Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord injury.However,the precise mechanism remains unclear.To investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial subpopulations.We found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high levels.Subsequently,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord injury.Finally,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron cells.Inhibiting ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced pyroptosis.Furthermore,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling pathway.Inhibiting ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological function.Pla2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling pathway.Collectively,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

Olfactory receptors in neural regeneration in the central nervous system

Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental monitoring.The ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous system.Insights gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent deficits.Understanding the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's disease.Olfa ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian body.This ectopic expression provides insights into the chemical structures that can activate olfactory receptors.In addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing microbiota.The analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation mechanisms.This review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative processes.Evidence suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous system injuries.

Secure Channel Estimation Using Norm Estimation Model for 5G Next Generation Wireless Networks

The emergence of next generation networks(NextG),including 5G and beyond,is reshaping the technological landscape of cellular and mobile networks.These networks are sufficiently scaled to interconnect billions of users and devices.Researchers in academia and industry are focusing on technological advancements to achieve highspeed transmission,cell planning,and latency reduction to facilitate emerging applications such as virtual reality,the metaverse,smart cities,smart health,and autonomous vehicles.NextG continuously improves its network functionality to support these applications.Multiple input multiple output(MIMO)technology offers spectral efficiency,dependability,and overall performance in conjunctionwithNextG.This article proposes a secure channel estimation technique in MIMO topology using a norm-estimation model to provide comprehensive insights into protecting NextG network components against adversarial attacks.The technique aims to create long-lasting and secure NextG networks using this extended approach.The viability of MIMO applications and modern AI-driven methodologies to combat cybersecurity threats are explored in this research.Moreover,the proposed model demonstrates high performance in terms of reliability and accuracy,with a 20%reduction in the MalOut-RealOut-Diff metric compared to existing state-of-the-art techniques.

Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary target.Although progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease initiation.Based on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom onset.Since 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for regeneration.Current Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the disease.Skeletal muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal phase.The accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real time.The advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and metabolites.This technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of disease.There are two major goals of this review.The first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activity,evidence of a similar dysregulation in the SOD1G93A mouse during presymptomatic stages,and evidence of progressive change during disease progression.The second goal is to review the molecular pathways these biomarkers reflect and their potential role in mitigating or promoting disease progression,and as such,their potential as therapeutic targets in amyotrophic lateral sclerosis.

On the Cosmic Evolution of the Quantum Vacuum Using Two Variable G Models and Winterberg’s Thesis

We work within a Winterberg framework where space, i.e., the vacuum, consists of a two component superfluid/super-solid made up of a vast assembly (sea) of positive and negative mass Planck particles, called planckions. These material particles interact indirectly, and have very strong restoring forces keeping them a finite distance apart from each other within their respective species. Because of their mass compensating effect, the vacuum appears massless, charge-less, without pressure, net energy density or entropy. In addition, we consider two varying G models, where G, is Newton’s constant, and G-1, increases with an increase in cosmological time. We argue that there are at least two competing models for the quantum vacuum within such a framework. The first follows a strict extension of Winterberg’s model. This leads to nonsensible results, if G increases, going back in cosmological time, as the length scale inherent in such a model will not scale properly. The second model introduces a different length scale, which does scale properly, but keeps the mass of the Planck particle as, ± the Planck mass. Moreover we establish a connection between ordinary matter, dark matter, and dark energy, where all three mass densities within the Friedman equation must be interpreted as residual vacuum energies, which only surface, once aggregate matter has formed, at relatively low CMB temperatures. The symmetry of the vacuum will be shown to be broken, because of the different scaling laws, beginning with the formation of elementary particles. Much like waves on an ocean where positive and negative planckion mass densities effectively cancel each other out and form a zero vacuum energy density/zero vacuum pressure surface, these positive mass densities are very small perturbations (anomalies) about the mean. This greatly alleviates, i.e., minimizes the cosmological constant problem, a long standing problem associated with the vacuum.

