IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-24 DOI: 10.1016/j.gene.2026.150023

Kaifeng Li , Mengran Wang , Yanhong Liu , Ruining Lu , Heng Zhang , Xiaohui Sui , Guiju Zhang , Xuan Li

Objective: Childhood obesity (CO) has become a global epidemic, leading to rising burden of many diseases and premature death. Thus, this study was conducted to screen the mitochondria-associated biomarkers for patients with CO, as well as the involved molecular mechanism.

Methods: After downloading GSE29718 and GSE104815 datasets from GEO database, differential expression analysis was conducted to screen the DEGs. Then the obtained DEGs were intersected with the mitochondrial-associated genes, and mitochondrial-related genes in CO were acquired, followed by key mitochondrial-related genes screening utilizing three machine learning algorithms. The qRT-PCR and western blot were employed to determine the expression of key genes. Gain-of-function experiment was applied to investigate the function of NIPSNAP3B in CO in vitro.

Results: Total 364 DEGs were screened, then 18 mitochondrial-related genes in CO were obtained. These 18 mitochondrial-associated genes in CO enriched in pyruvate metabolism, arginine biosynthesis, and AMPK signaling pathway, etc. ACACB and NIPSNAP3B were considered as the key mitochondrial-related genes. Of note, NIPSNAP3B overexpression markedly reduced the TG level and the protein expression levels of PPARγ and C/EBPα in MDI-induced 3 T3-L1 cells. Also, ATP content, mitochondrial mass, MMP, and protein expression levels of PGC-1α, NRF1, and TFAM were changed after NIPSNAP3B upregulation in MDI-induced 3 T3-L1 cells. However, opposite results were observed after NIPSNAP3B downregulation. Compound C (AMPK inhibitor) or AMPK knockdown administration could reverse the effect of NIPSNAP3B on adipocyte lipid deposition and mitochondrial biogenesis.

Conclusion: NIPSNAP3B enhances mitochondrial biogenesis to attenuate lipid accumulation via AMPK pathway in CO.

目的：儿童肥胖（CO）已成为一种全球性流行病，导致许多疾病的负担不断增加和过早死亡。因此，本研究旨在筛选CO患者线粒体相关的生物标志物，以及相关的分子机制。方法：从GEO数据库下载GSE29718和GSE104815数据集，进行差异表达分析，筛选deg。然后将得到的deg与线粒体相关基因相交，获得CO中线粒体相关基因，然后利用三种机器学习算法筛选关键线粒体相关基因。采用qRT-PCR和western blot检测关键基因的表达情况。采用功能增益实验研究NIPSNAP3B在体外CO中的功能。结果：共筛选到364个deg，获得18个线粒体相关基因。CO中这18个线粒体相关基因富集于丙酮酸代谢、精氨酸生物合成、AMPK信号通路等。ACACB和NIPSNAP3B被认为是线粒体相关的关键基因。值得注意的是，NIPSNAP3B过表达显著降低了mdi诱导的3 T3-L1细胞中TG水平以及PPARγ和C/EBPα的蛋白表达水平。在mdi诱导的3 T3-L1细胞中，NIPSNAP3B上调后，ATP含量、线粒体质量、MMP以及PGC-1α、NRF1和TFAM的蛋白表达水平也发生了变化。然而，NIPSNAP3B下调后观察到相反的结果。化合物C （AMPK抑制剂）或AMPK敲低给药可逆转NIPSNAP3B对脂肪细胞脂质沉积和线粒体生物发生的影响。结论：NIPSNAP3B通过AMPK途径增强线粒体生物发生，减轻CO中脂质积累。

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引用次数: 0

Genome-wide identification of the rosaceae bHLH gene family and functional characterization of PybHLH182 involved in stone cell formation in pear 蔷薇科bHLH基因家族的全基因组鉴定及参与梨石细胞形成的PybHLH182基因的功能表征

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-23 DOI: 10.1016/j.gene.2026.150022

Wei Wei , Yueyuan Liu , Chong Pan , Jiahao Liu , Shaozhuo Xu , Yanfei Shan , Cheng Li , Jiahao Zeng , Cheng Xue , Jun Wu

