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Therapeutic advances in neural regeneration for Huntington’s disease

Neural Regeneration Research 2024年第9期19卷 1991-1997页

作者： Francesco D’Egidio Vanessa Castelli Giorgia Lombardozzi Fabrizio Ammannito Annamaria Cimini Michele d’Angelo department of life Health and Environmental SciencesUniversity of L’AquilaL’AquilaItaly

Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to overcome the neurodegeneration. In this view, num

关键词： cell therapy exosomes extracellular vesicles Huntingtin Huntington’s disease medium spiny neurons neurodegenerative disease neurogenesis neuronal loss stem cells

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Impact of tourism on the vigilance behavior of the Cyprus rock agama(Laudakia cypriaca)

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Integrative Zoology 2024年第3期19卷 577-583页

作者： Artur GOLAWSKI Iris CHARALAMBIDOU Sylwia GOLAWSKA Faculty of sciences Siedlce University of Natural Sciences and HumanitiesSiedlcePolandand department of life sciences School of Life and Health SciencesUniversity of NicosiaNicosiaCyprus

Escape behavior is a common antipredator strategy among wild animals.Here,we investigated the effect of four factors on the vigilance behavior of the endemic Cyprus rock agama(Laudakia cypriaca).Flight initiation distance(FID,the minimum distance to which an observer can approach a lizard before it flees)was measured in relation to the type of location(tourist vs.nontourist area),the observer’s starting distance,air temperature,and substrate temperature.We collected data for 39 agamas in tourist areas and 34 of these lizards in nontourist areas.As a whole,the mean starting distance was 10.5 m and the FID was 3.6 m.The average substrate temperature was 34.0℃ and the average air temperature 29.6℃.Only the type of area affected the agamas’escape decisions with FID being 1.8 m shorter in tourist areas than in nontourist areas(2.7 m vs.4.5 m).This is probably due to the habituation of lizards to the presence of humans in the former areas.This study shows that tourism strongly affects the behavior of lizards,which may have consequences for the functioning of the population.Tourists can increase the safety of lizards by creating a human shield to deter predators.Once the tourist season is over,lizards may become more vulnerable to predators.

关键词： anthropogenic disturbance flight initiation distance lizards tourism vigilance behavior

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NFXL1 functions as a transcriptional activator required for thermotolerance at reproductive stage in Arabidopsis

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Journal of Integrative Plant Biology 2024年第1期66卷 54-65页

作者： Qiao‐Yun Zhu Lin‐Lin Zhang Jian‐Xiang Liu State Key Laboratory of Plant environmental Resilience College of Life SciencesZhejiang UniversityHangzhou 310027China

Plants are highly susceptible to abiotic stresses,particularly heat stress during the reproductive stage.However,the specific molecular mechanisms underlying this sensitivity remain largely unknown.In the current study,we demonstrate that the Nuclear Transcription Factor,X-box Binding Protein 1-Like 1(NFXL1),directly regulates the expression of DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN 2A(DREB2A),which is crucial for reproductive thermotolerance in Arabidopsis.NFXL1 is upregulated by heat stress,and its mutation leads to a reduction in silique length(seed number)under heat stress conditions.RNA-Seq analysis reveals that NFXL1 has a global impact on the expression of heat stress responsive genes,including DREB2A,Heat Shock Factor A3(HSFA3)and Heat Shock Protein 17.6(HSP17.6)in flower buds.Interestingly,NFXL1 is enriched in the promoter region of DREB2A,but not of either HSFA3 or HSP17.6.Further experiments using electrophoretic mobility shift assay have confirmed that NFXL1 directly binds to the DNA fragment derived from the DREB2A promoter.Moreover,effector-reporter assays have shown that NFXL1 activates the DREB2A promoter.The DREB2A mutants are also heat stress sensitive at the reproductive stage,and DEREB2A is epistatic to NFXL1 in regulating thermotolerance in flower buds.It is known that HSFA3,a direct target of DREB2A,regulates the expression of heat shock proteins genes under heat stress conditions.Thus,our findings establish NFXL1 as a critical upstream regulator of DREB2A in the transcriptional cassette responsible for heat stress responses required for reproductive thermotolerance in Arabidopsis.

