Magterpenes A-C: Three Meroterpenoids with an Unprecedented 6/6/6/6/6 Polycyclic Skeleton Extracted from Magnolia officinalis Rehd. et Wils.

Magterpenes A-C (1-3), three unprecedented meroterpenoids featuring a unique 6/6/6/6/6 polycyclic skeleton, were isolated from the ethanol extract of Magnolia officinalis Rehd. et Wils. The compounds were obtained as racemic mixtures that were completely resolved through chiral columns. Their structures were elucidated by extensive analyses of one-dimensional (1D) and 2D nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, chemical calculations of 1H/13C NMR, and electronic circular dichroism calculations. The compounds were constructed via two Diels-Alder reactions in the proposed biosynthetic pathway. All isolates were evaluated for their nephroprotective and hepatoprotective activities. The results demonstrated that (+)-1 and (-)-1 possessed promising nephroprotective activities in a dose-dependent manner, while (-)-2 and (+)-3 exhibited moderate hepatoprotective activities.

Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial.

BACKGROUND: Transvaginal oocyte retrieval is frequently followed by adverse events related to anesthesia and the procedure. Some research showed that transcutaneous electrical acupoint stimulation (TEAS) can relieve intraoperative pain and postoperative nausea. OBJECTIVE: This study examined whether TEAS can alleviate pain and relieve adverse symptoms after oocyte retrieval. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Altogether 128 patients were randomly divided into the TEAS group and the mock TEAS group. The two groups received a 30-minute-long TEAS or mock TEAS treatment that began 30 min after oocyte retrieval. MAIN OUTCOME MEASURES: The primary outcome was the visual analog scale (VAS) pain score. Secondary outcomes were pressure pain threshold, McGill score, pain rating index (PRI), present pain intensity (PPI), VAS stress score, VAS anxiety score, and postoperative adverse symptoms. RESULTS: The baseline characteristics of the two groups were comparable (P > 0.05). The VAS pain scores of the TEAS group were lower than those of the mock TEAS group at 60 and 90 min after oocyte retrieval (P < 0.05). The McGill score, PRI and PPI in the TEAS group were significantly lower than those in the control group at 60 min after oocyte retrieval (P < 0.05). However, the two groups had equivalent beneficial effects regarding the negative emotions, such as nervousness and anxiety (P > 0.05). The TEAS group was superior to the mock TEAS group for relieving postoperative adverse symptoms (P < 0.05). CONCLUSION: TEAS treatment can relieve postoperative pain and postoperative adverse symptoms for patients undergoing oocyte retrieval. Please cite this article as: Liu LY, Su Y, Wang RR, Lai YY, Huang L, Li YT, Tao XY, Su MH, Zheng XY, Huang SC, Wu YN, Yu SY, Liang FR, Yang J. Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial. J Integr Med. 2024; 22(1): 32-38.

Sprayable chitosan nanogel with nitric oxide to accelerate diabetic wound healing through bacteria inhibition, biofilm eradication and macrophage polarization.

Bacterial infection and chronic inflammation are two major risks in diabetic wound healing, which increase patient mortality. In this study, a multifunctional sprayable nanogel (Ag-G@CS) based on chitosan has been developed to synergistically inhibit bacterial infection, eradicate biofilm, and relieve inflammation of diabetic wounds. The nanogel is successfully crafted by encapsulating with a nitric oxide (NO) donor and performing in-situ reduction of silver nanoparticles (Ag). The released NO enhances the antibacterial efficacy of Ag, nearly achieving complete eradication of biofilms in vitro. Upon application on both normal or diabetic chronic wounds, the combination effects of released NO and Ag offer a notable antibacterial effect. Furthermore, after bacteria inhibition and biofilm eradication, the NO released by the nanogel orchestrates a transformation of M1 macrophages into M2 macrophages, significantly reducing tumor necrosis factor α (TNF-α) release and relieving inflammation. Remarkably, the released NO also promotes M2a to M2c macrophages, thereby facilitating tissue remodeling in chronic wounds. More importantly, it upregulates the expression of vascular endothelial growth factor (VEGF), further accelerating the wound healing process. Collectively, the formed sprayable nanogel exhibits excellent inhibition of bacterial infections and biofilms, and promotes chronic wound healing via inflammation resolution, which has excellent potential for clinical use in the future.

