Effect of tire wear particle accumulation on nitrogen removal and greenhouse gases abatement in bioretention systems: Soil characteristics, microbial community, and functional genes.

Tire wear particles (TWPs), as predominant microplastics (MPs) in road runoff, can be captured and retained by bioretention systems (BRS). This study aimed to investigate the effect of TWPs accumulation on nitrogen processes, focusing on soil characteristics, microbial community, and functional genes. Two groups of lab-scale bioretention columns containing TWPs (0 and 100 mg g-1) were established. The removal efficiencies of NH4+-N and TN in BRS significantly decreased by 7.60%-24.79% and 1.98%-11.09%, respectively, during the 101 days of TWPs exposure. Interestingly, the emission fluxes of N2O and CO2 were significantly decreased, while the emission flux of CH4 was substantially increased. Furthermore, prolonged TWPs exposure significantly influenced the contents of soil organic matter (increased by 27.07%) and NH4+-N (decreased by 42.15%) in the planting layer. TWPs exposure also significantly increased dehydrogenase activity and substrate-induced respiration rate, thereby promoting microbial metabolism. Microbial sequencing results revealed that TWPs decreased the relative abundance of nitrifying bacteria (Nitrospira and Nitrosomonas) and denitrifying bacteria (Dechloromonas and Thauera), reducing the nitrification rate by 42.24%. PICRUSt2 analysis further indicated that TWPs changed the relative abundance of functional genes related to nitrogen and enzyme-coding genes.

Downregulation of CPSF6 leads to global mRNA 3' UTR shortening and enhanced antiviral immune responses.

Alternative polyadenylation (APA) is a widespread mechanism of gene regulation that generates mRNA isoforms with alternative 3' untranslated regions (3' UTRs). Our previous study has revealed the global 3' UTR shortening of host mRNAs through APA upon viral infection. However, how the dynamic changes in the APA landscape occur upon viral infection remains largely unknown. Here we further found that, the reduced protein abundance of CPSF6, one of the core 3' processing factors, promotes the usage of proximal poly(A) sites (pPASs) of many immune related genes in macrophages and fibroblasts upon viral infection. Shortening of the 3' UTR of these transcripts may improve their mRNA stability and translation efficiency, leading to the promotion of type I IFN (IFN-I) signalling-based antiviral immune responses. In addition, dysregulated expression of CPSF6 is also observed in many immune related physiological and pathological conditions, especially in various infections and cancers. Thus, the global APA dynamics of immune genes regulated by CPSF6, can fine-tune the antiviral response as well as the responses to other cellular stresses to maintain the tissue homeostasis, which may represent a novel regulatory mechanism for antiviral immunity.

Insights into RAG Evolution from the Identification of "Missing Link" Family A RAGL Transposons.

A series of "molecular domestication" events are thought to have converted an invertebrate RAG-like (RAGL) transposase into the RAG1-RAG2 (RAG) recombinase, a critical enzyme for adaptive immunity in jawed vertebrates. The timing and order of these events are not well understood, in part because of a dearth of information regarding the invertebrate RAGL-A transposon family. In contrast to the abundant and divergent RAGL-B transposon family, RAGL-A most closely resembles RAG and is represented by a single orphan RAG1-like (RAG1L) gene in the genome of the hemichordate Ptychodera flava (PflRAG1L-A). Here, we provide evidence for the existence of complete RAGL-A transposons in the genomes of P. flava and several echinoderms. The predicted RAG1L-A and RAG2L-A proteins encoded by these transposons intermingle sequence features of jawed vertebrate RAG and RAGL-B transposases, leading to a prediction of DNA binding, catalytic, and transposition activities that are a hybrid of RAG and RAGL-B. Similarly, the terminal inverted repeats (TIRs) of the RAGL-A transposons combine features of both RAGL-B transposon TIRs and RAG recombination signal sequences. Unlike all previously described RAG2L proteins, RAG2L-A proteins contain an acidic hinge region, which we demonstrate is capable of efficiently inhibiting RAG-mediated transposition. Our findings provide evidence for a critical intermediate in RAG evolution and argue that certain adaptations thought to be specific to jawed vertebrates (e.g. the RAG2 acidic hinge) actually arose in invertebrates, thereby focusing attention on other adaptations as the pivotal steps in the completion of RAG domestication in jawed vertebrates.

