Forebrain excitatory neuron-specific loss of Brpf1 attenuates excitatory synaptic transmission and impairs spatial and fear memory

Bromodomain and plant homeodomain(PHD)finger containing protein 1(Brpf1)is an activator and scaffold protein of a multiunit complex that includes other components involving lysine acetyltransferase(KAT)6A/6B/7.Brpf1,KAT6A,and KAT6B mutations were identified as the causal genes of neurodevelopmental disorders leading to intellectual disability.Our previous work revealed strong and specific expression of Brpf1 in both the postnatal and adult forebrain,especially the hippocampus,which has essential roles in learning and memory.Here,we hypothesized that Brpf1 plays critical roles in the function of forebrain excitatory neurons,and that its deficiency leads to learning and memory deficits.To test this,we knocked out Brpf1 in forebrain excitatory neurons using CaMKIIa-Cre.We found that Brpf1 deficiency reduced the frequency of miniature excitatory postsynaptic currents and downregulated the expression of genes Pcdhgb1,Slc16a7,Robo3,and Rho,which are related to neural development,synapse function,and memory,thereby damaging spatial and fear memory in mice.These findings help explain the mechanisms of intellectual impairment in patients with BRPF1 mutation.

Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.

Transcriptional regulation in the development and dysfunction of neocortical projection neurons

Glutamatergic projection neurons generate sophisticated excitatory circuits to integrate and transmit information among different cortical areas,and between the neocortex and other regions of the brain and spinal cord.Appropriate development of cortical projection neurons is regulated by certain essential events such as neural fate determination,proliferation,specification,differentiation,migration,survival,axonogenesis,and synaptogenesis.These processes are precisely regulated in a tempo-spatial manner by intrinsic factors,extrinsic signals,and neural activities.The generation of correct subtypes and precise connections of projection neurons is imperative not only to support the basic cortical functions(such as sensory information integration,motor coordination,and cognition)but also to prevent the onset and progression of neurodevelopmental disorders(such as intellectual disability,autism spectrum disorders,anxiety,and depression).This review mainly focuses on the recent progress of transcriptional regulations on the development and diversity of neocortical projection neurons and the clinical relevance of the failure of transcriptional modulations.

基于数据挖掘技术的税务风险检测方法评述

Tax risk behavior causes serious loss of fiscal revenue,damages the country’s public infrastructure,and disturbs the market economic order of fair competition.In recent years,tax risk detection,driven by information technology such as data mining and artificial intelligence,has received extensive attention.To promote the high-quality development of tax risk detection methods,this paper provides the first comprehensive overview and summary of existing tax risk detection methods worldwide.More specifi-cally,it first discusses the causes and negative impacts of tax risk behaviors,along with the development of tax risk detection.It then focuses on data-mining-based tax risk detection methods utilized around the world.Based on the different principles employed by the algorithms,existing risk detection methods can be divided into two categories:relationship-based and non-relationship-based.A total of 14 risk detection methods are identified,and each method is thoroughly explored and analyzed.Finally,four major technical bottlenecks of current data-driven tax risk detection methods are analyzed and discussed,including the difficulty of integrating and using fiscal and tax fragmented knowledge,unexplainable risk detection results,the high cost of risk detection algorithms,and the reliance of existing algorithms on labeled information.After investigating these issues,it is concluded that knowledge-guided and datadriven big data knowledge engineering will be the development trend in the field of tax risk in the future;that is,the gradual transition of tax risk detection from informatization to intelligence is the future development direction.

