Gliotoxin elicits immunotoxicity in the early innate immune system of ducks.

Gliotoxin (GT) belongs to the epipolythiodioxopiperazine (ETP) family, which is considered a crucial virulence determinant among the secondary metabolites produced by Aspergillus fumigatus. The metabolites are commonly found in food and feed, contributing to the invasion and immune escape of Aspergillus fumigatus, thereby posing a significant threat to the health of livestock, poultry, and humans. Heterophil extracellular traps (HETs), a novel form of innate immune defense, have been documented in the chicken's innate immune systems for capturing and eliminating invading microbes. However, the effects and mechanisms of GT on the production of duck HETs in vitro remain unknown. In this study, we first confirmed the presence of HETs in duck innate immune systems and further investigated the molecular mechanism underlying GT-induced HETs release. Our results demonstrate that GT can trigger typical release of HETs in duck. The structures of GT-induced HETs structures were characterized by DNA decoration, citrullinated histones 3, and elastase. Furthermore, NADPH oxidase, glycolysis, ERK1/2 and p38 signaling pathway were found to regulate GT-induced HETs. In summary, our findings reveal that gliotoxin activates HETs release in the early innate immune system of duck while providing new insights into the immunotoxicity of GT towards ducks.

Multiple H-Bonding Cross-Linked Supramolecular Solid-Solid Phase Change Materials for Thermal Energy Storage and Management.

Solid-solid phase change materials (SSPCMs) are considered among the most promising candidates for thermal energy storage and management. However, the application of SSPCMs is consistently hindered by the canonical trade-off between high TES capacity and mechanical robustness. In addition, they suffer from poor recyclability due to chemical cross-linking. Herein, a straightforward but effective strategy for fabricating supramolecular SSPCMs with high latent heat and mechanical strength is proposed. The supramolecular polymer employs multiple H-bonding interactions as robust physical cross-links. This enables SSPCM with a high enthalpy of phase transition (142.5 J g-1 ), strong mechanical strength (36.9 MPa), and sound shape stability (maintaining shape integrity at 120 °C) even with a high content of phase change component (97 wt%). When SSPCM is utilized to regulate the operating temperature of lithium-ion batteries, it significantly diminishes the battery working temperature by 23 °C at a discharge rate of 3 C. The robust thermal management capability enabled through solid-solid phase change provides practical opportunities for applications in fast discharging and high-power batteries. Overall, this study presents a feasible strategy for designing linear SSPCMs with high latent heat and exceptional mechanical strength for thermal management.

DNase I rescues goat sperm entrapped by neutrophil extracellular traps.

Artificial insemination has been a predominant technique employed in goat husbandry for breeding purposes. Subsequent to artificial insemination, sperm can elicit inflammation in the reproductive tract, resulting in substantial the accumulation of neutrophils. Recognized as foreign entities, sperm may become entrapped within neutrophil extracellular traps (NETs) released by neutrophils, thereby exploiting their properties of pathogen elimination. Deoxyribonuclease I (DNase I), which is known for disintegrating NETs and causing loss of function, has been utilized to ameliorate liver and brain damage resulting from NETs, as well as to enhance sperm quality. This study investigated the mechanism of sperm-induced NETs and further explored the impact of DNase I on NETs. Sperm quality was evaluated using optical microscopy, while the structure of NETs was observed through immunofluorescence staining. The formation mechanism of NETs was examined using inhibitors and PicoGreen. The findings revealed that sperm induced the formation of NETs, a process regulated by glycolysis, NADPH oxidase, ERK1/2, and p38 signaling pathways. The composition of NETs encompassed DNA, citrullinated histone H3 (citH3), and elastase (NE). DNase I protects sperm by degrading NETs, thereby concurrently preserving the integrity of plasma membrane and motility of sperm. In summary, the release of sperm-induced NETs leads to its damage, but this detrimental effect is counteracted by DNase I through degradation of NETs. These observations provide novel insights into reproductive immunity in goats.

