Activation of Interleukin-1β Release by the Classical Swine Fever Virus Is Dependent on the NLRP3 Inflammasome, Which Affects Virus Growth in Monocytes

Classical swine fever virus (CSFV) is a classic Flavivirus that causes the acute, febrile, and highly contagious disease known as classical swine fever (CSF). Inflammasomes are molecular platforms that trigger the maturation of proinflammatory cytokines to engage innate immune defenses that are induced upon cellular infection or stress. However, the relationship between the inflammasome and CSFV infection has not been thoroughly characterized. To understand the function of the inflammasome response to CSFV infection, we infected porcine peripheral blood monocytes (PBMCs) with CSFV. Our results indicated that CSFV infection induced both the generation of pro-interleukin-1β (pro-IL-1β) and its processing in monocytes, leading to the maturation and secretion of IL-1β through the activation of caspase 1. Moreover, CSFV infection in PBMCs induced the production and cleavage of gasdermin D (GSDMD), which is an inducer of pyroptosis. Additional studies showed that CSFV-induced IL-1β secretion was mediated by NLRP3 and that CSFV infection could sufficiently activate the assembly of the NLRP3 inflammasome in monocytes. These results revealed that CSFV infection inhibited the expression of NLRP3, and knockdown of NLRP3 enhanced the replication of CSFV. In conclusion, these findings demonstrate that the NLRP3 inflammasome plays an important role in the innate immune response to CSFV infection

A convenient synthesis of β,β’-dioxochlorins: New application for Bobbitt's salt

Oxidation of β-aminoporphyrins with 4-acetamido-2,2,6,6-tetramethylpiperidine−1-oxoammonium tetrafluoroborate (Bobbitt's salt) provides an efficient synthesis of the corresponding 2,3-dioxochlorins. The synthesis is simple and exhibit good universality. In addition, Bobbitt's salt can be further applied to oxidize more aromatic amines. Preliminary studies have shown that aromatic amines with structures similar to 9-aminophenanthrene can be selectively oxidized to corresponding ortho-diketones

Refining the ERA5-based global model for vertical adjustment of zenith tropospheric delay

Abstract Tropospheric delay is an important factor affecting high precision Global Navigation Satellite System (GNSS) positioning and also the basic data for GNSS atmospheric research. However, the existing tropospheric delay models have some problems, such as only a single function used for the entire atmosphere. In this paper, an ERA5-based (the fifth generation of European Centre for Medium-Range Weather Forecasts Reanalysis) global model for vertical adjustment of Zenith Tropospheric Delay (ZTD) using a piecewise function is developed. The ZTD data at 611 radiosonde stations and the MERRA-2 (second Modern-Era Retrospective analysis for Research and Applications) atmospheric reanalysis data were used to validate the model reliability. The Global Zenith Tropospheric Delay Piecewise (GZTD-P) model has excellent performance compared with the Global Pressure and Temperature (GPT3) model. Validated at radiosonde stations, the performance of the GZTD-P model was improved by 0.96 cm (23%) relative to the GPT3 model. Validated with MERRA-2 data, the quality of the GZTD-P model is improved by 1.8 cm (50%) compared to the GPT3 model, showing better accuracy and stability. The ZTD vertical adjustment model with different resolutions was established to enrich the model's applicability and speed up the process of tropospheric delay calculation. By providing model parameters with different resolutions, users can choose the appropriate model according to their applications

The Resonance and Adaptation of Neurospora crassa Circadian and Conidiation Rhyth ms to Short Light-Dark Cycles

Circadian clocks control the physiological and behavioral rhythms to adapt to the environment with a period of ~24 h. However, the influences and mechanisms of the extreme light/dark cycles on the circadian clock remain unclear. We showed that, in Neurospora crassa, both the growth and the microconidia production contribute to adaptation in LD12:12 (12 h light/12 h dark, periodically). Mathematical modeling and experiments demonstrate that in short LD cycles, the expression of the core clock protein FREQUENCY was entrained to the LD cycles when LD > 3:3 while it free ran when T ≤ LD3:3. The conidial rhythmicity can resonate with a series of different LD conditions. Moreover, we demonstrate that the existence of unknown blue light photoreceptor(s) and the circadian clock might promote the conidiation rhythms that resonate with the environment. The ubiquitin E3 ligase FWD-1 and the previously described CRY-dependent oscillator system were implicated in regulating conidiation under short LD conditions. These findings shed new light on the resonance of Neurospora circadian clock and conidiation rhythms to short LD cycles, which may benefit the understandings of both the basic regulatory aspects of circadian clock and the adaptation of physiological rhythms to the extreme conditions

Duodenal ferroportin is up-regulated in patients with chronic hepatitis C.

Hepatitis C virus (HCV) infection is a leading cause of liver-related mortality. Chronic hepatitis C (CHC) is frequently associated with disturbances in iron homeostasis, with serum iron and hepatic iron stores being elevated. Accumulating evidence indicates that chronic HCV infection suppresses expression of hepatic hepcidin, a key mediator of iron homeostasis, leading to iron overload conditions. Since hepcidin mediates degradation of ferroportin, a basolateral transporter involved in the release of iron from cells, diminished hepcidin expression probably leads to up-regulation of ferroportin-1 (Fpn1) in patients with CHC. In this study, we determined the protein levels of duodenal Fpn1, and found that its expression was significantly up-regulated in patients with CHC. The expression of duodenal Fpn1 is negatively correlated with mRNA levels of hepcidin, and positively correlated with serum iron parameters. Although iron is a critical factor for growth of a variety of pathogenic bacteria, our results suggest that iron overload in blood does not increase the infection rate of bacteria in patients with CHC

