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  • 1
    In: Journal of Virology, American Society for Microbiology, Vol. 97, No. 1 ( 2023-01-31)
    Abstract: Type I interferon (IFN) response is the first line of host-based innate immune defense against viral infections. However, viruses have developed multiple strategies to counter host IFN responses, so they may continue infecting hosts via effective replication. Avian reovirus (ARV), an RNA virus, causes viral arthritis or tenosynovitis in chickens. Previous studies have shown that ARV is highly resistant to the antiviral effects of IFN. However, the underlying mechanisms that enable ARV to block the IFN pathway remain unclear. In this study, we found that ectopic expression of ARV protein, σA, significantly inhibited the production of IFN-β induced by melanoma-differentiation-associated gene 5 (MDA5) and poly(I·C). Knockdown of σA during ARV infection enhances the IFN-β response and suppresses viral replication. ARV σA inhibited the MDA5-mediated IFN-β activation by targeting interferon regulatory factor 7 (IRF7). Further studies demonstrated that σA interacts with IRF7, thereby blocking IRF7 dimerization and nuclear translocation, finally leading to the inhibition of IFN-β production. These findings reveal a novel mechanism that allows ARV to evade host antiviral immunity. IMPORTANCE ARV, the causative agent of viral arthritis or tenosynovitis in chickens, has a significant economic impact as it results in poor weight gain and increased feed conversion ratios. The MDA5-mediated IFN-β signal pathway plays an important role in host antiviral defense. Therefore, RNA viruses have developed mechanisms to counter this signaling pathway and successfully establish infection. However, the strategies adopted by ARV to block MDA5-IRF7 signaling remain unclear. In the current study, we demonstrated that ARV σA inhibits this pathway by binding to IRF7, which blocked IRF7 dimerization and nuclear translocation. Our findings may provide insights into how avian reovirus counteracts the innate antiviral immunity of the host to ensure viral replication.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 1495529-5
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  • 2
    In: Journal of Virology, American Society for Microbiology, Vol. 96, No. 24 ( 2022-12-21)
    Abstract: Cyclic GMP-AMP synthase (cGAS), a key DNA sensor, detects cytosolic viral DNA and activates the adaptor protein stimulator of interferon genes (STING) to initiate interferon (IFN) production and host innate antiviral responses. Duck enteritis virus (DEV) is a duck alphaherpesvirus that causes an acute and contagious disease with high mortality in waterfowl. In the present study, we found that DEV inhibits host innate immune responses during the late phase of viral infection. Furthermore, we screened DEV proteins for their ability to inhibit the cGAS-STING DNA-sensing pathway and identified multiple viral proteins, including UL41, US3, UL28, UL53, and UL24, which block IFN-β activation through this pathway. The DEV tegument protein UL41, which exhibited the strongest inhibitory effect, selectively downregulated the expression of interferon regulatory factor 7 (IRF7) by reducing its mRNA accumulation, thereby inhibiting the DNA-sensing pathway. Ectopic expression of UL41 markedly reduced viral DNA-triggered IFN-β production and promoted viral replication, whereas deficiency of UL41 in the context of DEV infection increased the IFN-β response to DEV and suppressed viral replication. In addition, ectopic expression of IRF7 inhibited the replication of the UL41-deficient virus, whereas IRF7 knockdown facilitated its replication. This study is the first report identifying multiple viral proteins encoded by a duck DNA virus, which inhibit the cGAS-STING DNA-sensing pathway. These findings expand our knowledge of DNA sensing in ducks and reveal a mechanism through which DEV antagonizes the host innate immune response. IMPORTANCE Duck enteritis virus (DEV) is a duck alphaherpesvirus that causes an acute and contagious disease with high mortality, resulting in substantial economic losses in the commercial waterfowl industry. The evasion of DNA-sensing pathway-mediated antiviral innate immunity is essential for the persistent infection and replication of many DNA viruses. However, the mechanisms used by DEV to modulate the DNA-sensing pathway remain poorly understood. In the present study, we found that DEV encodes multiple viral proteins to inhibit the cGAS-STING DNA-sensing pathway. The DEV tegument protein UL41 selectively diminished the accumulation of interferon regulatory factor 7 (IRF7) mRNA, thereby inhibiting the DNA-sensing pathway. Loss of UL41 potently enhanced the IFN-β response to DEV and impaired viral replication in ducks. These findings provide insights into the host-virus interaction during DEV infection and help develop new live attenuated vaccines against DEV.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1495529-5
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  • 3
    In: Bioorganic & Medicinal Chemistry, Elsevier BV, Vol. 93 ( 2023-10), p. 117455-
    Type of Medium: Online Resource
    ISSN: 0968-0896
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 1501507-5
    SSG: 15,3
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  • 4
