Infection Genetics and Evolution最新文献_第7页

Single-cell RNA sequencing in high-burden viral respiratory infections: Decoding immune cell subsets and immune-related differential gene expression 高负荷病毒性呼吸道感染的单细胞RNA测序：解码免疫细胞亚群和免疫相关差异基因表达

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution

Pub Date : 2025-09-23 DOI: 10.1016/j.meegid.2025.105834

Milad Sheervalilou, Mostafa Ghanei, Masoud Arabfard

Respiratory infections remain a major global health burden, ranking among the leading causes of mortality worldwide. Single-cell RNA sequencing (scRNA-seq) has emerged as a transformative technology for dissecting the cellular and molecular complexity of these infections. This review focuses on recent scRNA-seq studies investigating the immune landscape of high-burden viral respiratory infections, particularly COVID-19 and influenza, which are characterized by high transmissibility and clinical impact. We provide an overview of publicly available scRNA-seq datasets derived from human peripheral blood and bronchoalveolar lavage fluid (BALF), as well as lung tissues and explants from murine models, emphasizing their value in profiling immune heterogeneity. scRNA-seq has revealed significant remodeling of immune cell populations during infection, including the identification of novel subsets such as CD4⁺ c13-MKI67⁺ CCL5^low T cells, CD8⁺ CXCR3^high GZMA⁺ T cells, and CD56^high CD16⁻ GZMB⁺ NK cells. These subsets are frequently associated with differential expression of cytokines, chemokines, and interferon-stimulated genes that reflect disease severity and progression. In addition, scRNA-seq has highlighted key pathogen-induced pathways, including type I interferon, NF-κB, and JAK/STAT signaling, and has identified emerging immune-related biomarkers—such as PTX3, MCEMP1, CXCR4, IFIT1, ISG15, and STAT1—with potential diagnostic and prognostic utility. While scRNA-seq applications in respiratory infections of other microbial origins are limited, its role in mapping immune responses and guiding biomarker discovery in viral infections is rapidly expanding. This review synthesizes these findings to inform future translational research and immunodiagnostic strategies.

呼吸道感染仍然是一个主要的全球健康负担，是全世界死亡的主要原因之一。单细胞RNA测序（scRNA-seq）已经成为一种革命性的技术，用于解剖这些感染的细胞和分子复杂性。本文综述了最近的scRNA-seq研究，研究了高负担病毒性呼吸道感染的免疫景观，特别是COVID-19和流感，这些疾病具有高传染性和临床影响。我们概述了来自人类外周血和支气管肺泡灌洗液（BALF）以及小鼠模型肺组织和外植体的公开可用scRNA-seq数据集，强调了它们在分析免疫异质性方面的价值。scRNA-seq揭示了感染期间免疫细胞群的显著重塑，包括鉴定出新的亚群，如CD4+ c13-MKI67+ CCL5low T细胞、CD8+ CXCR3high GZMA+ T细胞和cd56高CD16- GZMB+ NK细胞。这些亚群通常与反映疾病严重程度和进展的细胞因子、趋化因子和干扰素刺激基因的差异表达有关。此外，scRNA-seq还发现了关键的病原体诱导通路，包括I型干扰素、NF-κB和JAK/STAT信号，并发现了新兴的免疫相关生物标志物，如PTX3、MCEMP1、CXCR4、IFIT1、ISG15和stat1，具有潜在的诊断和预后价值。虽然scRNA-seq在其他微生物来源的呼吸道感染中的应用有限，但它在绘制免疫反应和指导病毒感染中生物标志物发现方面的作用正在迅速扩大。这篇综述综合了这些发现，为未来的转化研究和免疫诊断策略提供信息。

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引用次数: 0

Analysis of novel African swine fever variants circulating in wild boars in South Korea isolated in 2021 by deep sequencing 通过深度测序分析2021年在韩国分离的野猪中流行的新型非洲猪瘟变体

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution

Pub Date : 2025-09-20 DOI: 10.1016/j.meegid.2025.105833

Van Dam Lai , Yong-kwan Kim , Min-Ho Kim , Yeeun Moon , Hyeok-Il Kwon , Weon-hwa Jheong , Jong-Soo Lee , Sung-Sik Yoo , In Pil Mo