Basic helix-loop-helix (bHLH) transcription factors play central regulatory roles in plant development and responses to environmental stress. However, the evolutionary dynamics of the bHLH gene family in Rosaceae fruit species remain largely unexplored. In particular, the expression profiles and functional roles of PybHLH genes during stone cell formation in pear fruit are not well understood. In this study, a total of 910 bHLH genes were identified across seven Rosaceae species—Asian pear, European pear, apple, peach, sweet cherry, Japanese apricot, and strawberry—with 198 genes detected in pear (Pyrus spp.). The PybHLH genes were classified into 13 major clusters (A–M) comprising 17 subfamilies. Inter-species collinearity analyses revealed strong macrosyntenic conservation among apple, Asian pear, and European pear. Whole-genome duplication (WGD) and dispersed duplication (DSD) were identified as the main drivers of bHLH gene family expansion. Transcriptome analysis across multiple tissues identified eight PybHLH genes with specific expression in fruit flesh. Integration of differential expression data during stone cell development with a co-expression network of lignin biosynthetic genes further narrowed down four PybHLH candidates associated with lignification. Among them, RT-qPCR and transient expression assays confirmed that PybHLH182 positively regulates stone cell lignification. This study presents the first comprehensive analysis of the bHLH gene family across seven Rosaceae species, clarifying the evolutionary trajectory of bHLHs and the tissue-specific expression patterns of PybHLHs. The Maloideae subfamily maintains gene family stability via WGD and DSD, whereas the genus Prunus drives gene divergence through frequent genomic rearrangements. Meanwhile, PybHLH182 was identified as a core regulator governing stone cell formation in pear fruits. These findings provide a theoretical basis for molecular breeding of Rosaceae fruit trees and elucidating the mechanisms underlying pear fruit quality formation.

碱性螺旋-环-螺旋转录因子在植物发育和环境胁迫反应中起着重要的调控作用。然而，bHLH基因家族在蔷蔷科果实物种中的进化动力学仍未得到充分研究。特别是PybHLH基因在梨果实石细胞形成过程中的表达谱和功能作用尚不清楚。本研究共在亚洲梨、欧洲梨、苹果、桃子、甜樱桃、日本杏和草莓7个蔷蔷科物种中鉴定出910个bHLH基因，其中在梨（Pyrus spp.）中检测到198个基因。PybHLH基因可分为13个主要簇（A-M）和17个亚家族。种间共线性分析表明，苹果、亚洲梨和欧洲梨具有较强的宏观同步保守性。全基因组重复（WGD）和分散重复（DSD）被确定为bHLH基因家族扩展的主要驱动因素。多个组织的转录组分析鉴定出8个PybHLH基因在果肉中特异表达。将石细胞发育过程中的差异表达数据与木质素生物合成基因的共表达网络相结合，进一步缩小了与木质素化相关的四个PybHLH候选基因。其中，RT-qPCR和瞬时表达实验证实PybHLH182正调控石细胞木质化。本研究首次对蔷蔷科7种植物的bHLH基因家族进行了全面分析，阐明了bHLH的进化轨迹和pybhlh的组织特异性表达模式。Maloideae亚科通过WGD和DSD维持基因家族的稳定性，而Prunus属通过频繁的基因组重排驱动基因分化。同时，PybHLH182被鉴定为梨果实石细胞形成的核心调控因子。这些发现为蔷薇科果树分子育种和阐明梨果实品质形成机制提供了理论依据。

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引用次数: 0

Small extracellular vesicles carrying miRNA34 in Alzheimer’s disease: effects on oxidative stress, neuroinflammation, cognitive function, and mitochondrial/ferroptosis-related protein regulation 阿尔茨海默病中携带miRNA34的细胞外小泡：对氧化应激、神经炎症、认知功能和线粒体/铁中毒相关蛋白调控的影响

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-17 DOI: 10.1016/j.gene.2026.150014

Hamit Çelik , Oğuz Çelik , Şeyma Aydın , Sefa Küçükler , Selim Çomaklı , Ahmet Topal , Ramazan Akay , Sinan Gönüllü , Mustafa Onur Yıldız , Bülent Alım , Selçuk Özdemir

