[Analysis of Field Inspection Issues and Some Suggestions for Software as Medical Device].

With the encouragement of policies and the rapid development of the biopharmaceutical industry, the number of software as medical device (SaMD) registration applications in Shanghai has continued to increase in recent years, and this paper summarizes the GMP nonconformities found in the field inspection of SaMD in Shanghai from 2020 to 2023, and the results show that nearly 70% of the problems were found in the software development process. Through in-depth analysis, this paper proposes the corresponding countermeasures for the problems found in the five most common stages such as software requirements, software design, software testing, software defect management and software configuration management, combined with the characteristics of software development. These suggested measures have certain reference significance for medical device software development and quality control personnel, and technical reviewer and inspectors.

"Cage Walking" Synthetic Strategy for Unusual Unsymmetrical Supramolecular Cages.

Developing novel assembly methods for supramolecular compounds has long been a research challenge. Herein, we describe how to integrate the B-C coupling reaction and "cage walking" process into coordination self-assembly to construct supramolecular cages. In this strategy, dipyridine linkers containing alkynes react with the metallized carborane backbone through B-C coupling and then "cage walking" resulting in metallacages. However, dipyridine linkers without alkynyl groups can form only metallacycles. We can regulate the size of metallacages based on the length of the alkynyl bipyridine linkers. When tridentate-pyridine linkers participate in this reaction, a new type of ravel is formed. The metallization of carboranes, the B-C coupling reaction, and especially the "cage walking" process of carborane cages play a vital role in this reaction. This work provides a promising principle for the synthesis of metallacages and opens up a novel opportunity in the supramolecular field.

Synthesis of Carborane-Backbone Metallacycles for Highly Selective Capture of n-Pentane.

The specific recognition and separation of alkanes with similar molecular structures and close boiling points face significant scientific challenges and industrial demands. Here, rectangular carborane-based metallacycles were designed to selectively encapsulate n-pentane from n-pentane, iso-pentane, and cyclo-pentane mixtures in a simple-to-operate and more energy-efficient way. Metallacycle 1, bearing 1,2-di(4-pyridyl) ethylene, can selectively separate n-pentane from these three-component mixtures with a purity of 97%. The selectivity is ascribed to the capture of the preferred guest with matching size, C-H···π interactions, and potential B-Hδ-···Hδ+-C interactions. Besides, the removal of n-pentane gives rise to original guest-free carborane-based metallacycles, which can be recycled without losing performance. Considering the variety of substituted carborane derivatives, metal ions, and organic linkers, these new carborane-based supramolecular coordination complexes (SCCs) may be broadly applicable to other challenging recognition and separation systems with good performance.

Demonstration of an ultra-compact 8-channel sinusoidal silicon waveguide array for optical phased array.

Here we demonstrate an ultra-compact 8-channel sinusoidal silicon waveguide array for an optical phased array. In our device, based on sinusoidal bending, the cross talk (CT) between waveguides can be efficiently reduced with a waveguide pitch of only 695 nm. For the transverse electric (TE) mode, the simulation results show that the insertion loss (IL) of the 100-µm-long device is 0.1 dB and the CT between all waveguides is lower than -25 dB at 1550 nm. In the measurements, an IL of less than 1 dB and CT lower than -18 dB are obtained. Since the pitch is related to the beam-steering range and power consumption of the optical phased array, such an ultra-compact device could potentially be a good candidate to build the emitter for an energy-efficient optical phased array with a large field of view.

Steric-Effects-Directed B-H Bond Activation of para-Carboranes.

The controllable B-H bond activation of carboranes has long been a compelling challenge. However, as the symmetry of para-carborane places the same charge on all of its ten boron atoms, controlling the regiochemistry of B-H bond activation in these molecules has remained out of reach ever since their discovery. Herein, we describe how to use steric effects to achieve a regioselective process for B-H activation of para-carborane. In this strategy, B(2,8)-H or B(2,7)-H activation patterns were achieved by taking advantage of the π-π interactions between pyridine ligands. Interestingly, by employing host-guest interactions in metallacage compounds, B(2,8)-H bond activation could be avoided and exclusive B(2,9)-H bond activation can be achieved. Steric hindrance was also found to be beneficial for regioselective B(2,8)-H bond activation in metallacage species. In this work, we demonstrate that steric effects can be a promising driving force for controllable activation of the B-H bonds of carboranes and open new opportunities in this field.