African swine fever (ASF) is major infectious disease of concern currently circulating in swine species, causing high mortality and significant economic damage on the global scale. Since the first incident of ASF outbreak in Korea in 2019, the disease has continued to spread throughout the country despite enhanced biosecurity measures, with wild boars playing a key role. Thus, characterizing the domestic African swine fever virus (ASFV) strains including its genetic variants is crucial for both monitoring and diagnostic purposes. In this study, we sequenced and analyzed the full genome of seven Korean ASFV strains isolated from ASFV positive wild boar samples collected in 2021 from various regions. The sequences were compared with previously isolated ASFV strains to track the origin and the evolutionary trend of the ASFV variants residing in the wild boar population in Korea. A total of thirty single-nucleotide polymorphisms (SNPs) were detected which consists of ten synonymous and eighteen non-synonymous mutations, a single mutation at intergenic region (IGR), and a truncation mutation which led to a premature stop codon. Out of the mutations, thirteen were present in the MGF 505-9R gene. All seven strains contained an additional ten-nucleotides (nt) long tandem repeat sequence (TRS) between the I73R and I179L gene, similar to strains previously studied in Korea. Additionally, a new seventeen-nt long tandem repeat sequence insertion, adjacent to the MGF 505-10R, has been observed at the IGR between the MGF 505-9R and 10R genes. The results of the study provide extra insight for characterizing the ASFV virus in Korea and suggesting new molecular genetic markers for epidemiological monitoring, thus minimizing the risk of new ASF outbreaks in Korea.

非洲猪瘟（ASF）是目前在猪种中流行的令人关注的主要传染病，在全球范围内造成高死亡率和重大经济损失。自2019年韩国首次出现非洲猪瘟疫情以来，尽管加强了生物安全措施，但疫情仍在全国范围内持续蔓延，其中野猪发挥了关键作用。因此，确定国内非洲猪瘟病毒（ASFV）毒株的特征，包括其遗传变异，对于监测和诊断目的都至关重要。在这项研究中，我们对从2021年从不同地区收集的ASFV阳性野猪样本中分离的7株韩国ASFV毒株进行了全基因组测序和分析。将这些序列与先前分离的ASFV毒株进行比较，以追踪韩国野猪种群中ASFV变异的起源和进化趋势。共检测到30个单核苷酸多态性（SNPs），包括10个同义突变和18个非同义突变，1个基因间区突变（IGR）和1个截断突变（导致过早终止密码子）。在这些突变中，有13个存在于MGF 505-9R基因中。所有菌株在I73R和I179L基因之间都含有一个额外的10个核苷酸（nt）长串联重复序列（TRS），与之前在韩国研究的菌株相似。此外，在MGF 505-10R基因和MGF 505-9R基因之间的IGR上发现了一个新的17 nt长的串联重复序列插入，邻近MGF 505-10R基因。该研究结果为韩国ASFV病毒的特征提供了额外的见解，并为流行病学监测提供了新的分子遗传标记，从而最大限度地降低了韩国新的ASF暴发的风险。

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引用次数: 0

Targeted next-generation sequencing reveals pathogen mono- and co-detection patterns in pediatric Mycoplasma pneumoniae pneumonia 靶向下一代测序揭示了儿童肺炎支原体肺炎的病原体单一和共同检测模式。

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution

Pub Date : 2025-09-18 DOI: 10.1016/j.meegid.2025.105832

Genfeng Wu , Yuejie Zheng , Kangyan Yuan , Yanmin Bao , Li Li , Yuzheng Li , Wenjian Wang , Heping Wang

Background

Following pandemic control optimization, Mycoplasma pneumoniae (MP) has emerged as a predominant pediatric respiratory pathogen in Shenzhen. Understanding its epidemiological patterns and drug resistance is critical for managing severe MP-associated pneumonia.

Methods

This retrospective study analyzed 607 hospitalized children (February–November 2023) using targeted next-generation sequencing (tNGS) of bronchoalveolar lavage fluid. MP-positive cases were stratified by age, gender, clinical features, drug resistance genes, and co-detection profiles.

