Gene Reports最新文献_第9页

Evaluation of the antimicrobial activity of Arnebia euchroma extract and its influence on quorum sensing gene expression in Pseudomonas aeruginosa 紫草提取物抑菌活性评价及其对铜绿假单胞菌群体感应基因表达的影响

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-10-18 DOI: 10.1016/j.genrep.2025.102362

Leila Yadegari , Maryam Mohammadi-Sichani , Soodabeh Rostami

Background

Antibiotic resistance in Pseudomonas aeruginosa has become a significant public health concern, particularly in burn patients. This study aimed to evaluate the effect of Arnebia euchroma extract on the expression of the lasR and lasI genes, which are crucial for the pathogenicity of this bacterium.

Methods

Five P. aeruginosa strains were isolated from burn wounds, identified with selective media and differential tests. The methanolic extract of A. euchroma was prepared by maceration and tested for antimicrobial activity. Antibiotic susceptibility was assessed using the disc diffusion method. The presence of lasI and lasR genes in clinical strains was confirmed by PCR, and their expression levels were quantified by Real-Time PCR. Active compounds in the extract were identified using gas chromatography–mass spectrometry.

Results

The A. euchroma root extract exhibited significant antibacterial effects, forming clear inhibition zones on agar plates. Its minimum inhibitory concentration ranged from 62.5 to 250 μg/mL, while the minimum bactericidal concentration was between 125 and 250 μg/mL. All tested P. aeruginosa isolates were positive for the lasI and lasR genes, with gene expression significantly reduced in the presence of the extract. The extract inhibited over 75 % of lasI and lasR expression, comparable to tobramycin. Diacetone alcohol, alpha-terpinenyl acetate, and xanthosine were identified as the most abundant compounds in the root.

Conclusion

The findings suggest that A. euchroma extract has potential as an antimicrobial and quorum sensing inhibitor. However, further studies with larger strain collections and in vivo validation are needed to confirm its therapeutic relevance.

铜绿假单胞菌的抗生素耐药性已成为一个重要的公共卫生问题，特别是在烧伤患者中。本研究旨在评价紫草提取物对该细菌致病性关键基因lasR和lasI表达的影响。方法从烧伤创面分离5株铜绿假单胞菌，采用选择性培养基和鉴别试验进行鉴定。采用浸渍法制备了赤藓醇提物，并进行了抑菌活性试验。采用椎间盘扩散法评估抗生素敏感性。通过PCR证实临床菌株中存在lasI和lasR基因，Real-Time PCR检测其表达量。采用气相色谱-质谱联用技术对提取物中的活性成分进行鉴定。结果真彩根提取物具有明显的抑菌作用，在琼脂平板上形成明显的抑菌带。其最低抑菌浓度为62.5 ~ 250 μg/mL，最低杀菌浓度为125 ~ 250 μg/mL。所有测试的铜绿假单胞菌分离株lasI和lasR基因均呈阳性，在提取物存在下基因表达显著降低。该提取物抑制了超过75%的lasI和lasR表达，与妥布霉素相当。二丙酮醇、-萜烯乙酸酯和黄嘌呤是根中含量最多的化合物。结论赤原草提取物具有抗菌和群体感应抑制剂的作用。然而，进一步的研究需要更大的菌株收集和体内验证来证实其治疗相关性。

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引用次数: 0

A study of the cutting-edge general-purpose compressors’ performance on the normalized genome sequence 基于归一化基因组序列的前沿通用压缩器性能研究

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-10-17 DOI: 10.1016/j.genrep.2025.102358

Subhankar Roy , Arnab Charit , Mriganka Patra , Ananya Sadhukhan , Diya Chakraborty , Partha Ghosh , Kingshuk Chatterjee , Anirban Mukhopadhyay