Manganese-nitrogen co-doped biochar (MnN@BC) as particle electrode for three-dimensional (3D) electro-activation of peroxydisulfate: Active sites enhanced radical/non-radical oxidation.

A novel manganese-nitrogen co-doped biochar (MnN@BC) was synthesized and used as particle electrodes in three-dimensional (3D) electro-activation of peroxydisulfate (PDS) for the degradation of refractory organic pollutants. All the spectroscopy (EDS, XRD, XPS, FTIR, and Raman) results indicated that Mn-N nanoclusters were successfully deposited and embedded in BC. The material appeared graphitized structure with more defects after Mn-N doping. MnN@BC in 3D electro-activation of PDS (E/MnN@BC/PDS) exhibited excellent performance in carbamazepine (CBZ) removal, with removal efficiency and degradation rates of 96.84% and 0.0582 min-1, respectively. Besides, MnN@BC was favorable for adsorption, electron transfer, and reactive oxidizing species (ROS) formation. MnN@BC had good recyclability in the E/MnN@BC/PDS system by the recycled experiments and characterization. Furthermore, quenching experiments, probe experiments, and electron paramagnetic resonance (EPR) analyses suggested that •OH and 1O2 were the main ROS in the E/MnN@BC/PDS system, and the non-radical oxidation take a key part. In addition, this system achieved excellent CBZ degradation under wide pH range of 3-11, had good tolerance to natural organic matter and inorganic ions, and was efficient to various water matrices and other refractory organic pollutants. These findings provided new insights into particle electrode design and mechanisms enhancement in electro-activated PDS systems.

Obesity-induced inflammatory miR-133a mediates apoptosis of granulosa cells and causes abnormal folliculogenesis.

Obesity has been reported to promote disordered folliculogenesis, but the exact molecular mechanisms are still not fully understood. In this study, we find that miR-133a is involved in obesity-induced follicular development disorder. After feeding with a high-fat diet (HFD) and fructose water for nine weeks, the mouse body weight is significantly increased, accompanied by an inflammatory state and increased expression of miR-133a in the adipose tissues and ovaries as well as accelerated follicle depletion. Although miR-133a is increased in the fat and ovaries of HFD mice, the increased miR-133a in the HFD ovaries is not derived from exosome transferred from obese adipose tissues but is synthesized by ovarian follicular cells in response to HFD-induced inflammation. In vivo experiments show that intrabursal injection of miR-133a agomir induces a decrease in primordial follicles and an increase in antral follicles and atretic follicles, which is similar to HFD-induced abnormal folliculogenesis. Overexpression of miR-133a modestly promotes granulosa cell apoptosis by balancing the expression of anti-apoptotic proteins such as C1QL1 and XIAP and pro-apoptotic proteins such as PTEN. Overall, this study reveals the function of miR-133a in obesity-induced ovarian folliculogenesis dysfunction and sheds light on the etiology of female reproductive disorders.

Characterization of GSDME in amphioxus provides insights into the functional evolution of GSDM-mediated pyroptosis.

Members of the gasdermin (GSDM) family are pore-forming effectors that cause membrane permeabilization and pyroptosis, a lytic proinflammatory type of cell death. To reveal the functional evolution of GSDM-mediated pyroptosis at the transition from invertebrates to vertebrates, we conducted functional characterization of amphioxus GSDME (BbGSDME) and found that it can be cleaved by distinct caspase homologs, yielding the N253 and N304 termini with distinct functions. The N253 fragment binds to cell membrane, triggers pyroptosis, and inhibits bacterial growth, while the N304 performs negative regulation of N253-mediated cell death. Moreover, BbGSDME is associated with bacteria-induced tissue necrosis and transcriptionally regulated by BbIRF1/8 in amphioxus. Interestingly, several amino acids that are evolutionarily conserved were found to be important for the function of both BbGSDME and HsGSDME, shedding new lights on the functional regulation of GSDM-mediated inflammation.

The effect of using internet hospitals on the physician-patient relationship: Patient perspective.