Results

Pathogens were identified in 605 cases (99.7 %), with MP constituting 85.0 % of detected pathogens. Among 209 cases with resistance genes, A2063G mutation predominated (98.1 %). Patients were categorized into: MP-positive (n = 444), MP-carriage (n = 72), and MP-negative (n = 91) groups. Age stratification revealed significantly older MP-positive patients (median 72 months, IQR 48–96) versus carriages (29.5 months, IQR 14–60) and negatives (36 months, IQR 16–60) (P < 0.001). Gender distribution showed no significant intergroup differences (χ² = 2.619, p = 0.270). The MP-positive group demonstrated lower co-detection rates of Haemophilus influenzae (12.2 % vs 37.5 %/31.5 %) and Moraxella catarrhalis (10.6 % vs 25.0 %/20.2 %) compared to carriages and negatives (P < 0.001). tNGS uncovered atypical pathogens including Tropheryma whipplei (13.3 %) and Fusobacterium nucleatum (6.3 %).

Conclusion

Post-pandemic MP resurgence correlates with increased severe pediatric pneumonia despite declining macrolide resistance rates (23.2 % in 2023 vs historical 80–90 %). MP primarily manifests as monoinfections, while M. catarrhalis and H. influenzae co-detection may confer observed co-detection pattern. These findings underscore tNGS's clinical utility in identifying atypical pathogens and guiding antimicrobial stewardship in pediatric pneumonia management.

背景：随着大流行控制的优化，肺炎支原体（MP）已成为深圳主要的儿科呼吸道病原体。了解其流行病学模式和耐药性对于管理严重的mp相关性肺炎至关重要。方法：采用支气管肺泡灌洗液靶向新一代测序（tNGS）对607例住院儿童（2023年2 - 11月）进行回顾性研究。mp阳性病例按年龄、性别、临床特征、耐药基因和共检概况进行分层。结果：检出病原菌605例（99.7 %），其中MP占检出病原菌的85.0% %。209例耐药基因中以A2063G突变为主（98.1% %）。患者分为：mp阳性组（n = 444）、mp携带组（n = 72）和mp阴性组（n = 91）。年龄分层显示，mp阳性患者（中位72 个月，IQR 48-96）与阴性患者（中位29.5 个月，IQR 14-60）和阴性患者（中位36 个月，IQR 16-60）相比（P 2 = 2.619,P = 0.270）具有显著性差异。MP-positive集团展示了co-detection利率下降的流感嗜血杆菌(12.2 vs 37.5  % % / 31.5 %)和莫拉克斯氏菌属复活(10.6 vs 25.0  % % / 20.2 %)相比,车厢和底片(P 结论:流行后议员复苏与增长尽管大环内酯物电阻率下降,严重的小儿肺炎(23.2 % 2023年和80 - 90年的历史 %)。MP主要表现为单感染，而卡塔卡分枝杆菌和流感嗜血杆菌共同检测可能会产生观察到的共同检测模式。这些发现强调了tNGS在鉴别非典型病原体和指导儿科肺炎抗菌药物管理方面的临床应用。

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引用次数: 0

Unravelling ecological factors influencing phylodynamics of Kyasanur Forest Disease in India 揭示影响印度Kyasanur森林病害系统动力学的生态因素。

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution

Pub Date : 2025-09-17 DOI: 10.1016/j.meegid.2025.105831

Sahal Paladan , Bhimanagoud Kumbar , Dharani Govindasamy , Shweta Patil , H.B. Chethan Kumar , Revanaiah Yogisharadhya , Pragya Yadav , T. Jeromie Wesley Vivian , Sathish S. Gaekwad , Naveen Kumar , Baldev Raj Gulati , Sathish Bhadravati Shivachandra , Mohammed Mudassar Chanda