Animal models of mpox virus infection and disease.

Mpox (monkeypox) virus (MPXV), which causes a mild smallpox-like disease, has been endemic in Africa for several decades, with sporadic cases occurring in other parts of the world. However, the most recent outbreak of mpox mainly among men that have sex with men has affected several continents, posing serious global public health concerns. The infections exhibit a wide spectrum of clinical presentation, ranging from asymptomatic infection to mild, severe disease, especially in immunocompromised individuals, young children, and pregnant women. Some therapeutics and vaccines developed for smallpox have partial protective and therapeutic effects against MPXV historic isolates in animal models. However, the continued evolution of MPXV has produced multiple lineages, leading to significant gaps in the knowledge of their pathogenesis that constrain the development of targeted antiviral therapies and vaccines. MPXV infections in various animal models have provided a central platform for identification and comparison of diseased pathogenesis between the contemporary and historic isolates. In this review, we discuss the susceptibility of various animals to MPXV, and describe the key pathologic features of rodent, rabbit and nonhuman primate models. We also provide application examples of animal models in elucidating viral pathogenesis and evaluating effectiveness of vaccine and antiviral drugs. These animal models are essential to understand the biology of MPXV contemporary isolates and to rapidly test potential countermeasures. Finally, we list some remaining scientific questions of MPXV that can be resolved by animal models.

Toxoplasma gondii-induced neutrophil extracellular traps are relevant to glycolysis, TLR2, and TLR4 MAPK signaling pathway in goats.

Toxoplasma gondii (T. gondii) exhibits a significantly high prevalence of infection in goats, leading to adverse consequences such as abortion and stillbirth in ewes, thereby posing a substantial challenge to the goat farming industry. Neutrophil extracellular traps (NETs) have been shown to capture T. gondii in goats; however, the precise mechanisms underlying NET release in goats remain poorly understood. Therefore, the aim of our research was to elucidate the involved mechanism. We assessed the cytotoxicity of T. gondii on neutrophils using CCK-8 assay, visualized the structure of T. gondii-induced goat NETs through immunofluorescence, quantified ROS release during T. gondii-induced NET formation using fluorescence microplate analysis, and employed inhibitors targeting TLR 2, TLR4, NADPH oxidase, ERK1/2, and P38 MAPK signaling pathways as well as glycolysis to dissect the mechanisms underlying T. gondii-induced NET release. Within 1 h, T. gondii did not exhibit significant cytotoxicity towards neutrophils in our findings. The formation of typical NET structures induced by T. gondii involved DNA, citrullinated histone 3 (citH3), and neutrophil elastase (NE). Additionally, T. gondii significantly stimulated the release of NETs in goats. The process was accompanied by the production of reactive oxygen species (ROS) mediated through NADPH oxidase, p38, and ERK1/2 signaling pathways. Inhibition of these pathways resulted in a decrease in NET release. Moreover, inhibition of TLR 2, TLR4, and glycolysis also led to a reduction in T. gondii-induced NET release. Overall, our study demonstrates that T. gondii can induce characteristic NET structures and elucidates the involvement of various mechanisms including TLR2/TLR4 signaling pathway activation, NADPH oxidase activity modulation via ROS production regulation through p38 MAPK and ERK1/2 signaling pathways, and glycolysis regulation during the innate immune response against T. gondii infection in goats.

Cryo-EM structure of severe fever with thrombocytopenia syndrome virus.

The severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne human-infecting bunyavirus, which utilizes two envelope glycoproteins, Gn and Gc, to enter host cells. However, the structure and organization of these glycoproteins on virion surface are not yet known. Here we describe the structure of SFTSV determined by single particle reconstruction, which allows mechanistic insights into bunyavirus assembly at near-atomic resolution. The SFTSV Gn and Gc proteins exist as heterodimers and further assemble into pentameric and hexameric peplomers, shielding the Gc fusion loops by both intra- and inter-heterodimer interactions. Individual peplomers are associated mainly through the ectodomains, in which the highly conserved glycans on N914 of Gc play a crucial role. This elaborate assembly stabilizes Gc in the metastable prefusion conformation and creates some cryptic epitopes that are only accessible in the intermediate states during virus entry. These findings provide an important basis for developing vaccines and therapeutic drugs.

