Rapid and accurate detection of cinnamon oil adulteration in perilla leaf oil using atmospheric solids analysis probe-mass spectrometry.

Perilla leaf oil (PLO) is a global premium vegetable oil with abundant nutrients and substantial economic value, rendering it susceptible to potential adulteration by unscrupulous entrepreneurs. The addition of cinnamon oil (CO) is one of the main adulteration avenues for illegal PLOs. In this study, new and real-time ambient mass spectrometric methods were developed to detect CO adulteration in PLO. First, atmospheric solids analysis probe tandem mass spectrometry combined with principal component analysis and principal component analysis-linear discriminant analysis was employed to differentiate between authentic and adulterated PLO. Then, a spectral library was established for the instantaneous matching of cinnamaldehyde in the samples. Finally, the results were verified using the SRM mode of ASAP-MS/MS. Within 3 min, the three methods successfully identified CO adulteration in PLO at concentrations as low as 5% v/v with 100% accuracy. The proposed strategy was successfully applied to the fraud detection of CO in PLO.

Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis.

Inflammasomes are multi-protein complexes that assemble within the cytoplasm of mammalian cells in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), driving the secretion of the pro-inflammatory cytokines IL-1ß and IL-18, and pyroptosis. The best-characterized inflammasome complexes are the NLRP3, NAIP-NLRC4, NLRP1, AIM2, and Pyrin canonical caspase-1-containing inflammasomes, and the caspase-11 non-canonical inflammasome. Newer inflammasome sensor proteins have been identified, including NLRP6, NLRP7, NLRP9, NLRP10, NLRP11, NLRP12, CARD8, and MxA. These inflammasome sensors can sense PAMPs from bacteria, viruses and protozoa, or DAMPs in the form of mitochondrial damage, ROS, stress and heme. The mechanisms of action, physiological relevance, consequences in human diseases, and avenues for therapeutic intervention for these novel inflammasomes are beginning to be realized. Here, we discuss these emerging inflammasome complexes and their putative activation mechanisms, molecular and signaling pathways, and physiological roles in health and disease.

MRI-based deep learning for differentiating between bipolar and major depressive disorders.

Mood disorders, particularly bipolar disorder (BD) and major depressive disorder (MDD), manifest changes in brain structure that can be detected using structural magnetic resonance imaging (MRI). Although structural MRI is a promising diagnostic tool, prevailing diagnostic criteria for BD and MDD are predominantly subjective, sometimes leading to misdiagnosis. This challenge is compounded by a limited understanding of the underlying causes of these disorders. In response, we present SE-ResNet, a Residual Network (ResNet)-based framework designed to discriminate between BD, MDD, and healthy controls (HC) using structural MRI data. Our approach extends the traditional Squeeze-and-Excitation (SE) layer by incorporating a dedicated branch for spatial attention map generation, equipped with soft-pooling, a 7 × 7 convolution, and a sigmoid function, intended to detect complex spatial patterns. The fusion of channel and spatial attention maps through element-wise addition aims to enhance the model's ability to discriminate features. Unlike conventional methods that use max-pooling for downsampling, our methodology employs soft-pooling, which aims to preserve a richer representation of input features and reduce data loss. When evaluated on a proprietary dataset comprising 303 subjects, the SE-ResNet achieved an accuracy of 85.8 %, a recall of 85.7 %, a precision of 85.9 %, and an F1 score of 85.8 %. These performance metrics suggest that the SE-ResNet framework has potential as a tool for detecting psychiatric disorders using structural MRI data.

The Science of Cholesteatoma.

Cholesteatoma is a potential end-stage outcome of chronic ear infections that can result in the destruction of temporal bone structures with potential resultant hearing loss, vertigo, and intracranial infectious complications. There is currently no treatment apart from surgery for this condition, and despite years of study, the histopathogenesis of this disease remains poorly understood. This review is intended to summarize our accumulated knowledge of the mechanisms of cholesteatoma development and the underlying molecular biology. Attention will be directed particularly to recent developments, covering many potential pharmacologic targets that could be used to treat this disease in the future.

Auditory processing in patients with temporal lobe epilepsy: A systematic review and meta-analysis.