Kyasanur Forest Disease Virus (KFDV) is a tick-borne flavivirus endemic to the Western Ghats region of India, with increasing reports of geographic expansion. This study employs phylogenetic analysis and spatial diffusion modeling to understand the evolutionary dynamics and transmission patterns of KFDV. Whole genome and E-gene sequences were analysed to identify major phylogenetic clusters, transmission velocity, and environmental factors influencing viral spread. The analysis revealed two primary phylogenetic clusters: Cluster A, originating in Karnataka, and linked to initial outbreaks (1957–1972) and subsequent re-emergence post-2010 in Karnataka, Kerala, and Goa; and Cluster B, which expanded from Maharashtra in the late 1970s into Tamil Nadu, Karnataka, and Kerala. Phylogenetic findings indicated a slow mutation rate, indicative of long-term viral persistence in sylvatic reservoirs rather than sustained human-human transmission.

Spatial diffusion analysis estimated a median transmission velocity of 59.67 km/year. Environmental factors such as deforestation, land cover change, and livestock density acted as facilitators of viral spread, while urbanization, open water bodies, and precipitation served as resistance factors. The findings underscore the need for enhanced surveillance, ecological monitoring, and public health interventions to mitigate the increasing risk of KFD outbreaks. This study provides a comprehensive framework for understanding KFDV transmission and evolution, integrating phylogenetic and ecological data to improve risk assessment and guide control strategies in both endemic and emerging regions.

喀萨努尔森林病病毒（KFDV）是印度西高止山脉地区的一种地方性蜱传黄病毒，有越来越多的地理扩展报告。本研究采用系统发育分析和空间扩散模型来了解KFDV的进化动力学和传播模式。分析全基因组和e基因序列，以确定主要的系统发育集群、传播速度和影响病毒传播的环境因素。分析揭示了两个主要的系统发育聚集性：聚集性A，起源于卡纳塔克邦，与卡纳塔克邦、喀拉拉邦和果阿邦的最初暴发（1957-1972年）和2010年后的再次暴发有关；B集群在20世纪70年代末从马哈拉施特拉邦扩展到泰米尔纳德邦、卡纳塔克邦和喀拉拉邦。系统发育结果表明突变率缓慢，表明病毒在森林水库中长期存在，而不是持续的人类传播。空间扩散分析估计中位传播速度为59.67 km/年。森林砍伐、土地覆盖变化和牲畜密度等环境因素是病毒传播的促进因素，而城市化、开放水体和降水是病毒传播的阻力因素。研究结果强调需要加强监测、生态监测和公共卫生干预，以减轻口蹄疫爆发日益增加的风险。该研究为了解KFDV的传播和进化提供了一个全面的框架，整合了系统发育和生态数据，以改善流行地区和新兴地区的风险评估和指导控制策略。

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引用次数: 0

Genomic insights of two Acinetobacter non-baumannii strains with uncommon mechanisms of resistance leading to cefiderocol resistance 两种非鲍曼不动杆菌菌株的基因组见解，具有罕见的耐药机制，导致头孢地罗耐药。

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution

Pub Date : 2025-09-16 DOI: 10.1016/j.meegid.2025.105820

Usman Akhtar , Samyar Moheb , Carol Davies-Sala , Joshua Gutierrez , Fernando Pasteran , Marisel R. Tuttobene , Tomás Subils , Chun Fu Cheng , Quentin Valle , Rajnikant Sharma , Marcelo E. Tolmasky , Gauri Rao , Robert A. Bonomo , German M. Traglia , María Soledad Ramírez

The emergence of antimicrobial resistance in Acinetobacter species poses a significant clinical challenge, particularly in non-baumannii species, which are often overlooked in healthcare settings. In this study, we characterized two Acinetobacter clinical isolates, AMA204 and AMA207—identified as A. junii and A. haemolyticus, respectively—which exhibit uncommon resistance mechanisms that enable survival in the presence of cefiderocol, regardless of their initial minimum inhibitory concentration values. Whole-genome sequencing and comparative genomic analyses were performed to investigate the genetic determinants associated with their resistance profiles. Antimicrobial susceptibility testing confirmed multidrug resistance, with both isolates harboring key β-lactamase genes, including bla_OXA-58, and bla_NDM-1 in AMA204, and bla_OXA-58 and bla_PER-2 in AMA207. Phylogenomic analyses revealed genetic relatedness to geographically diverse isolates, suggesting possible evolutionary trends and transmission dynamics. Additionally, iron uptake systems were analysed, highlighting potential mechanisms contributing to cefiderocol resistance together with the presence of listed β-lactamase. This study underscores the clinical relevance of non-baumannii Acinetobacter species in antimicrobial resistance and emphasizes the need for continued surveillance and novel therapeutic strategies to combat these emerging threats.