P200 family protein IFI204 negatively regulates type I interferon responses by targeting IRF7 in nucleus.

Interferon-inducible p200 family protein IFI204 was reported to be involved in DNA sensing, and subsequently induces the production of type I interferons and proinflammatory mediators. However, its function in the regulation of antiviral innate immune signaling pathway remains unclear. Here we reported a novel role of IFI204 that specifically inhibits the IRF7-mediated type I interferons response during viral infection. IFI204 and other p200 family proteins are highly expressed in mouse hepatitis coronavirus-infected bone marrow-derived dendritic cells. The abundant IFI204 could significantly interact with IRF7 in nucleus by its HIN domain and prevent the binding of IRF7 with its corresponding promoter. Moreover, other p200 family proteins that possess HIN domain could also inhibit the IRF7-mediated type I interferons. These results reveal that, besides the positive regulation function in type I interferon response at the early stage of DNA virus infection, the interferon-inducible p200 family proteins such as IFI204 could also negatively regulate the IRF7-mediated type I interferon response after RNA virus infection to avoid unnecessary host damage from hyper-inflammatory responses.

Identification and characterization of a novel carboxylesterase EstQ7 from a soil metagenomic library.

A novel lipolytic gene, estq7, was identified from a fosmid metagenomic library. The recombinant enzyme EstQ7 consists of 370 amino acids with an anticipated molecular mass of 42 kDa. Multiple sequence alignments showed that EstQ7 contained a pentapeptide motif GHSMG, and a putative catalytic triad Ser174-Asp306-His344. Interestingly, EstQ7 was found to have very little similarity to the characterized lipolytic enzymes. Phylogenetic analysis revealed that EstQ7 may be a member of a novel family of lipolytic enzymes. Biochemical characterization of the recombinant enzyme revealed that it constitutes a slightly alkalophilic, moderate thermophilic and highly active carboxylesterase against short-chain fatty acid esters with optimum temperature 50 ℃ and pH 8.2. The Km and kcat values toward p-nitrophenyl acetate were determined to be 0.17 mM and 1910s-1, respectively. Moreover, EstQ7 was demonstrated to have acyltransferase activity by GC-MS analysis. Structural modeling of the three-dimensional structure of this new enzyme showed that it exhibits a typical α/ß hydrolase fold, and the catalytic triad residues are spatially close. Molecular docking revealed the interactions between the enzyme and the ligand. The high levels of lipolytic activity of EstQ7, combined with its moderate thermophilic property and acyltransferase activity, render this novel enzyme a promising candidate biocatalyst for food, pharmaceutical and biotechnological applications.

Hepatitis B virus-triggered PTEN/ß-catenin/c-Myc signaling enhances PD-L1 expression to promote immune evasion.

Hepatitis B virus (HBV) exploits multiple strategies to evade host immune surveillance. Programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling plays a critical role in regulating T cell homeostasis. However, it remains largely unknown as to how HBV infection elevates PD-L1 expression in hepatocytes. A mouse model of HBV infection was established by hydrodynamic injection with a vector containing 1.3-fold overlength HBV genome (pHBV1.3) via the tail vein. Coculture experiments with HBV-expressing hepatoma cells and Jurkat T cells were established in vitro. We observed significant decrease in the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and increase in ß-catenin/PD-L1 expression in liver tissues from patients with chronic hepatitis B and mice subjected to pHBV1.3 hydrodynamic injection. Mechanistically, decrease in PTEN enhanced ß-catenin/c-Myc signaling and PD-L1 expression in HBV-expressing hepatoma cells, which in turn augmented PD-1 expression, lowered IL-2 secretion, and induced T cell apoptosis. However, ß-catenin disruption inhibited PTEN-mediated PD-L1 expression, which was accompanied by decreased PD-1 expression, and increased IL-2 production in T cells. Luciferase reporter assays revealed that c-Myc stimulated transcriptional activity of PD-L1. In addition, HBV X protein (HBx) and HBV polymerase (HBp) contributed to PTEN downregulation and ß-catenin/PD-L1 upregulation. Strikingly, PTEN overexpression in hepatocytes inhibited ß-catenin/PD-L1 signaling and promoted HBV clearance in vivo. Our findings suggest that HBV-triggered PTEN/ß-catenin/c-Myc signaling via HBx and HBp enhances PD-L1 expression, leading to inhibition of T cell response, and promotes HBV immune evasion.NEW & NOTEWORTHY This study demonstrates that during HBV infection, HBV can increase PD-L1 expression via PTEN/ß-catenin/c-Myc signaling pathway, which in turn inhibits T cell response and ultimately promotes HBV immune evasion. Targeting this signaling pathway is a potential strategy for immunotherapy of chronic hepatitis B.