Dietary choline activates the Ampk/Srebp signaling pathway and decreases lipid levels in Pacific white shrimp (Litopenaeus vannamei).

An 8-week feeding trial was conducted in Pacific white shrimp (Litopenaeus vannamei) to evaluate the effects of dietary choline supplementation on choline transport and metabolism, hepatopancreas histological structure and fatty acid profile, and regulation of lipid metabolism. Six isonitrogenous and isolipidic diets were formulated to contain different choline levels of 2.91 (basal diet), 3.85, 4.67, 6.55, 10.70 and 18.90 g/kg, respectively. A total of 960 shrimp (initial weight, 1.38 ± 0.01 g) were distributed randomly into twenty-four 250-L cylindrical fiber-glass tanks, with each diet assigned randomly to 4 replicate tanks. The results indicated that dietary choline significantly promoted the deposition of choline, betaine and carnitine (P < 0.05). The diameters and areas of R cells, total lipid and triglyceride contents in hepatopancreas, and triglyceride and non-esterified fatty acid contents in hemolymph were negatively correlated with dietary choline level. The contents of functional fatty acids in hepatopancreas, the activity of acetyl-CoA carboxylase (Acc), and the mRNA expression of fas, srebp and acc were highest in shrimp fed the diet containing 4.67 g/kg choline, and significantly higher than those fed the diet containing 2.91 g/kg, the lowest level of choline (P < 0.05). The number of R cells, content of very low-density lipoprotein (VLDL), activities of carnitine palmitoyl-transferase (Cpt1), lipoprotein lipase and hepatic lipase, and the mRNA expression levels of cpt1, fabp, fatp, ldlr, and ampk in hepatopancreas increased significantly as dietary choline increased (P < 0.05). In addition, hepatopancreas mRNA expression levels of ctl1, ctl2, oct1, badh, bhmt, ck, cept, and cct were generally up-regulated as dietary choline level increased (P < 0.01). In conclusion, dietary choline promoted the deposition of choline and its metabolites by up-regulating genes related to choline transport and metabolism. Moreover, appropriate dietary choline level promoted the development of hepatopancreas R cells and maintained the normal accumulation of lipids required for development, while high dietary choline not only promoted hepatopancreas lipid export by enhancing VLDL synthesis, but also promoted fatty acid ß-oxidation and inhibited de novo fatty acid synthesis by activating the Ampk/Srebp signaling pathway. These findings provided further insight and understanding of the mechanisms by which dietary choline regulated lipid metabolism in L. vannamei.

Copper-induced injectable hydrogel with nitric oxide for enhanced immunotherapy by amplifying immunogenic cell death and regulating cancer associated fibroblasts.

BACKGROUND: Immunogenic cell death (ICD) induced by different cancer treatments has been widely evaluated to recruit immune cells and trigger the specific antitumor immunity. However, cancer associated fibroblasts (CAFs) can hinder the invasion of immune cells and polarize the recruited monocytes to M2-type macrophages, which greatly restrict the efficacy of immunotherapy (IT). METHODS: In this study, an injectable hydrogel induced by copper (Cu) has been designed to contain antibody of PD-L1 and nitric oxide (NO) donor. The therapeutic efficacy of hydrogel was studied in 4T1 cells and CAFs in vitro and 4T1 tumor-bearing mice in vivo. The immune effects on cytotoxic T lymphocytes, dendritic cells (DCs) and macrophages were analyzed by flow cytometry. Enzyme-linked immunosorbent assay, immunofluorescence and transcriptome analyses were also performed to evaluate the underlying mechanism. RESULTS: Due to the absorbance of Cu with the near-infrared laser irradiation, the injectable hydrogel exhibits persistent photothermal effect to kill cancer cells. In addition, the Cu of hydrogel shows the Fenton-like reaction to produce reactive oxygen species as chemodynamic therapy, thereby enhancing cancer treatment and amplifying ICD. More interestingly, we have found that the released NO can significantly increase depletion of CAFs and reduce the proportion of M2-type macrophages in vitro. Furthermore, due to the amplify of ICD, injectable hydrogel can effectively increase the infiltration of immune cells and reverse the immunosuppressive tumor microenvironment (TME) by regulating CAFs to enhance the therapeutic efficacy of anti-PD-L1 in vivo. CONCLUSIONS: The ion induced self-assembled hydrogel with NO could enhance immunotherapy via amplifying ICD and regulating CAFs. It provides a novel strategy to provoke a robust antitumor immune response for clinical cancer immunotherapy.