不动杆菌物种抗菌素耐药性的出现构成了重大的临床挑战，特别是在非鲍曼原虫物种中，这在卫生保健环境中经常被忽视。在这项研究中，我们鉴定了两种临床分离的不动杆菌，AMA204和ama207，分别鉴定为朱尼假杆菌和溶血假杆菌，它们表现出罕见的耐药机制，能够在头孢地罗存在下存活，而不管它们的初始最低抑制浓度值如何。进行了全基因组测序和比较基因组分析，以调查与其抗性谱相关的遗传决定因素。药敏试验证实两株菌株均存在多药耐药，其中AMA204中含有blaOXA-58和blaNDM-1基因，AMA207中含有blaOXA-58和blaPER-2基因。系统基因组学分析揭示了地理上不同分离株的遗传相关性，提示可能的进化趋势和传播动态。此外，还分析了铁摄取系统，强调了导致头孢地罗耐药的潜在机制以及所列β-内酰胺酶的存在。这项研究强调了非鲍曼不动杆菌在抗菌素耐药性中的临床相关性，并强调需要持续监测和新的治疗策略来对抗这些新出现的威胁。

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引用次数: 0

Modeling and sensitivity analysis of cholera dynamics under fuzzy imprecision 模糊不精确条件下霍乱动力学建模及敏感性分析。

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution

Pub Date : 2025-09-16 DOI: 10.1016/j.meegid.2025.105821

Sara Riaz , Asghar Ali , Muhammad Munir

This article presents a sensitivity analysis of the cholera transmission model, in which all parameters related to disease dynamics are considered as fuzzy numbers. Classical and system sensitivities of this fuzzy system have been analyzed to provide a real world approximation to cholera outbreaks. Graphical results indicate that the susceptible population is most sensitive to the new recruitment and disease-induced mortality rates of the infected and treated populations, whereas the infected population is found to be more sensitive to immune loss and disease transmission rate. The treated individuals have proven sensitivity towards the contact rate, while the recovered ones are more sensitive to the recovery and disease-induced death rates. The cumulative effect of these sensitivities with respect to induced fuzzy parameters on the model output has been reflected in the system sensitivities. As a consequence of this analysis, treatment and the disease transmission rate are identified as the most influential parameters for this newly structured model.

本文提出了霍乱传播模型的敏感性分析，其中所有与疾病动力学有关的参数都被认为是模糊数。分析了该模糊系统的经典灵敏度和系统灵敏度，以提供一个真实世界的近似霍乱暴发。图形结果表明，易感人群对感染和治疗人群的新招募率和疾病引起的死亡率最为敏感，而感染人群对免疫丧失和疾病传播率更为敏感。经治疗的个体已证实对接触率敏感，而康复的个体对康复率和疾病引起的死亡率更为敏感。这些灵敏度相对于诱导模糊参数对模型输出的累积效应已反映在系统灵敏度中。作为分析的结果，治疗和疾病传播率被确定为这个新结构模型中最具影响力的参数。

引用次数: 0

Characterization of genes involved in hemoglobin degradation in Plasmodium vivax isolates from Chennai, India, and species of non-human primate malaria 印度金奈间日疟原虫分离株和非人灵长类疟疾种血红蛋白降解相关基因的研究

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution

Pub Date : 2025-09-11 DOI: 10.1016/j.meegid.2025.105823

Sneh Shalini , Neelima Mishra , Sonia Verma , Sonal Kale , Prashant K. Mallick , Surendra K. Prajapati , Anil Kumar , Nalini Srivastava , Hema Joshi , Alex Eapen , Om P. Singh

Background

Plasmodium vivax poses a persistent obstacle to global malaria elimination efforts. While no detectable chloroquine (CQ) resistance has been found in patient samples from India, this observation awaits confirmation. The mechanism of action of CQ continues to be debated. Hemoglobin degradation within the parasite's food vacuole (FV) is integral to its survival and serves as a promising target for antimalarial drug development.