Advanced general-purpose compressors like gzip and zstd have difficulties when compressing genome sequences. The lack of sequence-specific traits and limited-scale features leads to inferior performance. However, molecular sequence databases have preferred these compressors for years. To get around these limitations, this article proposes a compressor called NGC (Normalized Genome Compressor) to make general-purpose compressors work better to compress genome sequences. NGC is a reference-free compression tool consisting of two phases. Initially, it takes the primary domain of the genome, i.e., A, C, G, and T, and then proceeds with normalization. In the subsequent phase, based on user specifications, it utilizes one of the eight general-purpose compressors, including 7-zip, paq8px, bsc, gzip, zstd, bzip2, zpaq, or cmix. We compare the standard version (S) of each compressor, known as the S-compressor, the sequence normalized file (nf), and the S-compressor applied to the nf format, referred to as the proposed compressor (P-compressor). Subsequently, we evaluate the performance of NGC in two genome datasets, including seventeen and eleven primary genome sequences, respectively. The result is the weighted average compression ratio (WACR) for the initial dataset of 4.13 for P-gzip vs. 3.63 for S-gzip and 4.8 for P-zstd vs. 4.3 for S-zstd. P-gzip is

\sim

91.101 times and P-zstd is

\sim

22.734 times faster than the S-compressor. The outcomes for the remaining six compressors are likewise beneficial. The findings indicate that the use of a general-purpose compressor in the nf significantly enhances the results.

高级通用压缩器（如gzip和zstd）在压缩基因组序列时存在困难。缺乏序列特异性特征和有限规模特征导致性能较差。然而，分子序列数据库多年来一直倾向于使用这些压缩器。为了克服这些限制，本文提出了一种称为NGC（归一化基因组压缩器）的压缩器，以使通用压缩器更好地压缩基因组序列。NGC是一个无参考的压缩工具，由两个阶段组成。最初，它取基因组的主要域，即A、C、G和T，然后进行归一化。在后续阶段，根据用户规范，它使用8个通用压缩器之一，包括7-zip、paq8px、bsc、gzip、zstd、bzip2、zpaq或cmix。我们比较了每个压缩器的标准版本(S)，称为S压缩器，序列规范化文件（nf），以及应用于nf格式的S压缩器，称为建议压缩器（p压缩器）。随后，我们在两个基因组数据集（分别包括17个和11个初级基因组序列）中评估了NGC的性能。结果是初始数据集的加权平均压缩比（WACR）， P-gzip为4.13，S-gzip为3.63，P-zstd为4.8，S-zstd为4.3。P-gzip和P-zstd分别比S-compressor快~ 91.101倍和22.734倍。其余6台压缩机的结果同样是有益的。研究结果表明，在nf中使用通用压缩器可显著提高结果。

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引用次数: 0

Genomic surveillance of SARS-CoV-2 in the State of Mato Grosso, Midwest Brazil 巴西中西部马托格罗索州SARS-CoV-2基因组监测

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-10-17 DOI: 10.1016/j.genrep.2025.102361

Stephanni Figueiredo da Silva , Klaucia Rodrigues Vasconcelos , Julia Deffune Profeta Cidin Almeida , Natália Rocha Guimarães , Luiz Marcelo Ribeiro Tomé , Vagner Fonseca , Diniz Pereira Leite Júnior , Marta Giovanetti , Elaine Cristina de Oliveira , Luiz Carlos Júnior Alcântara

The emergence of SARS-CoV-2 in December 2019 impacted global public health as the most severe modern pandemic ever recorded. Remarkably, it was possible to monitor its evolution in real-time, including viral evolution and the emergence of new lineages, thanks to technology and the speed of communication via the internet. Understanding the circulating viral variants and their characteristics within the population was crucial for effectively guiding public health actions in combating the disease. In this study, we conducted detailed phylogenetic analyses as a result of a recently established genomic surveillance hub at LACEN-MT. The samples were sequenced and subsequently deposited on the GISAID platform between October 21, 2021 and March 31, 2023. The findings of this study suggest that the SARS-CoV-2 epidemic in Mato Grosso State was characterized by the successive introduction of new strains from different countries, leading to the generation of waves of infection. Overall, this study underscores the importance of investigating the spatiotemporal evolution of the SARS-CoV-2 epidemic and how its variants spread across the state, contributing to pandemic peaks in the region. It also highlights the significance of disseminating this information to the management team in Mato Grosso to help implement monitoring strategies that could reduce cases and deaths in the state.