Metalloradicals Supported by a meta-Carborane Ligand.

In this work, a pincer-type complex [Cp*Ir-(SNPh)(SNHPh)(C2 B10 H9 )] (2) was synthesized and its reactivity studied in detail. Interestingly, molecular hydrogen can induce the transformation between the metalloradical [Cp*Ir-(SNPh)2 (C2 B10 H9 )] (5. ) and 2. A mixed-valence complex, [(Cp*Ir)2 -(SNPh)2 (C2 B10 H8 )] (7.+ ), was also synthesized by one-electron oxidation. Studies show that 7.+ is fully delocalized, possessing a four-centered-one-electron (S-Ir-Ir-S) bonding interaction. DFT calculations were also in good agreement with the experimental results.

Inhibition of hepatitis B virus replication by activation of the cGAS-STING pathway.

Cyclic GMP-AMP (cGAMP) synthase (cGAS) senses cytosolic DNA and catalyses synthesis of the second messenger cGAMP, which activates the downstream signalling adaptor protein STING, leading to the expression of type I interferons. Hepatitis B virus (HBV) is a small DNA virus, and the cGAS-STING pathway may inhibit HBV RNA synthesis and viral assembly in cell culture, but the exact roles of the cGAS pathway in the restriction of HBV replication in infection systems remain to be elucidated. In this study, replication of HBV was significantly inhibited both in cell culture and in vivo in a mouse model when the cGAS-STING pathway was activated by dsDNA or cGAMP. In contrast, the presence of enzymatically inactive cGAS mutant did not influence HBV replication. Moreover, knockdown of cGAS in human peripheral blood monocytes led to a higher level of intracellular HBV DNA. Collectively, our data indicate that the cGAS-STING pathway plays a role in the surveillance of HBV infection and may be exploited for development of novel anti-HBV strategies.

Interaction between anemia and hyperuricemia in the risk of all-cause mortality in patients with chronic kidney disease.

Aim: Both hyperuricemia and anemia are not only the manifestation of chronic kidney disease (CKD) but also related to its occurrence and development. A recent study has found that there was a synergetic effect between hyperuricemia and anemia on new-onset CKD. Herein we aimed to explore the roles of hyperuricemia and anemia in the all-cause mortality in patients with CKD. Methods: Data of adult patients with CKD were extracted from the National Health and Nutrition Examination Surveys (NHANES) database in 2009-2018 in this retrospective cohort study. Weighted univariate and multivariate COX regression analyses were used to investigate the associations of hyperuricemia and anemia with all-cause mortality, and the evaluation indexes were hazard ratios (HRs) and 95% confidence intervals (CIs). The interaction effect between hyperuricemia and anemia on the risk of all-cause mortality was assessed via relative excess risk due to interaction (RERI) and attributable proportion of interaction (AP). Subgroup analyses of age, gender, CVD, hypertension, DM, and cancer were also performed to assess this interaction effect. Results: Among 3,678 eligible patients, 819 died from all causes. After adjusting for covariables, we found that CKD patients with anemia (HR = 1.72, 95%CI: 1.42-2.09) or hyperuricemia (HR = 1.21, 95%CI: 1.01-11.45) had a higher risk of all-cause mortality. There was a potential synergetic effect between anemia and hyperuricemia on all-cause mortality, with RERI of 0.630 and AP of 0.291. Moreover, this synergetic effect was also observed in ≥65 years old (AP = 0.330), male (AP = 0.355), hypertension (AP = 0.736), non-hypertension (AP = 0.281), DM (AP = 0.371), and cancer (AP = 0.391) subgroups. Conclusion: A potential synergetic effect between anemia and hyperuricemia on all-cause mortality was found in patients with CKD. However, further studies are needed to clarify the causal relationship between them.

Prelimbic cortical pyramidal neurons to ventral tegmental area projections promotes arousal from sevoflurane anesthesia.