Nicotine in Complex Samples: Recent Updates on the Pretreatment and Analysis Method.

Nicotine is a significant evaluation index of tobacco and its related products' quality, but nicotine overdose can pose serious health hazards and cause addiction and dependence, thus it can be seen that it is necessary to find suitable and efficient detection methods to precisely detect nicotine in diverse samples and complex matrices. In this review, an updated summary of the latest trends in pretreatment and analytical techniques for nicotine is provided. We reviewed various sample pretreatment methods, such as solid phase extraction, solid phase microextraction, liquid phase microextraction, QuEChERS, etc., and diverse nicotine assay methods including liquid chromatography, gas chromatography, electrochemical sensors, etc., focusing on the developments since 2015. Furthermore, the recent progress in the applications and applicability of these techniques as well as our prospects for future developments are discussed.HighlightsUpdated pretreatment and analysis methods of nicotine were systematically summarized.Microextraction and automation were main development trends of nicotine pretreatment.The introduction of novel materials added luster to nicotine pretreatment.The evolutions of ion source and mass analyzer were emphasized.

Polydopamine-coated thalidomide nanocrystals promote DSS-induced murine colitis recovery through Macrophage M2 polarization together with the synergistic anti-inflammatory and anti-angiogenic effects.

High levels of proinflammatory cytokines, macrophage polarization status and immune-mediated angiogenesis play pivotal roles in the pathogenesis of inflammatory bowel disease (IBD). Thalidomide, an anti-inflammatory, immunomodulatory and antiangiogenic agent, is used off-label for treatment of IBD. The therapeutic potential of thalidomide is limited by its poor solubility and side effects associated with its systemic exposure. To address these issues and promote its therapeutic effects on IBD, thalidomide nanocrystals (Thali NCs) were prepared and coated with polydopamine (PDA), a potential macrophage polarization modulator, to form PDA coated Thali NCs (Thali@PDA). Thali@PDA possessed a high drug loading and displayed average particle size of 764.7 ± 50.30 nm. It showed a better anti-colitis effect than bare thalidomide nanocrystals at the same dose of thalidomide. Synergistic effects of polydopamine on anti-inflammatory and anti-angiogenic activities of thalidomide were observed. Furthermore, PDA coating could direct polarization of macrophages towards M2 phenotype, which boosted therapeutic effects of Thali@PDA on IBD. Upon repeated dosing of Thali@PDA for one week, symptoms of IBD in mice were significantly relieved, and histomorphology of the colitis colons were normalized. Key proinflammatory cytokine levels in the inflamed intestines were significantly decreased. Toxicity study also revealed that Thali@PDA is a safe formulation.

Dietary choline promotes growth, antioxidant capacity and immune response by modulating p38MAPK/p53 signaling pathways of juvenile Pacific white shrimp (Litopenaeus vannamei).

The objective of the present study was to evaluate the effects of dietary choline levels on growth performance, antioxidant capacity, innate immunity and hemocyte apoptosis of Litopenaeus vannamei. Six isonitrogenous and isolipidic diets were formulated to contain different choline levels: 2.91 (basal diet), 3.85, 4.67, 6.55, 10.70 and 18.90 g kg-1choline, respectively. The results indicated that shrimp fed diet with 4.67 g kg-1 choline had the highest final body weight (FBW), percent weight gain (PWG), specific growth rate (SGR), feed efficiency (FE), and activities of alkaline phosphatase (AKP) and phenoloxidase (PO) in hemolymph among all treatments. Shrimp fed diet with 18.90 g kg-1 choline exhibited significantly lower crude lipid in hepatopancreas than those fed diets with 2.91, 3.85, 4.67 and 6.55 g kg-1 choline (P < 0.05). The concentration of reactive oxygen species (ROS) and apoptosis rate in hemocytes significantly decreased with the increase of dietary choline levels (P < 0.05). Shrimp fed diets with 6.55, 10.70 and 18.90 g kg-1 choline had significantly higher scavenging ability of hydroxyl radical (SAHR) and total antioxidant capacity (T-AOC) in hemolymph than those fed diet with 2.91 g kg-1 choline (P < 0.05). Dietary choline supplementation down-regulated the expression of genes related to apoptosis such as caspase-1, caspase-3, caspase-8, p53, and p38MAPK in hemocytes (P < 0.05), while up-regulated the expression of anti-apoptosis gene bcl2 in hemocytes (P < 0.05). Overall, the results of the present study demonstrated that appropriate dietary choline could improve growth performance and feed utilization, enhance antioxidant capacity and innate immunity, and mitigate apoptosis in Litopenaeus vannamei. Moreover, the inhibition of hemocyte apoptosis by dietary choline may be regulated by the p38MAPK-p53 signaling pathway.