BACKGROUND: Hearing efficiency is known to influence and interact with communication and mental health. Hearing impairment may be hidden when co-occurring with neurological disorders. PURPOSE: We performed a systematic review and meta-analysis in order to address the following questions: 1) which specific tools of auditory processing show clear deficits, separating Temporal Lobe Epilepsy (TLE) patients from normal controls,2) How well is TLE evaluated in terms of hearing and auditory processing? METHODS: The study inclusion criteria were: 1) patients diagnosed with temporal lobe epilepsy, 2) presence of a normal control group, 3) auditory processing assessment using auditory stimuli with behavioral tests and/or P300 or Mitch Match Negativity (MMN) latency and/or amplitude, 4) publications written in English, 5) publication date after 2000. 132 articles were retrieved and based on PRISMA & PICO criteria 23 articles were analyzed. RESULTS: Temporal resolution and processing as measured by the behavioral tests of Gaps-In-Noise (GIN) and Duration Pattern Test (DPT) document deficiencies in TLE patients and separate them from normal controls. Electrophysiology as measured by MMN & P300 shows statistically significant differences in TLE patients compared to controls with patients showing deficient auditory processing. A clear difference between studies with psychoacoustic assessment as opposed to electrophysiology ones may be due to lacking or incomplete evaluation of peripheral hearing by gold standard tools (76.9% in electrophysiology studies). CONCLUSION: Auditory processing is deficient in patients with TLE. There is a clear need to evaluate hearing efficiency before proceeding to auditory processing evaluation with behavioral or electrophysiological tests.

Recognition of phylogenetically diverse pathogens through enzymatically amplified recruitment of RNF213.

Innate immunity senses microbial ligands known as pathogen-associated molecular patterns (PAMPs). Except for nucleic acids, PAMPs are exceedingly taxa-specific, thus enabling pattern recognition receptors to detect cognate pathogens while ignoring others. How the E3 ubiquitin ligase RNF213 can respond to phylogenetically distant pathogens, including Gram-negative Salmonella, Gram-positive Listeria, and eukaryotic Toxoplasma, remains unknown. Here we report that the evolutionary history of RNF213 is indicative of repeated adaptation to diverse pathogen target structures, especially in and around its newly identified CBM20 carbohydrate-binding domain, which we have resolved by cryo-EM. We find that RNF213 forms coats on phylogenetically distant pathogens. ATP hydrolysis by RNF213's dynein-like domain is essential for coat formation on all three pathogens studied as is RZ finger-mediated E3 ligase activity for bacteria. Coat formation is not diffusion-limited but instead relies on rate-limiting initiation events and subsequent cooperative incorporation of further RNF213 molecules. We conclude that RNF213 responds to evolutionarily distant pathogens through enzymatically amplified cooperative recruitment.

Enhanced Accumulation of Health-Promoting Cajaninstilbene Acid in Pigeon Pea Hairy Root Cultures Cocultured with an Endophytic Fungus during Early Stages of Colonization.

Endophytic fungi can effectively regulate the biosynthesis of health-beneficial metabolites in plants. However, few studies have revealed how the accumulation of host metabolites varies during interactions with endophytic fungi. Here, pigeon pea hairy root cultures (PPHRCs) were cocultured with an endophytic fungus Penicillium rubens to explore the impact on the biosynthesis and accumulation of cajaninstilbene acid (CSA). The results showed that CSA accumulation in PPHRCs increased significantly (15.29-fold) during the early stages of P. rubens colonization (fungal attachment and invasion phases). Once P. rubens successfully colonized the intercellular gap of hairy roots to form a symbiotic relationship, the CSA levels in PPHRCs decreased drastically. Moreover, P. rubens could be recognized by plant pattern recognition receptors that regulate immunity/symbiosis, triggering the expression of genes related to pathogenesis, CSA biosynthesis, and ABC transporter. Overall, P. rubens could enhance the accumulation of health-promoting CSA in PPHRCs during the early stages of colonization.

Infrared spectroscopy as a new approach for early fabry disease screening: a pilot study.