AIMS: General anesthesia has been used in surgical procedures for approximately 180 years, yet the precise mechanism of anesthetic drugs remains elusive. There is significant anatomical connectivity between the ventral tegmental area (VTA) and the prelimbic cortex (PrL). Projections from VTA dopaminergic neurons (VTADA ) to the PrL play a role in the transition from sevoflurane anesthesia to arousal. It is still uncertain whether the prelimbic cortex pyramidal neuron (PrLPyr ) and its projections to VTA (PrLPyr -VTA) are involved in anesthesia-arousal regulation. METHODS: We employed chemogenetics and optogenetics to selectively manipulate neuronal activity in the PrLPyr -VTA pathway. Electroencephalography spectra and burst-suppression ratios (BSR) were used to assess the depth of anesthesia. Furthermore, the loss or recovery of the righting reflex was monitored to indicate the induction or emergence time of general anesthesia. To elucidate the receptor mechanisms in the PrLPyr -VTA projection's impact on anesthesia and arousal, we microinjected NMDA receptor antagonists (MK-801) or AMPA receptor antagonists (NBQX) into the VTA. RESULTS: Our findings show that chemogenetic or optogenetic activation of PrLPyr neurons prolonged anesthesia induction and promoted emergence. Additionally, chemogenetic activation of the PrLPyr -VTA neural pathway delayed anesthesia induction and promoted anesthesia emergence. Likewise, optogenetic activation of the PrLPyr -VTA projections extended the induction time and facilitated emergence from sevoflurane anesthesia. Moreover, antagonizing NMDA receptors in the VTA attenuates the delayed anesthesia induction and promotes emergence caused by activating the PrLPyr -VTA projections. CONCLUSION: This study demonstrates that PrLPyr neurons and their projections to the VTA are involved in facilitating emergence from sevoflurane anesthesia, with the PrLPyr -VTA pathway exerting its effects through the activation of NMDA receptors within the VTA.

A new mechanism of therapeutic effect of stachydrine on heart failure by inhibiting myocardial ferroptosis.

Ferroptosis is a novel form of programmed cell death caused by iron-dependent lipid peroxidation and excessive production of ROS. Its morphology is characterized by mitochondrial atrophy, increased mitochondrial membrane density, mitochondrial cristae degeneration and rupture, and unchanged nuclear morphology. Here, we investigated whether a bioactive constituent extracted from the Chinese herb Leonurus japonicus Houtt. (Yimucao), stachydrine, could improve cardiac function by inhibiting myocardial ferroptosis. We found significant morphological features of ferroptosis in a TAC-induced mouse model of heart failure, in which increased lipid peroxidation in cardiac tissue was accompanied by abnormalities in cystine metabolism as well as iron metabolism. The contractile function of adult mouse cardiomyocytes was severely reduced after the occurrence of erastin-induced ferroptosis. We found that in heart failure mice and erastin-induced cardiomyocyte ferroptosis models, stachydrine significantly improved myocardial function, improving mitochondrial morphological features of ferroptosis and associated signaling pathway alterations, including lipid peroxidation levels, cystine metabolism, and iron metabolism. The results of studies on stachydrine provides new inspirations for the treatment of cardiac ferroptosis and chronic heart failure.

Fabrication and characterizations of Zn-doped SnO2-Ti4O7 anode for electrochemical degradation of hexafluoropropylene oxide dimer acid and its homologues.

Hexafluoropropylene oxide dimer acid (HFPO-DA) and its homologues, as perfluorinated ether alkyl substances with strong antioxidant properties, have rarely been reported by electrooxidation processes to achieve good results. Herein, we report the use of an oxygen defect stacking strategy to construct Zn-doped SnO2-Ti4O7 for the first time and enhance the electrochemical activity of Ti4O7. Compared with the original Ti4O7, the Zn-doped SnO2-Ti4O7 showed a 64.4% reduction in interfacial charge transfer resistance, a 17.5% increase in the cumulative rate of •OH generation, and an enhanced oxygen vacancy concentration. The Zn-doped SnO2-Ti4O7 anode exhibited high catalytic efficiency of 96.4% for HFPO-DA within 3.5 h at 40 mA/cm2. Hexafluoropropylene oxide trimer and tetramer acid exhibit more difficult degradation due to the protective effect of the -CF3 branched chain and the addition of the ether oxygen atom leading to a significant increase in the C-F bond dissociation energy. The degradation rates of 10 cyclic degradation experiments and the leaching concentrations of Zn and Sn after 22 electrolysis experiments demonstrated the good stability of the electrodes. In addition, the aqueous toxicity of HFPO-DA and its degradation products was evaluated. This study analyzed the electrooxidation process of HFPO-DA and its homologues for the first time, and provided some new insights.