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, oxidative stress, and persistent neuroinflammation. Recent studies have increasingly focused on the regulatory role of microRNAs in AD pathogenesis. In this study, we investigated the therapeutic potential of small extracellular vesicles (sEV) enriched with microRNA34 (miRNA34) to target key pathogenic mechanisms of AD. We hypothesized that miRNA34-loaded sEV could alleviate oxidative damage, inhibit neuroinflammatory responses and ferroptosis, reduce mitochondrial impairment, and ultimately improve cognitive function. We evaluated the effects of miRNA34 administration on oxidative stress markers, pro-inflammatory cytokines, synaptic plasticity indicators, and behavioral outcomes in an in vivo Aβ-induced mouse model of AD. The experimental design included five groups, each consisting of seven mice. The findings demonstrated that miRNA34-loaded sEV treatment significantly reduced oxidative stress and neuroinflammation while enhancing memory and learning performance. Overall, our results indicate that miRNA34-enriched sEV represent a promising and minimally invasive therapeutic strategy capable of modulating AD pathogenesis. This research provides a novel perspective on the potential clinical application of miRNA34 and sEVin neurodegenerative disorders.

阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是认知能力下降、氧化应激和持续的神经炎症。近年来的研究越来越关注microrna在AD发病机制中的调节作用。在这项研究中，我们研究了富含microRNA34 （miRNA34）的小细胞外囊泡（sEV）针对AD的关键致病机制的治疗潜力。我们假设装载mirna34的sEV可以减轻氧化损伤，抑制神经炎症反应和铁下垂，减少线粒体损伤，最终改善认知功能。在a β诱导的AD小鼠模型中，我们评估了miRNA34给药对氧化应激标志物、促炎细胞因子、突触可塑性指标和行为结果的影响。实验设计分为五组，每组7只小鼠。研究结果表明，装载mirna34的sEV治疗显著降低了氧化应激和神经炎症，同时增强了记忆和学习表现。总的来说，我们的研究结果表明，mirna34富集的sEV是一种有前景的微创治疗策略，能够调节AD的发病机制。本研究为miRNA34和sEVin在神经退行性疾病的潜在临床应用提供了新的视角。

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引用次数: 0

Emerging role of NEAT1 in skin pathology: from molecular regulation to clinical applications NEAT1在皮肤病理中的新作用：从分子调控到临床应用。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-16 DOI: 10.1016/j.gene.2026.150013

Wiam Saadi , Ahlam Fatmi , Auda Ameur , Salvatore Spicuglia , Denis Puthier , Mohamed Belhocine

Long non-coding RNAs (lncRNAs) are increasingly recognized as crucial regulators of gene expression, influencing a wide array of physiological and pathological processes. Among these, Nuclear Enriched Abundant Transcript 1 (NEAT1), an essential component of nuclear paraspeckles, has garnered significant attention for its diverse roles in various diseases, including immune-related disorders and certain cancers. While the involvement of lncRNAs in dermatologic conditions is an expanding field, the specific implications of NEAT1 in the onset and progression of skin diseases remain largely underexplored. This review aims to consolidate current knowledge regarding the multifaceted roles of NEAT1 in skin biology and pathology. Here, we summarize available evidence on NEAT1 in skin disorders, emphasizing its roles in regulating keratinocyte biology, modulating inflammatory pathways, and influencing disease progression. By consolidating current findings, the review provides a framework for understanding the potential role of NEAT1 as a biomarker and therapeutic target in dermatologic conditions.

长链非编码rna （lncRNAs）越来越被认为是基因表达的重要调控因子，影响着一系列广泛的生理和病理过程。其中，核富集丰富转录本1 （Nuclear enrichment Abundant Transcript 1, NEAT1）是核副斑的重要组成部分，因其在多种疾病（包括免疫相关疾病和某些癌症）中的多种作用而受到广泛关注。虽然lncrna在皮肤疾病中的参与是一个不断扩大的领域，但NEAT1在皮肤疾病发生和进展中的具体含义仍未得到充分探讨。这篇综述旨在巩固目前关于NEAT1在皮肤生物学和病理学中的多方面作用的知识。在这里，我们总结了NEAT1在皮肤疾病中的现有证据，强调了它在调节角质形成细胞生物学、调节炎症通路和影响疾病进展中的作用。通过巩固目前的研究结果，本综述为理解NEAT1作为生物标志物和皮肤病治疗靶点的潜在作用提供了一个框架。