2019年12月，SARS-CoV-2的出现影响了全球公共卫生，成为有史以来最严重的现代大流行。值得注意的是，由于技术和互联网的通信速度，实时监测其进化是可能的，包括病毒进化和新血统的出现。了解人群中流行的病毒变体及其特征对于有效指导抗击该疾病的公共卫生行动至关重要。在这项研究中，我们根据最近在LACEN-MT建立的基因组监测中心进行了详细的系统发育分析。在2021年10月21日至2023年3月31日期间，样品被测序并随后沉积在GISAID平台上。本研究结果表明，马托格罗索州SARS-CoV-2疫情的特点是来自不同国家的新毒株连续传入，导致感染浪潮的产生。总的来说，这项研究强调了调查SARS-CoV-2流行的时空演变及其变体如何在该州传播的重要性，这有助于该地区的大流行高峰。它还强调了向马托格罗索州管理团队传播这一信息的重要性，以帮助执行可减少该州病例和死亡的监测战略。

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引用次数: 0

Phylogenomic insights into a psychrotolerant, plant growth-promoting strain of Pseudomonas marginalis isolated from Xinantécatl volcano xinantacatl火山分离的一株促植物生长的耐寒边缘假单胞菌的系统基因组学研究

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-10-14 DOI: 10.1016/j.genrep.2025.102356

José Germán Serrano-Gamboa , José Tomás Tavarez-Arriaga , Mario L. Iza-Arteaga , Martín Romualdo Ide-Pérez , Irán Tapia-Vázquez , Jorge L. Folch-Mallol

A novel strain of the genus Pseudomonas was isolated from a high-altitude volcano in Toluca, Mexico. This isolate, designed as Pseudomonas marginalis BMH-2007, could grow at 4 °C, whereas other microbes usually stop growth at this temperature. The fact of its isolation from snow implies that the population was big enough to thrive at low temperature, making it a psychrotolerant bacterium.

Previous characterization of BMH-2007 revealed interesting characteristics related to plant growth promotion, including auxin production, siderophore production, and phosphate solubilization capacity. In this work, the ability of BMH-2007 to stimulate the early development of Capsicum annuum plants without signs of phytopathogenicity was proven. A thorough whole-genome analysis revealed that isolate BMH-2007 belongs to the Pseudomonas fluorescens species complex, specifically to the species P. marginalis, with a Mash distance of 0.0118927 from the closest reference genome (RefSeq: GCF_007858175.1).

The phylogenomic evidence allowed us to confirm the new strain designation. Notably, its genomic features were consistent with those of plant growth-promoting traits, and we observed coding sequences for IAA biosynthesis and iron and phosphate transport, among others. As it is a species associated with phytopathogenicity, the virulence factors encoded by the genome were analyzed, which revealed the presence of a type VI secretion system associated with both biological control and plant growth promotion.

一种假单胞菌属的新菌株从墨西哥托卢卡的一座高海拔火山中分离出来。这种分离物被设计为边缘假单胞菌BMH-2007，它可以在4°C下生长，而其他微生物通常在这个温度下停止生长。它与雪隔绝的事实表明，它的数量足够大，可以在低温下茁壮成长，这使它成为一种耐寒细菌。先前对BMH-2007的表征揭示了与植物生长促进有关的有趣特性，包括生长素产生、铁载体产生和磷酸盐溶解能力。在这项工作中，BMH-2007能够刺激无植物致病性迹象的辣椒植株的早期发育。全基因组分析表明，分离物BMH-2007属于荧光假单胞菌种复合体，与最近参考基因组（RefSeq: GCF_007858175.1）的Mash distance为0.0118927。系统基因组学的证据使我们能够确认新的菌株名称。值得注意的是，它的基因组特征与植物生长促进性状一致，我们观察到IAA生物合成和铁和磷酸盐运输等编码序列。由于它是一个与植物致病性相关的物种，我们分析了基因组编码的毒力因子，发现它存在一个与生物防治和促进植物生长相关的VI型分泌系统。

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引用次数: 0

In silico exploration of the metabolic and biosynthetic potential of Brevibacillus borstelensis UE10 through whole genome analysis 通过全基因组分析，在计算机上探索了波斯勒短芽孢杆菌UE10的代谢和生物合成潜力