Vascularized nanocomposite hydrogel mechanically reinforced by polyelectrolyte-modified nanoparticles.

Vascularization plays an important role in the initial stage of triggering bone defect repair. The combination of bioactive small molecule drugs and biomaterials has been a powerful strategy for vascularization in bone tissue engineering. In this study, an in situ crosslinked aldehyde hyaluronic acid (AHA)/N,O-carboxymethyl chitosan (NOCC) nanocomposite hydrogel doped with sphingosine 1-phosphate (S1P)-loaded polyelectrolyte-modified mesoporous silica nanoparticles (MSNs) was developed. The alginate/chitosan polyelectrolyte-modified MSNs (MSNs-ALG/CHI) were prepared via the electrostatic interaction. The incorporation of MSNs-ALG/CHI not only achieved a sustained release profile of the angiogenic drug, but also improved the mechanical property of the AHA/NOCC hydrogel due to the Schiff base reaction between the amino group in chitosan and the aldehyde group in AHA. In addition, in vitro cell experiments demonstrated that the nanocomposite hydrogel provided favorable support for cell adhesion and proliferation, and the S1P-loaded nanocomposite hydrogel was able to recruit endothelial cells. More importantly, the chicken chorioallantoic membrane (CAM) assay confirmed that the S1P-loaded nanocomposite hydrogel could significantly enhance capillary formation. More cell infiltration and better angiogenesis in the S1P loaded nanocomposite hydrogel were observed compared to the group without S1P loading after being implanted subcutaneously for 2 weeks. Furthermore, the subcutaneous implantation experiment further demonstrated that the incorporation of the S1P-loaded nanocomposite hydrogel could improve the tissue infiltration and new vessel formation within the macroporous poly(L-lactic acid)/polycaprolactone scaffold. Our results suggest that the nanocomposite hydrogel will be an excellent drug delivery system and the S1P-loaded nanocomposite hydrogel has great potential for vascularized bone regeneration application.

Regioselective B(3)-H bond activation based on an o-carboranyl dithiocarboxylate ligand and its derivatives.

Herein, we describe the synthesis of tetraphenylphosphonium o-carboranyl dithiocarboxylate (Ligand 1) and methyldithiocarboxyl-o-carborane (Ligand 2). The complexes [Cp*M(o-C2B10H11CS2)Cl] (M = Ir (3); Rh (4)) and [Cp*M(o-C2B10H11CS2)2] (M = Ir (5); Rh (6)) have been synthesized based on Ligand 1. The selective B-H bond activation of Ligand 2 has also been explored, leading to the synthesis of the B-H activated complex [Cp*Ir(o-C2B10H10CS2CH3)Cl] (7) and four of its substituted derivatives (8, 9, 10 and 11). All of these compounds have been characterised through single-crystal X-ray diffraction, NMR, IR spectroscopy and elemental analysis.

Transition metal-mediated B(4)-H hydroxylation/halogenation of o-carboranes bearing a 2-pyridylsulfenyl ligand.

The introduction of the 2-pyridylsulfenyl directing group to o-carboranes allowed either B(3)-Ir or B(4)-Ir bond formation using a steric effect strategy. Moreover, the reactivity of the B(4)-Rh o-carborane complexes with small molecules was probed by reactions with N-bromosuccinimide, N-iodosuccinimide and O2. Rhodium-mediated B(4)-hydroxylation and B(4)-halogenation which are seldom reported have been achieved under practical and mild conditions.

Stachytine Hydrochloride Improves Cardiac Function in Mice with ISO-Induced Heart Failure by Inhibiting the α-1,6-Fucosylation on N-Glycosylation of ß1AR.