Ku proteins promote DNA binding and condensation of cyclic GMP-AMP synthase.

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that plays a critical role in regulating antiviral signaling. cGAS binds to DNA and catalyzes the synthesis of cyclic GMP-AMP (cGAMP), which is essential for downstream signal transduction. The antiviral response is a rapid biological process; however, cGAS itself has relatively low DNA binding affinity, implying that formation of the cGAS-DNA complex requires an additional factor(s) that promotes cGAS-DNA binding, allowing efficient antiviral signal transduction. Here, we report that the Ku proteins (Ku80 and Ku70) directly interact with cGAS and positively regulate cGAS-mediated antiviral signaling. Mechanistically, we find that the interaction of the Ku proteins with cGAS significantly increases the DNA-binding affinity of cGAS and promotes cGAS condensation in the cytosol, thereby enhancing cGAS catalytic activity. Our results show that the Ku proteins are critical partners of cGAS in sensing DNA virus infection and ensuring efficient innate immune signal transduction.

Tumor immunotherapy boosted by R837 nanocrystals through combining chemotherapy and mild hyperthermia.

Melanoma is a malignant skin cancer that is prone to metastasis in the early stage and has a poor prognosis. Immunomodulatory therapy for melanoma has been a hot research topic in recent years. However, low immune cell infiltration and loss of tumor immunogenicity may occur in tumors, resulting in low response rates to immunotherapy. Thus, immunomodulatory therapy is usually used in combination with chemotherapy and radiotherapy. Development of combined therapeutic strategies with low systemic toxicity, high immune responsiveness and long-term inhibition of metastasis and recurrence of melanoma is the goal of current research. In this study, the insoluble immune adjuvant imiquimod (R837) was prepared as nanocrystals and coated with polydopamine (PDA) to form R837@PDA, which was then loaded into chitosan hydrogel (CGP) to form the drug-loaded gel system, R837@PDA@CGP (RPC), to combine immunomodulation effects, induction of immunogenic cell death (ICD) effects and immune-enhancement effects. After treatment with RPC, ICD in melanoma was induced, and the infiltration rate of cytotoxic T cells (CTLs) in melanoma was also significantly enhanced, which turned the tumor itself into an in situ vaccine and boosted the cancer-immunity cycle at the tumor site. Therefore, melanoma growth, metastasis and recurrence were notably inhibited.

Electron probe microanalysis of the elemental composition of phytoliths from woody bamboo species.

Electron probe microanalysis (EPMA) is promising for accurately determining elemental components in micro-areas of individual phytolith particles, interpreting compositional features and formation mechanisms of phytoliths in plants, identifying archeological and sedimental phytolith. However, the EPMA method of analyzing mounted slide phytoliths has not well been defined. In this study, we attempted different EPMA methods to determine the elemental compositions of phytoliths in mounted slides. Direct analysis of carbon (DAC) with other elements in phytolith could obtain abnormally high total values and carbon values. The method of carbon excluded in measuring elements (non-carbon analysis (NCA)) was feasible to obtain elemental compositions in phytolith. The NCA method was conducive to obtain the factual elemental compositions of an individual phytolith (morphotype) when the carbon content of phytolith was relatively low. The EPMA results of phytoliths from 20 bamboo species (three genera) showed that phytolith was dominantly composed of SiO2 but also included low contents of diverse other elements. The EPMA of phytoliths can provide the elemental composition of micro-areas of an individual phytolith particle. The elemental compositions of phytolith varied with their morphotypes, the genera and ecotype of bamboos. The EPMA of elemental compositions in phytoliths is a potential tool to study the formation mechanism of phytoliths, plant taxonomical identification, archaeological and paleoenvironmental reconstruction.