BACKGROUND: Internet hospitals are rapidly developing in China. Despite many studies regarding internet hospitals, there has been little further research that evaluates the impact of using internet hospitals on the physician-patient relationship during outpatient visits. METHODS: We developed a questionnaire based on the patient-doctor relationship questionnaire (PDRQ-9) to survey the physician-patient relationship. A sample of 505 patients who sought medical services from offline physical or internet hospitals was selected by convenience sampling. Multiple linear regression analysis was performed to determine whether the use of internet hospitals during outpatient visits was associated with the physician-patient relationship. RESULTS: Internet hospital users gave significantly lower scores than nonusers in total physician-patient relationship scores (P =.01) and in the 5 items of "My physician helps me" (P <.001), "I trust my physician" (P =.001), "My physician understands me" (P =.002), "My physician and I agree on the nature of my medical symptoms" (P =.01), and "I can talk to (communicate with) my physician freely" (P =.005). Multiple linear regression results showed that the use of internet hospitals during outpatient visits influenced the physician-patient relationship. And after controlling for other patient characteristics, the use of internet hospitals decreased the physician-patient relationship scores by 11.9%. CONCLUSIONS: Our findings suggest that the current use of internet hospitals could not significantly enhance the physician-patient relationship during outpatient visits. Therefore, we should work on improving physicians' online communication skills and strengthening the level of trust between physicians and their patients. Policymakers should also pay close attention to the gap of the physician-patient relationship between internet hospitals and offline physical hospitals.

ZNFX1 antisense RNA1 promotes antiviral innate immune responses via modulating ZNFX1 function.

Increasing evidence suggests that natural antisense transcriptional lncRNAs regulate their adjacent coding genes to mediate diverse aspects of biology. Bioinformatics analysis of the previously identified antiviral gene ZNFX1 revealed neighboring lncRNA ZFAS1 transcribed on the opposite strand from ZNFX1. Whether ZFAS1 exerts antiviral function via regulating the dsRNA sensor ZNFX1 is unknown. Here we found that ZFAS1 was upregulated by RNA and DNA viruses and type I IFNs (IFN-I) dependent on Jak-STAT signaling, similar to the transcription regulation of ZNFX1. Knockdown of endogenous ZFAS1 partially facilitated viral infection, while ZFAS1 overexpression showed opposite effects. In addition, mice were more resistant to VSV infection with the delivery of human ZFAS1. We further observed that ZFAS1 knockdown significantly inhibited IFNB1 expression and IFR3 dimerization, whereas ZFAS1 overexpression positively regulated antiviral innate immune pathways. Mechanistically, ZFAS1 positively regulated ZNFX1 expression and antiviral function by enhancing the protein stability of ZNFX1, thereby establishing a positive feedback loop to enhance antiviral immune activation status. In short, ZFAS1 is a positive regulator of antiviral innate immune response via regulating its neighbor gene ZNFX1, adding new mechanistic insight into lncRNA-mediated regulation of signaling in innate immunity.

Application of biochar as an innovative soil ameliorant in bioretention system for stormwater treatment: A review of performance and its influencing factors.

As an emerging environment functional material, biochar has become a research hotspot in environmental fields because of its excellent ecological and environmental benefits. Recently, biochar has been used as an innovative soil ameliorant in bioretention systems (BRS) to effectively enhance pollutant removal efficiency for BRS. This paper summarizes and evaluates the performance and involved mechanisms of biochar amendment in BRS with respect to the removal of nutrients (TN (34-47.55%) and PO43--P (47-99.8%)), heavy metals (25-100%), pathogenic microorganisms (Escherichia coli (30-98%)), and organic contaminants (77.2-100%). For biochar adsorption, the pseudo-second-order and Langmuir models are the most suitable kinetic and isothermal adsorption models, respectively. Furthermore, we analyzed and elucidated some factors that influence the pollutant removal performance of biochar-amended BRS, such as the types of biochar, the preparation process and physicochemical properties of biochar, the aging of biochar, the chemical modification of biochar, and the hydraulic loading, inflow concentration and drying-rewetting alternation of biochar-amended BRS. The high potential for recycling spent biochar in BRS as a soil ameliorant is proposed. Collectively, biochar can be used as an improved medium in BRS. This review provides a foundation for biochar selection in biochar-amended BRS. Future research and practical applications of biochar-amended BRS should focus on the long-term stability of treatment performances under field conditions, chemical modification with co-impregnated nanomaterials in biochar surface, and the durability, aging, and possible negative effects of biochar.

Deficiency of C1QL1 Reduced Murine Ovarian Follicle Reserve Through Intraovarian and Endocrine Control.