EGR1 functions as a new host restriction factor for SARS-CoV-2 to inhibit virus replication through the E3 ubiquitin ligase MARCH8.

IMPORTANCE: Emerging vaccine-breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants highlight an urgent need for novel antiviral therapies. Understanding the pathogenesis of coronaviruses is critical for developing antiviral drugs. Here, we demonstrate that the SARS-CoV-2 N protein suppresses interferon (IFN) responses by reducing early growth response gene-1 (EGR1) expression. The overexpression of EGR1 inhibits SARS-CoV-2 replication by promoting IFN-regulated antiviral protein expression, which interacts with and degrades SARS-CoV-2 N protein via the E3 ubiquitin ligase MARCH8 and the cargo receptor NDP52. The MARCH8 mutants without ubiquitin ligase activity are no longer able to degrade SARS-CoV-2 N proteins, indicating that MARCH8 degrades SARS-CoV-2 N proteins dependent on its ubiquitin ligase activity. This study found a novel immune evasion mechanism of SARS-CoV-2 utilized by the N protein, which is helpful for understanding the pathogenesis of SARS-CoV-2 and guiding the design of new prevention strategies against the emerging coronaviruses.

Pathological characteristics and congenital immunological responses of pigeons-infected with Neospora caninum.

Pigeons are natural intermediate host of Neospora caninum (N. caninum). In comparison to ruminants, N. caninum causes milder clinical symptoms and less financial loss to pigeons. Natural infectious rates and high prevalence of N. caninum in pigeons, and death cases of N. caninum-infected pigeons under experimental conditions have been reported, but the detailed pathological characteristics and congenital immunological responses of pigeons-infected with N. caninum remain not well described. In this study, pigeons were infected intraperitoneally with 107 N. caninum tachyzoites. N. caninum in tissues was detected by qPCR. Pathological changes of tissues were examined by hematoxylin-eosin staining. Blood smears were prepared for counting eosinophils changes in blood. Heterophil extracellular traps (HETs) in vivo and in vitro were quantified by Pico Green. N. caninum-induced HETs structures were observed by immunofluorescence staining. The model of pigeons-infected with N. caninum was successfully established. Lung and duodenum were the main target organs of pigeons-infected with N. caninum. N. caninum caused hemorrhage, edema and inflammatory cell infiltration in liver, pulmonary congestion and hemorrhage, organizational destruction in lung, and shorter villi or even disappear in duodenum. N. caninum also increased the number of eosinophils in blood of pigeons. Moreover, N. caninum-induced HETs release in the congenital immunological system of pigeons were first demonstrated, and the HETs structures were consisted of DNA as the skeleton and modified with citH3 and elastase. N. caninum-induced HETs release was related with NADPH oxidase, TLR 2 and 4, ERK1/2 and p38 MAPK signaling pathways, and glycolysis. In summary, it is the first report on the detailed pathological characteristics and congenital immunological responses of pigeons-infected with N. caninum, which may provide theoretical basis for the prevention and control of Neosporosis in pigeons.

Toxoplasma gondii triggers heterophil extracellular traps via NADPH oxidase, ERK1/2 and P38 signalling pathways, glycolysis and autophagy in chickens.