Dietary vitamin K3 activates mitophagy, improves antioxidant capacity, immunity and affects glucose metabolism in Litopenaeus vannamei.

An 8-week feeding experiment was conducted to appraise the influence of dietary vitamin K3 on the growth performance, antioxidant capacities, immune responses, mitophagy and glucose metabolism in Litopenaeus vannamei. Six diets containing graded dietary vitamin K3 (0.40(control), 9.97, 20.29, 39.06, 79.81 and 156.02 mg kg-1 of vitamin K3, respectively) levels were formulated. A total of 900 shrimp with 0.90 g initial weight were randomly assigned to six diets with three replications. Our results revealed that diets supplemented with 9.97-156.02 mg kg-1 vitamin K3 didn't affect the growth performance in L. vannamei. In general, compared with the control group, 39.06 mg kg-1 vitamin K3 group significantly increased (P < 0.05) the total antioxidative capacity, and the activities of catalase, glutathione, nitric oxide synthase, alkaline phosphatase and acid phosphatase in serum and hepatopancreas. 39.06 mg kg-1 vitamin K3 group significantly decreased (P < 0.05) the malondialdehyde in serum and hepatopancreas. The mRNA levels of antioxidant and immune related genes were increased synchronously (P < 0.05). In addition, 39.06 mg kg-1 vitamin K3 group increased glycogen content and levels of mitophagy (pink1, ampkα, parkin, lc3, atg13, atg12) genes. Expression levels of glucose transport related gene (glut1), glycolysis related genes (hk, pfk), glycogen synthesis related genes (gsk-3ß, gys), insulin-like peptides (ILPs)/AKT/PI3K pathway related genes (insr, irsl, akt, pi3k, pdpk1) were increased in the hepatopancreas of 39.06 mg kg-1 vitamin K3 group. In conclusion, the present results indicated that although dietary supplementing vitamin K3 had no influence on the growth performance, 39.06 mg kg-1 vitamin K3 could activate ampkα/pink1/parkin mediated mitophagy, improve antioxidant capacity and immune response. Moreover, vitamin K3 could trigger ILPs/AKT/PI3K signaling pathways and influence glucose metabolism in L. vannamei. This finding would help to advance the field of vitamin K3 nutrition and guide the development of future crustacean feeds.

Excess iron supplementation induced hepatopancreas lipolysis, destroyed intestinal function in Pacific white shrimp Litopenaeus vannamei.

So far, the adverse effects of excess Fe in shrimp have been ignored for years as it was thought that extra Fe supplementation was not needed in the practical diets. Nowadays, Fe concentration in commercial shrimp feed from feed enterprises could be around 301.34-545.5 mg/kg, which is mainly due to the fish meal containing up to 1500 mg/kg Fe. Therefore, the purpose of this experiment was to investigate the effects of Fe supplementation on the growth performance, tissue Fe deposition, hepatopancreas lipid metabolism, intestinal function in L. vannamei. The results showed that although growth performance was not influenced by the dietary Fe supplementation, excess Fe supplementation (955.00 mg/kg) significantly increased hepatopancreas Fe deposition and induced lipolysis. Moreover, excess Fe supplementation impaired intestinal immune function and disrupted microbiota homeostasis. These findings might provide partial theoretical evidence for the effect of dietary Fe supplementation on physiological metabolism in L. vannamei.

Effects of dietary vitamin D3 supplementation on the growth performance, tissue Ca and P concentrations, antioxidant capacity, immune response and lipid metabolism in Litopenaeus vannamei larvae.