Ovarian aging is associated with depletion of the ovarian follicle reserve, which is the key determinant of fertility potential in females. In this study, we found that the small, secreted protein complement 1Q-like (C1QL1) is involved in the regulation of follicle depletion through intraovarian and endocrine control in a multidimensional collaborative manner. C1ql1 was detected to be conserved in the ovary and showed high transcript levels during folliculogenesis. Blockade of C1QL1 by IP and ovarian intrabursal injection of C1QL1 antiserum into prepubertal mice impaired folliculogenesis accompanied by reductions in body weight, fat mass, and intraovarian lipid accumulation. An elevation of circulating estradiol levels, reduction of hypothalamic KISS1 and GnRH expression, and a decrease in serum FSH levels were found in C1QL1-deficient mice. In C1QL1-deficient ovaries, many primordial follicles were recruited and developed into medium follicles but underwent atresia at the large follicle stages, which resulted in depletion of follicle reserve. Depletion of C1QL1 alleviated the inhibitory effect of C1QL1 on granulosa cell apoptosis and the stimulatory effect of C1QL1 on granulosa cell autophagy, which resulted in accumulation in the preantral and early antral follicles and an increase in the atretic follicles. The abnormal profile of endocrine hormones accelerated the intraovarian effect of C1QL1 deficiency and further led to depletion of ovarian reserve. Altogether, this study revealed the expression patterns and the mechanism of action of C1QL1 during folliculogenesis and demonstrated that deficiency of C1QL1 caused ovarian follicular depletion.

New Insights Into the Lineage-Specific Expansion and Functional Diversification of Lamprey AID/APOBEC Family.

The AID/APOBEC family which converts cytidine to uridine on RNA or DNA experienced dynamic expansion in primates in order to resist exogenous viruses and endogenous retrotransposons. Recently, expansion of AID/APOBEC-like homologs has also been observed in the extant jawless vertebrate lamprey. To reveal what causes such expansion and leads to the functional diversification of lamprey cytosine deaminases (CDAs), we reassessed the CDA genes in Lethenteron japonicum (Lj). We first confirmed the expansion of LjCDA1L1 (CDA1-like 1) genes and found the expression correlation of LjCDA2 and LjCDA1L2 with LjVLRs (variable lymphocyte receptors). Among up to 14 LjCDA1L1 proteins, LjCDA1L1_4a has an extremely high deamination activity on ssDNA and buDNA and, unexpectedly, on dsDNA. LjCDA1L1s can also restrict the infection of HSV-1 particles. Thus, the arms race between the host and pathogens along with the recruitment by VLR assembly may participate together to form a driving force in the expansion and diversification of the lamprey AID/APOBEC family.

Degradation of WTAP blocks antiviral responses by reducing the m6 A levels of IRF3 and IFNAR1 mRNA.

N6 -methyladenosine (m6 A) is a chemical modification present in multiple RNA species and is most abundant in mRNAs. Studies on m6 A reveal its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. Although some recent discoveries indicate that m6 A can affect the life cycles of numerous viruses as well as the cellular antiviral immune response, the roles of m6 A modification in type I interferon (IFN-I) signaling are still largely unknown. Here, we reveal that WT1-associated protein (WTAP), one of the m6 A "writers", is degraded via the ubiquitination-proteasome pathway upon activation of IFN-I signaling. With the degradation of WTAP, the m6 A levels of IFN-regulatory factor 3 (IRF3) and interferon alpha/beta receptor subunit 1 (IFNAR1) mRNAs are reduced, leading to translational suppression of IRF3 and instability of IFNAR1 mRNA. Thus, the WTAP-IRF3/IFNAR1 axis may serve as negative feedback pathway to fine-tune the activation of IFN-I signaling, which highlights the roles of m6 A in the antiviral response by dictating the fate of mRNAs associated with IFN-I signaling.

Nitrogen process in stormwater bioretention: the impact of alternate drying and rewetting on nitrogen migration and transformation.