CNKSR2 interactome analysis indicates its association with the centrosome/microtubule system

The protein connector enhancer of kinase suppressor of Ras 2(CNKSR2),present in both the postsynaptic density and cytoplasm of neurons,is a scaffolding protein with several protein-binding domains.Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders,particularly intellectual disability,although the precise mechanism involved has not yet been fully understood.Research has demonstrated that CNKSR2 plays a role in facilitating the localization of postsynaptic density protein complexes to the membrane,thereby influencing synaptic signaling and the morphogenesis of dendritic spines.However,the function of CNKSR2 in the cytoplasm remains to be elucidated.In this study,we used immunoprecipitation and high-resolution liquid chromatography-mass spectrometry to identify the interactors of CNKSR2.Through a combination of bioinformatic analysis and cytological experiments,we found that the CNKSR2 interactors were significantly enriched in the proteome of the centrosome.We also showed that CNKSR2 interacted with the microtubule protein DYNC1H1 and with the centrosome marker CEP290.Subsequent colocalization analysis confirmed the centrosomal localization of CNKSR2.When we downregulated CNKSR2 expression in mouse neuroblastoma cells(Neuro 2A),we observed significant changes in the expression of numerous centrosomal genes.This manipulation also affected centrosome-related functions,including cell size and shape,cell proliferation,and motility.Furthermore,we found that CNKSR2 interactors were highly enriched in de novo variants associated with intellectual disability and autism spectrum disorder.Our findings establish a connection between CNKSR2 and the centrosome,and offer new insights into the underlying mechanisms of neurodevelopmental disorders.

元宇宙视域下的IP运营研究:概念层次、风险机制和口碑传播

元宇宙的出现推动了文化数字化的进程,通过整理相关文献可以看出,现有的IP研究依旧存在若干理论缺口。首先,鲜有研究针对IP具体提炼出其在运营过程中存在的风险机制,以及对口碑造成的影响。其次,目前研究也依旧缺乏对IP的概念化讨论。因此,对在元宇宙视域下IP运营和概念化的深化研究十分必要。使用深入访谈法,访谈了35名IP粉丝,IP概念的三个层次得以提炼,包括作为基础的知识产权、延伸的文化品牌和进阶的元宇宙。同时探讨了在元宇宙时代,IP运营中出现的风险机制和口碑传播机制。

The Role of Music Therapy in Supporting Intellectually Disabled Youth in Senegal

Introduction: Music therapy is a practice for helping and supporting people with intellectual and relational difficulties. This study illustrated the benefits of music therapy for young people living with intellectual disabilities (YLID) in an African context. Methodology: This study investigated six young individuals with intellectual disabilities who had undergone three years of music therapy. They were participants in the inclusive non-academic training program at the National School of Arts in Dakar from 2017 to 2019. Data collection utilized individual interviews with the youths, evaluation grids from teachers and psychiatrists. Guardians provided informed consent along with the assent of the young participants. Results: The six young were aged between 18 and 30 years old, with an average age of 24.6 years. Four of the YLID were male. Three young people with intellectual disabilities had delayed psychomotor development. Observations revealed the beneficial influence of music therapy on the health and well-being of young individuals. Music played a role in alleviating stress and anxiety among youth with intellectual disabilities (YLID), enhancing their mood and mental health. It assisted in navigating challenging situations and heightened alertness among YLID. Additionally, music therapy contributed to improvements in dyslexia, fine and gross motor skills, and memory development among intellectually disabled youth, ultimately facilitating their integration into society. Conclusion: In light of our results, music therapy makes a major contribution to the empowerment of YLID. Engaging in musical activities helps young people connect with others through instrumental expression and a sense of accomplishment. By facilitating music therapy, it becomes possible to combat discrimination and stigmatization, thus promoting the social inclusion of intellectually disabled youth. Therefore, it is important to promote music therapy in Senegal to meet the needs of YLID.