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-10-13 DOI: 10.1016/j.genrep.2025.102355

Hassan Ghayas , Uroosa Ejaz , Ayaz Taj , Sabiha Yousuf , Muhammad Sohail

Thermophilic microorganisms produce heat-stable metabolites with significant importance in industrial applications. In this study, we present the whole genome sequence of a thermophilic bacterium, Brevibacillus borstelensis UE10, isolated from a crocodile pond in Manghopir, Pakistan. In silico functional annotation and comparative genomic analyses provided valuable insights into the biosynthetic capabilities and metabolic potential of this strain. The draft genome of UE10 was assembled into 132 contigs with a total size of 5,322,029 bp and a GC content of 52 %. The genome contained 5080 coding sequences (CDSs), 116 tRNAs, and 4 rRNAs. Whole genome and 16S rRNA gene sequence comparisons confirmed the identification of the strain as B. borstelensis. Furthermore, seven putative biosynthetic gene clusters (BGCs) involved in the production of potentially antimicrobial and metal-chelating agents were identified. In addition to other metabolic pathways, the presence of a 13-gene xenobiotic degradation pathway, including benzoate degradation, demonstrates the strain's strong potential for bioremediation. Overall, in silico genomic evidence highlights the potential of B. borstelensis UE10 in biotechnological applications and environmental remediation.

嗜热微生物产生热稳定的代谢物，在工业应用中具有重要意义。在这项研究中，我们报道了从巴基斯坦Manghopir鳄鱼池塘分离的嗜热细菌——borstelbrevibacillus UE10的全基因组序列。计算机功能注释和比较基因组分析为该菌株的生物合成能力和代谢潜力提供了有价值的见解。UE10的基因组草图被组装成132个contigs，总大小为5,322,029 bp， GC含量为52%。该基因组包含5080个编码序列（CDSs）、116个trna和4个rrna。全基因组和16S rRNA基因序列比较证实该菌株为波斯勒螺旋藻。此外，还鉴定了七个可能参与生产潜在抗菌剂和金属螯合剂的生物合成基因簇（bgc）。除了其他代谢途径外，包括苯甲酸酯降解在内的13个基因的外源降解途径的存在表明该菌株具有很强的生物修复潜力。总体而言，硅基因组证据突出了波斯勒芽孢杆菌UE10在生物技术应用和环境修复方面的潜力。

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引用次数: 0

Carbapenem and quinolone resistance genes in multidrug-resistant Pseudomonas aeruginosa from drinking water sources within katsina metropolis, Nigeria 尼日利亚卡齐纳市饮用水水源中多重耐药铜绿假单胞菌的碳青霉烯类和喹诺酮类耐药基因

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-10-13 DOI: 10.1016/j.genrep.2025.102359

Anas Abdullahi , Emmanuel Dayo Alabi , Adetunji Misbau Kilani , Ayodele Timilehin Adesoji

Introduction

Multidrug-resistant (MDR) Pseudomonas aeruginosa in drinking water poses a significant public health risk in low-resource settings, resulting in increased morbidity and mortality. This study investigated the prevalence of MDR P. aeruginosa and the occurrence of carbapenem- and quinolone-resistance genes in isolates from drinking water within Katsina Metropolis, Nigeria.

Methods

Forty-five water samples were collected from wells (n = 15), boreholes (n = 15), and sachet-packaged water (n = 15) across five locations. Bacterial isolation and identification were performed using cetrimide agar and standard microbiological methods. Antibiotic susceptibility testing was performed by the disk diffusion method, with isolates resistant to ≥3 antibiotic classes classified as MDR. Carbapenemase production was assessed using the modified Carba NP test, and selected MDR isolates were screened for carbapenem and quinolone resistance genes by PCR.