Nitrogen migration and transformation in the stormwater bioretention system were studied in laboratory experiments, in which the effects of drying-rewetting were particularly investigated. The occurrence and distribution of nitrogen in the plants, the soil, and the pore water were explored under different drying-rewetting cycles. The results clearly showed that bioretention system could remove nitrogen efficiently in all drying-rewetting cycles. The incoming nitrogen could be retained in the topsoil (0-10 cm) and accumulated in the planted layer. However, the overlong dry periods (12 and 22 days) cause an increase in nitrate in the pore water. In addition, nitrogen is mostly stored in the plants' stem tissues. Up to 23.26% of the inflowing nitrogen can be immobilized in plant tissues after a dry period of 22 days. In addition, the relationships between nitrogen reductase activity in the soil and soil nitrogen content were explored. The increase of soil TN content could enhance the activity of nitrate reductase. Meanwhile, the activity of hydroxylamine reductase (HyR) could be enhanced with the increase of soil NO3- content. These results provide a reference for the future development of nitrogen transformation mechanism and the construction of stormwater bioretention systems.

Transformation pathways of chlorinated paraffins relevant for remediation: a mini-review.

In the past decades, the environmental presence and ecological risks of chlorinated paraffins (CPs), an emerging class of organic halogen compounds, have been receiving increasing attention worldwide. Short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) constitute the important CPs of considerable concern. In this review article, the state-of-the-art research status on the environmental transformation of CPs, including thermal decomposition, photolytic and photocatalytic degradation, biological metabolism, and atmospheric transformation, was summarized and integrated in detail. The degradation efficiency and transformation products of CPs in these environmental processes were evaluated, in which dechlorination was considered as the major reaction pathway. Notably, waste incineration of CPs has been demonstrated to generate a variety of persistent chlorinated aromatic hydrocarbons such as polychlorinated biphenyls and polychlorinated naphthalenes, which have more significant environmental impacts. Additionally, photodegradation and photocatalysis are suggested as the feasible techniques for efficient removal of SCCPs from water matrices. Overall, the current transformation studies of CPs could facilitate the comprehensive understanding of their environmental behaviors and fate as well as the development of promising remediation strategies for pollution control.

Exosome-Delivered LncHEIH Promotes Gastric Cancer Progression by Upregulating EZH2 and Stimulating Methylation of the GSDME Promoter.

Gastric cancer is the third leading cause of cancer-related deaths worldwide and is characterized by poor survival and high recurrence rates. Long non-coding RNAs (lncRNAs) have gained considerable attention in recent years as prognostic markers and gene regulators in various cancers. Here, we found that lncHEIH was upregulated in gastric cancer tissues and cell lines and positively correlated with high expression levels of EZH2. Mechanistically, the lncHEIH-EZH2 axis could promote the progression of gastric cancer. In addition, lncHEIH encapsulated in exosomes was released by gastric cancer cells and then absorbed by normal gastric cells. The uptake of lncHEIH resulted in the upregulation of EZH2, which inhibited the expression of the tumor suppressor GSDME by methylation of the GSDME promoter, promoting the malignant transformation of normal gastric cells. Overall, lncHEIH promotes gastric cancer progression by upregulating the expression of EZH2 and reducing the expression of GSDME in normal cells to induce malignant cell proliferation and migration, indicating its potential as a target in gastric cancer therapy.

Functional regulation of an ancestral RAG transposon ProtoRAG by a trans-acting factor YY1 in lancelet.

The discovery of ancestral RAG transposons in early deuterostomia reveals the origin of vertebrate V(D)J recombination. Here, we analyze the functional regulation of a RAG transposon, ProtoRAG, in lancelet. We find that a specific interaction between the cis-acting element within the TIR sequences of ProtoRAG and a trans-acting factor, lancelet YY1-like (bbYY1), is important for the transcriptional regulation of lancelet RAG-like genes (bbRAG1L and bbRAG2L). Mechanistically, bbYY1 suppresses the transposition of ProtoRAG; meanwhile, bbYY1 promotes host DNA rejoins (HDJ) and TIR-TIR joints (TTJ) after TIR-dependent excision by facilitating the binding of bbRAG1L/2 L to TIR-containing DNA, and by interacting with the bbRAG1L/2 L complex. Our data thus suggest that bbYY1 has dual functions in fine-tuning the activity of ProtoRAG and maintaining the genome stability of the host.

Functional requirement of terminal inverted repeats for efficient ProtoRAG activity reveals the early evolution of V(D)J recombination.

