaling dynamics show the greatest correlation with oscillatory brain activity. The activity of intracellular Ca²⁺ oscillations can be used to characterize promoters like ASCL-1 or neurogenin-2, which are related to luciferase reporter genes.<span>²</span> Characterizing these promoters helps to link the micro genes information and macro detectable information.</p><p>Recent research has focused on glioma cell network communication via Ca²⁺ transients and KCa3.1, a type of Ca²⁺-activated potassium ion (K⁺) channel.<span>³</span> These network communications can protect glioma cells after surgery, leading to local tumor recurrence. Glioma cells are closely connected to multicellular networks, and Ca²⁺ transients are transferred between individual cells through interconnecting tumor microtubes. This results in rhythmic Ca²⁺ fluctuations that periodically activate signaling pathways like MAPK and NF-κB, increasing the proliferation of tumor cells and promoting tumor growth. Glioma cells that display such periodic Ca²⁺ activity are known as periodic cells. Inhibiting cellular entry and chelation of Ca²⁺ or inhibiting tumor cell connectivity via gap junctions can also strongly reduce the proliferation of glioma cells. As a result, the rhythmic Ca²⁺ activity in glioma cell networks is a tumor cell-autonomous functional state, which is not affected by the external environment.</p><p>Functional tumor cell networks have scale-free and small-world properties, the two most common complex network features. These properties reflect the center and surrounding structures as the glioma to some extent. If the clustering coefficient of a certain network is significantly higher than that of the corresponding random network, and the average path length is equal, then the network can be classified as a small-world phenomenon. Networks where most connections are concentrated in a small number of centers are called scale-free networks. With these scale-free and small-world properties, periodic glioma cells at the center of networks are more resistant to random damage, as the center is protected in this network structure.</p><p>This protective mechanism has been analyzed using laser ablation as well as Ca²⁺ monitoring to detect the number of communicating ","PeriodicalId":94303,"journal":{"name":"Brain-X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brx2.8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50125467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New biosensors detect light deep inside the brain","authors":"Lei Luo,&nbsp;Dandan Yang,&nbsp;Yu Yang","doi":"10.1002/brx2.3","DOIUrl":"https://doi.org/10.1002/brx2.3","url":null,"abstract":"<p>In recent years, the field of biosensors has seen significant advances in the development of fluorescent sensors, including quantum dots,<span>¹</span> upconversion nanoparticles,<span>²</span> and fluorescent proteins,<span>³</span> to monitor the generation of information in living systems. The fluorescence of these sensors can be observed by shining a laser at them. However, conventional fluorescent sensors are limited in their ability to image signals in deep tissues because most of the light is absorbed or scattered as it penetrates the tissue. To address this challenge, a team led by Jasanoff developed a novel sensor that converts light into a magnetic signal that is unaffected by absorption or scattering. This allows the response of the light detector to be visualized using magnetic resonance imaging (MRI; Figure 1).<span>⁴</span> The development of this sensor has significant potential to improve our understanding of information processing in deep tissues.</p><p>To fabricate the photosensitive MRI probe, magnetic particles were encapsulated in light-responsive azobenzene-conjugated liposomes (called Light-LisNRs).<span>⁵</span> By adjusting the composition and proportion of the lipid bilayer molecules, these liposome nanoparticles can switch from being permeable to being impenetrable, depending on the type of light exposure. This property allowed modulation of the MRI contrast of the Light-LisNRs and facilitated the optimization of the switchable longitudinal relaxation time (T1). Specifically, upon exposure to ultraviolet (UV) light, the Light-LisNRs became more permeable to water, resulting in a strong interaction between the magnetic particles and water and thereby producing strong MRI signals. Conversely, exposure to blue light caused the Light-LisNRs to become impermeable to water, resulting in the lack of a detectable MRI signal.</p><p>The optimized Light-LisNRs could potentially be used to map light distribution in live animals. When these nanoparticles were injected into the living rat brain, they effectively diffused through the brain by convection, as evidenced by changes in the magnetic resonance signal. The probes exhibited exceptional light sensitivity, which could be demonstrated by changes in magnetic relaxation under blue and UV irradiation. Relative to the initial baseline, the probes showed significant differences in the mean MRI signals in response to UV and blue light, and the temporal characteristics of the light response observed during repeated photoperiods were consistent.