The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal ObstetriciansYun Zhong, Lan Peng
BACKGROUND: Listeriosis during pregnancy is a rare but life-threatening infection that often presents with nonspecific symptoms, making timely diagnosis difficult. This article reports a case in which the clinical presentation and immune profile were highly consistent with Listeria monocytogenes infection, leading to a presumptive clinical diagnosis. The patient was successfully treated following a diagnostic approach that integrated host immune profiling with AI-assisted decision-making, despite dual interference from Ureaplasma urealyticum detected by metagenomic next-generation sequencing (mNGS) and Staphylococcus capitis detected by blood culture. CASE PRESENTATION: A 25-year-old female patient, at 37+6 weeks of gestation, presented with persistent high fever following induced labor due to intrauterine fetal death. External hospital blood culture and our hospital's reproductive tract mNGS suggested Staphylococcus capitis and Ureaplasma urealyticum, respectively. However, intensified treatment targeting these pathogens was ineffective. DIAGNOSTIC PROCESS: Further investigation revealed a characteristic immune imbalance in the patient: a concurrent significant elevation of IFN-γ and IL-10, accompanied by activated CD8+ T cells. With AI-assisted analysis, this immune profile was found to be highly consistent with Listeria monocytogenes infection. TREATMENT AND OUTCOME: After switching to ampicillin combined with gentamicin, the patient's body temperature rapidly normalized, and she recovered and was discharged. CONCLUSION: When etiological diagnosis reaches an impasse, integrating host immune characteristics with AI-assisted decision-making can provide crucial diagnostic clues for infections caused by rare pathogens when microbiological confirmation is unavailable.
Scandinavian cardiovascular journal : SCJBjørn Edvard Seim, Yusuf Khan, Margrethe Flesvig Holt, Aleksandra Ratajska, Annika Michelsen, Monica Myklebust Ringseth, Runar Lundblad, Bente Halvorsen, Kirst…
Objectives. Thoracic aortic aneurysms (TAAs) are often found in younger individuals and approximately 20% may be associated with heritable thoracic aortic disease (HTAD). There are some data on genomic biomarkers reflecting inflammation and extracellular matrix remodelling in HTAD. However, data that accurately reflect the corresponding protein changes are scarce. Our aim was to quantify proteins by using targeted proteomics in HTAD patients versus healthy controls, to better understand the underlying pathophysiology. Methods. Patients with Loeys-Dietz syndrome (LDS, n = 8), Marfan syndrome (MFS, n = 11), and familial TAA 6, i.e. actin alpha 2 (ACTA2, n = 7) pathogenic variants were recruited at our outpatient clinic. For comparison, blood samples were drawn from 16 healthy controls. Plasma samples were analysed by targeted proteome analysis of 276 proteins using immunoaffinity proteomics. Results. Whereas oncostatin M and pentraxin 3 levels appeared generally higher in HTAD patients, after adjusting for several confounders, significantly higher levels for these markers as well as TNF receptor superfamily member 9 (TNFRSF9), granulysin (GNLY), CD5, vasorin and glycoprotein 1b-α (GP1BA) were only observed in LDS patients compared to healthy controls. Levels of TNFRSF9, GNLY, GP1BA and CD5 correlated positively with Th17 and platelet counts. Conclusions. This discovery study suggests that LDS could represent a particular inflammatory subgroup of HTAD patients potentially reflecting the involvement of Th17 and platelet related mechanisms in the progression of TAA. Larger studies are needed to evaluate if the identified proteins could be used as biomarkers in these patients.