5G数据通信演进研究

在当前的数字时代,上网已成为每个家庭和个人的生活刚需,而上网产生的通信就是数据通信。上网方式主要分为有线和无线两种,无线上网能够做到随时随地冲浪无忧,而5G上网能为用户提供高速上网新体验。文章描述2G时代GPRS(通用分组无线服务)网络和CDMA(码分多址)网络数据通信架构,分析3G时代WCDMA(宽带码分多址)网络数据通信架构变化,给出4G时代LTE(长期演进)上网原理,说明5G时代网络功能对上网的支撑作用。

计及5G基站及需求响应的综合能源系统日前优化调度

5G基站的大量接入为综合能源系统(IES)的低碳化发展注入了新的活力,通过激励5G基站参与需求响应并将其纳入IES的调度框架,可以有效促进IES的节能减排,并提高IES整体的经济效益。据此,提出了一种考虑5G基站低碳赋能的IES日前调度模型。首先,分析了5G基站内部的基本结构及主要能耗,构建了5G基站与IES系统的灵活互动模型;其次,构建了基于弹性矩阵的价格型需求响应模型以及基于电能-热能相互转换的替代型需求响应模型,并以调度成本最低为目标函数构建了IES日前调度模型;与此同时,针对可再生能源出力的不确定性,采用信息间隙决策理论对其进行处理,进一步构建了IES风险规避鲁棒模型。最后,以某IES系统为例,通过多种典型运行场景验证了所构模型以及所提算法的有效性。

Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Satellite Communications with 5G, B5G, and 6G: Challenges and Prospects

Satellite communications, pivotal for global connectivity, are increasingly converging with cutting-edge mobile networks, notably 5G, B5G, and 6G. This amalgamation heralds the promise of universal, high-velocity communication, yet it is not without its challenges. Paramount concerns encompass spectrum allocation, the harmonization of network architectures, and inherent latency issues in satellite transmissions. Potential mitigations, such as dynamic spectrum sharing and the deployment of edge computing, are explored as viable solutions. Looking ahead, the advent of quantum communications within satellite frameworks and the integration of AI spotlight promising research trajectories. These advancements aim to foster a seamless and synergistic coexistence between satellite communications and next-gen mobile networks.

5G向6G演进过程中的发展困境及未来6G发展建议

[目的/意义]5G及下一代移动通信网络作为落实网络强国、数字中国建设的重要新型基础设施之一,为深化传统产业数字化转型提供了升级动力。5G行业应用在我国得到快速发展的同时,也面临诸多的问题与困境,这是5G向6G演进过程中无法绕开的关键。本文旨在借鉴5G经验,探索方法提高6G关键能力和行业需求的匹配程度,为6G走出5G困境寻求方向。[方法/过程]本文结合未来数字化场景针对6G关键能力的全面梳理,从6G发展需要破解的两大困境出发,基于专家调研获取的未来数字化场景针对6G关键能力的需求程度数据,构建6G典型场景需求评估及6G垂直行业潜在价值空间评估模型。在此基础上,识别6G在各行业应用发展中具有共性的、应优先关注或值得推广的典型场景,为6G在不同行业的多波次推进提供策略依据。[结果/结论]基于模型输出,本文提出了“6G发展以场景为引、按需部署,破解需求和效益的发展困境”“尽早推动6G商业闭环顶层设计,提升技术与需求匹配度”“统筹5G和6G发展,加强产业培育,基于5G为6G挖掘需求并验证”等6G发展建议,并指出从需求和效益出发,优先针对潜在价值高的特定场景的技术演进是未来6G可持续发展的重要研究方向。

Information Centric Networking Based Cooperative Caching Framework for 5G Communication Systems

The demands on conventional communication networks are increasing rapidly because of the exponential expansion of connected multimedia content.In light of the data-centric aspect of contemporary communication,the information-centric network(ICN)paradigm offers hope for a solution by emphasizing content retrieval by name instead of location.If 5G networks are to meet the expected data demand surge from expanded connectivity and Internet of Things(IoT)devices,then effective caching solutions will be required tomaximize network throughput andminimize the use of resources.Hence,an ICN-based Cooperative Caching(ICN-CoC)technique has been used to select a cache by considering cache position,content attractiveness,and rate prediction.The findings show that utilizing our suggested approach improves caching regarding the Cache Hit Ratio(CHR)of 84.3%,Average Hop Minimization Ratio(AHMR)of 89.5%,and Mean Access Latency(MAL)of 0.4 s.Within a framework,it suggests improved caching strategies to handle the difficulty of effectively controlling data consumption in 5G networks.These improvements aim to make the network run more smoothly by enhancing content delivery,decreasing latency,and relieving congestion.By improving 5G communication systems’capacity tomanage the demands faced by modern data-centric applications,the research ultimately aids in advancement.