BACKGROUND: Fabry disease (FD) is a rare X-linked lysosomal storage disorder marked by alpha-galactosidase-A (α-Gal A) deficiency, caused by pathogenic mutations in the GLA gene, resulting in the accumulation of glycosphingolipids within lysosomes. The current screening test relies on measuring α-Gal A activity. However, this approach is limited to males. Infrared (IR) spectroscopy is a technique that can generate fingerprint spectra of a biofluid's molecular composition and has been successfully applied to screen numerous diseases. Herein, we investigate the discriminating vibration profile of plasma chemical bonds in patients with FD using attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. RESULTS: The Fabry disease group (n = 47) and the healthy control group (n = 52) recruited were age-matched (39.2 ± 16.9 and 36.7 ± 10.9 years, respectively), and females were predominant in both groups (59.6% and 65.4%, respectively). All patients had the classic phenotype (100%), and no late-onset phenotype was detected. A generated partial least squares discriminant analysis (PLS-DA) classification model, independent of gender, allowed differentiation of samples from FD vs. control groups, reaching 100% sensitivity, specificity and accuracy. CONCLUSION: ATR-FTIR spectroscopy harnessed to pattern recognition algorithms can distinguish between FD patients and healthy control participants, offering the potential of a fast and inexpensive screening test.

Effects of dietary Lactobacillus postbiotics and bacitracin on the modulation of mucosa-associated microbiota and pattern recognition receptors affecting immunocompetence of jejunal mucosa in pigs challenged with enterotoxigenic F18+ Escherichia coli.

BACKGROUND: Enterotoxigenic Escherichia coli (E. coli) is a threat to humans and animals that causes intestinal disorders. Antimicrobial resistance has urged alternatives, including Lactobacillus postbiotics, to mitigate the effects of enterotoxigenic E. coli. METHODS: Forty-eight newly weaned pigs were allotted to NC: no challenge/no supplement; PC: F18+ E. coli challenge/no supplement; ATB: F18+ E. coli challenge/bacitracin; and LPB: F18+ E. coli challenge/postbiotics and fed diets for 28 d. On d 7, pigs were orally inoculated with F18+ E. coli. At d 28, the mucosa-associated microbiota, immune and oxidative stress status, intestinal morphology, the gene expression of pattern recognition receptors (PRR), and intestinal barrier function were measured. Data were analyzed using the MIXED procedure in SAS 9.4. RESULTS: PC increased (P < 0.05) Helicobacter mastomyrinus whereas reduced (P < 0.05) Prevotella copri and P. stercorea compared to NC. The LPB increased (P < 0.05) P. stercorea and Dialister succinatiphilus compared with PC. The ATB increased (P < 0.05) Propionibacterium acnes, Corynebacterium glutamicum, and Sphingomonas pseudosanguinis compared to PC. The PC tended to reduce (P = 0.054) PGLYRP4 and increased (P < 0.05) TLR4, CD14, MDA, and crypt cell proliferation compared with NC. The ATB reduced (P < 0.05) NOD1 compared with PC. The LPB increased (P < 0.05) PGLYRP4, and interferon-γ and reduced (P < 0.05) NOD1 compared with PC. The ATB and LPB reduced (P < 0.05) TNF-α and MDA compared with PC. CONCLUSIONS: The F18+ E. coli challenge compromised intestinal health. Bacitracin increased beneficial bacteria showing a trend towards increasing the intestinal barrier function, possibly by reducing the expression of PRR genes. Lactobacillus postbiotics enhanced the immunocompetence of nursery pigs by increasing the expression of interferon-γ and PGLYRP4, and by reducing TLR4, NOD1, and CD14.

Analysis of electrode locations on limb condition effect for myoelectric pattern recognition.

BACKGROUND: Gesture recognition using surface electromyography (sEMG) has garnered significant attention due to its potential for intuitive and natural control in wearable human-machine interfaces. However, ensuring robustness remains essential and is currently the primary challenge for practical applications. METHODS: This study investigates the impact of limb conditions and analyzes the influence of electrode placement. Both static and dynamic limb conditions were examined using electrodes positioned on the wrist, elbow, and the midpoint between them. Initially, we compared classification performance across various training conditions at these three electrode locations. Subsequently, a feature space analysis was conducted to quantify the effects of limb conditions. Finally, strategies for group training and feature selection were explored to mitigate these effects. RESULTS: The results indicate that with the state-of-the-art method, classification performance at the wrist was comparable to that at the middle position, both of which outperformed the elbow, consistent with the findings from the feature space analysis. In inter-condition classification, training under dynamic limb conditions yielded better results than training under static conditions, especially at the positions covered by dynamic training. Additionally, fast and slow movement speeds produced similar performance outcomes. To mitigate the effects of limb conditions, adding more training conditions reduced classification errors; however, this reduction plateaued after four conditions, resulting in classification errors of 22.72%, 22.65%, and 26.58% for the wrist, middle, and elbow, respectively. Feature selection further improved classification performance, reducing errors to 19.98%, 19.75%, and 27.14% at the respective electrode locations, using three optimal features derived from single-condition training. CONCLUSIONS: The study demonstrated that the impact of limb conditions was mitigated when electrodes were placed near the wrist. Dynamic limb condition training, combined with feature optimization, proved to be an effective strategy for reducing this effect. This work contributes to enhancing the robustness of myoelectric-controlled interfaces, thereby advancing the development of wearable intelligent devices.