</p><p>The steady performance of Light-LisNRs in the rat brain suggests that they are suitable for the quantitative measurement of the light intensity distribution in tissues. In addition, the researchers used a hybrid model consisting of a beam spreading function combined with a homogeneous photon diffusion term to fit the experimental data and produced a quantitative map of the distributi","PeriodicalId":94303,"journal":{"name":"Brain-X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brx2.3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50153094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain-X: A new interdisciplinary journal for advancing neuroscience research","authors":"Kunlin Jin","doi":"10.1002/brx2.2","DOIUrl":"https://doi.org/10.1002/brx2.2","url":null,"abstract":"<p>Despite significant advancements in brain research, the intricacies of the brain remain a mystery. The Human Brain Project (HBP) is an international research initiative modeled<span>^1-3</span> after the Human Genome Project (HGP), launched in both the United States and Europe,<span>^{4, 5}</span> that aims to unravel the complex structure and function of the human brain. HBP takes an interdisciplinary approach, incorporating fields such as biology, medicine, informatics, chemistry, materials, and physics. Such an approach is necessary for furthering our understanding of the brain and advancing neuroscience as a field.</p><p>However, there is currently no professional journal that focuses specifically on interdisciplinary approaches to brain and neuroscience research. To fill this gap, we are proud to announce the launch of <i>Brain-X</i>. The “X” in the name represents the intersection of brain and neuroscience with a strong emphasis on interdisciplinary research. This international publication will showcase the latest discoveries and technological breakthroughs, providing novel insights into all aspects of brain, neuroscience, and neurology.</p><p>\u0000 <i>Brain-X</i> is dedicated to promoting interdisciplinarity and welcomes contributions from diverse fields. In particular, the journal strongly encourages studies that utilize mathematics, physics, chemistry, engineering, materials science, or information science to tackle issues in brain and neuroscience research across various disciplines. As a peer-reviewed and open-access journal, Brain-X partners with Wiley to enhance the visibility of interdisciplinary research in this field. The journal publishes a range of article types, including original research articles, data articles, methods articles, reviews, perspectives, research letters, commentaries, and correspondences.</p><p>\u0000 <i>Brain-X</i> will comprehensively cover a broad range of topics, including but not limited to aging and brain, brain-computer interface, brain injury and rehabilitation, brain-inspired computing and artificial intelligence (AI), brain-inspired 3D printing, brain rhythm and disease, brain-gut axis, cellular and molecular neuroscience, cerebral organoids, chemical neuroscience, clinical neurology, computational neuroscience, crosstalk between brain and other organs, nanoparticles for brain drug delivery, and nerve regeneration materials.</p><p>The editorial board of <i>Brain-X</i> comprises influential scientists from around the world who enthusiastically encourage contributions from researchers. The journal guarantees a rapid review process with fair and prompt decisions. Upon acceptance, high-quality support from the editorial team ensures that the manuscript reaches its full potential in brain and neuroscience research. <i>Brain-X</i> aims to serve as a platform for students, scientists, and clinicians to share their discoveries and perspectives on brain, neuroscience, and neu","PeriodicalId":94303,"journal":{"name":"Brain-X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/brx2.2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50153095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"La fortaleza medieval de Isso (Albacete) y su territorio","authors":"Julio Navarro Palazón","doi":"10.4995/fortmed2020.2020.11761","DOIUrl":"https://doi.org/10.4995/fortmed2020.2020.11761","url":null,"abstract":"This paper presents some of the information obtained during the archaeological surveys carried out in 2019 in the stately fortress known as Torre de Isso, located in the municipality of Hellín (Albacete). These fieldworks have attempted to answer some questions related to the historical interpretation of the preserved monumental remains, specifically two large towers and some walls from the second half of the thirteenth or fourteenth century. The initial study and graphical documentation were carried out to obtain the data needed to draft a conservation project in line with current scientific criteria.Extending the investigation to the whole neighborhood of houses that surrounds the towers resulted in the discovery of a quadrangular fortress of 44 x 42 m, which incorporates the towers and in which different construction phases have been identified, certainly prior to and subsequent to the Christian conquest. The remains found were reused in the load-bearing walls of some of the houses. Beside the fortress, we extended the study to the entire village of Isso, in order to find out if the medieval castle had an annexed relevant village. Finally, the surveys expanded throughout the entire territory of Isso, with the desire to know if its characteristic dispersed settlement, made up of small farmhouses, and its traditional irrigation system, have a medieval origin.This multidisciplinary research project has allowed us to obtain extensive data and produce significant information, although it should be noted that many issues and some of the interpretations offered in this article are still hypothetical. Therefore, only future development of additional archeological and historical works will make it possible to tackle those questions that remain to be answered.","PeriodicalId":94303,"journal":{"name":"Brain-X","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80110082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}