Study on the Performance of Asphalt Modified with Bio-Oil, SBS and the Crumb Rubber Particle Size Ratio.

To enhance the properties of SBS and crumb rubber-modified asphalts, four different amounts (5%, 10%, 15%, and 20%) of castor oil were added to crumb rubber-modified asphalts to mitigate the adverse effects of high levels of fine crumb rubber particles on the aging resistance of SBS and crumb rubber-modified asphalt. Initially, a conventional test was conducted to assess the preliminary effects of bio-oil on the high-temperature and anti-aging properties of SBS and crumb rubber-modified asphalt. Subsequently, dynamic shear rheometer and bending beam rheometer tests were employed to evaluate the impact of bio-oil on the high- and low-temperature and anti-fatigue properties of SBS and crumb rubber-modified asphalt. Finally, fluorescence microscopy and Fourier transform infrared spectroscopy were used to examine the micro-dispersion state of the modifier and functional groups in bio-oil, SBS and crumb rubber composite-modified asphalts. The experimental results indicated that bio-oil increased the penetration of SBS and crumb rubber-modified asphalt, decreased the softening point and viscosity, and significantly improved its aging resistance. The addition of bio-oil enhanced the anti-fatigue properties of SBS and crumb rubber-modified asphalt. The optimal amount of added bio-oil was identified. Bio-oil also positively influenced the low-temperature properties of SBS and crumb rubber-modified asphalt. Although the addition of bio-oil had some adverse effects on the asphalt's high-temperature properties, the asphalt mixture modified with bio-oil, SBS, and crumb rubber still exhibited superior high-temperature properties compared to unmodified asphalt. Furthermore, fluorescence microscopy and Fourier transform infrared spectroscopy results demonstrated that bio-oil can be uniformly dispersed in asphalt, forming a more uniform cross-linked structure and thereby enhancing the aging resistance of SBS and crumb rubber-modified asphalt. The modification process involved the physical blending of bio-oil, SBS, and crumb rubber within the asphalt. Comprehensive research confirmed that the addition of bio-oil has a significant and positive role in enhancing the properties of SBS and crumb rubber-modified asphalt with different composite crumb rubber particle size ratios.

DNase I rescues goat sperm entrapped by neutrophil extracellular traps.

Artificial insemination has been a predominant technique employed in goat husbandry for breeding purposes. Subsequent to artificial insemination, sperm can elicit inflammation in the reproductive tract, resulting in substantial the accumulation of neutrophils. Recognized as foreign entities, sperm may become entrapped within neutrophil extracellular traps (NETs) released by neutrophils, thereby exploiting their properties of pathogen elimination. Deoxyribonuclease I (DNase I), which is known for disintegrating NETs and causing loss of function, has been utilized to ameliorate liver and brain damage resulting from NETs, as well as to enhance sperm quality. This study investigated the mechanism of sperm-induced NETs and further explored the impact of DNase I on NETs. Sperm quality was evaluated using optical microscopy, while the structure of NETs was observed through immunofluorescence staining. The formation mechanism of NETs was examined using inhibitors and PicoGreen. The findings revealed that sperm induced the formation of NETs, a process regulated by glycolysis, NADPH oxidase, ERK1/2, and p38 signaling pathways. The composition of NETs encompassed DNA, citrullinated histone H3 (citH3), and elastase (NE). DNase I protects sperm by degrading NETs, thereby concurrently preserving the integrity of plasma membrane and motility of sperm. In summary, the release of sperm-induced NETs leads to its damage, but this detrimental effect is counteracted by DNase I through degradation of NETs. These observations provide novel insights into reproductive immunity in goats.

Postoperative analgesic efficacy and safety of imrecoxib versus celecoxib in hip osteoarthritis patients undergoing total hip arthroplasty: a multi-center, randomized, controlled, non-inferiority study.

