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Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis laboratory of Developmental biology Department of Biology University of Patras laboratory of Cellular and molecular Neurobiology-Stem Cells Hellenic Pasteur Institute 3. Department of Physiology School of Medicine University of Patras

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells (iPSCs) neurotrophic factors Parkinson's disease substantia

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Mitogenome-based phylogeny of mosquitoes(Diptera:Culicidae)

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Insect Science 2024年第2期31卷 599-612页

作者： De-Hong Chen Shu-Lin He Wen-Bo Fu Zhen-Tian Yan Yun-Jian Hu Huan Yuan Ming-Bin Wang Bin Chen Chongqing Key laboratory of Vector Insects Institute of Entomology and Molecular BiologyChongqing Normal UniversityChongqingChina

Mosquitoes are of great medical significance as vectors of many deadly diseases.Mitogenomes have been widely used in phylogenetic studies,but mitogenome knowledge within the family Culicidae is limited,and Culicidae phylogeny is far from resolved.In this study,we surveyed the mitogenomes of 149 Culicidae species,including 7 newly sequenced species.Comparative analysis of 149 mosquito mitogenomes shows gene composition and order to be identical to that of an ancestral insect,and the AT bias,length variation,and codon usage are all consistent with that of other reported Dipteran mitogenomes.Phylogenetic analyses based on the DNA sequences of the 13 protein-coding genes from the 149 species robustly support the monophyly of the subfamily Anophelinae and the tribes Aedini,Culicini,Mansonini,Sabethini,and Toxorhynchitini.To resolve ambiguous relationships between clades within the subfamily Culicinae,we performed topological tests and show that Aedini is a sister to Culicini and that Uranotaenini is a sister to(Mansonini)+(Toxorhynchitini+Sabethini).In addition,we estimated divergence times using a Bayesian relaxation clock based on the sequence data and 3 fossil calibration points.The results show mosquitoes diverged during the Early Jurassic with massive Culicinae radiations during the Cretaceous,coincident with the emergence of angiosperms and the burst of mammals and birds.Overall,this study,which uses the largest number of Culicidae mitogenomes sequenced to date,comprehensively reveals the mitogenome characteristics and mitogenome-based phylogeny and divergence times of Culicidae,providing information for further studies on the mitogenome,phylogeny,evolution,and taxonomic revision of Culicidae.

关键词： characterization Culicidae evolution mitogenomes mosquitoes phylogeny

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Classifying hepatitis B therapies with insights from covalently closed circular DNA dynamics

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Virologica Sinica 2024年第1期39卷 9-23页

作者： Jie-Li Hu Ai-Long Huang Key laboratory of molecular biology on Infectious Diseases Ministry of EducationChongqing Medical UniversityChongqing400016China

The achievement of a functional cure for chronic hepatitis B(CHB)remains limited to a minority of patients treated with currently approved drugs.The primary objective in developing new anti-HBV drugs is to enhance the functional cure rates for CHB.A critical prerequisite for the functional cure of CHB is a substantial reduction,or even eradication of covalently closed circular DNA(cccDNA).Within this context,the changes in cccDNA levels during treatment become as a pivotal concern.We have previously analyzed the factors influencing cccDNA dynamics and introduced a preliminary classification of hepatitis B treatment strategies based on these dynamics.In this review,we employ a systems thinking perspective to elucidate the fundamental aspects of the HBV replication cycle and to rationalize the classification of treatment strategies according to their impact on the dynamic equilibrium of cccDNA.Building upon this foundation,we categorize current anti-HBV strategies into two distinct groups and advocate for their combined use to significantly reduce cccDNA levels within a well-defined timeframe.