Anti-osteosarcoma trimodal synergistic therapy using NiFe-LDH and MXene nanocomposite for enhanced biocompatibility and efficacy

Osteosarcoma is usually resistant to immunotherapy and, thus primarily relies on surgical resection and high-dosage chemotherapy. Unfortunately, less invasive or toxic therapies such as photothermal therapy (PTT) and chemodynamic therapy (CDT) generally failed to show satisfactory outcomes. Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma. Herein, a simple nanocomposite that synergistically combines CDT, PTT, and chemotherapy for osteosarcoma treatment was fabricated. In this composite, small 2D NiFe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil (5-FU) with high loading capacity. The nanospheres were then adsorbed onto larger 2D Ti3C2 MXene monolayers and finally shielded by bovine serum albumin (BSA) to form 5-FU@NiFe-LDH/Ti3C2/BSA nanoplatforms (5NiTiB). Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy, NiFe-LDH driven chemodynamic effects, and MXene-based photothermal killing collectively exhibited a synergistic “all-in-one” anti-tumor effect. 5NiTiB improved tumor suppression rate from <5% by 5-FU alone to ∼80.1%. This nanotherapeutic platform achieved higher therapeutic efficacy with a lower agent dose, thereby minimizing side effects. Moreover, the composite is simple to produce, enabling the fine-tuning of dosages to suit different requirements. Thus, the platform is versatile and efficient, with potential for further development

Development of a ZTD Vertical Profile Model Considering the Spatiotemporal Variation of Height Scale Factor with Different Reanalysis Products in China

Tropospheric delay is one of the key factors that may affect high-precision satellite navigation and positioning and water vapor retrieval performance. Its variation in the vertical direction is much greater than that in the horizontal direction. Therefore, the vertical profile model of zenith total delay (ZTD) is important for the spatial interpolation of high-precision ZTD products and the development of ZTD models. However, in China, low spatial and temporal resolutions remain persistent in ZTD vertical profile models and limit their application. In this study, ZTD vertical profile grid models (CZTD-H model: CZTD-HM and CZTD-HE models) were developed by considering the time-varying height scale factor for China and employing ZTD layered profile information with high temporal-spatial resolution calculated using MERRA-2 data and ERA5 data based on the integration method during 2012&ndash;2016. The CZTD-H model accuracy was verified using the global navigation satellite system (GNSS) data acquired from the Crustal Movement Observation Network of China (CMONOC) and radiosonde data as reference and was compared with the canonical GPT3 model accuracy. The applicability of CZTD-HM and CZTD-HE models was discussed. The results showed that: (1) CZTD-HM and CZTD-HE models exhibited excellent performance for ZTD layered vertical interpolation in northwestern and southeastern China, respectively. Among ZTD layered profiles from 84 radiosonde stations, the RMSE of ZTD data interpolated using CZTD-HM and CZTD-HE models improved by 12.9/16.23% and 13.8/17.16% compared with GPT3-1 and GPT3-5 models, respectively. (2) The CZTD-H model maintained high performance for the spatial interpolation of GGOS grid ZTD data. Validation with ZTD data from 249 GNSS stations showed that the RMSEs of both CZTD-HM and CZTD-HE models improved by 2.8 mm (19.7%) and 2.6 mm (18.6%) compared with those of the GPT3-1 and GPT3-5 models, respectively. The CZTD-HE model showed excellent performance in summer among all the models. Only the location and day of the year were required for the application of the CZTD-H model, which showed excellent ZTD vertical correction performance in China. With the different performances of the CZTD-HE and CZTD-HM models in China, the ERA5 model can be recommended for practical applications. Therefore, these results can provide a reference for the data source selection of ZTD vertical profile model construction on the basis of high-precision reanalysis data, GNSS real-time high-precision positioning, and GNSS meteorology in China

Changes and Risk Factors of Skeletal Muscle Mass and Strength in Patients with Type 2 Diabetes over 60 Years Old: A Cross-Sectional Study from China

Objective. The accelerate loss of skeletal muscle mass, strength, and function, named sarcopenia, is a progressive and generalised skeletal muscle disorder, and it is always associated with increased outcomes including falls, frailty, and disability. Diabetes mellitus is associated with significant muscle and physical complications. We aimed at clarifying the changes and risk factors of skeletal muscle mass and strength in elderly with type 2 diabetes. Methods. The study consisted of patients with type 2 diabetes (n=120) and an older general population (n=126). The skeletal muscle mass and muscle strength, as well as the serum levels of chronic inflammation, oxidative stress, homocysteine, and insulin-like factor-1 were assessed, and the correlation and regression analysis were conducted to evaluate outcomes. Results. T2DM patients exhibited lower muscle strength compared with the non-T2DM subjects (P<0.01). Among T2DM patients, serum IGF-1 levels were positively correlated with muscle strength (r=0.255, P<0.01) and muscle mass (r=0.209, P<0.05), levels of 8-OHdG were inversely correlated with muscle strength (r=−0.252, P<0.01), and there was a negative association between HCY and muscle mass (r=−0.185, P<0.05). Muscle mass and strength of patients with higher education level were significantly higher than those with lower education level (P<0.05), in male patients, muscle mass and muscle strength were significantly lower in smokers (P<0.01), and muscle mass was lower in chronic drinkers (P<0.05). Conclusions. These findings suggest that diabetic patients may be more susceptible to sarcopenia at an older age. And it also provides evidences that among elderly with diabetes mellitus, oxidative damage and HCY as well as IGF-1 are important predictors of age-dependent sarcopenia