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Marine Science Vol. 9 ( 2022-9-5)
    In: Frontiers in Marine Science, Frontiers Media SA, Vol. 9 ( 2022-9-5)
    Abstract: Mangroves have high ecological service value and play an important role in achieving carbon neutrality. However, the ecological services provided by mangroves are gradually declining due to the threat of various pollutants, especially heavy metal (HM) pollution. Researching the status and history of heavy metals (HMs) in mangrove sediments improves understanding of how mangroves can be protected. We studied the Zhanjiang Bay mangroves, which is an important part of the Zhanjiang Mangrove National Nature Reserve, and is greatly affected by human activities, as an example. We analyzed the pollution levels and deposition process of HMs and their influencing factors. In the mangrove surface sediments of Zhanjiang Bay, Pb, Cr, and Co were slightly to moderate enriched and Cu was moderate-heavy enriched. Zn and Hg showed moderate-heavy enrichment and heavy enrichment, respectively. Cu, Zn, Hg, and Co were 1.5, 1.88, 2.66, and 1.27 times the local background, respectively. Cu, Zn, and Hg mainly originated from anthropogenic sources, and Co may have derived from natural sources. The HM data of mangrove sedimentary cores in Zhanjiang Bay were obtained for the first time; high HM content appeared in the deep layer of the cores but not in the mangrove surface sediments. Both cores were well documented for the effects of natural and anthropogenic factors on the deposition process of HMs. Among them, the high enrichment of Hg in 1909–1921 may be closely related to human activities rather than natural formation. Before 1954, dense mangroves favored the accumulation and gradual increase of HMs. The intense human activity in 1945–1963 during the period of economic construction and reclamation of the Nansan Island Engineering led to significant increases in Cu, Zn, Pb, Cr, and Co, which reached their highest values in more than one hundred years. After 1963, anthropic factors such as deforestation and conversion to aquaculture sharply reduced mangrove area. Reclamation engineering enhanced tidal erosion. Natural factors such as precipitation, storm surge, sea-level rise, and high tides have accelerated the erosion and dilution of mangrove sediments in Zhanjiang Bay. These factors have led to the gradual reduction of HM content in sedimentary cores.
    Type of Medium: Online Resource
    ISSN: 2296-7745
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2757748-X
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  • 5
    In: Nutrition Journal, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2024-06-13)
    Abstract: Nonalcoholic fatty liver disease (NAFLD) is a globally increasing health epidemic. Lifestyle intervention is recommended as the main therapy for NAFLD. However, the optimal approach is still unclear. This study aimed to evaluate the effects of a comprehensive approach of intensive lifestyle intervention (ILI) concerning enhanced control of calorie-restricted diet (CRD), exercise, and personalized nutrition counseling on liver steatosis and extrahepatic metabolic status in Chinese overweight and obese patients with NAFLD. Methods This study was a multicenter randomized controlled trial (RCT) conducted across seven hospitals in China. It involved 226 participants with a body mass index (BMI) above 25. These participants were randomly assigned to two groups: the ILI group, which followed a low carbohydrate, high protein CRD combined with exercise and intensive counseling from a dietitian, and a control group, which adhered to a balanced CRD along with exercise and standard counseling. The main measure of the study was the change in the fat attenuation parameter (FAP) from the start of the study to week 12, analyzed within the per-protocol set. Secondary measures included changes in BMI, liver stiffness measurement (LSM), and the improvement of various metabolic indexes. Additionally, predetermined subgroup analyses of the FAP were conducted based on variables like gender, age, BMI, ethnicity, hyperlipidemia, and hypertension. Results A total of 167 participants completed the whole study. Compared to the control group, ILI participants achieved a significant reduction in FAP (LS mean difference, 16.07 [95% CI: 8.90–23.25] dB/m) and BMI (LS mean difference, 1.46 [95% CI: 1.09–1.82] kg/m 2 ) but not in LSM improvement (LS mean difference, 0.20 [95% CI: -0.19–0.59] kPa). The ILI also substantially improved other secondary outcomes (including ALT, AST, GGT, body fat mass, muscle mass and skeletal muscle mass, triglyceride, fasting blood glucose, fasting insulin, HbA1c, HOMA-IR, HOMA-β, blood pressure, and homocysteine). Further subgroup analyses showed that ILI, rather than control intervention, led to more significant FAP reduction, especially in patients with concurrent hypertension ( p 〈 0.001). Conclusion In this RCT, a 12-week intensive lifestyle intervention program led to significant improvements in liver steatosis and other metabolic indicators in overweight and obese Chinese patients suffering from nonalcoholic fatty liver disease. Further research is required to confirm the long-term advantages and practicality of this approach. Trial registration This clinical trial was registered on ClinicalTrials.gov (registration number: NCT03972631) in June 2019.