Background: Cardiovascular diseases have become a major public health problem that seriously threatens human health. The cumulative effects of various cardiovascular events will eventually develop into chronic heart insufficiency and even heart failure, and the ß1 adrenergic receptor signal pathway plays an important role in this process. Stachytine hydrochloride is the main active ingredient of Yimucao, which is a traditional Chinese medicine used to treat gynecological diseases. Modern studies have found that stachytine hydrochloride has a good cardioprotective effect, but it is still unclear whether stachytine hydrochloride has an effect on the ß1 adrenergic receptor signal pathway. The purpose of this study is to explore the effect of stachytine hydrochloride on the ß1 adrenergic receptor signal pathway. Method: In this study, a continuous infusion of isoproterenol (40 mg/kg/day) was administered to mice and ventricular myocytes explored the potential mechanism of stachytine hydrochloride (12 mg/kg/day) on the ß1 adrenergic receptor signal pathway in the heart. Evaluate changes in cardiac morphology and function by echocardiography, cardiac hemodynamics, and histological methods, and detect molecular changes by Western blot and immunofluorescence. Treat primary cultured adult mouse or neonatal rat ventricular myocytes with or without isoproterenol (0.1 µMol), PNGase F (10-2 units/ml), and stachytine hydrochloride (10 µMol) at different time points. Detect α-1,6-fucosylation on N-glycosylation, calcium transient, contraction, and relaxation function and related signals. Results: Stachytine hydrochloride reduces cardiac remodeling and modulates hemodynamic parameters during chronic ß1 adrenergic receptor activation in vivo. The N-glycosylation of ß1 adrenergic receptors decreased after continuous isoproterenol stimulation, while stachytine hydrochloride can increase the N-glycosylation of ß1AR in the heart of mice with isoproterenol-induced heart failure. Decreased N-glycosylation of ß1 adrenergic receptors will downregulate the cAMP/PKA signal pathway and inhibit myocardial excitation and contraction coupling. Stachytine hydrochloride significantly reduced isoproterenol-induced cardiac N-linked glycoproteins with α-1,6-fucosylation. Conclusion: Our results show that stachytine hydrochloride inhibits the synthesis of α-1,6-fucosylation on the N-terminal sugar chain by reducing α-1,6-fucosyltransferase (FUT8) and α-1,3-mannosyl-glycoprotein 4-ß-N-acetylglucosaminyltransferase A (MGAT4a), upregulating the N-glycosylation level on ß1 adrenergic receptors, and maintaining cAMP/PKA signal pathway activation.

A novel selective autophagy receptor, CCDC50, delivers K63 polyubiquitination-activated RIG-I/MDA5 for degradation during viral infection.

Autophagy is a conserved process that delivers cytosolic substances to the lysosome for degradation, but its direct role in the regulation of antiviral innate immunity remains poorly understood. Here, through high-throughput screening, we discovered that CCDC50 functions as a previously unknown autophagy receptor that negatively regulates the type I interferon (IFN) signaling pathway initiated by RIG-I-like receptors (RLRs), the sensors for RNA viruses. The expression of CCDC50 is enhanced by viral infection, and CCDC50 specifically recognizes K63-polyubiquitinated RLRs, thus delivering the activated RIG-I/MDA5 for autophagic degradation. The association of CCDC50 with phagophore membrane protein LC3 is confirmed by crystal structure analysis. In contrast to other known autophagic cargo receptors that associate with either the LIR-docking site (LDS) or the UIM-docking site (UDS) of LC3, CCDC50 can bind to both LDS and UDS, representing a new type of cargo receptor. In mouse models with RNA virus infection, CCDC50 deficiency reduces the autophagic degradation of RIG-I/MDA5 and promotes type I IFN responses, resulting in enhanced viral resistance and improved survival rates. These results reveal a new link between autophagy and antiviral innate immune responses and provide additional insights into the regulatory mechanisms of RLR-mediated antiviral signaling.

The Ubiquitin E3 Ligase Parkin Inhibits Innate Antiviral Immunity Through K48-Linked Polyubiquitination of RIG-I and MDA5.

Innate immunity is the first-line defense against antiviral or antimicrobial infection. RIG-I and MDA5, which mediate the recognition of pathogen-derived nucleic acids, are essential for production of type I interferons (IFN). Here, we identified mitochondrion depolarization inducer carbonyl cyanide 3-chlorophenylhydrazone (CCCP) inhibited the response and antiviral activity of type I IFN during viral infection. Furthermore, we found that the PTEN-induced putative kinase 1 (PINK1) and the E3 ubiquitin-protein ligase Parkin mediated mitophagy, thus negatively regulating the activation of RIG-I and MDA5. Parkin directly interacted with and catalyzed the K48-linked polyubiquitination and subsequent degradation of RIG-I and MDA5. Thus, we demonstrate that Parkin limits RLR-triggered innate immunity activation, suggesting Parkin as a potential therapeutic target for the control of viral infection.