关键词： Arabidopsis DREB2A heat stress NFXL1 reproductive thermotolerance

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Breaking the brain barrier:cell competition in neural development and disease

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Neural Regeneration Research 2024年第9期19卷 1863-1864页

作者： Patrizia Morciano Daniela Grifoni department of“life Health and Environmental Sciences”University of L’AquilaItaly “INFN-Laboratori Nazionali del Gran Sasso” AssergiItaly

General information on cell competition:Social behaviors are the basis of biological life.Like species and populations,cell communities experience Darwinian ecological interactions,and in case space and nutrient avail... 详细信息

关键词： neural barrier throughout

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Immune checkpoint inhibitors:breakthroughs in cancer treatment

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Cancer Biology & Medicine 2024年第6期21卷 451-472页

作者： Xueqing Kong Jinyi Zhang Shuwei Chen Xianyang Wang Qing Xi Han Shen Rongxin Zhang Laboratory of Immunology and Inflammation School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University department of Biology School of Life Sciences and Biopharmaceutics Guangdong Pharmaceutical University

Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade(ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies(mAbs) are currently available as immune checkpoint inhibitors(ICIs). These ICIs target specific immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4) and programmed cell death protein 1(PD-1). Clinical trial results strongly support the feasibility of this immunotherapeutic approach. However, a substantial proportion of patients with cancer develop resistance or tolerance to treatment, owing to tumor immune evasion mechanisms that counteract the host immune response.Consequently, substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1, anti-programmed cell death ligand 1(anti-PD-L1), and anti-CTLA-4 treatments. Recently, several immune checkpoint molecular targets have been identified, such as T cell immunoreceptor with Ig and ITIM domains(TIGIT), mucin domain containing-3(TIM-3), lymphocyte activation gene-3(LAG-3), V-domain immunoglobulin suppressor of T cell activation(VISTA), B and T lymphocyte attenuator(BTLA), and signal-regulatory protein α(SIRPα). Functional m Abs targeting these molecules are under development. CTLA-4, PD-1/PD-L1, and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of research. This review discusses these structures, as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.

关键词： CTLA-4 ICIs Immunotherapy PD-1 cancer

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Botrytis cinerea-induced F-box protein 1 enhances disease resistance by inhibiting JAO/JOX-mediated jasmonic acid catabolism in Arabidopsis

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Molecular Plant 2024年第2期17卷 297-311页

作者： Min Zhang Weiwei Li Tingyu Zhang Yueyan Liu Lijing Liu The Key Laboratory of Plant Development and environmental Adaptation Biology Ministry of EducationSchool of Life SciencesShandong UniversityQingdao 266237China

Jasmonic acid(JA)is a crucial phytohormone that regulates plant immunity.The endogenous JA level is determined by the rates of its biosynthesis and catabolism in plants.The activation of JA biosynthesis has been well documented;however,how plants repress JA catabolism upon pathogen infection remains elusive.In this study,we identified and characterized Botrytis cinerea-induced F-box protein 1(BFP1)in Arabidopsis.The expression of BFP1 was induced by B.cinerea in a JA signaling-dependent manner,and BFP1 protein was critical for plant defense against B.cinerea and plant response to JA.In addition,BFP1 overexpression increased plant defenses against broad-spectrum pathogens without fitness costs.Further experiments demonstrated that BFP1 interacts with and mediates the ubiquitination and degrada-tion of jasmonic acid oxidases(JAOs,also known as jasmonate-induced oxygenases,JoXs),the enzymes that hydroxylate JA to 12OH-JA.Consistent with this,BFP1 affects the accumulation of JA and 12OH-JA during B.cinerea infection.Moreover,mutation of JAo2 complemented the phenotypes of the bfp1 mutant.Collectively,our results unveil a new mechanism used by plants to activate immune responses upon path-ogeninfection:suppressing JA catabolism.

关键词： plant immunity BFP1 JAO/JOXs JA catabolism ubiquitination-mediated degradation

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Antisense therapy:a potential breakthrough in the treatment of neurodegenerative diseases

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Neural Regeneration Research 2024年第5期19卷 1027-1035页

作者： Roberta Romano Cecilia Bucci department of Biological and environmental sciences and Technologies(DiSTeBA) University of SalentoLecceItaly

Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis antisense oligonucleotide Huntington’s disease neurodegenerative disorders Parkinson’s disease siRNA

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Dynamic foraging strategy adaptation to heterogeneous environments contributes to social aggregation in snub-nosed monkeys

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Zoological Research 2024年第1期45卷 39-54页