Historical tillage promotes grass-legume mixtures establishment and accelerates soil microbial activity and organic carbon decomposition

Perennial grass-legume mixtures have been extensively used to restore degraded grasslands,increasing grassland productivity and forage quality.Tillage is crucial for seedbed preparation and sustainable weed management for the establishment of grass-legume mixtures.However,a common concern is that intensive tillage may alter soil characteristics,leading to losses in soil organic carbon(SOC).We investigated the plant community composition,SOC,soil microbial biomass carbon(MBC),soil enzyme activities,and soil properties in long-term perennial grass-legume mixtures under two different tillage intensities(once and twice)as well as in a fenced grassland(FG).The establishment of grass-legume mixtures increased plant species diversity and plant community coverage,compared with FG.Compared with once tilled grassland(OTG),twice tilled grassland(TTG)enhanced the coverage of high-quality leguminous forage species by 380.3%.Grass-legume mixtures with historical tillage decreased SOC and dissolved organic carbon(DOC)concentrations,whereas soil MBC concentrations in OTG and TTG increased by 16.0%and 16.4%,respectively,compared with FG.TTG significantly decreased the activity of N-acetyl-β-D-glucosaminidase(NAG)by 72.3%,whereas soil enzymeβ-glucosidase(βG)in OTG and TTG increased by 55.9%and 27.3%,respectively,compared with FG.Correlation analysis indicated a close association of the increase in MBC andβG activities with the rapid decline in SOC.This result suggested that MBC was a key driving factor in soil carbon storage dynamics,potentially accelerating soil carbon cycling and facilitating biogeochemical cycling.The establishment of grass-legume mixtures effectively improves forage quality and boosts plant diversity,thereby facilitating the restoration of degraded grasslands.Although tillage assists in establishing legume-grass mixtures by controlling weeds,it accelerates microbial activity and organic carbon decomposition.Our findings provide a foundation for understanding the process and effectiveness of restoration management in degraded grasslands.

Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

Design of an Interconnection Architecture and Sizing of Two (2) EPC Core Networks: The Case of Orange-Guinea

With the arrival of the 4G and 5G,the telecommunications networks have experienced a large expansion of these networks.That enabled the integration of many services and adequate flow,thus enabling the operators to respond to the growing demand of users.This rapid evolution has given the operators to adapt,their methods to the new technologies that increase.This complexity becomes more important,when these networks include several technologies to access different from the heterogeneous network like in the 4G network.The dimensional new challenges tell the application and the considerable increase in demand for services and the compatibility with existing networks,the management of mobility intercellular of users and it offers a better quality of services.Thus,the proposed solution to meet these new requirements is the sizing of the EPC(Evolved Packet Core)core network to support the 5G access network.For the case of Orange Guinea,this involves setting up an architecture for interconnecting the core networks of Sonfonia and Camayenne.The objectives of our work are of two orders:(1)to propose these solutions and recommendations for the heart network EPC sizing and the deployment to be adopted;(2)supply and architectural interconnection in the heart network EPC and an existing heart network.In our work,the model of traffic in communication that we use to calculate the traffic generated with each technology has link in the network of the heart.

Integrated Sensing and Communication:Who Benefits More?

This paper compares the benefits of communication-assisted sensing and sensing-assisted communication in the context of integrated sensing and communication(ISAC).Communication-assisted sensing leverages the extensive cellular infrastructure to create a vast and cooperative sensor network,enhancing environmental perception accuracy and coverage.On the other hand,sensing-assisted communication utilizes advanced sensing technologies to improve predictive beamforming and channel estimation performance in high-frequency and highmobility scenarios,thereby increasing communication efficiency and reliability.To validate our analysis,we present an example of channel knowledge map(CKM)-assisted beam tracking.This example demonstrates the practical advantages of incorporating CKM in enhancing beam tracking accuracy.Our analysis confirms that communication-assisted sensing may offer greater development potential due to its wide coverage and cost-effectiveness in large-scale applications.