Toxoplasma gondii is a zoonotic parasite with a global distribution. Heterophil extracellular traps (HETs) are a novel innate immune mechanism of chickens against pathogens, but whether T. gondii can induce HETs release in chickens has not been reported. The effects of T. gondii on heterophils viability were assessed by using Cell Counting Kit-8. T. gondii-induced HETs were observed and analysed by the immunofluorescence method. T. gondii-induced reactive oxygen species (ROS) was determined by the DCFH-DA method. The mechanisms underlying T. gondii-triggered HETs were investigated by inhibitors and fluorescence microplate reader. T. gondii did not significantly affect heterophils viability at a 1:1 ratio within 1 h. It was demonstrated for the first time that T. gondii could induce HETs release in chicken, and the structure of HETs was comprised of DNA, elastase and citrullinated histone 3 (citH3). T. gondii increased ROS production in a dose-dependent manner. Inhibitors of NADPH oxidase, extracellular signal-regulated kinase 1/2 (ERK1/2 ) and P38 signalling pathways, glycolysis and autophagy significantly decreased the release of T. gondii-induced HETs. Taken together, T. gondii can induce HETs release in chickens, and ROS, NADPH oxidase, ERK1/2 and P38 signalling pathways, glycolysis and autophagy participate in the process of HETs release, which provides new insights into the innate immune mechanism of chickens against T. gondii infection.

Yezo Virus Infection in Tick-Bitten Patient and Ticks, Northeastern China.

We identified Yezo virus infection in a febrile patient who had a tick bite in northeastern China, where 0.5% of Ixodes persulcatus ticks were positive for viral RNA. Clinicians should be aware of this potential health threat and include this emerging virus in the differential diagnosis for tick-bitten patients in this region.

Quercetin alleviates gliotoxin-induced duckling tissue injury by inhibiting oxidative stress, inflammation and increasing heterophil extracellular traps release.

Aspergillus fumigatus causes aspergillosis with high morbidity and mortality in the duck industry. As a vital virulence factor produced by A. fumigatus, gliotoxin (GT) is widely present in food and feed, threatening duck industry and human health. Quercetin is a polyphenol flavonoid compound from natural plants with anti-inflammatory and antioxidant functions. However, the effects of quercetin on ducklings with GT poisoning are unknown. The model of ducklings with GT poisoning was established, and the protective effects and molecular mechanisms of quercetin on ducklings with GT poisoning were investigated. Ducklings were divided into control, GT, and quercetin groups. A model of GT (2.5 mg/kg) poisoning in ducklings was successfully established. Quercetin protected GT-induced liver and kidney functions and alleviated GT-induced alveolar wall thickening in lungs, cell fragmentation, and inflammatory cell infiltration in liver and kidney. Quercetin decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) and catalase (CAT) after GT treatment. Quercetin significantly reduced GT-induced mRNA expression levels of inflammatory factors. Furthermore, quercetin increased GT-reduced heterophil extracellular traps (HETs) in serum. These results indicated that quercetin protected ducklings against GT poisoning by inhibiting oxidative stress, inflammation and increasing HETs release, which confirms the potential applicability of quercetin in treating GT-induced duckling poisoning.

Exploring Self-Healing and Switchable Adhesives based on Multi-Level Dynamic Stable Structure.

It is a challenge to develop adhesives simultaneously capable of strong adhesion and efficient switchable ability. Herein, the authors report multifunctional switchable adhesives named Cu2+ -curcumin-imidazole-polyurethane (CIPUs:Cu2+ ) by introducing 1-(3-aminopropyl) imidazole and curcumin into polyurethane system crossed by Cu2+ forming dynamic metal-ligand bonds. This CIPUs:Cu2+ has strong adhesion (up to 2.46 MPa) on various material surfaces due to their specially designed functional groups alike the secretions from mussels. It can achieve fast switching speed (30 s) and high switch efficiency through multiple contactless remote stimulations. Importantly, density functional theory (DFT) calculation reveals that such metal-ligand bonds consisting of two components: stronger Cu2+ -curcumin complexes and weaker Cu2+ -imidazole complexes can aggregate to form multi-level dynamic stable structure . The special structure can not only be acted as sacrificial sites for easily broken and reformed, allowing efficient switchable adhesion and enormous energy dissipation but also acted as firm sites to maintain the cohesion of the adhesive and the reversible reconstruction network. Intriguingly, the CIPUs:Cu2+ can achieve self-healing at room temperature without needing external stimuli. Overall, this strategy can further broaden the design of switchable adhesives in the fields of intelligent gadgets, wearable bio-monitoring devices, etc.