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引用次数: 0

The rye photoreceptor ScphyB integrates light signals to control development and architecture in Arabidopsis thaliana 黑麦光感受器ScphyB整合光信号来控制拟南芥的发育和结构。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-14 DOI: 10.1016/j.gene.2026.150009

Mengdan Ning , Yankun Li , Luhao Yang , Yongtao Li , Yirong Yu , Yu Zhang , Yanpei Zhang , Tao Mu , Maciren Ni , Qiang Qin , Shaowei Li , Junxi Wu , Jianping Yang , Yong Shi

As an important food and feed crop, cultivated rye (Secale cereale L.) exhibits excellent resistance to biotic and abiotic stresses, making it a valuable genetic resource for wheat improvement. However, the functions of phytochromes in rye remain poorly characterized. Here, we cloned and characterized PhyB from the Weining rye variety (ScPhyB). The predicted protein contains conserved phytochrome domains—PAS, GAF, PHY, and HATPase—and phylogenetic analysis revealed that ScPhyB is most closely related to wheat TaPhyB, with both belonging to the monocot clade. Promoter analysis identified multiple cis-acting elements related to hormone response, meristem expression, low temperature responsiveness, light response, and MYB binding. Heterologous expression of ScPhyB in Arabidopsis enhanced photomorphogenesis under white light (WL), red light (R), and blue light (B). Furthermore, ScPhyB attenuated shade avoidance responses to 70 % and 90 % of wildtype seedlings measured by hypocotyl length by perceiving high and low R/FR red to far-red (R/FR) light ratio, respectively. ScPhyB also modulated plant architecture and delayed flowering (6-7d) by repressing FT expression. Yeast two-hybrid (Y2H) assays and split-luciferase (LUC) assay confirmed that ScPhyB interacts with both ScPIF3 and ScCOP1, indicating functional conservation within the PIF signaling pathway and the COP1-SPA1 complex. Our findings provide insight into the role of ScPhyB in light signaling and suggest its potential utility for improving crop traits.

作为重要的粮食和饲料作物，栽培黑麦对生物和非生物胁迫表现出优异的抗性，是小麦改良的宝贵遗传资源。然而，对裸麦光敏色素的功能研究尚不充分。本文从威宁黑麦品种（ScPhyB）中克隆并鉴定了PhyB。预测的蛋白含有保守的光敏色素结构域pas、GAF、PHY和hatpase，系统发育分析显示，ScPhyB与小麦的TaPhyB关系最为密切，都属于单子枝分支。启动子分析发现了多个与激素响应、分生组织表达、低温响应、光响应和MYB结合相关的顺式作用元件。在白光（WL）、红光(R)和蓝光(B)下，ScPhyB在拟南芥中的异源表达增强了光形态发生。此外，ScPhyB通过感知高R/FR和低R/FR远红（R/FR）光比，分别减弱了70% %和90% %的野生型幼苗下胚轴长度的避荫反应。ScPhyB还通过抑制FT表达调节植株结构和延迟开花（6-7d）。酵母双杂交（Y2H）实验和分裂荧光素酶（LUC）实验证实，ScPhyB与ScPIF3和ScCOP1相互作用，表明在PIF信号通路和COP1-SPA1复合物中具有功能保守性。我们的研究结果揭示了ScPhyB在光信号传导中的作用，并提出了其在改善作物性状方面的潜在用途。

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引用次数: 0

Identification and functional analysis of biallelic loss-of-function variants of WNT7B in a Chinese family affected with PDAC syndrome 中国PDAC综合征家族WNT7B双等位基因功能缺失变异的鉴定和功能分析

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-14 DOI: 10.1016/j.gene.2026.150012