Promoting High-quality Development of Grain and Oil in Ethnic Areas of the Yangtze River Economic Belt from the Perspective of Agricultural Power

Accelerating the construction of agricultural power,further promoting the high-quality development of the Yangtze River Economic Belt,and better supporting and serving Chinese-style modernization are the key issues at present.This paper first introduces the Yangtze River Economic Belt and its ethnic areas,and studies the characteristics of the grain and oil industry in the ethnic autonomous areas of the economic belt,as well as the current situation of various types of intellectual property resources,such as industrial cultural heritage,scientific and tech-nological innovation,and brand marking intellectual property.Besides,it analyzes the main problems in the high-quality development of grain and oil in the Yangtze River Economic Belt ethnic areas.Finally,it comes up with recommendations,including protecting the intellectual prop-erty rights of cultural heritage in the field of grain and oil,leading the inheritance and development of excellent traditional Chinese culture,use scientific and technological innovation intellectual property rights to promote the innovation-driven development strategy of the grain and oil in-dustry,and providing counterpart assistance to ethnic autonomous areas in the Yangtze River Economic Belt to further promote the high-quality development of the Yangtze River Economic Belt.

Scientific Data Intellectual Property Research by Literature Statistics

The main obstacle to the open sharing of scientific data is the lack of a legal protection system for intellectual property.This article analyzes the progress of research papers on intellectual property in scientific data in China through literature search and statistics.Currently,research subjects are unbalanced,research content is uneven,research methods are intellectual single,and research depth is insufficient.It is recommended that different stakeholders engage in deep cross disciplinary cooperation,further improve China’s legal and policy protection system for scientific data intellectual property,and promote the open sharing of scientific data.

Associated Factors of Dental Caries among Intellectually Disabled Persons in Specialized Centers of Ouagadougou

Introduction: Several studies have reported a high prevalence of dental caries among the people with intellectual disabilities. In order to identify the sociodemographic, clinical and behavioral factors associated with it, we conducted a study in specialized centers welcoming subjects with intellectual disabilities in Ouagadougou (Burkina Faso). Objectives: The objective of this study was to identify the factors associated with it among intellectually disabled in the specialized centers of Ouagadougou. Methods: The study was cross-sectional analytical. The survey took place between November 2020 and January 2021 among people with intellectual disabilities in reception centers receiving a grant from the Ministry of Women, National Solidarity, Family and Humanitarian Action. Data collection was done with a questionnaire adapted from the World Health Organization (WHO) and dental caries was recorded according to WHO criteria in decayed, missing or filled teeth generating a DMF index. Logistic regression was used to identify factors associated with the presence of dental caries. Results: A total of 193 participants were included in the study with an average age of 12.4 years ± 7.9. The overall prevalence of caries measured with the DMF index was 58.6% 95% CI [51.2 - 65.8]. It was significantly associated with female gender (OR = 4.2;95% CI [1.4 - 12.5], p = 0,01), the clinical form of mental illness (epilepsy OR = 3.8 95%;CI [1.2 - 12.7], p = 0,02, trisomy OR = 5.0;95% CI [1.1 - 22.9], p = 0,03, motor autonomy OR = 0.2 95%;CI [0.1 - 0.7], p = 0,01) and at use of toothpaste OR = 9.33;95% CI [1.05 - 82.7], p = 0,04. Conclusion: Dental caries remains a very present pathology in most people living with an intellectual disability. Also, it is necessary to put in place prevention strategies to reduce its prevalence and improve access to oral care for these people.

A Joint Cause

The World Intellectual Property Organization and Tsinghua University have jointly launched a master’s program to promote global intellectual property protection and innovation.

Understanding Behavioral Manifestations of Obsessive-Compulsive Disorder in People with Intellectual Disabilities—A Qualitative Study