An 8-week feeding trial was conducted to investigate the effects of dietary vitamin D3 supplementation on the growth performance, tissue Ca and P concentrations, antioxidant capacity, immune response and lipid metabolism in Litopenaeus vannamei larvae. A total of 720 shrimp (initial weight 0·50 ± 0·01 g) were randomly distributed into six treatments, each of which had three duplicates of forty shrimp per duplicate. Six isonitrogenous and isolipidic diets were formulated to contain graded vitamin D3 (0·18, 0·23, 0·27, 0·48, 0·57 and 0·98 mg/kg of vitamin D3, measured) supplementation levels. The results revealed that L. vannamei fed diet containing 0·48 mg/kg of vitamin D3 achieved the best growth performance. Compared with the control group, supplementing 0·48 mg/kg of vitamin D3 significantly increased (P < 0·05) the activities of catalase, total antioxidative capacity, alkaline phosphatase and acid phosphatase in serum and hepatopancreas. Expression levels of antioxidant and immune-related genes were synchronously increased (P < 0·05). Carapace P and Ca concentrations were increased (P < 0·05) with the increased vitamin D3 supplementation levels. Further analysis of lipid metabolism-related genes expression showed that shrimp fed 0·48 mg of vitamin D3 per kg diet showed the highest value in the expression of lipid synthesis-related genes, while shrimp fed 0·98 mg of vitamin D3 per kg diet showed the highest value in the expression of lipolysis-related genes. In conclusion, the results of present study indicated that dietary supplementation of 0·48 mg/kg of vitamin D3 could increase Ca and P concentrations, improve antioxidant capacity and immune response, and influence lipid metabolism in L. vannamei.

Dietary chromium modulates glucose homeostasis and induces oxidative stress in Pacific white shrimp (Litopenaeus vannamei).

While chromium (Cr) has been recognized as an essential nutrient for all animals, and dietary supplementation can be beneficial, it can also be toxic. The present study aimed to investigate the contrasting effects of dietary chromium in Pacific white shrimp Litopenaeus vannamei. Five experimental diets were formulated to contain Cr at levels of 0.82 (Cr0.82, unsupplemented diet), 1.01 (Cr1.01), 1.22 (Cu1.22), 1.43 (Cr1.43) and 1.63 (Cr1.63) mg/kg and were fed to shrimp for 8 weeks. Highest weight gain was recorded in shrimp fed the diet containing 1.22 mg/kg Cr. Shrimp fed the diet containing the highest level of Cr (1.63 mg/kg) showed the lowest weight gain and clear signs of oxidative stress and apoptosis as evidenced by higher levels of H2O2, malondialdehyde and 8-hydroxydeoxyguanosine, and expression of caspase 2, 3, 5, and lower contents of total and oxidized glutathione, and expression of Cu/Zn sod, cat, gpx, mt, bcl2. Chromium supplementation promoted glycolysis and inhibited gluconeogenesis as shown by increased activities of hexokinase, phosphofructokinase and pyruvate kinase, and reduced activity of phosphoenolpyruvate carboxykinase in shrimp fed the diet containing 1.43 mg/kg Cr. Shrimp fed the diet with 1.63 mg/kg Cr had lowest contents of crustacean hyperglycemic hormone and insulin like peptide in hemolymph. Expression of genes involved in insulin signaling pathway and glycose metabolism including insr, irs1, pik3ca, pdpk1, akt, acc1, gys, glut1, pk, hk were up-regulated, and foxO1, gsk-3ß, g6pc, pepck were down-regulated in shrimp fed the diets supplemented with Cr. This study demonstrated that optimum dietary supplementation of Cr had beneficial effects on glucose homeostasis and growth, whereas excess caused oxidative damage and impaired growth. The results contribute to our understanding of the biological functions of chromium in shrimp.

USP27X negatively regulates antiviral signaling by deubiquitinating RIG-I.

RIG-I plays important roles in pathogen sensing and activation of antiviral innate immune responses in response to RNA viruses. RIG-I-mediated signaling must be precisely controlled to maintain innate immune signaling homeostasis. Previous studies demonstrated that lysine 63 (K63)-linked polyubiquitination of RIG-I is vital for its activation, but the mechanisms through which RIG-I is deubiquitinated to control innate immune responses are not well understood. Here we identified USP27X as a negative regulator of antiviral signaling in response to RNA viruses through siRNA library screening. Further functional studies indicated that USP27X negatively modulated RIG-I-mediated antiviral signaling in a deubiquitinase-dependent manner. Mechanistically, we found that USP27X removed K63-linked polyubiquitin chains from RIG-I to negatively modulate type I interferon signaling. Collectively, these studies uncover a novel negative regulatory role of USP27X in targeting RIG-I to balance innate immune responses.