Liyan Qiu , Caisheng Xu , Renhua Lu , Shaobin Lin , Fang Yang

WNT7B-related pulmonary hypoplasia, diaphragmatic anomalies, anophthalmia/microphthalmia, and cardiac defects (PDAC) syndrome is rarely reported. To date, only two each nonsense and missense variants of WNT7B were identified in five pedigrees affected with a PDAC spectrum from two independent studies. Additionally, the gene-disease association between WNT7B and PDAC syndrome is not yet clarified in OMIM database. Here, the whole exome sequencing was used to identify biallelic novel loss-of-function (LoF) variants c.324C > G (p.Tyr108*) and c.668_669dup (p.Val224Argfs*6) of WNT7B in a fetus affected with a typical PDAC spectrum, including pulmonary hypoplasia/agenesis, bilateral microphthalmia, and absence of pulmonary arteries and veins, from a Chinese family. Subsequent functional analysis revealed that the two LoF variants decreased the RNA and protein expression levels of WNT7B, and significantly impaired the canonical WNT-β-Catenin signaling pathway, which is essential for regulation of human lung development. We broaden the variant spectrum of WNT7B, and provide genetic and experimental evidence to confirm the association between WNT7B pathogenic variants and PDAC spectrum.

wnt7b相关的肺发育不全、膈异常、眼无/小眼和心脏缺陷（PDAC）综合征很少报道。迄今为止，只有两个无义和错义的WNT7B变体被鉴定在5个家谱受影响的PDAC从两个独立的研究。此外，在OMIM数据库中，WNT7B与PDAC综合征之间的基因-疾病关联尚未明确。本研究利用全外显子组测序技术，鉴定了来自一个中国家庭的WNT7B双等位基因新型功能缺失（LoF）变异c.324C > G （p.Tyr108*）和c.668_669dup (p.Val224Argfs*6)，这些变异具有典型的PDAC谱系，包括肺发育不全/发育不全、双侧小眼和肺动脉静脉缺失。随后的功能分析显示，这两个LoF变异降低了WNT7B的RNA和蛋白表达水平，并显著损害了典型的WNT-β-Catenin信号通路，该信号通路是调节人类肺发育所必需的。我们拓宽了WNT7B的变异谱，并提供了遗传和实验证据来证实WNT7B致病变异与PDAC谱之间的关联。

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引用次数: 0

Next-generation sequencing as an applicable method: from technical basis to use in medical diagnosis 新一代测序作为一种适用方法：从技术基础到医学诊断应用。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-08 DOI: 10.1016/j.gene.2026.150002

Arman Moradi , Mina Mousavi , Majid Maleki , Seyedeh Zoha Tabatabaei , Mahshid Malakootian

Next-generation sequencing (NGS) is a high-throughput technology capable of determining the sequence of nucleotides in the genome. Over the past few years, the advent of NGS-based methods has provided timely and economical approaches for diagnosing and screening genetic conditions throughout an individual’s lifespan, and prenatal period. Prenatal screening for congenital abnormalities has opened the door to reducing the incidence of genetic disorders. Early detection of genetic diseases using NGS-based methods enables better management of these conditions, thereby improving the quality of life for patients. NGS has also played a pivotal role in pharmacogenetics and drug delivery, facilitating a more personalized approach to medicine. NGS-based methods are increasingly being utilized in genome editing to provide essential information that enhances the precision and effectiveness of editing techniques. This review presents information on how various NGS-based methods function from a technical perspective. Furthermore, we will explore the applications and benefits of these methods in the fields of diagnosis, screening, pharmacogenetics, and genome editing.

下一代测序（NGS）是一种高通量技术，能够确定基因组中的核苷酸序列。在过去的几年中，基于ngs的方法的出现为诊断和筛查整个个体生命周期和产前期间的遗传状况提供了及时和经济的方法。产前筛查先天性异常为减少遗传疾病的发病率打开了大门。使用基于ngs的方法早期发现遗传病，可以更好地管理这些疾病，从而改善患者的生活质量。NGS还在药物遗传学和给药方面发挥了关键作用，促进了更个性化的药物治疗方法。基于ngs的方法越来越多地用于基因组编辑，以提供必要的信息，提高编辑技术的准确性和有效性。这篇综述从技术角度介绍了各种基于ngs的方法如何发挥作用。此外，我们将探讨这些方法在诊断、筛查、药物遗传学和基因组编辑等领域的应用和益处。