Retinal ischemia-reperfusion injury (RIR) is the main pathogenic mechanisms of acute glaucoma, diabetic retinopathy, central retinal vein occlusion. As a common post-transcriptional modification of eukaryotic RNAs, N6-methyladenosine (m6A) is associated with the pathogenesis of different diseases, including angiogenesis, through the regulation of RNA metabolism and functions. The aim of this study was to identify the potential relevance of m6A RNA methylation in pathogenesis of RIR. A total of 10,851 mRNAs and 23,270 associated m6A methylation modified peaks were identified in the RIR group. Similarly, 10,391 mRNAs and 22,935 associated m6A methylation modified peaks were detected in the Sham group. MeRIP-seq identified 3,871 RIR-specific m6A peaks and 3,624 Sham-specific m6A peaks, in addition to 19,399 shared peaks between groups. Gene ontology (GO) analysis showed that hypermethylated mRNAs were enriched in cellular process, cellular anatomical entity, and binding, while hypomethylated mRNAs were enriched in synaptic signaling, synapse, and gated channel activity. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that hypermethylated mRNAs were involved in tight junction, hippo signaling pathway, and PI3K-Akt signaling pathway, while hypomethylated mRNAs were involved in Neuroactive ligand-receptor interaction, glutamatergic synapses, cholinergic synapses. Joint analysis identified mRNAs with differential m6A methylation and expression simultaneously. Among them, the expression patterns of Irx4, Kdr, and Lyz2 were confirmed by RT-qPCR to be consistent with the sequencing results. The results revealed an altered m6A epitranscriptome in RIR retinas. These methylated RNAs may act as novel modulators and targets in RIR.
HLA class I presentation of pathogen-derived peptides is essential for CD8+ T-cell recognition of Toxoplasma gondii. While in vitro MHC ligands have been documented, the in vivo ligandome during infection progression remains poorly characterized. Here, we employed an MS-based immunopeptidomics approach to directly profile the T. gondii immunopeptidome presented by HLA-A *02:01 in transgenic mice. By employing a hierarchical discovery funnel, our analysis identified a comprehensive repertoire of 3,744 unique T. gondii-derived peptides. Subsequent filtering for canonical 8-12mers, matching the typical binding length for HLA-A *02:01 ligands, established a high-confidence foundational ligandome of 3,433 peptides. Source protein analysis revealed that these peptides originate from diverse parasite proteins, including a substantial proportion of previously uncharacterized hypothetical proteins. Notably, specific ligands were consistently detected across both acute and chronic stages, suggesting stable MHC-I presentation throughout the infection cycle. By integrating in silico predictions with experimental validation, we prioritized 73 high-affinity candidates, five of which exhibited robust HLA-A *02:01 binding capacity in vitro and in vivo. Specifically, we identified a novel ligand derived from glycogen synthase (PGS) and determined its co-crystal structure with HLA-A *02:01, revealing favorable binding architecture. Overall, these findings expand the known HLA-A *02:01-restricted ligand landscape of T. gondii and provide a high-priority list of candidates for future functional validation of CD8+ T-cell immunogenicity.
Parasitology internationalChao Jiang, Yang Zhang, Zhiqun Wang, Xuguang Sun
Acanthamoeba keratitis (AK) is a severe, vision-threatening protozoan infection with a rising global incidence linked to contact lens use, necessitating robust genotyping to clarify its epidemiology and pathogenesis. This study analyzed the genotype distribution of 102 Acanthamoeba isolates collected from clinical settings in China between 1991 and 2014, comprising 100 isolates from corneal scrapings of clinically diagnosed AK patients, one from soil, and one from a patient's contact lens solution. Genetic analysis was conducted via amplification and sequencing of the 18S rRNA hypervariable DF3 region, followed by phylogenetic reconstruction and sequence identity assessment against reference clades. Twenty-eight distinct DF3 sequence types were identified, with genotype T4 demonstrating overwhelming dominance (99.0%; 101/102). Three novel T4 variants (T4/42-T4/44) were discovered, expanding the known diversity of this pathogenic lineage. Notably, T4/31 and T4/41 together accounted for 36% of clinical isolates, suggesting regionally endemic, infection-enriched variants. Only one isolate belonged to the rarely reported T11 genotype in China. Molecular source tracing confirmed two transmission chains: one linking a patient's corneal infection to their contact lens solution (both T4/6 variant), and another linking infection to periresidential soil (both T4/25 variant). These findings confirm the near-exclusive dominance of T4 among Chinese AK cases, identify prevalent local T4 variants, and demonstrate the utility of high-resolution DF3 genotyping for transmission tracing and disease control.