Non-Invasive Diagnostic Approaches for Kidney Disease: The Role of Electronic Nose Systems.

Kidney diseases are a group of conditions related to the functioning of kidneys, which are in turn unable to properly filter waste and excessive fluids from the blood, resulting in the presence of dangerous levels of electrolytes, fluids, and waste substances in the human body, possibly leading to significant health effects. At the same time, the toxins amassing in the organism can lead to significant changes in breath composition, resulting in halitosis with peculiar features like the popular ammonia breath. Starting from this evidence, scientists have started to work on systems that can detect the presence of kidney diseases using a minimally invasive approach, minimizing the burden to the individuals, albeit providing clinicians with useful information about the disease's presence or its main related features. The electronic nose (e-nose) is one of such tools, and its applications in this specific domain represent the core of the present review, performed on articles published in the last 20 years on humans to stay updated with the latest technological advancements, and conducted under the PRISMA guidelines. This review focuses not only on the chemical and physical principles of detection of such compounds (mainly ammonia), but also on the most popular data processing approaches adopted by the research community (mainly those relying on Machine Learning), to draw exhaustive conclusions about the state of the art and to figure out possible cues for future developments in the field.

Intelligent Evaluation and Dynamic Prediction of Oyster Freshness with Electronic Nose Based on the Distribution of Volatile Compounds Using GC-MS Analysis.

The quality of oysters is reflected by volatile organic components. To rapidly assess the freshness level of oysters and elucidate the changes in flavor substances during storage, the volatile compounds of oysters stored at 4, 12, 20, and 28 °C over varying durations were analyzed using GC-MS and an electronic nose. Data from both GC-MS and electronic nose analyses revealed that alcohols, acids, and aldehydes are the primary contributors to the rancidity of oysters. Notably, the relative and absolute contents of Cis-2-(2-Pentenyl) furan and other heterocyclic compounds exhibited an upward trend. This observation suggests the potential for developing a simpler test for oyster freshness based on these compounds. Linear Discriminant Analysis (LDA) demonstrated superior performance compared to Principal Component Analysis (PCA) in differentiating oyster samples at various storage times. At 4 °C, the classification accuracy of the optimal support vector machine (SVM) and random forest (RF) models exceeded 90%. At 12 °C, 20 °C, and 28 °C, the classification accuracy of the best SVM and RF models surpassed 95%. Pearson correlation analysis of the concentrations of various volatile compounds and characteristic markers with the sensor response values indicated that the selected sensors were more aligned with the volatiles emitted by oysters. Consequently, the volatile compounds in oysters during storage can be predicted based on the response information from the sensors in the detection system. This study also demonstrates that the detection system serves as a viable alternative to GC-MS for evaluating oysters of varying freshness grades.

Intra-tumoral delivery of 5'ppp-dsRNA induces robust anti-tumor response via RIG-I activation and Bcl-2 gene downregulation in murine model of prostate cancer.