Methods

This study investigates the molecular and structural characteristics of three key FV enzymes—plasmepsin IV (PM_IV), heme detoxification protein (HDP), and falcilysin (FLN)—in P. vivax isolates from India. Genomic DNA from 30 clinical isolates and three chloroquine (CQ)-resistant reference strains was analyzed to identify mutations and assess structural implications through homology modelling.

Results

Several nonsynonymous mutations were detected, including c.493G>A (Val165Ile) in PM_IV, c.1537A>G (Asn513Asp), and c.2027G>A (Gly676Asp) in FLN, and a novel in-frame duplication c.28_33dup (ATCGCC) in HDP. Structural modelling revealed that these mutations did not affect the active binding sites of the enzymes.

Conclusions

The genes were highly conserved across isolates, underscoring their important (essential) roles in parasite survival and their potential as drug targets. These are the first findings from the Indian subcontinent that provide critical insights into the mechanisms of chloroquine (CQ) action and resistance, paving the way for novel therapeutic strategies against Plasmodium vivax malaria.

背景：间日疟原虫对全球消除疟疾的努力构成了持续的障碍。虽然在印度患者样本中未发现可检测到的氯喹耐药性，但这一观察结果有待证实。CQ的作用机制仍有争议。寄生虫食物液泡（FV）内的血红蛋白降解是其生存所不可或缺的，也是抗疟疾药物开发的一个有希望的靶点。方法：研究印度间日疟原虫分离株中三种关键酶——plasmepsin IV （PM_IV）、血红素解毒蛋白（HDP）和falcilysin （FLN）的分子结构特征。分析了30株临床分离株和3株氯喹耐药参考株的基因组DNA，通过同源性建模鉴定突变并评估结构意义。结果：检测到多个非同同义词突变，包括PM_IV中的c.493G > A (Val165Ile)， FLN中的c.1537G > A （Asn513Asp）和c.2027G > A (Gly676Asp)，以及HDP中新的帧内重复c.36_41dup （ATCGCC）。结构模型显示，这些突变不影响酶的活性结合位点。结论：这些基因在整个分离株中高度保守，强调了它们在寄生虫生存中的重要（基本）作用和它们作为药物靶点的潜力。这些是来自印度次大陆的首次发现，为氯喹（CQ）的作用和耐药性机制提供了重要见解，为针对间日疟原虫疟疾的新治疗策略铺平了道路。

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引用次数: 0

Exploratory interaction of Chionis alba (snowy sheathbill) with the amatoxin-producing mushroom Galerina marginata in Antarctica 南极雪鞘喙菌与产蛋黄素的蘑菇Galerina marginata的探索相互作用。

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution

Pub Date : 2025-09-11 DOI: 10.1016/j.meegid.2025.105822

Fernando Augusto Bertazzo-Silva , Alice Lemos Costa , Jorge Renato Pinheiro Velloso , Flavia Helena Aires Sousa , Carlos Ernesto Gonçalves Reynaud Schaefer , Jair Putzke

We report a rare behavioral observation involving an individual of Chionis alba (snowy sheathbill) attempting to consume a basidiome of the toxic mushroom Galerina marginata on Livingston Island, Antarctica. The bird briefly picked up the basidiome before rejecting it. This event, to our knowledge, represents the first recorded interaction between an Antarctic bird and this deadly fungus, suggesting possible chemical or gustatory deterrence mechanisms. Such interactions, though anecdotal, contribute to the understanding of trophic dynamics and fungal ecology in polar environments.