Microbiological researchJuan Li, Lei Zhao, Mei Yang, Jingyu Hu, Haimin Li, Wei Yin, Yan Yan, Jinyan Gu, Jiyong Zhou
Pseudorabies virus (PRV) reprograms host inflammatory responses and epitranscriptomics, yet how these processes are connected remains unclear. Here, we report a JNK-WTAP-m⁶A-DUSP5 regulatory circuit that coordinates viral replication and inflammatory responses. PRV infection activated c-Jun N-terminal kinase (JNK), which phosphorylated wilms tumor-associated protein (WTAP) to drive its nuclear export and disrupt the activity of the m⁶A methyltransferase complex. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and biochemical analyses revealed a global reduction of N6-methyladenosine (m⁶A) on host transcripts, particularly on proinflammatory cytokines, alongside widespread m⁶A modification sites on viral transcripts. Consequently, reduced m⁶A prolonged the half-lives of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18) mRNAs, as well as viral transcripts, thereby synergistically promoting PRV replication. Inhibition of JNK activity or restoration of m⁶A modification suppressed PRV replication in vitro and in vivo. Moreover, the m⁶A hypomethylation stabilized dual-specificity phosphatase 5 (DUSP5) transcripts at early infection, transiently restraining JNK activation and forming a negative feedback loop. These findings demonstrate that PRV reprograms the m⁶A machinery via JNK-mediated WTAP phosphorylation and highlights RNA methylation restoration as a promising antiviral strategy.
Microbiological researchJie Wang, Changying Guo, Xiaojian Pu
Climate-driven lake expansion across the Qinghai-Tibet Plateau induces profound edaphic shifts, but how these abiotic changes shape soil microbial assembly remains unclear. Soil metagenomics and metabolomics were integrated along a 0-10 km spatial gradient at Gahai. Redundancy analysis (RDA) identified moisture (NDWI) and salinity (SI) as primary ecosystem drivers. Structural equation modeling (SEM) provided exploratory evidence consistent with a mediation pathway (P = 0.64, CFI = 1, RMSEA = 0), in which environmental factors potentially influenced microbial community structure indirectly, via reshaping the soil metabolome rather than through a direct path. Moisture availability exerted a strong negative effect on soil metabolic profiles (λ = -0.93), leading to a pronounced negative correlation between the metabolome and microbial community (λ= -0.97). Multi-omics integration attributed this pattern to stress-induced accumulation of defensive metabolites, including Feruloylputrescine and 3-Methylthiopropyl-desulfoglucosinolate. These compounds showed significant negative correlations with dominant genera (e.g., Candidatus Kryptobacter). This "metabolic filtering" is hypothesized to selectively limit the presence of non-adapted taxa based solely on correlational SEM and network analyses, supporting our tentative hypothesis that increasing environmental stress may promote a transition from competitive interactions toward patterns consistent with stronger deterministic filtering. Our exploratory findings suggest that the soil metabolome acts as a functional interface mediating microbial adaptation and strategic resource allocation to lake expansion in this high-altitude saline-alkali system. However, due to regional heterogeneity, these patterns provide a theoretical baseline for plateau lake ecosystems and should be applied with caution to broader geographic areas.
RNA biologyMerin Joy, Alice Cleynen, Nikolay E Shirokikh
RNA modifications have emerged as central regulators of cancer translational control. Unlike transcriptional reprogramming, which unfolds over hours, modification-dependent translational rewiring enables rapid proteomic adaptation to the nutrient-deprived, hypoxic, and immunologically hostile tumour microenvironment. Yet most existing reviews organize epitranscriptomic mechanisms by modification type or cancer hallmark, obscuring the mechanistic logic by which chemical marks collectively reshape the translational apparatus. This review adopts a translation-centric framework, examining how the most abundant modifications on mRNAs, tRNAs, and rRNAs regulate each stage of protein synthesis in malignant cells. We survey the epitranscriptomic toolkit, including modification chemistries, enzymatic writers, readers, and erasers, and detection technologies including nanopore direct RNA sequencing. We then trace how modifications control initiation (m6A-driven mRNA circularization, cap-independent translation via eIF3 and eIF4G2, rRNA 2'-O-methylation-directed cap-to-IRES switching), elongation (m6A-induced ribosome stalling coupled to mRNA decay, tRNA mcm5s2U-mediated codon-biased translation, YTHDF1-dependent elongation factor recruitment), and termination (pseudouridine-mediated stop codon readthrough, NMD evasion). Crucially, we show that mRNA, tRNA, and rRNA modifications do not act in isolation but form integrated networks. For example, mRNA m6A and tRNA mcm5s2U operate on opposing arms of the same regulatory axis, with direct implications for therapeutic design. We assess the expanding drug pipeline, from the METTL3 inhibitor STC-15 now in Phase 1b/2 trials and METTL3-targeting PROTACs to FTO and ADAR1 inhibitors, and argue that biology-informed combination strategies targeting multiple modification axes will be essential for durable clinical responses.