The discovery of ProtoRAG in amphioxus indicated that vertebrate RAG recombinases originated from an ancient transposon. However, the sequences of ProtoRAG terminal inverted repeats (TIRs) were obviously dissimilar to the consensus sequence of mouse 12/23RSS and recombination mediated by ProtoRAG or RAG made them incompatible with each other. Thus, it is difficult to determine whether or how 12/23RSS persisted in the vertebrate RAG system that evolved from the TIRs of ancient RAG transposons. Here, we found that the activity of ProtoRAG is highly dependent on its asymmetric 5'TIR and 3'TIR, which are composed of conserved TR1 and TR5 elements and a partially conserved TRsp element of 27/31 bp to separate them. Similar to the requirements for the recombination signal sequences (RSSs) of RAG recombinase, the first CAC in TR1, the three dinucleotides in TR5 and the specific length of the partially conserved TRsp are important for the efficient recombination activity of ProtoRAG. In addition, the homologous sequences flanking the signal sequences facilitate ProtoRAG- but not RAG-mediated recombination. In addition to the diverged TIRs, two differentiated functional domains in BbRAG1L were defined to coordinate with the divergence between TIRs and RSSs. One of these is the CTT* domain, which facilitates the specific TIR recognition of the BbRAGL complex, and the other is NBD*, which is responsible for DNA binding and the protein stabilization of the BbRAGL complex. Thus, our findings reveal that the functional requirement for ProtoRAG TIRs is similar to that for RSS in RAG-mediated recombination, which not only supports the common origin of ProtoRAG TIRs and RSSs from the asymmetric TIRs of ancient RAG transposons, but also reveals the development of RAG and RAG-like machineries during chordate evolution.

Recent advances of SBA-15-based composites as the heterogeneous catalysts in water decontamination: A mini-review.

As an emerging class of silica-based mesoporous materials with incorporation of active components (e.g., transition metals/metal oxides and nanocarbons), SBA-15-based composites (X@SBA-15) have been attracting increasing attention in the field of water treatment owing to their unique characteristics and excellent remediation performance. This paper reviews recent advances in catalytic applications of X@SBA-15 to remove organic contaminants from water. Emphasis is made on the use of X@SBA-15 in four advanced oxidation processes (AOPs) (i.e., photocatalysis, Fenton-like oxidation, catalytic ozonation, and sulfate radical-based oxidation). Impregnation and hydrothermal methods are two most widely used synthetic approaches to combine the active composites with SBA-15, obtaining a synergistic effect with significant improvement in their individual catalytic activity for pollution remediation. The enhanced generation of highly reactive hydroxyl radicals from the surface of X@SBA-15 was widely recognized as being responsible for water decontamination using these AOPs, while sulfate radicals were also involved during activation of persulfate or peroxymonosulfate. Especially, X@SBA-15 could significantly enhance the light harvest and reduce the recombination of photo-induced electrons and holes during photocatalytic treatment, which also played the critical role in oxidizing the organics. The superior catalytic performance of X@SBA-15 without leaching metal ions during successive runs demonstrated the excellent reusability and structural stability. Together with the reduced toxicity of the treated solutions and the cost-effective characteristics of X@SBA-15 nanohybrids reported in the published literature, their great potential as the efficient and environmentally friendly heterogeneous catalysts in a real use scenario is suggested. Finally, the future perspectives on the development and practical utilization of X@SBA-15 are addressed.

Mitochondria-localised ZNFX1 functions as a dsRNA sensor to initiate antiviral responses through MAVS.

In the past two decades, emerging studies have suggested that DExD/H box helicases belonging to helicase superfamily 2 (SF2) play essential roles in antiviral innate immunity. However, the antiviral functions of helicase SF1, which shares a conserved helicase core with SF2, are little understood. Here we demonstrate that zinc finger NFX1-type containing 1 (ZNFX1), a helicase SF1, is an interferon (IFN)-stimulated, mitochondrial-localised dsRNA sensor that specifically restricts the replication of RNA viruses. Upon virus infection, ZNFX1 immediately recognizes viral RNA through its Armadillo-type fold and P-loop domain and then interacts with mitochondrial antiviral signalling protein to initiate the type I IFN response without depending on retinoic acid-inducible gene I-like receptors (RLRs). In short, as is the case with interferon-stimulated genes (ISGs) alone, ZNFX1 can induce IFN and ISG expression at an early stage of RNA virus infection to form a positively regulated loop of the well-known RLR signalling. This provides another layer of understanding of the complexity of antiviral immunity.