BACKGROUND: Imrecoxib, a novel cyclooxygenase-2 inhibitor, possesses a certain postoperative analgesic effect for several orthopedic surgeries. This multi-center, randomized, controlled, non-inferiority study intended to investigate the postoperative analgesic efficacy and safety profile of imrecoxib (versus celecoxib) in hip osteoarthritis patients undergoing total hip arthroplasty (THA). METHODS: 156 hip osteoarthritis patients planned for THA were randomized into imrecoxib (N = 78) and celecoxib (N = 78) groups. Patients were orally administrated with imrecoxib or celecoxib 200 mg at 2 h (h) after THA, 200 mg every 12 h to day (D)3, and 200 mg every 24 h to D7; additionally, each patient received patient-controlled analgesia (PCA) for 2 days. RESULTS: Resting pain visual analogue scale (VAS) score at 6 h, 12 h, D1, D2, D3, and D7 post THA was not varied between imrecoxib and celecoxib groups (all P > 0.050), neither was moving pain VAS score (all P > 0.050). Importantly, the upper of 95% confidence interval of pain VAS score margin between imrecoxib and celecoxib groups was within the non-inferiority threshold (Δ = 1.0), indicating the fact that non-inferiority was established. The additional and total consumption of PCA was not varied between imrecoxib and celecoxib groups (both P > 0.050). Also, no difference was seen in Harris hip score, European Quality of Life 5-Dimensions (EQ-5D) total and VAS scores at month (M)1, M3 between the two groups (all P > 0.050). Besides, the incidences of all adverse events were not different between imrecoxib and celecoxib groups (all P > 0.050). CONCLUSION: Imrecoxib is non-inferior to celecoxib for postoperative analgesia in hip osteoarthritis patients undergoing THA.

Quercetin alleviates gliotoxin-induced duckling tissue injury by inhibiting oxidative stress, inflammation and increasing heterophil extracellular traps release.

Aspergillus fumigatus causes aspergillosis with high morbidity and mortality in the duck industry. As a vital virulence factor produced by A. fumigatus, gliotoxin (GT) is widely present in food and feed, threatening duck industry and human health. Quercetin is a polyphenol flavonoid compound from natural plants with anti-inflammatory and antioxidant functions. However, the effects of quercetin on ducklings with GT poisoning are unknown. The model of ducklings with GT poisoning was established, and the protective effects and molecular mechanisms of quercetin on ducklings with GT poisoning were investigated. Ducklings were divided into control, GT, and quercetin groups. A model of GT (2.5 mg/kg) poisoning in ducklings was successfully established. Quercetin protected GT-induced liver and kidney functions and alleviated GT-induced alveolar wall thickening in lungs, cell fragmentation, and inflammatory cell infiltration in liver and kidney. Quercetin decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) and catalase (CAT) after GT treatment. Quercetin significantly reduced GT-induced mRNA expression levels of inflammatory factors. Furthermore, quercetin increased GT-reduced heterophil extracellular traps (HETs) in serum. These results indicated that quercetin protected ducklings against GT poisoning by inhibiting oxidative stress, inflammation and increasing HETs release, which confirms the potential applicability of quercetin in treating GT-induced duckling poisoning.

Forsythin inhibits ß-hydroxybutyrate-induced oxidative stress in bovine macrophages by regulating p38/ERK, PI3K/Akt, and Nrf2/HO-1 signaling pathways.

Ketosis is a metabolic disease of dairy cows in the perinatal period, ß-hydroxybutyrate (ß-HB) is the main component of ketosis. High levels of ß-HB can trigger oxidative stress and inflammatory response in dairy cows, leading to decreased milk yield and multiple postpartum diseases. Forsythin (FOR), the major constituent of the herbal medicine Forsythia, has anti-inflammatory, anti-oxidant, and antiviral effects. FOR was demonstrated to have an antioxidant effect on PC12 cells. However, the effects of FOR on ß-HB-stimulated bovine macrophages (BMs) has not been reported. Thus, the aim of the present study was to investigate the effects of FOR on ß-HB-stimulated BMs. Firstly, the CCK8 test confirmed that FOR (50, 100, 200 µg/mL) has no effect on BMs activity, and we selected these concentrations for subsequent experiments. Secondly, through detecting the oxidation indexes ROS, MDA and antioxidant indexes CAT and SOD, we confirmed the antioxidant effect of FOR on BMs. Next, qRT-PCR confirmed that FOR dramatically reduced the mRNA levels of IL-1ß and IL-6. Furthermore, the western blotting confirmed that FOR observably down-regulated ß-HB-stimulated phosphorylation of p38, ERK and Akt and up-regulated expression of Nrf2, and HO-1. Above results suggested that FOR plays antioxidant effects on ß-HB-induced BMs through p38, ERK and PI3K/Akt, Nrf2 and HO-1 signaling pathways. Therefore, we speculated that FOR may be a potential medicine to alleviate ß-HB-induced inflammatory response and provide a preliminary reference for the research and development of FOR.

Zinc oxide nanoparticles (ZnO-NPs) exhibit immune toxicity to crucian carp (Carassius carassius) by neutrophil extracellular traps (NETs) release and oxidative stress.