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引用次数: 0

Genetic diversity and genome-wide association mapping for salt stress tolerance in diverse parental lines of hybrid rice 杂交稻不同亲本耐盐性遗传多样性及全基因组关联图谱研究。

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-08 DOI: 10.1016/j.gene.2026.150003

Md. Ruhul Quddus , M. Akhlasur Rahman , Mehfuz Hasan , Md. Golam Rasul , Md. Abdul Mannan , Md. Jamil Hasan

Salinity, exacerbated by climate change, is a major threat to rice production. Seedling biomass under salt stress is one of the key indicators of salinity tolerance. This is the first study that involved 276 diverse hybrid rice parental lines to analyze GWAS on critical trait seedling biomass under 12 dS/m salt stress. Genetic diversity analysis using UPGMA clustering separated the genotypes into three major and three small distinct groups. Path analysis among 25 traits revealed that root biomass was important determinant for maintaining seedling biomass under salt stress. Genome-wide association analysis (GWAS) for seedling biomass traits under salt stress detected seven significant SNP markers on chromosomes 2, 4, 6, 7, 10, and 11. We report three novel candidate genes associated with seedling biomass maintenance under salt stress: LOC_Os02g55630.1 (chloroplast activity), LOC_Os07g04240.1 (mitochondrial function), and the uncharacterized LOC_Os04g06520.1. In conclusion, a robust root system is vital for seedling biomass retention under salt stress, and identified genetic markers will be useful for the development of salt-resilient hybrid and inbred rice.

气候变化加剧的盐碱化是水稻生产的主要威胁。盐胁迫下幼苗生物量是耐盐性的重要指标之一。本研究首次利用276个不同杂交稻亲本，分析了12 dS/m盐胁迫下幼苗生物量的GWAS变化。遗传多样性分析采用UPGMA聚类法将基因型划分为3个大群和3个小群。25个性状的通径分析表明，根系生物量是盐胁迫下维持幼苗生物量的重要决定因素。对盐胁迫下幼苗生物量性状进行全基因组关联分析（GWAS），在第2、4、6、7、10和11号染色体上检测到7个显著SNP标记。我们报道了三个与盐胁迫下幼苗生物量维持相关的新候选基因：LOC_Os02g55630.1（叶绿体活性）、LOC_Os07g04240.1（线粒体功能）和未鉴定的LOC_Os04g06520.1。综上所述，一个强健的根系对盐胁迫下幼苗生物量的保持至关重要，鉴定出的遗传标记将为耐盐杂交和自交系水稻的培育提供参考。

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引用次数: 0

Computational epitope discovery and in silico design of a bispecific antibody model (COMED hook) to block Plasmodium invasion into erythrocytes 阻断疟原虫侵入红细胞的双特异性抗体模型（COMED hook）的计算表位发现和计算机设计

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-05 DOI: 10.1016/j.gene.2026.149999

Ahmet Efe Köseoğlu , Nadir Gül , Tuğçe Duran , Cenk Öztürk , Nezih Hekim

Malaria remains a major global health threat, with Plasmodium species, especially P. falciparum, increasingly resistant to drugs and vaccines. Novel strategies are needed to address antigenic diversity and the parasite’s intracellular immune evasion. This study aimed to identify conserved and immunogenic B-cell epitopes in P. falciparum and human erythrocytes to design a bispecific antibody model, COMED hook, capable of blocking erythrocyte invasion. Surface and secretory proteins of P. falciparum and erythrocytes were retrieved from public databases. B-cell epitopes were predicted and filtered based on antigenicity, allergenicity, and toxicity. Conservancy was assessed via BLAST. Selected epitopes were structurally modeled, docked to B-cell receptors, and used for antibody design via DiffAb. A total of 123 antigenic P. falciparum B-cell epitopes were identified, with 58 conserved across species. Additionally, 92 non-conserved human erythrocyte B-cell epitopes were discovered, of which 12 were selected as host-targeting domains. Two highly conserved Plasmodium epitopes (KHVETWTQRVQNM, LHSNFYIKRF) were predicted to have favorable Fab binding. Designed antibodies likewise exhibited computationally suggested sequence and docking profiles compatible with COMED hook construction. Overall, this study presents an in silico computational design framework for a bispecific antibody model targeting both Plasmodium and host erythrocytes, generating testable predictions for future work. The predicted interactions and the proposed COMED hook concept will require experimental validation to assess biological feasibility.