    Type of Medium: Online Resource
    ISSN: 1475-2891
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 2091602-4
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  • 6
    In: Journal of Inflammation Research, Informa UK Limited, Vol. Volume 16 ( 2023-07), p. 3049-3062
    Type of Medium: Online Resource
    ISSN: 1178-7031
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2023
    detail.hit.zdb_id: 2494878-0
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  • 7
    In: Microbiology Spectrum, American Society for Microbiology, Vol. 10, No. 6 ( 2022-12-21)
    Abstract: The cytosolic DNA sensing pathway mediates innate immune defense against infection by many DNA viruses; however, viruses have evolved multiple strategies to evade the host immune response. Duck enteritis virus (DEV) causes an acute and contagious disease with high mortality in waterfowl. The mechanisms employed by DEV to block the DNA sensing pathway are not well understood. Here, we sought to investigate the role of DEV US3, a serine/threonine protein kinase, in the inhibition of DNA sensing. We found that ectopic expression of DEV US3 significantly inhibited the production of IFN-β and expression of interferon-stimulated genes induced by interferon-stimulatory DNA and poly(dA-dT). US3 also inhibited viral DNA-triggered IFN-β activation and promoted DEV replication in duck embryo fibroblasts, while knockdown of US3 during DEV infection enhances the IFN-β response and suppresses viral replication. US3 inhibited the DNA-sensing signaling pathway by targeting interferon regulatory factor 7 (IRF7), and the kinase activity of US3 was indispensable for its inhibitory function. Furthermore, we found that US3 interacts with the activation domain of IRF7, phosphorylating IRF7, blocking its dimerization and nuclear translocation, and finally leading to the inhibition of IFN-β production. These findings expand our knowledge on DNA sensing in ducks and reveal a novel mechanism whereby DEV evades host antiviral immunity. IMPORTANCE Duck enteritis virus (DEV) is a duck alphaherpesvirus that causes an acute and contagious disease with high mortality, resulting in substantial economic losses in the commercial waterfowl industry. The evasion of DNA-sensing pathway-mediated antiviral innate immunity is essential for the persistent infection and replication for many DNA viruses. However, the strategies used by DEV to block the DNA-sensing pathway are not well understood. In this study, DEV US3 protein kinase was demonstrated to inhibit the DNA-sensing signaling via binding to the activation domain of interferon regulatory factor 7 (IRF7), which induced the hyperphosphorylation of IRF7 and abolished IRF7 dimerization and nuclear translocation. Our findings provide insights into how duck herpesviral kinase counteracts host antiviral innate immunity to ensure viral replication and spread.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 2807133-5
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  • 8
    In: Frontiers in Nutrition, Frontiers Media SA, Vol. 10 ( 2023-4-25)
    Abstract: Primary membranous nephropathy (PMN) is an immune-related disease with increased morbidity and the most common cause of adult nephrotic syndrome (NS). The serum 25-hydroxyvitamin D [25(OH)D)], a biomarker of vitamin D (VD) status, tends to decline in patients with kidney disease. However, the relationship between 25(OH)D and PMN is still unclear. Therefore, this study aims to clarify the association between 25(OH)D and disease severity and therapy response of PMN. Methods A total of 490 participants diagnosed with PMN by biopsy from January 2017 to April 2022 were recruited at the First Affiliated Hospital of Nanjing Medical University. The correlations between baseline 25(OH)D and manifestations of nephrotic syndrome (NS) or seropositivity of anti-PLA2R Ab were confirmed by univariate and multivariate logistic analyses. Spearman’s correlations were used to examine the associations between baseline 25(OH)D and other clinical parameters. In the follow-up cohort, Kaplan-Meier analysis was used to assess remission outcomes among groups with low, medium, and high levels of 25(OH)D. Furthermore, the