Zinc oxide nanoparticles (ZnO-NPs) are widely used in sunscreens, cosmetics, paint, construction materials, and other products. ZnO-NPs released into the environment can harm aquatic creatures and pose a health risk to humans through the food chain. ZnO-NPs are toxic to fish, but there are few reports on its immunotoxicity on crucian carp (Carassius carassius). In this study, ZnO-NPs increased the biochemical indexes of the liver in serum, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In histopathological observation, many inflammatory cells were filled in the liver's central vein stimulated by ZnO-NPs. Furthermore, ZnO-NPs could increase malondialdehyde (MDA) level, lessen superoxide dismutase (SOD) level, and elevate the level of neutrophil extracellular traps (NETs). However, deoxyribonuclease I (DNase I) alleviated all biochemical indexes and histopathological changes. Immunofluorescence in vitro confirmed that NETs were composed of citrullinated histone 3, myeloperoxidase, and neutrophil elastase. ZnO-NPs-increased NETs were dependent on reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase and were also related to partial processes of glycolysis. Our study confirms that ZnO-NPS has a toxic effect on the liver of crucian carp. DNase I can prevent liver damage caused by ZnO-NPs, which provides a new insight into the immunotoxicity of ZnO-NPs to fish.

CuO-NPs-triggered heterophil extracellular traps exacerbate liver injury in chicks by promoting oxidative stress and inflammatory responses.

With the widespread use of copper oxide nanoparticles (CuO-NPs), their potential toxicity to the environment and biological health has attracted close attention. Heterophil extracellular traps (HETs) are an innate immune mechanism of chicken heterophils against adverse stimuli, but excessive HETs cause damage. Here, we explored the effect and mechanism of CuO-NPs on HETs formation in vitro and further evaluated the potential role of HETs in chicken liver and kidney injury. Heterophils were exposed to 5, 10, and 20 µg/mL of CuO-NPs for 2 h. The results showed that CuO-NPs induced typical HETs formation, which was dependent on NADPH oxidase, P38 and extracellular regulated protein kinases (ERK1/2) pathways, and glycolysis. In in vivo experiments, fluorescence microplate and morphological analysis showed that CuO-NPs elevated the level of HETs in chicken serum and caused liver and kidney damage. Meanwhile, CuO-NPs caused hepatic oxidative stress (MDA, SOD, CAT, and GSH-PX imbalance), and also induced an increase in mRNA expression of their inflammatory and apoptosis-related factors (IL-1ß, IL-6, TNF-α, COX-2, iNOS, NLRP3, and Caspase-1, 3, 11). However, these results were significantly altered by DNase I (HETs degradation reagent). In conclusion, the present study demonstrates for the first time that CuO-NPs induce the formation of HETs and that HETs exacerbate pathological damage in chicken liver and kidney by promoting oxidative stress and inflammation, providing insights into immunotoxicity and potential prevention and treatment targets caused by CuO-NPs overexposure.

Study on the Seismic Performance of Stiffened Corrugated Steel Plate Shear Walls with Atmospheric Corrosion.

Corrugated steel plate shear walls (CSPWs) with three different stiffening methods are proposed in this paper, including unstiffened CSPWs (USWs), cross stiffened CSPWs (CSWs) and asymmetric diagonal-stiffened CSPWs (ASWs). A numerical model was established by ABAQUS 6.13 based on the validation of an existing cyclic test on a CSPW. This paper presents an investigation of the lateral performance under monotonic loading, seismic performance under cyclic loading and seismic performance under atmospheric corrosion of USW, CSW and ASW. The results show that (1) Stiffeners can improve the elastic critical buckling load, the initial stiffness and the ultimate shear resistance of CSPWs, and the effect of asymmetric diagonal stiffeners is more significant than that of cross stiffeners; (2) Stiffeners can improve the energy dissipation capacity and ductility, delay stiffness degradation and reduce the out-of-plane deformation of CSPWs, and the hysteretic performance of ASWs is obviously better than that of CSWs; and (3) Under atmospheric corrosion, stiffeners are conducive to inhibiting buckling and improving the seismic performance of CSPWs, while the seismic performance of CSWs is significantly affected by corrosion, so asymmetric diagonal stiffeners are better than cross stiffeners in improving the seismic performance of CSPWs. Meanwhile, the formula of ultimate shear resistance of corroded specimens is also fitted in this paper, which can provide design suggestions for practical engineering.

Chicken heterophils extracellular traps act as early effectors against cyclopiazonic acid dependent upon NADPH oxidase, ROS and glycolysis.