作者： Lan Zhao Sheng-Nan Ji Xiao-Bing Du Jia-Hui Liu Bo-Lun Zhang Pei-Hua Li Yi-Jun Yang Bao-Guo Li Yan-Qing Guo Xiao-Guang Qi College of life sciences Northwest UniversityXi’anShaanxi 710069China Chengdu Institute of Biology Chinese Academy of SciencesChengduSichuan 610041China State Key Laboratory of environmental Criteria and Risk Assessment Chinese Research Academy of Environmental SciencesBeijing 100012China

The dynamics of animal social structures are heavily influenced by environmental patterns of competition and cooperation.In folivorous colobine primates,prevailing theories suggest that larger group sizes should be favored in rainforests with a year-round abundance of food,thereby reducing feeding competition.Yet,paradoxically,larger groups are frequently found in high-altitude or high-latitude montane ecosystems characterized by a seasonal scarcity of leaves.This contradiction is posited to arise from cooperative benefits in heterogeneous environments.To investigate this hypothesis,we carried out a six-year field study on two neighboring groups of golden snub-nosed monkey(Rhinopithecus roxellana),a species representing the northernmost distribution of colobine primates.Results showed that the groups adjusted their movement and habitat selection in response to fluctuating climates and spatiotemporal variability of resources,indicative of a dynamic foraging strategy.Notably,during the cold,resource-scarce conditions in winter,the large group occupied food-rich habitats but did not exhibit significantly longer daily travel distances than the smaller neighboring group.Subsequently,we compiled an eco-behavioral dataset of 52 colobine species to explore their evolutionary trajectories.Analysis of this dataset suggested that the increase in group size may have evolved via home range expansion in response to the cold and heterogeneous climates found at higher altitudes or latitudes.Hence,we developed a multi-benefits framework to interpret the formation of larger groups by integrating environmental heterogeneity.In cold and diverse environments,even smaller groups require larger home ranges to meet their dynamic survival needs.The spatiotemporal distribution of high-quality resources within these expanded home ranges facilitates more frequent interactions between groups,thereby encouraging social aggregation into larger groups.This process enhances the benefits of collaborative actions and reproductive opportunities,whi

关键词： Social evolution Folivore paradox MLS Rhinopithecus roxellana Multi-benefits framework

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How variable progenitor clones construct a largely invariant neocortex

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National Science Review 2024年第1期11卷 129-144页

作者： Zhongfu Shen Jiajun Yang Qiangqiang Zhang Kuiyu Wang Xiaohui Lv Xiaolin Hu Jian Ma Song-Hai Shi New Cornerstone Science Laboratory IDG/McG overn Institute for Brain Research Tsinghua-Peking Center for Life Sciences Beijing Frontier Research Center for Biological Structure School of Life Sciences Tsinghua University department of Computer sciences Tsinghua University College of life sciences Nankai University Chinese Institute for Brain Research

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors(RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.

关键词： neocortex radial glial progenitor intermediate progenitor neurogenesis clonal variability layer formation

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TBBPA rather than its main derivatives enhanced growth of endometrial cancer via p53 ubiquitination

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Journal of environmental sciences 2024年第3期137卷 82-95页

作者： Hongyan Yu Jingxu Zhang Jing Liu Ruonan Pan Yu Wang Xiaoting Jin Rifat Zubair Ahmed Yuxin Zheng department of Occupational Health and environmental Health School of Public HealthQingdao UniversityQingdao 266071China State Key Laboratory of environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China department of Genetics University of KarachiKarachi 75270Pakistan

Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and biota.Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer(EC),the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain unclear.The present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC,and the crucial mechanism on the progression of EC caused by bromine fame retardants exposure.In this research,TBBPA and two of the most common TBBPA derivatives including TBBPA bis(2-hydroxyethyl ether)(TBBPABHEE)and TBBPA bis(dibromopropyl ether)(TBBPA-BDBPE)were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice model.Under environmental concentrations,TBBPA promoted the proliferation of EC,the main derivatives of TBBPA(TBBPA-BHEE and TBBPA-BDBPE)did not present the similar facilitation effects.The ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation,which resulted in the increase of downstream cell cycle and decrease of apoptosis.The further molecular docking result suggested the high affinity between TBBPA and ubiquitinated proteasome.This finding revealed the effects of TBBPA and its derivatives on EC proliferation,thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.

关键词： Tetrabromobisphenol A(TBBPA) Endometrial cancer(EC) Derivatives Ubiquitin proteases p53

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