independent risk factors for non-remission (NR) were explored by COX regression analysis. Results At baseline, 25(OH)D was negatively related to 24-h urinary protein and serum anti-PLA2R Ab. The lower level of baseline 25(OH)D was associated with an increased risk for the incidence of NS in PMN (model 2, OR 6.8, 95% CI 4.4, 10.7, P & lt; 0.001) and seropositivity of anti-PLA2R Ab (model 2, OR 2.4, 95% CI 1.6, 3.7, P & lt; 0.001). Furthermore, the lower level of 25(OH)D during follow-up was demonstrated as an independent risk factor for NR even after adjusting age, gender, MBP, 24 h UP, serum anti-PLA2R Ab, serum albumin, and serum C3 [25(OH)D (39.2–62.3 nmol/L): HR 4.90, 95% CI 1.02, 23.53 P = 0.047; 25(OH)D & lt; 39.2 nmol/L: HR 17.52, 95% CI 4.04, 76.03 P & lt; 0.001); vs. 25(OH)D ≥ 62.3 nmol/L]. The Kaplan-Meier survival analysis also demonstrated that th e higher level of follow-up 25(OH)D had a higher possibility of remission than the lower one (log-rank test, P & lt; 0.001). Conclusion Baseline 25(OH)D was significantly correlated with nephrotic proteinuria and seropositivity of anti-PLA2R Ab in PMN. As an independent risk factor for NR, a low level of 25(OH)D during follow-up might serve as a prognostic tool for sensitively identifying cases with a high probability of poor treatment response.
    Type of Medium: Online Resource
    ISSN: 2296-861X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2776676-7
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  • 9
    Online Resource
    Online Resource
    World Scientific Pub Co Pte Ltd ; 2016
    In:  Journal of Circuits, Systems and Computers Vol. 25, No. 01 ( 2016-01), p. 1640006-
    In: Journal of Circuits, Systems and Computers, World Scientific Pub Co Pte Ltd, Vol. 25, No. 01 ( 2016-01), p. 1640006-
    Abstract: In this paper, a wide input range supply voltage tolerant capacitive sensor readout circuit using on-chip solar cell is presented. Based on capacitance controlled oscillators (CCOs) for ultra-low voltage/power consumption, the sensor readout circuit is directly powered by the on-chip solar cell to improve the overall system energy efficiency. An extended sensing range with high sensing accuracy is achieved using a two-step successive approximation register (SAR) and delta-sigma ([Formula: see text]) analog-to-digital (A/D) conversion (ADC) scheme. Digital controls are generated on-chip using a customized sub-threshold digital standard cell library. Systematic error analysis and optimization including the finite switch on-resistance, buffer input-dependent delay, and SAR quantization nonlinearity are also outlined. High power supply rejection ratio (PSRR) is ensured by using a pseudo-differential topology with ratiometric readout. The complete sensing system is implemented using a standard 0.18[Formula: see text] [Formula: see text]m complementary metal-oxide-semiconductor (CMOS) process. Simulation results show that the readout circuit achieves a wide input range from 1.5[Formula: see text] pF to 6.5[Formula: see text]pF with a worst case PSRR of 0.5% from 0.3[Formula: see text] V to 0.42[Formula: see text]V (0.67% from 0.3[Formula: see text] V to 0.6[Formula: see text]V). With a 3.5[Formula: see text] pF input capacitance and a 0.3[Formula: see text]V supply, the [Formula: see text] stage achieves a resolution of 7.1-bit (corresponding to a capacitance of 2.2[Formula: see text]fF/LSB) with a conversion frequency of 371[Formula: see text] Hz. With an average power consumption of 40[Formula: see text]nW and a sampling frequency of 47.5[Formula: see text] kHz, a figure-of-merit (FoM) of 0.78[Formula: see text]pJ/conv-step is achieved.
    Type of Medium: Online Resource
    ISSN: 0218-1266 , 1793-6454
    Language: English
    Publisher: World Scientific Pub Co Pte Ltd
    Publication Date: 2016
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  • 10
    In: ACS Catalysis, American Chemical Society (ACS), Vol. 13, No. 1 ( 2023-01-06), p. 169-178
    Type of Medium: Online Resource
    ISSN: 2155-5435 , 2155-5435
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2023
    detail.hit.zdb_id: 2584887-2
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