Cyclopiazonic acid (CPA) is a secondary metabolite produced by Aspergillus and Penicillium, which is present in contaminated crops and food, causing severe toxicity to humans and animals. Heterophil extracellular traps (HETs) are a novel host innate immune mechanism of chicken heterophils against pathogen infection. However, whether CPA can cause immunotoxicity of heterophils on HETs release remains unclear. Here, we attempt to detect the effects of CPA on HETs release, and further investigate the molecular mechanisms underlying these processes. We exposed heterophils to 2.5, 5, 10 µM CPA for 90 min. The results showed that CPA induced the release of HETs in heterophils, consisting of DNA-modified citrullinated histone 3 and elastase. The quantitative analysis of HETs content was positively correlated with CPA concentration. CPA also promoted reactive oxygen species production and phosphorylation of ERK1/2 and p38. In addition, CPA-triggered HETs formation was reduced by NADPH oxidase, ERK1/2, and p38 signaling pathway and glycolysis inhibitors, indicating that CPA-induced HETs were related to the production of ROS dependent on NADPH oxidase, ERK1/2, and p38 signaling pathways, as well as glycolysis. Our study describes the underlying mechanism of CPA-induced HETs release, which may provide a further understanding of the immunotoxicology of CPA poisoning.

Nanosilver-stimulated heterophil extracellular traps promoted liver and kidney injury in chicken.

Nanosilver is a metallic silver monomer with a diameter of <100 nm, which has excellent antibacterial activity and is widely used in the fields of medicine and sanitation, disinfection of drinking water in daily life and feed additives in livestock and poultry farming. Heterophil extracellular traps (HETs) are an important part of innate immunity in chickens and have an excellent antimicrobial effect, but their excessive release caused tissue damage. Nanosilver overdose caused toxic effects in chickens, while immunotoxic effects of nanosilver on chickens have not been reported. In this study, we explored the effects of nanosilver-induced HETs on chicken liver and kidney damage and further investigated the molecular mechanism of nanosilver-induced HETs release. The results showed that nanosilver significantly upregulated serum HETs and caused liver and kidney damage. The classical structure of nanosilver-induced HETs was also observed, and nanosilver-induced HETs were dependent on reactive oxygen species (ROS), extracellular regulatory protein kinase (ERK)1/2, p38 and glycolysis pathways. In summary, this research suggests that nanosilver induced HETs release, but excessive HETs release also caused damage to chicken. It also helps to understand the importance of moderate application of nanosilver, which may improve animal immunity but avoid negative effects in safeguarding the economic efficiency of poultry farming.

Characteristics and Treatment Strategy of Isolated Calf Deep Venous Thrombosis after Fractures: A Review of Recent Literature.

Isolated calf deep venous thrombosis (ICDVT) includes thrombosis located at the far end of the popliteal vein, such as the anterior tibial vein, posterior tibial vein, fibular vein, and intramuscular vein of the soleus and gastrocnemius. This type of thrombosis has the highest incidence, accounting for approximately half of all deep vein thrombosis (DVT) cases; however, there is no consistent recommendation for ICDVT treatment across countries, and there is also no optimal management strategy. In recent years, increasing evidence has shown that ICDVT can develop into proximal DVT, even causing pulmonary embolism (PE). Therefore, some experts suggest anticoagulant therapy for this type of DVT, while others hold an opposing attitude. Therefore, the treatment strategy for this type of DVT has become a hot and difficult research topic. The purpose of this review is to summarize the characteristics of ICDVT and the effects of different treatment strategies by analyzing recent and important classical works in the literature in an attempt to provide recommendations for the treatment of this most common type of DVT in orthopaedic clinics.

Alumina nanoparticles-induced heterophil extracellular traps exacerbate liver injury by regulating oxidative stress and inflammation in chickens.

Widely used alumina nanoparticles (Al2O3 NPs) exposed to the environment pose a serious threat to human and animal health. The formation of heterophil extracellular traps (HETs) is a mechanism of innate immune defense against infection, but excessive HETs cause pathological damage. Here, we aim to explore the influence and mechanism of Al2O3 NPs on the formation of HETs in vitro, and further investigate the role of HETs release in histopathological damage after Al2O3 NPs treatment. Immunofluorescence analysis showed that Al2O3 NPs induced the formation of HETs, which was characterized by modified histones and elastase in the DNA backbone. Fluorescence microplate analysis showed that HETs formation was dependent on NADPH oxidase, P38, extracellular regulated protein kinases (ERK1/2) pathways and glycolysis. In vivo investigation showed that Al2O3 NPs significantly caused HETs release and liver damage. Biochemical analysis showed that Al2O3 NPs inhibited the activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX). Real-time fluorescence quantification results showed that Al2O3 NPs caused the overexpression of inflammation-related molecules interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), caspase-1 and caspase-11. All these changes were significantly changed by DNase I (Degradation reagent for HETs). Together, these suggest that Al2O3 NPs-induced HETs exacerbate liver injury by regulating oxidative stress and inflammatory responses, which provide a new perspective and potential prophylaxis and treatment targets for Al2O3 NPs toxicological research.