Flavivirus prM interacts with MDA5 and MAVS to inhibit RLR antiviral signaling.

BACKGROUND: Vector-borne flaviviruses, including tick-borne encephalitis virus (TBEV), Zika virus (ZIKV), West Nile virus (WNV), yellow fever virus (YFV), dengue virus (DENV), and Japanese encephalitis virus (JEV), pose a growing threat to public health worldwide, and have evolved complex mechanisms to overcome host antiviral innate immunity. However, the underlying mechanisms of flavivirus structural proteins to evade host immune response remain elusive. RESULTS: We showed that TBEV structural protein, pre-membrane (prM) protein, could inhibit type I interferon (IFN-I) production. Mechanically, TBEV prM interacted with both MDA5 and MAVS and interfered with the formation of MDA5-MAVS complex, thereby impeding the nuclear translocation and dimerization of IRF3 to inhibit RLR antiviral signaling. ZIKV and WNV prM was also demonstrated to interact with both MDA5 and MAVS, while dengue virus serotype 2 (DENV2) and YFV prM associated only with MDA5 or MAVS to suppress IFN-I production. In contrast, JEV prM could not suppress IFN-I production. Overexpression of TBEV and ZIKV prM significantly promoted the replication of TBEV and Sendai virus. CONCLUSION: Our findings reveal the immune evasion mechanisms of flavivirus prM, which may contribute to understanding flavivirus pathogenicity, therapeutic intervention and vaccine development.

Forsythin inhibits ß-hydroxybutyrate-induced oxidative stress in bovine macrophages by regulating p38/ERK, PI3K/Akt, and Nrf2/HO-1 signaling pathways.

Ketosis is a metabolic disease of dairy cows in the perinatal period, ß-hydroxybutyrate (ß-HB) is the main component of ketosis. High levels of ß-HB can trigger oxidative stress and inflammatory response in dairy cows, leading to decreased milk yield and multiple postpartum diseases. Forsythin (FOR), the major constituent of the herbal medicine Forsythia, has anti-inflammatory, anti-oxidant, and antiviral effects. FOR was demonstrated to have an antioxidant effect on PC12 cells. However, the effects of FOR on ß-HB-stimulated bovine macrophages (BMs) has not been reported. Thus, the aim of the present study was to investigate the effects of FOR on ß-HB-stimulated BMs. Firstly, the CCK8 test confirmed that FOR (50, 100, 200 µg/mL) has no effect on BMs activity, and we selected these concentrations for subsequent experiments. Secondly, through detecting the oxidation indexes ROS, MDA and antioxidant indexes CAT and SOD, we confirmed the antioxidant effect of FOR on BMs. Next, qRT-PCR confirmed that FOR dramatically reduced the mRNA levels of IL-1ß and IL-6. Furthermore, the western blotting confirmed that FOR observably down-regulated ß-HB-stimulated phosphorylation of p38, ERK and Akt and up-regulated expression of Nrf2, and HO-1. Above results suggested that FOR plays antioxidant effects on ß-HB-induced BMs through p38, ERK and PI3K/Akt, Nrf2 and HO-1 signaling pathways. Therefore, we speculated that FOR may be a potential medicine to alleviate ß-HB-induced inflammatory response and provide a preliminary reference for the research and development of FOR.

Extensive diversity of RNA viruses in ticks revealed by metagenomics in northeastern China.