我们报告了一个罕见的行为观察，涉及到一只Chionis alba（雪鞘喙）个体试图消耗有毒蘑菇Galerina marginata的担子子。这只鸟短暂地捡起了担子架，然后拒绝了它。据我们所知，这一事件代表了南极鸟类与这种致命真菌之间首次有记录的相互作用，表明可能存在化学或味觉威慑机制。这种相互作用，虽然道听途说，有助于理解营养动力学和真菌生态在极地环境。

引用次数: 0

Early plasma cytokines associated with multi-drug resistant ventilator-associated pneumonia after neurosurgery: A retrospective cohort study 神经外科术后早期血浆细胞因子与多药耐药呼吸机相关肺炎相关：一项回顾性队列研究

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution

Pub Date : 2025-09-11 DOI: 10.1016/j.meegid.2025.105824

Yuanrun Zhu , Zhaodi Liao , Jianan Su , Feng Zhang , Jin Huang , Ping He , Zhifeng Wu , Kangli Xu , Xiaofeng Yang , Chen Jiang , Yadong Wang

Ventilator-associated pneumonia (VAP) is a major infectious complication in the neurologic intensive care unit (NICU). VAP caused by multi-drug resistant (MDR) pathogens is related to poor clinical outcomes. This study investigates the relationship between early plasma cytokine profiles and the development of MDR VAP following neurosurgery. We retrospectively analyzed neurosurgical patients admitted to the NICU who developed VAP between January 2021 and January 2024. A receiver operating characteristic (ROC) curve was used to determine the predictive value of the cytokines. Among 67 VAP patients, MDR VAP cases exhibited lower Glasgow Coma Scale (GCS) scores on admission and a higher incidence of prolonged hospitalization (>5 days) before infection. Significantly elevated levels of IL-2, IL-6, IL-10 and IL-17a were observed in MDR VAP patients, while IL-4, TNFα and IFNγ presented no statistical difference. ROC curves revealed that IL-2 (AUC: 0.722, 95 % CI: 0.599–0.845) and IL-10 (AUC: 0.798, 95 % CI: 0.687–0.909) had the strongest predictive value, with optimal cut-off values of 2.635 pg/mL (IL-2, sensitivity 57.1 %, specificity 84.4 %) and 8.495 pg/mL (IL-10, sensitivity 77.1 %, specificity 84.4 %), respectively. A combined IL-2 + IL-10 model further improved predictive performance (AUC: 0.827, 95 % CI: 0.726–0.927). This was confirmed by a multivariate analysis (OR: 23.1, p = 0.007). In conclusion, early elevations in plasma IL-2, IL-6, IL-10 and IL-17a (at 24 h of admission to the NICU) are associated with MDR VAP in NICU patients. The combined measurement of IL-2 and IL-10 may serve as a useful adjunctive tool for predicting post-neurosurgery MDR VAP risk, aiding in early clinical intervention.

呼吸机相关性肺炎（VAP）是神经重症监护病房（NICU）的主要感染性并发症。多药耐药（MDR）病原菌引起的VAP与临床预后差有关。本研究探讨了早期血浆细胞因子谱与神经外科术后MDR VAP发生的关系。我们回顾性分析了2021年1月至2024年1月期间入住NICU的发生VAP的神经外科患者。采用受试者工作特征（ROC）曲线确定细胞因子的预测价值。在67例VAP患者中，MDR VAP患者入院时格拉斯哥昏迷评分（GCS）较低，感染前住院时间延长（bbb50 天）的发生率较高。MDR VAP患者IL-2、IL-6、IL-10、IL-17a水平显著升高，IL-4、TNFα、IFNγ水平差异无统计学意义。ROC曲线显示，IL-2 （AUC: 0.722, 95 % CI: 0.599-0.845）和IL-10 （AUC: 0.798, 95 % CI: 0.687-0.909）具有最强的预测价值，最佳临界值分别为2.635 pg/mL （IL-2，敏感性57.1 %，特异性84.4 %）和8.495 pg/mL （IL-10，敏感性77.1 %，特异性84.4 %）。联合IL-2 + IL-10模型进一步提高了预测性能（AUC: 0.827, 95 % CI: 0.726-0.927）。多变量分析证实了这一点（OR: 23.1, p = 0.007）。综上所述，NICU患者早期血浆IL-2、IL-6、IL-10和IL-17a升高（入院24 h）与MDR VAP相关。联合测量IL-2和IL-10可作为预测术后MDR VAP风险的有用辅助工具，有助于早期临床干预。

