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Cardiac-Adaptive Conductive Hydrogel Patch Enabling Construction of Mechanical–Electrical Anisotropic Microenvironment for Heart Repair

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Research 2024年第1期2023卷 489-507页

作者： Xiaoping Song Jifeng Zhang Si Shen Dan Liu Jie Zhang Wenming Yin Genlan Ye Leyu Wang Liu Cai Honghao Hou Xiaozhong Qiu Central Laboratory The Fifth Affiliated HospitalSouthern Medical UniversityGuangzhouGuangdong 510910China Department of Anatomy Neuroscience Laboratory for Cognitive and Developmental DisordersMedical College of Jinan UniversityGuangzhou 510630China Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering School of Basic Medical ScienceBiomaterials Research CenterSchool of Biomedical EngineeringSouthern Medical UniversityGuangzhouGuangdong 510515China

The biomimetic construction of a microstructural–mechanical–electrical anisotropic microenvironment adaptive to the native cardiac tissue is essential to repair myocardial infarction(MI).Inspired by the 3D anisotropic characteristic of the natural fish swim bladder(FSB),a novel flexible,anisotropic,and conductive hydrogel was developed for tissue-specific adaptation to the anisotropic structural,conductive,and mechanical features of the native cardiac extracellular *** results revealed that the originally stiff,homogeneous FSB film was tailored to a highly flexible anisotropic hydrogel,enabling its potential as a functional engineered cardiac patch(ECP).In vitro and in vivo experiments demonstrated the enhanced electrophysiological activity,maturation,elongation,and orientation of cardiomyocytes(CMs),and marked MI repair performance with reduced CM apoptosis and myocardial fibrosis,thereby promoting cell retention,myogenesis,and vascularization,as well as improving electrical *** findings offer a potential strategy for functional ECP and provides a novel strategy to bionically simulate the complex cardiac repair environment.

关键词： bladder thereby patch

PACS gene family-related neurological diseases: limited genotypes and diverse phenotypes

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World Journal of Pediatrics 2024年第1期20卷 82-91页

作者： Han Zhang Kai Gao Shuang Wang Yue-Hua Zhang Zhi-Xian Yang Ye Wu Yu-Wu Jiang Department of Pediatrics Peking University First Hospital.No.1 Xi'an Men StreetWest DistrictBeijing 100034China Bejing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases BeijingChina Children Epilepsy Center Peking University First HospitalBeijingChina Key Laboratory for neuroscience Ministry of Education/National Health and Family Planning CommissionPeking UniversityBeijingChina Center of Epilepsy Beijing Institute for Brain DisordersBeijingChina

Background The PACS gene family has been demonstrated to be related to intracellular vesicular *** phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy,intellectual disability/developmental delay,and malformations,such as facial *** We identified seven new cases with pathogenic or likely pathogenic PACS variants using next-generation *** information obtained from these patients was analyzed along with that obtained from previously reported *** With the inclusion of the newly diagnosed cases in this study,103 cases with PACS gene family-related neurological diseases were reported,of which 43 were PACS2-related cases and the remaining were PACSI-related *** patients had seizures,which have been reported to be effectively controlled by several types of anti-seizure medications(ASMs).The most efficacious and frequently prescribed ASMs included sodium valproate(43.3%,13/30),oxcarbazepine/carbamazepine(26.7%,8/30),and levetiracetam(20%,6/30).Almost all patients had intellectual disability/developmental *** most common pathogenic missense variants were PACSI ***203Trp and PACS2 *** addition,we report a patient carrying a likely pathogenic copy number variation(CNV)(de novo heterozygous deletion of chr14:105821380-106107443,286 kilobase,destroyed part of the furin-binding region domain and the protein structure after it)with more severe and refractory late-onset *** The clinical phenotypes of the different PACS heterozygous missense variants were *** pathogenic variant sites of PACSI and PACS2 were quite limited but located in different regions.A CNV destroying part of the PACS2 gene might also be *** findings may provide an important clue for further functional studies on the pathogenic mechanism of neurological disorders related to the PACS gene family.