VirulenceXia Li, Xin' Ao Ma, Xiaoyu Wang, Qingjun Li, Qi Yuan, Jiahua Wang, He Bai, Yong Liu, Feipeng Zhao
Porcine sapelovirus (PSV) is increasingly detected in swine enteric disease complexes, but its evolutionary dynamics and transmission patterns remain insufficiently characterized. In this study, we analyzed 327 fecal samples collected from diarrheic piglets between 2015 and 2022 and identified persistent PSV detection in northeastern China. Because PSV was detected in the context of mixed enteric viral infections in this dataset, our data do not establish PSV as an independent causative agent of diarrhea. Comparative whole-genome and evolutionary analyses of globally circulating PSV strains revealed substantial genetic diversity, with higher apparent short-term substitution-rate estimates observed in the African and Japanese datasets. In China, inter-strain genetic recombination appeared to represent an additional driver of viral diversification. Temporal evolutionary analyses indicated a dynamic and complex evolutionary landscape within China. Phylogeographic reconstruction identified multiple putative transmission nodes within the currently available genome dataset, suggesting broad geographic dissemination of PSV lineages but not definitive source-sink relationships. These findings enhance our understanding of PSV genomic epidemiology and provide useful information for molecular surveillance of PSV and other diarrhea-associated viruses in swine populations.
Melioidosis, caused by Burkholderia pseudomallei, is an endemic infectious disease with high mortality in tropical and subtropical regions. Large-scale epidemiological data remain insufficient in China, while comprehensive data integrating genomic epidemiology are rare worldwide. Herein, performed a retrospective analysis of 554 culture-confirmed melioidosis cases in southern China from 2003 to 2022. Genomic characteristics and their relationship with antimicrobial susceptibility and clinical characteristics were analyzed via whole genome sequencing. Core-genome SNP phylogenies were constructed from recombination-masked alignments and compared them with 3,573 publicly available global B. pseudomallei genomes to define their population structure and phylogeographic patterns. Melioidosis predominantly affected male patients (86.8%, 481/554) and those aged 45 -64 years (57.7%). Bacteremia (OR=5.91, p<0.001), diabetes mellitus (OR=2.27, p=0.008), and pulmonary infection (OR=2.26, p=0.005) were identified as risk factors for mortality. Antimicrobial susceptibility testing showed B. pseudomallei exhibited high in vitro susceptibility to imipenem (100%) and ceftazidime (99.6%). Pan-genome analysis confirmed chromosomal functional compartmentalization of the bipartite genome, and genome-wide association study identified high-confidence genetic markers (OR >3 or <0.33) significantly associated with mortality and bacteremia. Furthermore, global phylogenomic analysis identified 10 evolutionary clusters; Chinese isolates were significantly enriched in Cluster 1, a clade shared with Thai strains, and were phylogenetically distinct from Cluster 5, as predominantly composed of Australian isolates. In summary, this large-scale genomic and clinical analysis provides the most comprehensive overview of melioidosis in southern China. The genomic analysis highlighted substantial regional and global genetic diversity, and phylogeographic structuring of B. pseudomallei, underscoring the importance of continued genomic surveillance.