Background: There is limited knowledge about obsessive-compulsive disorder (OCD) in people with intellectual disabilities (IDs). This paper describes the manifestation of compulsive behaviors associated with OCD at the behavioral level in people with ID in institutionalized settings. The aim was to gain nuanced insight into appropriate understanding and classification in this specific context, and derive implications for research and practice. Methods: Individual cases of people with ID (n = 7) were studied to assess compulsive symptoms through two days of on-site observation of the person with ID within the institution, guided group discussions (n = 28), and semi-structured interviews with key informants and caregivers of the person with ID (n = 20). Caregiver ratings of the compulsive behavior checklist were compiled. Data were analyzed using qualitative content analysis. Results: All forms of OCD were present. Characteristics of compulsive behaviors in people with ID at the behavioral level included less complex and more obvious compulsive acts, immediate responses, signs of tension, motor restlessness, facial expression changes, repetition, need for predictability, time-consuming behaviors, and aggressive reactions when these acts were interrupted. Some of the compulsive behaviors corresponded to the ICD-11 OCD code 6B20, and others to compulsions as a psychological symptom (MB23.4). Conclusions: OCD may manifest atypically at the behavioral level in people with ID, posing significant challenges for accurate classification due to symptom ambiguity. Follow-up differential diagnostic studies are needed to more accurately identify and differentiate OCD symptoms in people with ID. Further, disorder-specific guidelines for recognizing OCD in people with ID are needed for institutionalized settings without psychiatric-psychotherapeutic expertise.

Application of Automation and Intellectualization Technology in Steelmaking Plant

Steelmaking plant of Fujian San Gang min Guang Co.,Ltd.is keeping pace with the trend of the times.Under the new situation that the labor cost is rising day by day.Constantly introducing intelligent technology to improve the level of automation operation and reducing labor intensity of staff and workers.Especially under the support of MES information system.Advanced and practical technology is adopted in converter,refining and continuous casting process.In recent years,production management and control,energy management and control,material tracking,cost control and equipment operation and maintenance and reducing personnel to new achieve-ments in reducing personnel.

The basic core traditional C hinese medicine for the prevention and treatment of COVID-19 and its active mechanisms

Background:COVID-19 has had a dramatic impact on human health,economies,societies,and livelihoods around the world.Traditional Chinese medicine(TCM)formulae have played an important role in the prevention and treatment of COVID-19.WHO evaluated the role of TCM in treating of COVID-19 and encouraged other countries to promote the use of TCM formulae.However,the key is to find the basic core traditional Chinese medicine(BC-TCM)among those formulae.Methods:For the first time,we mined the data of TCM formulae in CNIPA and analyzed herb characteristics and association rules.We then determined the BC-TCM and screened main compounds and therapeutic targets.Finally,the potential molecular mechanisms were explored by using enrichment analyses and molecular docking.Results:This study screened 123 patented TCM formulae,including 312 herbs.According to frequency statistics and association rules,nine herbs(Gan Cao,Jin Yinhua,Guang Huoxiang,Fu Ling,Huang Qi,Jie Geng,Lian Qiao,Cang Zhu,Ku Xingren)were selected as the BC-TCM.The BC-TCM involved 166 main compounds and 48 therapeutic targets.The active compounds Hederagenin,Spinasterol,Beta-sitosterol,and Liquiritin had high binding activity to the COVID-19 targets 3CL,ACE2,and core targets RELA,HSP90AA1,STAT3,MAPK3,and TP53 according to molecular docking results.Interestingly,Hederagenin might be a potential compound for the prevention and treatment of COVID-19.Conclusion:Our research predicted and confirmed the preventive therapeutic effect of BC-TCM on COVID-19.This has the potential to broaden the scope of TCM,guide people in using clinical formulae,and provide valuable insights for future TCM discovery research.

Cyberattack Ramifications, The Hidden Cost of a Security Breach

In this in-depth exploration, I delve into the complex implications and costs of cybersecurity breaches. Venturing beyond just the immediate repercussions, the research unearths both the overt and concealed long-term consequences that businesses encounter. This study integrates findings from various research, including quantitative reports, drawing upon real-world incidents faced by both small and large enterprises. This investigation emphasizes the profound intangible costs, such as trade name devaluation and potential damage to brand reputation, which can persist long after the breach. By collating insights from industry experts and a myriad of research, the study provides a comprehensive perspective on the profound, multi-dimensional impacts of cybersecurity incidents. The overarching aim is to underscore the often-underestimated scope and depth of these breaches, emphasizing the entire timeline post-incident and the urgent need for fortified preventative and reactive measures in the digital domain.