关键词： Developmental delay Epilepsy Intellectual disability PACSI PACS2

Treadmill exercise in combination with acousto-optic and olfactory stimulation improves cognitive function in APP/PS1 mice through the brain-derived neurotrophic factor-and Cygb-associated signaling pathways

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Neural Regeneration Research 2025年第9期20卷 2706-2726页

作者： Biao Xiao Chaoyang Chu Zhicheng Lin Tianyuan Fang Yuyu Zhou Chuxia Zhang Jianghui Shan Shiyu Chen Liping Li Department of Physiology and Pharmacology Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Ningbo Key Laboratory of Behavioral neuroscience Health Science CenterNingbo UniversityNingboZhejiang ProvinceChina Key Laboratory of Addiction Research of Zhejiang Province NingboZhejiang ProvinceChina

A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's ***,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and ***,nonpharmacological interventions aimed at inducing adult neurogenesis are currently *** individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully *** this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 *** deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease ***,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus *** findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 ***,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice

关键词： acousto-optic stimulation adult neurogenesis Alzheimer's disease amyloid precursor protein/presenilin 1 mice amyloid-beta deposition brain cell apoptosis cognitive impairment depression-like behavior involuntary treadmill exercise olfactory stimulation serum metabolites

Nitric oxide:a newly discovered function on wound healing

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Acta Pharmacologica Sinica 2005年第3期26卷 259-264页

作者： Alex F CHEN Departments of Pharmacology and Neurology and the neuroscience program Michigan State University East Lansing MI 48824-1317 USA

Wound healing impairment represents a particularly challenging clinical problemto which no efficacious treatment regimens currently *** factors ensuringappropriate intercellular communication during wound repair are not *** protein-type mediators are well-established players in thisprocess,emerging evidence from both animal and human studies indicates thatnitric oxide (NO) plays a key role in wound *** beneficial effects of NO onwound repair may be attributed to its functional influences on angiogenesis,inflammation,cell proliferation,matrix deposition,and *** find-ings from in vitro and in vivo studies of NO on wound repair are summarized inthis *** unveiled novel mechanisms support the use of NO-containingagents and/or NO synthase gene therapy as new therapeutic regimens for im-paired wound healing.

关键词： angiogenesis inflammation nitric oxide proliferation wound healing

Using AI and Precision Nutrition to Support Brain Health during Aging

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Advances in Aging Research 2024年第5期13卷 85-106页

作者： Sabira Arefin Gideon Kipkoech Global Healthcare Leadership program Harvard University Boston USA Independent Researcher University of Embu Nairobi Kenya

Artificial intelligence, often referred to as AI, is a branch of computer science focused on developing systems that exhibit intelligent behavior. Broadly speaking, AI researchers aim to develop technologies that can think and act in a way that mimics human cognition and decision-making [1]. The foundations of AI can be traced back to early philosophical inquiries into the nature of intelligence and thinking. However, AI is generally considered to have emerged as a formal field of study in the 1940s and 1950s. Pioneering computer scientists at the time theorized that it might be possible to extend basic computer programming concepts using logic and reasoning to develop machines capable of “thinking” like humans. Over time, the definition and goals of AI have evolved. Some theorists argued for a narrower focus on developing computing systems able to efficiently solve problems, while others aimed for a closer replication of human intelligence. Today, AI encompasses a diverse set of techniques used to enable intelligent behavior in machines. Core disciplines that contribute to modern AI research include computer science, mathematics, statistics, linguistics, psychology and cognitive science, and neuroscience. Significant AI approaches used today involve statistical classification models, machine learning, and natural language processing. Classification methods are widely applicable to problems in various domains like healthcare, such as informing diagnostic or treatment decisions based on patterns in data. Dean and Goldreich, 1998, define ML as an approach through which a computer has to learn a model by itself from the data provided but no specification on the sort of model is provided to the computer. They can then predict values for things that are different from the values used in training the models. NLP looks at two interrelated concerns, the task of training computers to understand human languages and the fact that since natural languages are so complex, they le

关键词： Artificial Intelligence (AI) Precision Nutrition Brain Health Aging Research Gerontology Cognitive Functions Temporal Reasoning Medication Adherence Electronic Health Records (EHRs) Machine Learning (ML) Healthcare Technology

Brain circuits for retching-like behavior

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National Science Review 2024年第1期11卷 145-160页