Cercarial dermatitis is an important occupational health problem among rice farmers in Assam and other parts of India. We surveyed 1657 paddy farmers from sixteen villages across four districts of Assam, Northeast India, to determine the prevalence of cercarial dermatitis. Of these, 555 (33.5%) reported dermatitis during the preceding three months, and a subset of affected farmers from Barpeta district showed a high proportion of moderate-to-severe disease, often complicated by secondary bacterial infection. Snail surveys were conducted in thirteen villages across eight districts. Examination of 13,309 freshwater snails representing six species identified Indoplanorbis exustus as the only intermediate host shedding Schistosome cercariae, with an infection prevalence of 6.3% among I. exustus. Experimental infections in mice yielded adult worms that were used for morphological, molecular, immunological, and proteomic studies. Molecular identification based on partial 28S rDNA sequencing confirmed the Assamese isolates as Schistosoma spindale, and phylogenetic analysis placed them firmly within the S. spindale clade together with reference sequences from Nepal and Sri Lanka. SDS-PAGE and immunoblotting identified four dominant immunoreactive antigens of approximately 25, 38, 60, and 100 kDa. Two-dimensional PAGE coupled with MALDI-TOF/TOF MS identified several conserved proteins, including paramyosin, tropomyosin, actin, and heat shock protein 70, based on best database matches. ELISA developed using adult worm antigen showed high diagnostic performance (96% sensitivity and 100% specificity) and outperformed the cercarial antigen-based ELISA. This integrated epidemiological, malacological, molecular, proteomic, and immunological investigation provides comprehensive insight into S. spindale the causative agent of cercarial dermatitis in Assam. The findings highlight the need to recognize cercarial dermatitis as a neglected occupational and zoonotic disease within a One Health framework.
Microbiological researchXiaowei He, Kemin Mao, Kaige Peng, Jinrong Zhao, Xianghong Wang, Jie Gao, Yaxin Sang
To systematically evaluate the potential fermentation and probiotic-related properties of E. durans B21 isolated from kefir, this study integrated whole-genome sequencing, comparative genomics, genome-scale metabolic model (GEM) reconstruction, and in vitro phenotypic assays to comprehensively analyze its genetic characteristics, metabolic potential, safety, and probiotic-related functions. The results showed that E. durans B21 possesses a 3.14 Mb circular chromosome and three plasmids, with a total of 2935 predicted coding genes. The genome encodes 91 carbohydrate-active enzymes (CAZymes) and multiple lactose metabolism-related genes, indicating strong carbohydrate utilization potential. Comparative genomic analysis revealed high genomic similarity between B21 and the potential probiotic strain E. durans A8-1, and 27 probiotic-related functional genes were identified in B21. Additionally, the reconstructed GEM achieved a MEMOTE score of 86.7%. Flux balance analysis predicted that the strain could produce acetaldehyde and other flavor-related metabolites through lactose metabolism, which was experimentally validated by in vitro assays showing an acetaldehyde yield of 0.2137 mM in M17 medium. In vitro functional assays demonstrated that the strain exhibited certain tolerance to simulated intestinal fluid and bile salts, along with strong auto-aggregation and biofilm formation abilities. Nevertheless, multiple antimicrobial resistance-associated genes and several virulence-related factors were also identified in the genome, suggesting that its safety still requires further evaluation through antimicrobial resistance transferability analysis and animal experiments. Overall, E. durans B21 exhibits fermentation-associated and probiotic-related traits and may serve as a potential functional fermentation strain for further investigation.
Tuberculosis (TB) remains a significant public health threat in urbanizing regions of China, where shifting population dynamics and migration may amplify TB transmission. We conducted a nine-year prospective epidemiological study of culture-positive TB patients diagnosed in Shenzhen, between 1 January 2014 and 31 December 2022, and employed whole-genome sequencing analysis to describe local transmission of Mycobacterium tuberculosis (Mtb). Mtb transmission hotspots were identified using a non-parametric distance-based mapping approach. We applied a spatially structured logistic regression and hierarchical Bayesian pairwise regression analysis to identify demographic, pathogen, and spatial factors associated with local transmission. A Bayesian phylogenetic analysis was used to infer probable transmission events. Among 4,560 individuals with culture-positive TB, 93.4% (4,261) were internal migrants in China. 21.8% (996/4,560) of individuals had Mtb isolates that belonged to genomic clusters, with multiple transmission foci detected in the central business district and suburban industrial areas. Transmission was more likely to occur among patients of similar age, close geographic proximity, and migrants with a shared provincial origin. Mtb isolates from communities with higher proportions of migrants had an increased risk of clustering. In this rapidly growing urban setting, a significant proportion of cases were documented to arise as a result of local transmission, which appears to be driven by specific social and geographical factors, particularly within migrant populations. Control strategies should therefore move beyond static models toward dynamic interventions that specifically target social networks, high-risk communities, and urban hotspots in dynamic urban environments.