Results

P. aeruginosa was detected in 71.1 % (32/45) of samples, with the highest prevalence in wells (93.3 %) and the lowest in sachet water (33.3 %). High resistance was observed to ampicillin (100 %), tetracycline (80–100 %), ceftriaxone (20–100 %), and ertapenem (100 %), with lower resistance to ciprofloxacin (20–60 %), chloramphenicol (10–70 %), and imipenem (10–70 %). Carbapenemase production was confirmed in 28.1 % (9/32) of isolates, and 84.3 % (27/32) were MDR. Selected MDR isolates from boreholes carried bla_VIM and qnrA, while bla_NDM and ParC were detected among well-water isolates.

Conclusion

This study provides baseline data of the prevalence of MDR and carbapenemase-producing P. aeruginosa in drinking water in Katsina Metropolis and underscores the need for enhanced surveillance of water sources for WHO-priority pathogens.

饮用水中的耐多药铜绿假单胞菌在低资源环境中构成重大公共卫生风险，导致发病率和死亡率增加。本研究调查了尼日利亚卡齐纳市饮用水中耐多药铜绿假单胞菌的流行情况以及碳青霉烯类和喹诺酮类耐药基因的发生情况。方法从5个地点的水井（n = 15）、钻孔（n = 15）和袋装水（n = 15）中采集45份水样。采用头孢啶脂琼脂和标准微生物学方法进行细菌分离和鉴定。采用纸片扩散法进行药敏试验，分离株对≥3类抗生素耐药，分类为MDR。采用改良的碳青霉烯酶NP试验评估碳青霉烯酶产量，并采用pcr方法筛选耐多药菌株的碳青霉烯烯和喹诺酮类耐药基因。铜绿菌检出率为71.1%(32/45)，其中水井检出率最高（93.3%），小袋水检出率最低（33.3%）。对氨苄西林（100%）、四环素（80 - 100%）、头孢曲松（20 - 100%）、厄他培南（100%）耐药较高，对环丙沙星（20 - 60%）、氯霉素（10 - 70%）、亚胺培南（10 - 70%）耐药较低。28.1%（9/32）的菌株产生碳青霉烯酶，84.3%（27/32）为耐多药菌株。井水分离株中检出blaNDM和ParC，井水分离株中检出blaNDM和ParC。结论本研究提供了卡齐纳市饮用水中耐多药和产碳青霉烯酶铜绿假单胞菌流行率的基线数据，并强调需要加强对水源中世卫组织重点病原体的监测。

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引用次数: 0

Association of ACTN3 and ACE gene polymorphisms with Indian elite boxer status ACTN3和ACE基因多态性与印度优秀拳击手地位的关系

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-10-10 DOI: 10.1016/j.genrep.2025.102357

Vijmendra Kumar Grover , Jai Prakash Verma , Ashish Kumar , Nivedita Sharma , Pramod Kumar Tiwari

Genetic variations are considered important for athletic performance. In this regard, α-actinin-3 (ACTN3) and angiotensin I-converting enzyme (ACE) gene polymorphisms are widely studied for their association with elite athlete status. The ACE gene regulates circulatory homeostasis, with the I variant of the ACE insertion/deletion (ACE I/D) gene polymorphism being associated with endurance performance, while the R allele of the R577X polymorphism of the ACTN3 gene, crucial for fast glycolytic muscle fibers, has been associated with speed and power performances. The present study investigated the association of these genetic variants with elite boxer (N = 57) status and compared with elite power/speed athletes (N = 40), endurance athletes (N = 44) and nonathletes (N = 98) in the Indian population. The R allele frequency was significantly higher in boxers than the nonathletes (p < 0.05). The allele and genotype frequencies of boxers, endurance and power/speed athletes did not differ significantly (p > 0.05). After analyzing the overall athletic cohort on the basis of their level of performance, the frequency of RR genotype (24.1 %) and R allele (47.7 %) in national level athletes was found significantly higher than in nonathletes (8.7 % and 34.2 %, respectively), with a significant difference (p < 0.05) between national level endurance athletes and nonathletes only. The ACE I/D gene polymorphism was not associated with any of the athletic cohorts (p > 0.05). Taken altogether, our study showed that the R allele of ACTN3 gene polymorphism is associated with elite boxer status as compared to the nonathletes.

