Brain-X最新文献

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.

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.

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.¹ Thus, lowering post-procedure systolic pressure is a potential approach to improving patients' outcomes. The guideline² recommends a systolic pressure of <180 mmHg before and after mechanical thrombectomy without randomized clinical trial evidence.

Recently, Yang et al.³ 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 >10 min). The randomization arms were <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.

This study again proved the complex relationship between blood pressure and functional outcomes after acute large-vessel occlusion ischemic stroke.¹ 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 (<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.

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 paper³ suggested that a systolic pressure of <120 mmHg was only narrowly achieved in the more intensive treatment group during the first 3 days. Although current guidelines² recommend a blood pressure of <180 mmHg, no optimal blood pressure target for patients with ischemic stroke who undergo mechanical thrombectomy h

Considering their substantial morbidity and mortality rates, tumors of the brain and central nervous system (CNS) are among the most fatal cancers.¹ 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.² Characterizing these promoters helps to link the micro genes information and macro detectable information.

Recent research has focused on glioma cell network communication via Ca²⁺ transients and KCa3.1, a type of Ca²⁺-activated potassium ion (K⁺) channel.³ 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.

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.

This protective mechanism has been analyzed using laser ablation as well as Ca²⁺ monitoring to detect the number of communicating

In recent years, the field of biosensors has seen significant advances in the development of fluorescent sensors, including quantum dots,¹ upconversion nanoparticles,² and fluorescent proteins,³ 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).⁴ The development of this sensor has significant potential to improve our understanding of information processing in deep tissues.

To fabricate the photosensitive MRI probe, magnetic particles were encapsulated in light-responsive azobenzene-conjugated liposomes (called Light-LisNRs).⁵ 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.

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.

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

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^1-3 after the Human Genome Project (HGP), launched in both the United States and Europe,^{4, 5} 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.

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 Brain-X. 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.

Brain-X 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.

Brain-X 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.

The editorial board of Brain-X 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. Brain-X aims to serve as a platform for students, scientists, and clinicians to share their discoveries and perspectives on brain, neuroscience, and neu