Analytical biochemistryWenbo Zhou, Nguyen Quoc Khanh Le, Matthew Chin Heng Chua
Protein function prediction remains a central problem in bioinformatics, with broad implications for understanding biological processes, disease mechanisms, and drug discovery. Due to the high cost and time required for experimental characterization, only a small fraction of proteins have reliable functional annotations, highlighting the need for accurate computational approaches. Recent advances in protein structure prediction, particularly AlphaFold2, have enabled large-scale access to high-quality three-dimensional structures, creating new opportunities for structure-informed function prediction. In this study, we propose UniRES-GO (Unified Residue-level Early Fusion for Gene Ontology prediction), a novel framework that integrates protein sequence features with AlphaFold2-predicted structural information via residue-level early fusion. The fused representations are modeled as protein contact graphs and processed using a Graph Attention Network to capture both local residue interactions and global structural context, yielding discriminative protein-level embeddings for multi-label function prediction. We evaluate UniRES-GO on a human protein dataset across the three Gene Ontology categories: Biological Process, Cellular Component, and Molecular Function. Experimental results demonstrate that UniRES-GO consistently outperforms representative sequence- and interaction-based methods across multiple evaluation metrics, including Fmax, AUC, and AUPR. In particular, UniRES-GO achieves strong performance in Molecular Function prediction, reaching an AUC of 0.970, while maintaining high stability across multiple runs. Ablation studies further confirm the effectiveness of the residue-level fusion strategy and graph-based modeling. Overall, UniRES-GO provides an effective and generalizable approach for protein function prediction by leveraging predicted structural information, offering practical advantages for annotating proteins lacking homologous sequences or interaction data.
Gut microbesJordan B Hernandez, Mayowa Abiodun, Shivdeep S Hayer, Timothy Dickson, Paul Ayayee, Jonathan B Clayton
Broad-spectrum antibiotics are invaluable tools for treating pathogenic infections, but their sustained use can contribute to changes in gut microbiome membership and the emergence of antimicrobial resistance. While these unintended side effects are independently well documented, the relationship between them has seldom been investigated. To address this, we quantified the effects of 28-d antibiotic cocktail exposure on metagenome-assembled genomes and antibiotic resistance genes in common marmosets using a custom whole-genome shotgun sequencing pipeline and quantitative polymerase chain reaction assays. We observed contrasting genus-level reductions in Bifidobacterium abundance and Fusobacterium growth, both during antibiotic treatment and a 2-week post-treatment period. Total bacterial abundance was not significantly affected by antibiotics, likely due to the presence of antibiotic-resistant opportunists. Genes for vancomycin resistance and multidrug efflux pumps were identified in metagenome-assembled genomes of an unclassified Sarcina sp. and Escherichia coli, respectively, and were accompanied by increased abundance of these species during treatment. Additionally, we detected 11 dysregulated metagenomic pathways related to carbohydrate metabolism, including 2 pathways relevant to short-chain fatty acid production, following antibiotic exposure. This study provides insights into the species-dependent emergence of antimicrobial resistance mechanisms in non-human primates following antibiotic exposure that could be relevant for antibiotic therapies and resistance management.