疟疾仍然是一个主要的全球健康威胁，各种疟原虫，特别是恶性疟原虫，对药物和疫苗的耐药性日益增强。需要新的策略来解决抗原多样性和寄生虫的细胞内免疫逃避。本研究旨在鉴定恶性疟原虫和人红细胞中保守的免疫原性b细胞表位，设计一种能够阻断红细胞侵袭的双特异性抗体模型COMED hook。从公共数据库中检索恶性疟原虫和红细胞的表面和分泌蛋白。根据抗原性、过敏原性和毒性对b细胞表位进行预测和筛选。通过BLAST对保护进行评估。选择的表位进行结构建模，与b细胞受体对接，并通过DiffAb进行抗体设计。共鉴定出123个抗原恶性疟原虫b细胞表位，其中58个在物种间保守。此外，还发现了92个非保守的人红细胞b细胞表位，其中12个被选为宿主靶向结构域。两个高度保守的疟原虫表位（KHVETWTQRVQNM， LHSNFYIKRF）预计具有有利的Fab结合。设计的抗体同样显示出计算建议的序列和对接轮廓，与COMED钩子结构兼容。总的来说，这项研究提出了一个针对疟原虫和宿主红细胞的双特异性抗体模型的计算机计算设计框架，为未来的工作产生了可测试的预测。预测的相互作用和提出的COMED钩子概念将需要实验验证来评估生物学可行性。

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引用次数: 0

cGAS-STING activation in Parkinson’s Disease: From mechanisms to Disease-Modifying therapeutic strategies cGAS-STING在帕金森病中的激活：从机制到疾病改善治疗策略

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY

Gene

Pub Date : 2026-01-05 DOI: 10.1016/j.gene.2026.150000

Jemimol Solomon , Snehashis Mandal , Khadga Raj Aran

Parkinson’s disease (PD) is a progressive degenerative neuronal disorder that involves the selective loss of dopaminergic neurons in the substantia nigra, resulting in severe motor and non-motor impairments. Key pathological hallmarks include the accumulation of misfolded α-synuclein and mitochondrial dysfunction. Emerging evidence indicates that innate immune signalling, particularly the cGAS-STING pathway, contributes to PD pathogenesis. It acts as a cytosolic DNA sensor; cGAS can recognise genomic instability or mitochondrial damage by generating an IFN-I response through STING activation. Persistent stimulation of the cGAS-STING pathway in microglia promotes chronic neuroinflammation and contributes to dopaminergic neuronal loss. Mitochondrial dysfunction, impaired DNA repair, and α-Synuclein aggregation may converge to sustain pathway activation, establishing a self-reinforcing cycle of inflammation and neurodegeneration. Understanding the interaction of cGAS-STING signalling, mitochondrial integrity, and protein aggregation offers important mechanistic insights into PD pathology. It suggests meaningful targets for disease-modifying therapeutic approaches for PD that address neuroinflammation and neuronal survival.

帕金森病（PD）是一种进行性退行性神经元疾病，涉及黑质多巴胺能神经元的选择性丧失，导致严重的运动和非运动损伤。关键的病理标志包括α-突触核蛋白错误折叠的积累和线粒体功能障碍。新出现的证据表明，先天免疫信号，特别是cGAS-STING通路，参与PD的发病机制。它充当细胞质DNA传感器；cGAS可以通过STING激活产生IFN-I反应来识别基因组不稳定或线粒体损伤。持续刺激小胶质细胞中的cGAS-STING通路可促进慢性神经炎症并导致多巴胺能神经元丢失。线粒体功能障碍、DNA修复受损和α-突触核蛋白聚集可能会聚在一起维持通路激活，建立炎症和神经变性的自我强化循环。了解cGAS-STING信号传导、线粒体完整性和蛋白质聚集的相互作用，为帕金森病的病理机制提供了重要的见解。这为PD的疾病改善治疗方法提供了有意义的靶点，可以解决神经炎症和神经元存活问题。

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