BACKGROUND: Ticks act as important vectors of infectious agents, and several emerging tick-borne viruses have recently been identified to be associated with human diseases in northeastern China. However, little is known about the tick virome in northeastern China. METHODS: Ticks collected from April 2020 to July 2021 were pooled for metagenomic analysis to investigate the virome diversity in northeastern China. RESULTS: In total, 22 RNA viruses were identified, including four each in the Nairoviridae and Phenuiviridae families, three each in the Flaviviridae, Rhabdoviridae, and Solemoviridae families, two in the Chuviridae family, and one each in the Partitiviridae, Tombusviridae families and an unclassified virus. Of these, eight viruses were of novel species, belonging to the Nairoviridae (Ji'an nairovirus and Yichun nairovirus), Phenuiviridae (Mudanjiang phlebovirus), Rhabdoviridae (Tahe rhabdovirus 1-3), Chuviridae (Yichun mivirus), and Tombusviridae (Yichun tombus-like virus) families, and five members were established human pathogens, including Alongshan virus, tick-borne encephalitis virus, Songling virus, Beiji nairovirus, and Nuomin virus. I. persulcatus ticks had significant higher number of viral species than H. japonica, H. concinna, and D. silvarum ticks. Significant differences in tick viromes were observed among Daxing'an, Xiaoxing'an and Changbai mountains. CONCLUSIONS: These findings showed an extensive diversity of RNA viruses in ticks in northeastern China, revealing potential public health threats from the emerging tick-borne viruses. Further studies are needed to explain the natural circulation and pathogenicity of these viruses.

An interpretable approach for automatic aesthetic assessment of remote sensing images.

The increase of remote sensing images in recent decades has resulted in their use in non-scientific fields such as environmental protection, education, and art. In this situation, we need to focus on the aesthetic assessment of remote sensing, which has received little attention in research. While according to studies on human brain's attention mechanism, certain areas of an image can trigger visual stimuli during aesthetic evaluation. Inspired by this, we used convolutional neural network (CNN), a deep learning model resembling the human neural system, for image aesthetic assessment. So we propose an interpretable approach for automatic aesthetic assessment of remote sensing images. Firstly, we created the Remote Sensing Aesthetics Dataset (RSAD). We collected remote sensing images from Google Earth, designed the four evaluation criteria of remote sensing image aesthetic quality-color harmony, light and shadow, prominent theme, and visual balance-and then labeled the samples based on expert photographers' judgment on the four evaluation criteria. Secondly, we feed RSAD into the ResNet-18 architecture for training. Experimental results show that the proposed method can accurately identify visually pleasing remote sensing images. Finally, we provided a visual explanation of aesthetic assessment by adopting Gradient-weighted Class Activation Mapping (Grad-CAM) to highlight the important image area that influenced model's decision. Overall, this paper is the first to propose and realize automatic aesthetic assessment of remote sensing images, contributing to the non-scientific applications of remote sensing and demonstrating the interpretability of deep-learning based image aesthetic evaluation.

CuO-NPs-triggered heterophil extracellular traps exacerbate liver injury in chicks by promoting oxidative stress and inflammatory responses.

With the widespread use of copper oxide nanoparticles (CuO-NPs), their potential toxicity to the environment and biological health has attracted close attention. Heterophil extracellular traps (HETs) are an innate immune mechanism of chicken heterophils against adverse stimuli, but excessive HETs cause damage. Here, we explored the effect and mechanism of CuO-NPs on HETs formation in vitro and further evaluated the potential role of HETs in chicken liver and kidney injury. Heterophils were exposed to 5, 10, and 20 µg/mL of CuO-NPs for 2 h. The results showed that CuO-NPs induced typical HETs formation, which was dependent on NADPH oxidase, P38 and extracellular regulated protein kinases (ERK1/2) pathways, and glycolysis. In in vivo experiments, fluorescence microplate and morphological analysis showed that CuO-NPs elevated the level of HETs in chicken serum and caused liver and kidney damage. Meanwhile, CuO-NPs caused hepatic oxidative stress (MDA, SOD, CAT, and GSH-PX imbalance), and also induced an increase in mRNA expression of their inflammatory and apoptosis-related factors (IL-1ß, IL-6, TNF-α, COX-2, iNOS, NLRP3, and Caspase-1, 3, 11). However, these results were significantly altered by DNase I (HETs degradation reagent). In conclusion, the present study demonstrates for the first time that CuO-NPs induce the formation of HETs and that HETs exacerbate pathological damage in chicken liver and kidney by promoting oxidative stress and inflammation, providing insights into immunotoxicity and potential prevention and treatment targets caused by CuO-NPs overexposure.