遗传变异被认为对运动成绩很重要。在这方面，α-肌动素-3 （ACTN3）和血管紧张素i转换酶（ACE）基因多态性与优秀运动员状态的关系被广泛研究。ACE基因调节循环稳态，其中ACE插入/缺失基因多态性的I变体与耐力表现有关，而ACTN3基因R577X多态性的R等位基因对快速糖酵解肌纤维至关重要，与速度和力量表现有关。本研究调查了这些基因变异与优秀拳击手（N = 57）状态的关系，并与印度人群中的优秀力量/速度运动员（N = 40）、耐力运动员（N = 44）和非运动员（N = 98）进行了比较。拳击手R等位基因频率显著高于非运动员（p < 0.05）。拳击手、耐力运动员和力量/速度运动员的等位基因频率和基因型频率无显著差异（p > 0.05）。根据运动员成绩水平对整个运动员队列进行分析后发现，国家级运动员中RR基因型（24.1%）和R等位基因（47.7%）的频率显著高于非运动员（分别为8.7%和34.2%），国家级耐力运动员与非运动员之间存在显著差异（p < 0.05）。ACE I/D基因多态性与任何运动组均无相关性（p > 0.05）。综上所述，我们的研究表明，与非运动员相比，ACTN3基因多态性的R等位基因与优秀拳击手的状态有关。

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引用次数: 0

Comprehensive genomic analysis of the novel PAX6:c.194G>A (p.Gly65Glu) mutation: Highlighting a potential association with aniridia and autism spectrum disorder 新型PAX6:c基因的综合基因组分析。194G >a （p.Gly65Glu）突变：与无输卵管和自闭症谱系障碍的潜在关联

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-10-08 DOI: 10.1016/j.genrep.2025.102353

Mohammad Salimi Asl , Yousef Jafari Abarghan , Narjes Bakhtari , Sepideh Shohani , Mina Mohammadi Sarband , Sorayya Ghasemi

Background

Aniridia is a congenital eye disorder characterized by a partially or completely missing iris, frequently accompanied by other eye abnormalities. Communication difficulties, social interaction issues, and repetitive behaviors are hallmarks of autism spectrum disorder (ASD), a neurodevelopmental disorder. Identifying a causal gene(s) that is involved in aniridia and ASD in a patient is the goal of this research.

Methods

Genetic counseling, pedigree analysis, and a thorough clinical evaluation were performed on a 9-year-old female patient who presented with congenital aniridia and ASD. Karyotyping, Comparative Genomic Hybridization (CGH)-array, Whole-Exome Sequencing (WES), Sanger sequencing, and STR-based paternity testing were performed. In silico structural modeling was done using I-TASSER, and PyMOL 3.1.1 was used to find putative genetic variants.

Results

WES identified a novel de novo heterozygous point mutation, c.194G>A (p.Gly65Glu), in the PAX6 gene. Sanger sequencing confirmed this mutation, which was not discovered in population databases. STR-based paternity testing verified its de novo mutation. In silico tools (PolyPhen-2: 0.998; SIFT: 0.01; CADD: 35.0) predicted a deleterious effect.

Conclusions

This study provides the first report of a novel de novo PAX6:c.194G>A (p.Gly65Glu) mutation associated with aniridia and ASD. The findings highlight the pleiotropic role of PAX6 and support the utility of WES in detecting rare variants in complex phenotypes. Functional studies are necessary to confirm the pathogenic mechanism.

虹膜缺失是一种先天性眼部疾病，其特征是虹膜部分或完全缺失，通常伴有其他眼部异常。沟通困难、社会互动问题和重复行为是自闭症谱系障碍（ASD）的特征，这是一种神经发育障碍。本研究的目标是确定与患者无虹膜和ASD有关的致病基因。方法对1例9岁女性先天性无虹膜伴ASD患者进行遗传咨询、家系分析和全面临床评估。进行核型分析、比较基因组杂交（CGH）阵列、全外显子组测序（WES）、Sanger测序和基于str的亲子鉴定。使用I-TASSER进行硅结构建模，使用PyMOL 3.1.1寻找假定的遗传变异。结果在PAX6基因中发现了一个新的从头杂合点突变c.194G> a （p.Gly65Glu）。Sanger测序证实了这种在人口数据库中未发现的突变。基于str的亲子鉴定证实了其从头突变。在硅工具（polyphen2: 0.998; SIFT: 0.01; CADD: 35.0）预测有害影响。结论本研究首次报道了一种新的PAX6:c.194G> a （p.Gly65Glu）突变与无视网膜和ASD相关。这些发现强调了PAX6的多效性作用，并支持WES在检测复杂表型中的罕见变异方面的应用。功能研究是确认致病机制的必要条件。