Rape Breeding and Its Intellectual Property Protection in China

Rape is the third largest oil crop in the world and the first one in China.The national average rapeseed yield is only 2077.5 kg/hm^(2),and the rapeseed oil yield is 894 kg/hm^(2).This paper introduced the main types,germplasm resources,breeding bases and breeding progress of Chinese rape,and studied its high-quality varieties,breeding patents and new varieties of agricultural plants.We analyzed the main problems such as serious loss of germplasm resources in Brassica campestris L.and Brassica juncea(L.)Czern.et Coss and weak"agricultural chip"in rape field,and put forward strategies such as strengthening the protection of rape germplasm resources,encouraging the development of"agricultural chip"in rape industry clusters with national advantages and characteristics,and strengthening the protection of agricultural intellectual property rights.

Inheritance,Innovation and High-quality Development of Herbaceous Edible Oils in Hubei Province under the Strategy of Strengthening the Country with Intellectual Property

Only by improving the production capacity of domestic herbal edible oil can China ensure the safety of the supply chain of the important industrial chain of vegetable edible oil in China and practice the big food concept.In addition to rice,maize,and soybean for using as grain and oil,there are eight kinds of herbaceous edible oil crops in Hubei Province,including rape,peanut,sesame,sunflower,perilla(perilla seed),cotton,linen and tiger nut(Cyperus esculentus).This paper studies the main industries of herbaceous edible oil crops and their intellectual property resources in Hubei Province,and analyzes the main problems of its inheritance,innovation and high-quality development under the strategy of strengthening the country with intellectual property.Finally,it proposes the countermeasures of carrying forward and inheriting traditional knowledge and traditional culture,maintaining the biodiversity of crops,strengthening the creation of new plant varieties and breeding patents,and opening up the whole chain of intellectual property rights.

Intellectual Property Protection,Inheritance,Innovation and Development of Woody Edible Oilseeds in Hubei Province

Only by developing woody edible oilseeds industry can we ensure the safety of the important industrial chain and supply chain of vegetable edible oil in China.There are 13 kinds of woody edible oil plants in Hubei,including Camellia oleifera Abel(oil tea),Juglans regia L.(walnut),Olea europaea L.(olive)and Paeonia suffruticosa(oil peony).This paper studies the main industries of woody edible oilseeds in Hubei Province and their intellectual property resources,and analyzes the main problems in their intellectual property protection,inheritance,innovation and development.Finally,it proposes some strategies,including carrying forward the traditional knowledge related to woody edible oilseeds,innovating the"agricultural chip",creating key counties of national woody edible oil seeds,and developing industrial clusters with national advantages and characteristics.

Intellectual Property Protection and High-quality Development of Grape Industrial Clusters in Xinjiang

This paper introduced the grape industry in Xinjiang and its agricultural intellectual property resources,and analyzed six major problems such as the ineffective leading role of intellectual property rights in high-quality development.Finally,it proposed eight strategies to build a national-level regional fine-grain breeding base for grapes and develop“agricultural chips”in the context of the strategy of strengthening the country with intellectual property and innovation-driven development strategy.

Intellectual Property Protection and New Development Pattern Construction of Xinjiang Jujube

"Three new developments"is the guiding ideology of Chinese-style high-quality development in the new era.Jujube(Zizyphus jujube Mill.)is a plant of Zizyphus of Rhamnaceae,which originated in China and has been listed as one of the"five fruits"since ancient times.Xinjiang is the most important jujube producing area in China,and its yield has accounted for 50%of the national jujube yield.In the five prefectures and cities of southern Xinjiang,as well as the regimental farms of southern and eastern Xinjiang of Xinjiang Production and Construction Corps,the jujube industry is an advantageous characteristic industry in agriculture.This paper studied Xinjiang jujube industry and its agricultural intellectual property resources,analyzed six major issues to be further implemented,such as the"three new developments"thinking and the strategy of building an intellectual property power,and puts forward eight strategies such as coordinating the two markets and two resources to accelerate the construction of a new development pattern and dual circulation of jujube.