关键词： Hepatitis B cccDNA Functional cure Dynamics Treatment Strategy

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Microglia in drug addiction:A perspective from neuroimmunopharmacology

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Zoological Research 2024年第3期45卷 704-706页

作者： Cong Lin Xiaohui Wang laboratory of Chemical biology Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchunJilin 130022China Beijing National laboratory for molecular Sciences Beijing 100190China School of applied Chemistry and Engineering University of Science and Technology of ChinaHefeiAnhui 230026China

Drug addiction refers to a state of dependence that arises from habitual drug intake and can result in specific withdrawal symptoms upon cessation.The most commonly abused substances include psychostimulants,cannabinoids,and opioids.When drugs are consumed,they stimulate the release of dopamine,a neurotransmitter crucial for the pleasure and reward centers of the brain.With repeated drug use,the brain undergoes various changes,leading to tolerance,dependence,and addiction(Lüscher et al.,2020).The mechanisms involved in drug addiction are highly complex and involve diverse cell types within the brain.

关键词： addiction drugs intake

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Wood of trees:Cellular structure,molecular formation,and genetic engineering

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Journal of Integrative Plant biology 2024年第3期66卷 443-467页

作者： Yingying Zhu Laigeng Li State Key laboratory of Herbage Improvement and Grassland Agro-ecosystems and College of Ecology Lanzhou UniversityLanzhou 730000China National Key laboratory of Plant molecular Genetics CAS Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghai 200032China

Wood is an invaluable asset to human society due to its renewable nature,making it suitable for both sustainable energy production and material manufacturing.Additionally,wood derived from forest trees plays a crucial role in sequestering a significant portion of the carbon dioxide fixed during photosynthesis by terrestrial plants.Nevertheless,with the expansion of the global population and ongoing industrialization,forest coverage has been substantially decreased,resulting in significant challenges for wood production and supply.Wood production practices have changed away from natural forests toward plantation forests.Thus,understanding the underlying genetic mechanisms of wood formation is the foundation for developing high-quality,fast-growing plantation trees.Breeding ideal forest trees for wood production using genetic technologies has attracted the interest of many.Tremendous studies have been carried out in recent years on the molecular,genetic,and cell-biological mechanisms of wood formation,and considerable progress and findings have been achieved.These studies and findings indicate enormous possibilities and prospects for tree improvement.This review will outline and assess the cellular and molecular mechanisms of wood formation,as well as studies on genetically improving forest trees,and address future development prospects.

关键词： cambium cell wall Populus wood formation xylem

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Pyruvate kinase M in germ cells is essential for sperm motility and male fertility but not spermatogenesis

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Asian Journal of Andrology 2024年第2期26卷 212-219页

作者： Gao-Qing Qian Xiao-Chen Wang Xi Zhang Bin Shen Qiang Liu State Key laboratory of Reproductive Medicine and Offspring Health Nanjing Medical UniversityNanjing 211166China Shanghai Key laboratory of Reproductive Medicine Department of HistoembryologyGenetics and Developmental BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China State Key laboratory of molecular biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China

Male germ cells employ specific metabolic pathways throughout their developmental stages.In a previous study,we discovered heightened expression of pyruvate kinase M(PKM),a pivotal glycolytic enzyme,in spermatogonia and spermatids.To gain deeper insights into PKM's roles in spermatogenesis,sperm function,and male fertility,we engineered a conditional-knockout mouse model(Pkm-vkO mice)to selectively disrupt the Pkm gene within germ cells.Despite maintaining regular testicular histology and sperm morphology,the male Pkm-vko mice were infertility,characterized by significant impairments in sperm motility and adenosine triphosphate(ATP)generation.In addition,Pkm-null spermatozoa exhibited similar deficits in protein tyrosine phosphorylation linked to capacitation,as well as compromised performance in in vitro fertilization experiments.To conclude,PKM's presence is not obligatory for the entirety of spermatogenesis in male germ cells;however,it emerges as a critical factor influencing sperm motility and overall male fertility.