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引用次数: 0

ZnO nanoparticle effects on Arabidopsis thaliana: Insights into miRNA and metabolite profiles ZnO纳米颗粒对拟南芥的影响：对miRNA和代谢物谱的见解

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-10-07 DOI: 10.1016/j.genrep.2025.102352

Nikola Vintrlikova , Marek Dvorak , Martina Kolackova , Monika Damyanov , Andrea Ridoskova , Martin Brtnicky , Tomas Vaculovic , Dalibor Huska

The application of zinc oxide nanoparticles (ZnO NPs) in agriculture and plant research is a topic of significant debate. In this study, we explored the molecular responses of Arabidopsis thaliana (Columbia (Col-0) ecotype) to ZnO NP exposure, with a primary focus on miRNA expression and metabolite profiles, providing new insights into the mechanisms underlying plant responses. ZnO NPs were applied at three concentrations (8, 40, 80 mg·kg⁻¹) in peat tablets (Jiffy®). Our results reveal dose-dependent negative effects on plant phenotypic traits, particularly reductions in growth and chlorophyll content. Notably, ZnO NPs caused significant disruptions in metal homeostasis, with elevated zinc accumulation and altered uptake of manganese, iron, and calcium. Gene expression analysis of antioxidant defense responses demonstrated concentration-specific regulation, indicating a shift towards more specialized antioxidants under ZnO NP stress. Specifically, the lower concentrations (8 and 40 mg·kg⁻¹) led to the overexpression of genes related to H₂O₂ scavenging and glutathione synthesis, while the 80 mg·kg⁻¹ concentration induced the upregulation of genes associated with superoxide scavenging, highlighting a dose-dependent shift in oxidative stress response mechanisms. These molecular changes were accompanied by significant alterations in miRNA expression and metabolite profiles, in a non-linear and dose-dependent manner. A significant role was observed for the miR156-SPL regulatory module at the 40 and 80 mg·kg⁻¹ concentrations. Furthermore, proline (approx. 20 % increase, 8, 80 mg·kg⁻¹), taurine (16 %, 80 mg·kg⁻¹), fumaric acid (31 %, 40 mg·kg⁻¹), and glutamic acid (50 %, 8 mg·kg⁻¹) were implicated in the plant's adaptive response to ZnO NPs, contributing to antioxidant defense and metal-binding mechanisms. Together, these results highlight that ZnO NP exposure elicits complex and multi-layered adaptive mechanisms involving the interplay of elemental stress, antioxidant responses, miRNA regulation, and metabolic adjustments.

氧化锌纳米颗粒（ZnO NPs）在农业和植物研究中的应用是一个备受争议的话题。在这项研究中，我们探索了拟南芥（Columbia （col0）生态型）对ZnO NP暴露的分子响应，主要关注miRNA表达和代谢物谱，为植物响应机制提供了新的见解。以3种浓度（8、40、80 mg·kg−1）的ZnO NPs作用于泥炭片（Jiffy®）中。我们的研究结果揭示了剂量依赖性对植物表型性状的负面影响，特别是生长和叶绿素含量的降低。值得注意的是，ZnO NPs引起了金属稳态的显著破坏，锌积累增加，锰、铁和钙的吸收改变。抗氧化防御反应的基因表达分析显示出浓度特异性调控，表明在ZnO NP胁迫下，抗氧化剂向更专门化的方向转变。具体来说，较低浓度（8和40 mg·kg−1）导致H2O2清除和谷胱甘肽合成相关基因的过度表达，而80 mg·kg−1浓度诱导超氧化物清除相关基因的上调，突出了氧化应激反应机制的剂量依赖性转变。这些分子变化伴随着miRNA表达和代谢物谱的显著改变，以非线性和剂量依赖的方式。在40和80 mg·kg−1浓度下，miR156-SPL调控模块的作用显著。此外，脯氨酸(约。20%的增加（8,80 mg·kg−1）、牛磺酸（16%,80 mg·kg−1）、富马酸（31%,40 mg·kg−1）和谷氨酸（50%,8 mg·kg−1）参与了植物对ZnO NPs的适应性反应，参与了抗氧化防御和金属结合机制。总之，这些结果表明ZnO NP暴露引发了复杂的多层适应机制，涉及元素胁迫、抗氧化反应、miRNA调节和代谢调节的相互作用。