Onco-immunotherapy via blocking checkpoint-inhibitors has revolutionized the treatment-landscape of several malignancies, though not in the metastatic castration-resistant prostate cancer (PCa) owing to immunosuppressive and poorly immunogenic "cold" tumor microenvironment (TME). Turning up the heat of such cold TME via triggering innate immunity is now of increasing interest to restore immune-surveillance. Retinoic acid-inducible gene- I (RIG-I)-like receptors (RLRs) are cytosolic innate-sensors that can detect exogenous RNAs and induce type-I interferons and other pro-inflammatory signaling. RIG-I activation is suggested to be a valuable addition to the treatment approaches for several cancers. However, the knowledge about RIG-I signaling in PCa remains elusive. The present study evaluated the expression of two important RLRs, RIG-I and melanoma differentiation-associated protein 5 (MDA5) along with their downstream partners, mitochondrial antiviral-signaling protein (MAVS) and ERA G-protein-like 1 (ERAL1) during PCa progression in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The early stage of PCa revealed a significant increment in the expression of RLRs, but not MAVS. However, the advanced stage showed downregulated RLR signaling. Further, the therapeutic implication of 5'ppp-dsRNA, a synthetic RIG-I agonist and Bcl2 gene silencer has been investigated in vitro and in vivo. Intra-tumoral delivery of 5'ppp-dsRNA regressed tumor growth via triggering tumor cells apoptosis, immunomodulation, and inducing phagocytic "eat me" signals. These findings highlight that, for the first time, RIG-I activation and Bcl-2 silencing with 5'ppp-dsRNA can serve as a potent tumor-suppressor strategy in PCa and has a significant clinical implication in transforming "cold" TME into immunogenic "hot" TME of PCa.

The role of pattern recognition receptors in the innate immune system of Chinese mitten crab (Eriocheir sinensis).

Eriocheir sinensis (Chinese mitten crab) is one of the main economic species in China, which has evolved an extremely sophisticated innate immune system to fend off disease invasions. However, bacterial and viral infections have caused significant financial losses for the E. sinensis aquaculture in recent years. Making well-informed judgments for the control microbial infections would require a thorough understanding and clarification of the intricate innate immune system of E. sinensis. Innate immunity is essential for the host's defense against invasive pathogens. Pattern recognition receptors (PRRs) initially recognize pathogen-associated molecular patterns (PAMPs) and trigger an innate immune response, causing the generation of inflammatory cytokine and promoting the clearance and control of pathogens. In E. sinensis, Toll/Toll-like receptors, lipopolysaccharide and ß-1,3-glucan binding proteins, C-type lectins, galactoside-binding lectins, L-type lectins, scavenger receptors, and down syndrome cell adhesion molecules have been identified to be PRRs that are involved in the recognition of bacteria, fungi, and viruses. In this review, we give a comprehensive overview of the literature regarding PRRs' roles in the immunological defenses of E. sinensis, with the aim of providing clues to the mechanisms of innate immunity.

Antimicrobial resistance dataset for pattern recognition in machine learning application.

This study presents a dataset of bacterial isolates collected from abattoirs in Osun State, Nigeria, designed to support research on antimicrobial resistance (AMR). The environment plays a critical role in the development and spread of AMR, posing a growing threat to global health. This dataset aims to address challenges in antibiotic selection by enabling the prediction of effective drugs for specific bacterial infections.

Hepatocyte-specific RIG-I loss attenuates metabolic dysfunction-associated steatotic liver disease in mice via changes in mitochondrial respiration and metabolite profiles.

Pattern recognition receptor (PRR)-mediated inflammation is an important determinant of the initiation and progression of metabolic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we investigated whether RIG-I is involved in hepatic metabolic reprogramming in a high-fat diet (HFD)-induced MASLD model in hepatocyte-specific RIG-I-KO (RIG-I∆hep) mice. Our study revealed that hepatic deficiency of RIG-I improved HFD-induced metabolic imbalances, including glucose impairment and insulin resistance. Hepatic steatosis and liver triglyceride levels were reduced in RIG-I-deficient hepatocytes in HFD-induced MASLD mice, and this was accompanied by the reduced expression of lipogenesis genes, such as PPARγ, Dga2, and Pck1. Hepatic RIG-I deficiency alters whole-body metabolic rates in the HFD-induced MASLD model; there is higher energy consumption in RIG-I∆hep mice. Deletion of RIG-I activated glycolysis and tricarboxylic acid (TCA) cycle-related metabolites in hepatocytes from both HFD-induced MASLD mice and methionine-choline-deficient diet (MCD)-fed mice. RIG-I deficiency enhanced AMPK activation and mitochondrial function in hepatocytes from HFD-induced MASLD mice. These findings indicate that deletion of RIG-I can activate cellular metabolism in hepatocytes by switching on both glycolysis and mitochondrial respiration, resulting in metabolic changes induced by a HFD and stimulation of mitochondrial activity. In summary, RIG-I may be a key regulator of cellular metabolism that influences the development of metabolic diseases such as MASLD. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-024-00264-x.