关键词： glycolysis male fertility pyruvate kinase M sperm motility spermatogenesis

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The piRNA size matters

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National Science Review 2024年第2期11卷 96-98页

作者： Jingwen Liu Falong Lu State Key laboratory of molecular Developmental biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences University of Chinese Academy of Sciences

Small RNAs, including small interfering RNAs(siRNAs), microRNAs(miRNAs) and PIWI-interacting RNAs(piRNAs), serve as pivotal agents in the post-transcriptional regulation of gene expression [1–3]. Among these,piRNAs t... 详细信息

关键词： PIWI

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Potential of molecular chaperones for treating Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2343-2344页

作者： Gefei Chen Jan Johansson Department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Department of Cell and molecular biology Uppsala UniversityUppsalaSweden

Alzheimer’s disease(AD)is the most prevalent form of dementia,i.e.,progressive memory loss and profound cognitive dysfunction,resulting in a considerable societal burden.At the neuropathological level,the brains of AD patients exhibit amyloid-β(Aβ)plaques,neurofibrillary tangles,and neuroinflammation(Sala Frigerio and De Strooper,2016).

关键词： Alzheimer inflammation Aβ

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Stereoselective recognition of morphine enantiomers by μ-opioid receptor

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National Science Review 2024年第3期11卷 183-191页

作者： Yibo Wang Van A.Ngo Xiaohui Wang laboratory of Chemical biology Changchun Institute of Applied ChemistryChinese Academy of Sciences Advanced Computing for Life Sciences and Engineering Group Science Engagement Section National Center for Computational Sciences Oak Ridge National Lab School of applied Chemistry and Engineering University of Science and Technology of China Beijing National laboratory for molecular Sciences

Stereospecific recognition of chiral molecules plays a crucial role in biological systems. The μ-opioid receptor（MOR） exhibits binding affinity towards（-）-morphine, a well-established gold standard in pain management, while it shows minimal binding affinity for the（+）-morphine enantiomer, resulting in a lack of analgesic activity. Understanding how MOR stereoselectively recognizes morphine enantiomers has remained a puzzle in neuroscience and pharmacology for over half-a-century due to the lack of direct observation techniques. To unravel this mystery, we constructed the binding and unbinding processes of morphine enantiomers with MOR via molecular dynamics simulations to investigate the thermodynamics and kinetics governing MOR's stereoselective recognition of morphine enantiomers. Our findings reveal that the binding of（-）-morphine stabilizes MOR in its activated state, exhibiting a deep energy well and a prolonged residence time. In contrast,（+）-morphine fails to sustain the activation state of MOR.Furthermore, the results suggest that specific residues, namely D1142.50and D1473.32, are deprotonated in the active state of MOR bound to（-）-morphine. This work highlights that the selectivity in molecular recognition goes beyond binding affinities, extending into the realm of residence time.

关键词： stereoselective recognition thermodynamics and kinetics residence time morphine enantiomers μ-opioid receptor

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Mechanisms underlying key agronomic traits and implications for molecular breeding in soybean

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Journal of Genetics and Genomics 2024年第4期51卷 379-393页

作者： Chao Fang Haiping Du Lingshuang Wang Baohui Liu Fanjiang Kong Guangdong Key laboratory of Plant Adaptation and molecular Design Guangzhou Key Laboratory of Crop Gene EditingInnovative Center of Molecular Genetics and EvolutionSchool of Life SciencesGuangzhou UniversityGuangzhouGuangdong 510006China

Soybean(Glycine max[L.]Merr.)is an important crop that provides protein and vegetable oil for human consumption.As soybean is a photoperiod-sensitive crop,its cultivation and yield are limited by the photoperiodic conditions in the field.In contrast to other major crops,soybean has a special plant architecture and a special symbiotic nitrogen fixation system,representing two unique breeding directions.Thus,flowering time,plant architecture,and symbiotic nitrogen fixation are three critical or unique yielddetermining factors.This review summarizes the progress made in our understanding of these three critical yield-determining factors in soybean.Meanwhile,we propose potential research directions to increase soybean production,discuss the application of genomics and genomic-assisted breeding,and explore research directions to address future challenges,particularly those posed by global climate changes.

关键词： Soybean Grain yield Flowering time Plant architecture Nodulation Symbiotic nitrogen fixation Genome study

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