Annals of medicineZizhen Zhou, Qiwei Liu, Shuangshuang Ma, Anke Shi, Yuzhi Tao, Tianpeng Hu, Shengtao Yan, Yinong Chen, Xiaofan Ji, Lu Sun, Hong Zhang, Wanlu Song, Zhu Zhang, Pe…
BACKGROUND: COVID-19 has been closely associated with coagulation abnormalities. However, existing biomarkers, including D-dimer and fibrin degradation products (FDP), exhibit limited accuracy in stratifying disease severity and predicting long-term clinical outcomes. OBJECTIVES: This study aimed to use proteomic analysis to identify plasma biomarkers associated with COVID-19 severity and prognosis, and validate their predictive utility for mortality and thromboembolic complications. METHODS: Plasma proteomic profiles were analyzed across three COVID-19 severity classes. Differential expression analysis and functional analysis were performed. Clustering analysis was used to identify proteins correlated with disease severity. Candidate biomarkers were validated in an independent cohort. Predictive performance of the biomarkers for mortality, sepsis and venous thromboembolism was evaluated using bootstrap-corrected ROC analyses and multivariable regression analyses. RESULTS: Proteomic analysis revealed progressive involvement of the coagulation and complement pathway with increasing disease severity. SERPINA1 and CD59 were identified as candidate biomarkers and exhibited significantly higher plasma levels in severe cases. Bootstrap-corrected ROC analyses demonstrated strong predictive performance: SERPINA1 achieved AUCs of 0.775 and 0.924 for 30-day and 12-month mortality, and CD59 achieved AUCs of 0.720 for sepsis; the combined model further improved prediction of 12-month mortality (AUC 0.946) and sepsis (AUC 0.904), outperforming D-dimer and FDP. Multivariable regression confirmed their independent prognostic value. CONCLUSION: This exploratory study identifies SERPINA1 and CD59 as candidate prognostic biomarkers in COVID-19, highlighting the role of coagulation and complement-related pathways in disease severity and warranting further prospective validation.
Food research international (Ottawa, Ont.)Xin Wang, Linli Dai, Jae-Hyung Mah, Wen Qin, Shuxiang Liu
Developing low-salt foods is crucial to address health concerns associated with hsigh-salt diets, yet it poses a technical challenge: supporting microbial control through low water activity (aw) regulation without high-salt concentrations requires reducing the moisture content of the substrate, which poses a physiological challenge to conventional fermentative microbes. This study aims to bridge this gap by isolating yeasts capable of thriving under such low-salt (4-12% dry basis, d.b.), low-aw (0.87-0.92), and low-moisture content conditions. Using controlled fermentation of two chili varieties as a model system, we analyzed microbial community succession and its correlation with volatile flavor profiles. A total of 72 indigenous yeasts were isolated via multi-stage phenotypic screening. The dominant strain, M13, exhibited superior aroma-producing capability, yielding 1.32 g/kg of total esters, and pronounced tolerance to key fermentation stresses, including low pH (2.0), high ethanol (9%), and growth retention at the fermentation temperature of 40 °C. Whole-genome sequencing and functional annotation suggested that these phenotypic traits were associated with a genomic architecture enriched in metabolic and stress-responsive functions, including a 12.97 Mbp genome in which 54.5% of annotated genes were assigned to metabolic categories. This integrated study provides a novel functional yeast candidate and a screening framework that may help improve the balance between flavor quality and microbial control in low-salt fermentation. This approach and the microbial principles highlighted here may be applicable to the development of a wider range of flavorful, reduced‑sodium fermented products, offering a potential route to reduce reliance on both added salts and high-water content in food fermentation.
Food research international (Ottawa, Ont.)Peipei Cheng, Qian Wang, Wanting He, Xueyuan Zhu, Yu Cheng, Linlin Xiao, Qingli Dong
Antimicrobial resistance has become a major global public health challenge. However, conventional antimicrobial resistance risk assessment has largely focused on phenotypes while overlooking the dynamic dissemination of resistance genes and their mobility. This review systematically examines how genomics is reshaping microbial antimicrobial resistance risk assessment, with particular emphasis on the integration of key dimensions including clinically important antimicrobials, resistance gene mobility, evidence of ARG transmission along exposure pathways, and data quality and uncertainty. It discusses recent advances in qualitative, semi-quantitative, and quantitative assessment approaches, while also highlighting major challenges such as the parameterization of horizontal gene transfer, the integration of antimicrobial selection pressure, and the reliability of genomic-context evidence for resistance. Representative applications include WGS-based quantitative microbial risk assessment of foodborne pathogens, such as the Listeria monocytogenes case in which strain-level genomic heterogeneity was used to refine hazard characterization and exposure assumptions. Looking ahead, the integration of artificial intelligence is expected to further improve high-quality genome reconstruction, resistance phenotype inference, and transmission risk prediction, thereby facilitating more precise risk management.