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引用次数: 0

Whole genome characterisation of DS-1-like G8P[4] rotavirus A strains circulating in South Africa between 2009 and 2021 reveals endemic sub-lineages and evidence of radical epitope changes 2009年至2021年在南非流行的ds -1样G8P[4]轮状病毒A株的全基因组特征揭示了地方性亚谱系和根本表位改变的证据

IF 2.6 4区医学 Q3 INFECTIOUS DISEASES

Infection Genetics and Evolution

Pub Date : 2025-09-05 DOI: 10.1016/j.meegid.2025.105818

Nkosazana D. Shange , Milton T. Mogotsi , Ayodeji E. Ogunbayo , Nicola Page , Hlengiwe Sondlane , Matthew D. Esona , Benjamin Kumwenda , Chimwemwe Mhango , Flywell Kawonga , Ernest Matambo , Samuel N.K. Mingle , Francis E. Dennis , Jere C. Khuzwayo , Nigel A. Makoah , Celeste M. Donato , Martin M. Nyaga

The sub-Saharan African region bears the highest burden of rotavirus-associated morbidity and mortality, with substantial genetic diversity observed in circulating strains despite vaccine introduction. The G8 genotype, originally predominant in bovine strains, has increasingly become prevalent in humans, suggesting a possible interface of animal-to-human transmission and highlighting its role in African strain diversity. In this study, we performed whole genome sequencing and evolutionary analysis of 21 archival G8P[4] strains collected through gastroenteritis surveillance in South Africa between 2009 and 2021 from children under five years of age. All strains exhibited DS-1-like genome constellations and phylogenetically clustered closely with sub-Saharan African G8P[4] strains across all 11 genome segments. A time-resolved phylogeny indicated the co-circulation of multiple G8 sub-lineages, with specific variants persisting for nearly a decade. The mean evolutionary rate for the G8 lineage V sequences was estimated at 1.49 × 10⁻³ substitutions per site per year, with a time to most common recent ancestor of 1981.8, suggesting long-term endemic divergence. Radical amino acid substitutions were identified in neutralising epitopes of VP4 (11 variations) and VP7 (18 variations) relative to the Rotarix® vaccine strain. These changes may impact antigenicity and immune recognition. These findings within the key antigenic sites of G8P[4] strains may reflect ongoing viral adaptation with potential implications for infectivity and sustained circulation in African regions. Taken together, the findings underscore the significance of continued genomic surveillance to monitor evolution and guide the reassessment, optimisation of current vaccines and the development of future vaccines with broader protective efficacy.

撒哈拉以南非洲区域轮状病毒相关发病率和死亡率负担最重，尽管引入了疫苗，但在循环毒株中观察到大量遗传多样性。最初在牛株中占优势的G8基因型在人类中越来越普遍，这表明可能存在动物-人传播的界面，并突出了其在非洲菌株多样性中的作用。在这项研究中，我们对2009年至2021年在南非通过胃肠炎监测收集的21株档案G8P[4]菌株进行了全基因组测序和进化分析，这些菌株来自5岁以下儿童。所有菌株都表现出类似ds -1的基因组群，并且在系统发育上与撒哈拉以南非洲G8P[4]菌株在所有11个基因组片段上紧密聚集。一个时间分辨的系统发育表明多个G8亚谱系的共循环，特定的变异持续了近十年。G8谱系V序列的平均进化速率估计为每位点每年1.49 × 10−3次替换，与最共同的最近祖先的时间为1981.8，表明长期的地方性分化。与Rotarix®疫苗株相比，在VP4（11个变异）和VP7（18个变异）的中和表位上发现了自由基氨基酸取代。这些变化可能影响抗原性和免疫识别。这些在G8P[4]毒株关键抗原位点的发现可能反映了正在进行的病毒适应，对非洲地区的传染性和持续传播具有潜在影响。综上所述，这些发现强调了继续进行基因组监测的重要性，以监测进化并指导对现有疫苗的重新评估和优化，以及开发具有更广泛保护功效的未来疫苗。

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