作者： Lifang Huo Zhimin Ye Meiling Liu Ziqing He Meizhu Huang Dapeng Li Qian Wu Qian Wang Xiaoqun Wang Peng Cao Ji Dong Congping Shang School of Basic Medical Sciences Guangzhou National Laboratory The Fifth Afflliated Hospital Guangzhou Medical University Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) Department of Neurobiology School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and Repair Advanced Innovation Center for Human Brain Protection Capital Medical University State Key Laboratory of Cognitive neuroscience and Learning IDG/McGovern Institute for Brain Research Beijing Normal University Changping Life Science Laboratory National Institute of Biological Sciences

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract(NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive(Calb1+) NTS neurons that are molecularly distinct from Tac1+*** Calb1+neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.

关键词： vomiting nausea nucleus of the solitary tract Calbindin1 neural circuits

Ferroptosis:copper-iron connection in cuprizone-induced demyelination

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Neural Regeneration Research 2022年第1期17卷 89-90页

作者： Priya Jhelum Samuel David Centre for Research in neuroscience and Brain program The Research Institute of the McGill University Health CentreMontrealQCCanada

Redox active metals such as iron,copper,zinc,and manganese play important roles in promoting a variety of biochemical reactions essential for cellular *** is made possible by the ability of these metals to accept and donate *** in the form of iron-sulfur clusters and heme plays a key role in adenosine triphosphate generation in mitochondria as well as numerous other enzymatic *** the other hand.

关键词： function. copper metals

Estimation of the density of neural,glial,and endothelial lineage cells in the adult mouse dentate gyrus

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Neural Regeneration Research 2022年第6期17卷 1286-1292页

作者： Joshua D.Rieskamp Patricia Sarchet Bryon M.Smith Elizabeth D.Kirby neuroscience Graduate program The Ohio State UniversityColumbusOHUSA Department of Psychology The Ohio State UniversityColumbusOHUSA Department of neuroscience The Ohio State UniversityColumbusOHUSA Chronic Brain Injury program The Ohio State UniversityColumbusOHUSA

The dentate gyrus subregion of the mammalian hippocampus is an adult neural stem cell niche and site of lifelong *** regarding the role of adult-born neuron synaptic integration in hippocampal circuit function are framed by robust estimations of adultborn versus pre/perinatally-born neuron *** contrast,the non-neurogenic functions of adult neural stem cells and their immediate progeny,such as secretion of bioactive growth factors and expression of extracellular matrix-modifying proteins,lack similar framing due to few estimates of their number versus other prominent secretory ***,we apply immunohistochemical methods to estimate cell density of neural stem/progenitor cells versus other major classes of glial and endothelial cell types that are potentially secretory in the dentate gyrus of adult *** the cell types quantified,we found that GFAP^(+)SOX2^(+)stellate astrocytes were the most numerous,followed by CD31^(+)endothelia,GFAP-SOX2^(+)intermediate progenitors,Olig2^(+)oligodendrocytes,Iba1+microglia,and GFAP^(+)SOX2^(+)radial glia-like neural stem *** did not observe any significant sex differences in density of any cell ***,neural stem/progenitor cells were present at a similar density as several cell types known to have potent functional roles via their *** findings may be useful for refining hypotheses regarding the contributions of these cell types to regulating hippocampal function and their potential therapeutic *** experimental protocols were approved by the Ohio State University Institutional Animal Care and Use Committee(protocol#2016A00000068)on July 14,2016.

关键词： adult neurogenesis dentate gyrus endothelia glia hippocampus neural stem cell secretome stereology

Ependymal cells and multiple sclerosis: proposing a relationship

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Neural Regeneration Research 2020年第2期15卷 263-264页

作者： Dale Hatrock Nina Caporicci-nucci Jo Anne Stratton The Montreal Neurological Institute McGill UniversityMontrealCanada Integrated program in neuroscience McGill UniversityMontrealCanada

Multiple sclerosis (MS) currently affects ~2.5 million people worldwide. MS is typically diagnosed in young adults and is usually not fatal, meaning people live long lives with MS. Affected individuals usually suffer from progressive physical and/or cognitive disability, often including fatigue (89.6%), depression (53.9%), memory loss (49.0%), motor or sensory dysfunction (76.4%, 70.4%) and urinary incontinence (50.8%).

关键词： multiple sclerosis relationship dysfunction