A robust myoelectric pattern recognition framework based on individual motor unit activities against electrode array shifts.

BACKGROUND AND OBJECTIVE: Electrode shift is always one of the critical factors to compromise the performance of myoelectric pattern recognition (MPR) based on surface electromyogram (SEMG). However, current studies focused on the global features of SEMG signals to mitigate this issue but it is just an oversimplified description of the human movements without incorporating microscopic neural drive information. The objective of this work is to develop a novel method for calibrating the electrode array shifts toward achieving robust MPR, leveraging individual motor unit (MU) activities obtained through advanced SEMG decomposition. METHODS: All of the MUs from decomposition of SEMG data recorded at the original electrode array position were first initialized to train a neural network for pattern recognition. A part of decomposed MUs could be tracked and paired with MUs obtained at the original position based on spatial distribution of their MUAP waveforms, so as to determine the shift vector (describing both the orientation and distance of the shift) implicated consistently by these multiple MU pairs. Given the known shift vector, the features of the after-shift decomposed MUs were corrected accordingly and then fed into the network to finalize the MPR task. The performance of the proposed method was evaluated with data recorded by a 16 × 8 electrode array placed over the finger extensor muscles of 8 subjects performing 10 finger movement patterns. RESULTS: The proposed method achieved a shift detection accuracy of 100 % and a pattern recognition accuracy approximating to 100 %, significantly outperforming the conventional methods with lower shift detection accuracies and lower pattern recognition accuracies (p < 0.05). CONCLUSIONS: Our method demonstrated the feasibility of using decomposed MUAP waveforms' spatial distributions to calibrate electrode shift. This study provides a new tool to enhance the robustness of myoelectric control systems via microscopic neural drive information at an individual MU level.

Comparative genomic analysis of copepod humoral immunity genes with sex-biased expression in Labidocera rotunda.

Studies of innate immune system function in invertebrates have contributed significantly to our understanding of the mammalian innate immune system. However, in-depth research on innate immunity in marine invertebrates remains sparse. We generated the first de novo genome and transcriptome sequences of copepod Labidocera rotunda using Illumina paired-end data and conducted a comparative genome analysis including five crustaceans (four copepods and one branchiopod species). We cataloged the presence of Toll, Imd, JAK/STAT, and JNK pathway components among them and compared them with 17 previously reported diverse arthropod species representative of insects, myriapods, chelicerates, and malacostracans. Our results indicated that copepod Gram-negative binding proteins may function in direct digestion or pathogen killing. The phylogenetic analysis of arthropod TEP and copepod-specific GCGEQ motif patterns suggested that the evolutionary history of copepod TEPs may have diverged from that of other arthropods. We classified the copepod Toll-like receptors identified in our analysis as either vertebrate or protostome types based on their cysteine motifs and the tree built with their Toll/interleukin-1 receptor domains. LrotCrustin, the first copepod AMP, was identified based on the structure of its WAP domain and deep-learning AMP predictors. Gene expression level analysis of L. rotunda innate immunity-related transcripts in each sex showed higher Toll pathway-related expression in male L. rotunda than in females, which may reflect an inverse correlation between allocation of reproductive investment and elevated immune response in males. Taken together, the results of our study provide insight into copepod innate immunity-related gene families and illuminate the evolutionary potential of copepods relative to other crustaceans.

Polymorphisms in the genes encoding RLR and TLR3 and CMV DNAemia in subjects coinfected with human immunodeficiency virus and cytomegalovirus.