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引用次数: 0

Bioinformatics and immunoinformatics-assisted design studies of a heavy chain multi-epitope vaccine for botulinum toxin type A a型肉毒毒素重链多表位疫苗的生物信息学和免疫信息学辅助设计研究

IF 0.9 Q4 GENETICS & HEREDITY

Gene Reports

Pub Date : 2025-10-06 DOI: 10.1016/j.genrep.2025.102351

Yulin Li , Yanli Liu , Yunyang Song , Yifeng Yin , Rui Bai , Fanghui Wu , Yanfang Wang

Background

Botulinum toxin type A (BoNT/A) has been growing applications in the medical field, yet concerns regarding its biosafety persist. Currently, recombinant vaccines targeting the Hc structural domain is the predominant focus of research. However, their large molecular weight and tendency to form inclusion bodies during expression reduces vaccine activity. Therefore, in this study, cutting-edge bioinformatics and immunoinformatics tools were utilized to develop a low-cost, highly active and safe BONT/A-Hc multi-epitope vaccine.

Methods

The complete sequence of BONT/A was obtained from the NCBI database, and the IEDB platform was used to screen B and T cell antigenic epitopes, and construct a multi-epitope vaccine, and conduct predictive analyses of its antigenicity, allergenicity, and toxicity. The designed multi-epitope vaccine genes were cloned into vectors and expressed using a prokaryotic system to determine their expression forms and activities. Finally, the accuracy of the predicted results was verified by SDS-PAGE and Western blot.

Results

The constructed multi-epitope vaccine contains six dominant epitopes, exhibits strong antigenicity, non-sensitization and non-toxicity. Computer simulations indicate it can effectively elicit the desired immune response. The multi-epitope vaccine was successfully cloned into vectors and expressed in soluble form with detectable activity.

Conclusion

The multi-epitope vaccine constructed based on bioinformatics and immunoinformatics screening was predicted to have good immune effects. This study not only provides new ideas for solving the technical challenges in the design and production of multi-epitope vaccines, but also provides important guidance for the efficient development of a vaccine effective against BoNT/A poisoning.

A型肉毒毒素（BoNT/A）在医学领域的应用越来越广泛，但对其生物安全性的担忧仍然存在。目前，针对Hc结构域的重组疫苗是研究的主要焦点。然而，它们的大分子量和在表达过程中形成包涵体的倾向降低了疫苗的活性。因此，本研究利用尖端的生物信息学和免疫信息学工具，开发了一种低成本、高活性、安全的BONT/ a - hc多表位疫苗。方法从NCBI数据库获取BONT/A的完整序列，利用IEDB平台筛选B细胞和T细胞抗原表位，构建多表位疫苗，并对其抗原性、致敏性和毒性进行预测分析。将设计的多表位疫苗基因克隆到载体中，利用原核系统进行表达，以确定其表达形式和活性。最后通过SDS-PAGE和Western blot验证预测结果的准确性。结果构建的多表位疫苗含有6个优势表位，具有较强的抗原性、无致敏性和无毒性。计算机模拟表明，该方法可以有效地引发所需的免疫反应。该多表位疫苗成功克隆到载体中，并以可溶性形式表达，具有可检测的活性。结论基于生物信息学和免疫信息学筛选构建的多表位疫苗具有良好的免疫效果。本研究不仅为解决多表位疫苗设计和生产中的技术难题提供了新思路，也为高效研制有效抗BoNT/ a中毒的疫苗提供了重要指导。

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引用次数: 0