Zinc oxide nanoparticles (ZnO-NPs) exhibit immune toxicity to crucian carp (Carassius carassius) by neutrophil extracellular traps (NETs) release and oxidative stress.

Zinc oxide nanoparticles (ZnO-NPs) are widely used in sunscreens, cosmetics, paint, construction materials, and other products. ZnO-NPs released into the environment can harm aquatic creatures and pose a health risk to humans through the food chain. ZnO-NPs are toxic to fish, but there are few reports on its immunotoxicity on crucian carp (Carassius carassius). In this study, ZnO-NPs increased the biochemical indexes of the liver in serum, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In histopathological observation, many inflammatory cells were filled in the liver's central vein stimulated by ZnO-NPs. Furthermore, ZnO-NPs could increase malondialdehyde (MDA) level, lessen superoxide dismutase (SOD) level, and elevate the level of neutrophil extracellular traps (NETs). However, deoxyribonuclease I (DNase I) alleviated all biochemical indexes and histopathological changes. Immunofluorescence in vitro confirmed that NETs were composed of citrullinated histone 3, myeloperoxidase, and neutrophil elastase. ZnO-NPs-increased NETs were dependent on reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and were also related to partial processes of glycolysis. Our study confirms that ZnO-NPS has a toxic effect on the liver of crucian carp. DNase I can prevent liver damage caused by ZnO-NPs, which provides a new insight into the immunotoxicity of ZnO-NPs to fish.

Virome of Rhipicephalus ticks by metagenomic analysis in Guangdong, southern China.

Tick-borne viruses (TBVs) have increasingly caused a global public health concern. This study collected Rhipicephalus ticks in Guangdong, southern China to identify RNA viruses. Meta-transcriptome analysis revealed the virome in Rhipicephalus ticks, resulting in the discovery of 10 viruses, including Lihan tick virus, Brown dog tick phlebovirus 1 and 2 in the family Phenuiviridae, Mivirus and Wuhan tick virus 2 in the family Chuviridae, Wuhan tick virus 1 in the family Rhabdoviridae, bovine hepacivirus in the family Flaviviridae, Guangdong tick quaranjavirus (GTQV) in the family Orthomyxoviridae, Guangdong tick orbivirus (GTOV) in the family Reoviridae, and Guangdong tick Manly virus (GTMV) of an unclassified family. Phylogenetic analysis showed that most of these TBVs were genetically related to the strains in countries outside China, and GTQV, GTOV, and GTMV may represent novel viral species. These findings provided evidence of the long-distance spread of these TBVs in Guangdong, southern China, suggesting the necessity and importance of TBV surveillance.

The global succinylation of SARS-CoV-2-infected host cells reveals drug targets.

SARS-CoV-2, the causative agent of the COVID-19 pandemic, undergoes continuous evolution, highlighting an urgent need for development of novel antiviral therapies. Here we show a quantitative mass spectrometry-based succinylproteomics analysis of SARS-CoV-2 infection in Caco-2 cells, revealing dramatic reshape of succinylation on host and viral proteins. SARS-CoV-2 infection promotes succinylation of several key enzymes in the TCA, leading to inhibition of cellular metabolic pathways. We demonstrated that host protein succinylation is regulated by viral nonstructural protein (NSP14) through interaction with sirtuin 5 (SIRT5); overexpressed SIRT5 can effectively inhibit virus replication. We found succinylation inhibitors possess significant antiviral effects. We also found that SARS-CoV-2 nucleocapsid and membrane proteins underwent succinylation modification, which was conserved in SARS-CoV-2 and its variants. Collectively, our results uncover a regulatory mechanism of host protein posttranslational modification and cellular pathways mediated by SARS-CoV-2, which may become antiviral drug targets against COVID-19.