Cytomegalovirus (CMV) is a pathogen that is common worldwide and is often present in individuals infected with human immunodeficiency virus (HIV). Pattern recognition receptors (PRRs) are host sensors that activate the immune response against infectious agents. However, it is unclear whether PRR single-nucleotide polymorphisms (SNPs) are associated with the occurrence of CMV DNAemia in subjects coinfected with HIV and CMV. HIV/CMV-coinfected patients with and without CMV DNAemia were recruited for this study. The DDX58 rs10813831 and IFIH1 (rs3747517 and rs1990760) polymorphisms were genotyped using the TaqMan Allelic Discrimination Assay, whereas the DDX58 rs12006123 and TLR3 (rs3775291 and rs3775296) SNPs were analyzed using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. A mutation present in at least one allele of the DDX58 rs12006123 SNP occurred at least two times more frequently in HIV/CMV-coinfected patients with CMV DNAemia than in coinfected subjects without CMV DNAemia (OR, 2.50; 95% CI, 1.33-4.68; p = 0.004, in the dominant model). A higher level of CMV DNAemia was observed in subjects who had the heterozygous (GA) or homozygous recessive (AA) genotype for the DDX58 rs12006123 SNP compared with those who had the wild-type (GG) genotype (p = 0.0003). Moreover, in subjects with a mutation detected in at least one allele of the DDX58 rs12006123 SNP, a lower serum IFN-ß concentration was found compared with those who had a wild-type (GG) genotype for this polymorphism (p = 0.024). The DDX58 rs12006123 SNP is associated with CMV DNAemia in HIV/CMV-coinfected patients.

An arms race between 5'ppp-RNA virus and its alternative recognition receptor MDA5 in RIG-I-lost teleost fish.

The incessant arms race between viruses and hosts has led to numerous evolutionary innovations that shape life's evolution. During this process, the interactions between viral receptors and viruses have garnered significant interest since viral receptors are cell surface proteins exploited by viruses to initiate infection. Our study sheds light on the arms race between the MDA5 receptor and 5'ppp-RNA virus in a lower vertebrate fish, Miichthys miiuy. Firstly, the frequent and independent loss events of RIG-I in vertebrates prompted us to search for alternative immune substitutes, with homology-dependent genetic compensation response (HDGCR) being the main pathway. Our further analysis suggested that MDA5 of M. miiuy and Gallus gallus, the homolog of RIG-I, can replace RIG-I in recognizing 5'ppp-RNA virus, which may lead to redundancy of RIG-I and loss from the species genome during evolution. Secondly, as an adversarial strategy, 5'ppp-RNA SCRV can utilize the m6A methylation mechanism to degrade MDA5 and weaken its antiviral immune ability, thus promoting its own replication and immune evasion. In summary, our study provides a snapshot into the interaction and coevolution between vertebrate and virus, offering valuable perspectives on the ecological and evolutionary factors that contribute to the diversity of the immune system.

Before the immune system can eliminate a bacterium, virus or other type of pathogen, it needs to be able to recognize these foreign elements. To achieve this, cells in the immune system have proteins called pattern recognition receptors (PRRs) which can identify distinct molecular features of certain pathogens. One specific group of PRRs is a family of retinoic acid-induced RIG-I-like receptors (RLRs), which help immune cells detect different types of viruses. Members of this family recognize distinct motifs on the genetic material of viruses known as RNA. For instance, RIG-I recognizes a marker known as 5'ppp on the end of single-stranded RNA molecules, whereas MDA5 recognizes long strands of double-stranded RNA. Many vertebrates ­ including various mammals, birds, and fish ­ lost the RIG-I receptor over the course of evolution. However, Geng et al. predicted that some animals lacking the RIG-I receptor may still be able to activate an immune response against viruses that contain the 5'ppp-RNA motif. To investigate this possibility, Geng et al. studied chickens and miiuy croakers (a type of ray-finned fish) which no longer have a RIG-I receptor. They found that both animals can still sense and eliminate two 5'ppp-RNA viruses called VSV and SCRV. Further experiments revealed that these two viruses are detected by a modified MDA5 receptor that had evolved to bind to 5'-ppp and activate the antiviral response. Viruses are also continuously evolving new ways to escape the immune system. This led Geng et al. to investigate whether SCRV, which causes serious harm to marine fish, has evolved a way to evade the MDA5 protection mechanism. Using miiuy croakers as a model, they found that SCRV causes the transcripts that produce the MDA5 protein to contain more molecules of m6a. This molecular tag degrades the transcript, leading to lower levels of MDA5, reducing the antiviral response against SCRV. The findings of Geng et al. offer valuable perspectives on how the immune system adapts over the course of evolution, and highlight the diversity of antiviral responses in vertebrates. Chickens and miiuy croakers are commonly farmed animals, and further work investigating how viruses invade these species could prevent illnesses from spreading and having a negative impact on the economy.