Kisspeptin regulates gonadotropin-releasing hormone secretion in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats

Kisspeptin is essential for activation of the hypothalamo-pituitary-gonadal axis. In this study, we established gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. Rats were injected with 1, 10, or 100 pM kisspeptin-10, a peptide derived from full-length kisspeptin, into the arcuate nucleus and medial preoptic area, and with the kJsspeptJn antagonist peptJde 234 into the lateral cerebral ventricle. The results of immunohistochemical staining revealed that pulsatile luteinizing hormone secretion was suppressed after injection of antagonist peptide 234 into the lateral cerebral ventricle, and a significant increase in luteinizing hormone level was observed after kisspeptin-10 injection into the arcuate nucleus and medial preoptic area. The results of an enzyme-linked immunosorbent assay showed that luteinizing hormone levels during the first hour of kisspeptin-10 infusion into the arcuate nucleus were significantly greater in the 100 pM kisspeptin-10 group than in the 10 pM kisspeptin-10 group. These findings indicate that kisspeptin directly promotes gonadotropin-releasing hormone secretion and luteinizing hormone release in gonadotropin-releasing hormone/enhanced green fluorescent protein transgenic rats. The arcuate nucleus is a key component of the kisspeptin-G protein-coupled receptor 54 signaling pathway underlying regulating luteinizing hormone pulse secretion.

免疫球蛋白G4相关性疾病研究进展

免疫球蛋白G4相关性疾病(IgG4-related disease IgG4-RD)是一种影响多器官的慢性系统性自身免疫性疾病。几乎可以累及全身任何组织器官,其中消化系统受累较为常见。IgG4-RD病因及发病机制仍未完全阐明,其诊断需联合辅助检查,综合评估,但组织病理活检仍是诊断IgG4-RD的金标准。目前认为糖皮质激素仍是IgG4-RD的一线治疗。本文通过对IgG4-RD的研究进展进行综述,旨在为临床提供参考。

宿主细胞敲除G3BP2基因对塞内卡病毒复制的影响

利用CRISPR/Cas9基因编辑技术构建Ras GTP酶激活蛋白SH3结构域结合蛋白2(G3BP2)基因敲除的293T细胞系,并初步探讨了G3BP2基因缺失对于塞内卡病毒A(Senecavirus A,SVA)增殖的影响。采用激光共聚焦试验观察病毒感染是否引起应激颗粒的产生;设计、构建靶向G3BP2基因的px459-sgRNA表达载体并转染进293T细胞;通过嘌呤霉素压力筛选以及亚克隆得到细胞株,经过Western blot、基因测序的方式鉴定细胞株;CCK-8法测定细胞增殖速度;Western blot、RT-qPCR、噬斑试验分别检测SVA感染后病毒蛋白VP1的表达水平、VP1的拷贝数和细胞上清液的病毒滴度;设计并构建SVA核糖体进入位点(IRES)的双荧光素酶报告系统,双荧光素酶报告试验测定病毒启动子的启动活性。结果:病毒感染引起应激颗粒的产生;筛选得到1株G3BP2基因缺失10 bp的293T细胞系(HEK 293T G3BP2^(-/-)),其细胞活力与未敲除细胞相比无显著差异;Western blot、RT-qPCR、噬斑试验均显示G3BP2敲除后显著抑制了病毒的增殖;双荧光素酶报告试验表明G3BP2敲除后下调了病毒的翻译启动活性。综上,本研究获得了1株HEK 293T G3BP2^(-/-)细胞系,该细胞通过下调病毒的启动活性抑制病毒的增殖,为进一步探讨G3BP2对SVA复制的影响奠定基础。

人工智能加速GPCR配体的发现

G protein-coupled receptors(GPCRs)are crucial players in various physiological processes,making them attractive candidates for drug discovery.However,traditional approaches to GPCR ligand discovery are time-consuming and resource-intensive.The emergence of artificial intelligence(AI)methods has revolutionized the field of GPCR ligand discovery and has provided valuable tools for accelerating the identification and optimization of GPCR ligands.In this study,we provide guidelines for effectively utilizing AI methods for GPCR ligand discovery,including data collation and representation,model selection,and specific applications.First,the online resources that are instrumental in GPCR ligand discovery were summarized,including databases and repositories that contain valuable GPCR-related information and ligand data.Next,GPCR and ligand representation schemes that can convert data into computer-readable formats were introduced.Subsequently,the key applications of AI methods in the different stages of GPCR drug discovery were discussed,ranging from GPCR function prediction to ligand design and agonist identification.Furthermore,an AI-driven multi-omics integration strategy for GPCR ligand discovery that combines information from various omics disciplines was proposed.Finally,the challenges and future directions of the application of AI in GPCR research were deliberated.In conclusion,continued advancements in AI techniques coupled with interdisciplina ry collaborations will offer great potential for improving the efficiency of GPCR ligand discovery.