Food microbiologyWen Si Hu, So Hyeon An, Dong Woo Kim, Hyeong Uk Im, Seung Hun Lee, Yu Bao Li, Zi Xuan Liu, Zhi Wei Wang, A Ram Lee, Ui In Kim, Hyeon Ji Je, Yeon Ju Seo, Jin Sa…
Listeria monocytogenes is a gram-positive and facultatively anaerobic foodborne pathogen causing listeriosis. The detection of L. monocytogenes in enoki mushrooms sourced from South Korea and China is particularly critical, given their confirmed implication in recent serious listeriosis outbreaks across the global food supply chain. This study investigates the prevalence, genetic diversity, and phenotypical characteristics of L. monocytogenes in enoki mushrooms from South Korea and China. Out of 129 samples, 24 (18.6%) tested positive, with contamination rates of 17.5% in Korean mushrooms and 19.7% in Chinese mushrooms. Whole-genome sequencing, cgMLST, and pan-genome analyses resolved lineage and sequence-type distributions, revealing predominant serogroup 1/2a (83.3%) and lineage II (90.9%). The pan-genomic assessment of L. monocytogenes strains originating from diverse geographical locations indicated the presence of open genomes, which establishes a strong genetic underpinning for adaptation to varied environments. These strains carrying a multitude of virulence genes that significantly contribute to their heightened pathogenic potential. The phylogenetic tree further demonstrated that these highly related Korean and Chinese isolates were intricately intermingled with outbreak-related strains from the USA, Canada, and Europe, confirming a minimal core-genome genetic distance across the global supply chain. This highly homogenous clone, which was ultimately traced back to enoki mushrooms in South Korea and China, suggests that the globalization of the food trade is the primary driver of its rapid, international dissemination.
Food microbiologyAhmed Elsheshtawy, Benjamin G J Clokie, Sasha Saugh, Karen D Adler, Slawomir M Michniewski, Simon MacKenzie, Martha R J Clokie, Thomas Sicheritz-Pontén, Amaya …
The Norway lobster (Nephrops norvegicus) is a high-value seafood product with limited shelf-life under chilled storage. This study investigated microbial succession and spoilage dynamics during ice storage (0 °C, 16 days) using an integrated multi-omics approach combining sensory assessment (Quality Index Method), physicochemical indicators (muscle pH and K-value), culture-dependent microbiology, absolute bacterial load quantification (16S rRNA qPCR), 16S rRNA gene amplicon sequencing and shotgun metagenomics. Quality deterioration was characterised by progressive increases in sensory scores, nucleotide degradation and muscle pH, with rejection occurring at day 7. This transition coincided with a marked increase in bacterial load following an initial lag phase (days 0-5), indicating a critical shift in spoilage progression. Amplicon sequencing revealed a transition from a diverse early community (days 0-3) to a Proteobacteria-dominated assemblage from day 5 onwards, driven by increases in Moritella, Pseudoalteromonas and Aliivibrio. Metagenomic analysis further resolved these dynamics at species-level resolution and identified a limited number of dominant taxa associated with mid-to late-stage spoilage. The convergence of sensory rejection, physicochemical changes and microbial restructuring identifies a mid-storage tipping point in spoilage development. By integrating multi-omics with established quality indicators, this study links microbial succession to measurable spoilage outcomes. The dominant taxa are consistent with known spoilage-associated activities, including proteolysis and off-odour production, while highlighting Moritella as a potential contributor in crustacean spoilage. These findings provide a temporal framework for spoilage progression in N. norvegicus and inform targeted strategies for shelf-life management.