Aflatoxin B1-activated heterophil extracellular traps result in the immunotoxicity to liver and kidney in chickens.

Aflatoxin B1 (AFB1) is a mycotoxin with strong toxicity and play a large proportion in aspergillosis. Heterophil extracellular traps (HETs) was considered as an innate immune response of chickens to resist pathogens. AFB1 has been reported to trigger macrophages extracellular traps (METs) in THP-1 cells and RAW264.7 cells, but whether AFB1 could also activate HETs release, and the mechanism underlying AFB1-activated HETs in chicken remains unclear. In this study, we confirmed that AFB1could induce HETs release, which was a network of DNA-based structures consist of citrullinated histone 3 (citH3) and elastase. Meanwhile, AFB1-activated HETs rely on the glycolytic process to provide energy, NADPH oxidase and p38 signaling pathway. Moreover, it has been verified that AFB1-activated HETs release could significantly increase the biochemical indexes of liver (ALT and AST) and kidney (CRE and BUN) in serum. In addition, histopathological observation showed that AFB1 caused swelling, necrosis and vacuolation of hepatocytes in liver, and necrosis, exfoliated of nephrocyte in kidney. Further investigation demonstrated that AFB1 significantly decreased the levels of SOD and GSH-PX but increased the level of MDA, and meanwhile induced the mRNA expressions of TNF-α, IL-6 and IL-1ß, iNOS, COX-2, NLRP3, caspase-1, caspase-3 and caspase-11. However, all these AFB1-induced biochemical indexes and histopathological changes were effectively alleviated by DNase I (the standard degradant for HETs). In conclusion, it has preliminary confirmed that AFB1-activated HETs formation contributed to the immunotoxicity in chicken and provide new strategies for the therapy in aspergillosis.

Morin alleviates aflatoxin B1-induced liver and kidney injury by inhibiting heterophil extracellular traps release, oxidative stress and inflammatory responses in chicks.

Aflatoxin B1 (AFB1) is a secondary metabolite produced by Aspergillus flavus and parasitic aspergillus, mainly existing in cereals, peanuts, corn, and other crops, which seriously endanger poultry, human health, and environment. Morin, a flavonoid compound extracted from moraceae plants, possess antioxidant, antibacterial, and anti-inflammatory effects. However, whether morin has a protective effect on AFB1-induced liver and kidney damage in chicks has not been specifically reported. In this study, we mainly confirmed the protective effect of morin on AFB1-induced liver and kidney damage in chicks and clarified its mechanism. It was found that morin can significantly reduce the liver biochemical indicators of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and kidney indicators of creatinine (CRE) and urea nitrogen (BUN) levels. Meanwhile, histopathological examination showed that morin effectively relieved AFB1-caused liver damage, including hepatocyte disruption, swelling, and inflammatory cell infiltration, and effectively relieved kidney damage, including renal cell necrosis, exfoliation, and vacuolization. Further investigation of its mechanism demonstrated that morin significantly inhibited AFB1-induced heterophil extracellular traps (HETs) release, and decreased the level of malondialdehyde (MDA) but increased the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in vivo. Moreover, quantitative real-time PCR (qRT-PCR) analysis showed that morin also significantly decreased AFB1-induced mRNA expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), caspase-1, caspase-3, and caspase-11. In conclusion, all results confirmed that morin could protect AFB1-caused liver and kidney damage by inhibiting HETs release, regulating oxidative stress, and inhibiting inflammatory response, suggesting that morin can be utilized as a potential drug for prevention and treatment of aflatoxicosis in poultry breeding industry.

Glycolysis and Reactive Oxygen Species Production Participate in T-2 Toxin-Stimulated Chicken Heterophil Extracellular Traps.

T-2 toxin (T-2) is a kind of trichothecene toxin produced from Fusarium fungi, which is an environmental pollutant that endangers poultry and human health. Heterophil extracellular traps (HETs) are not only a form of chicken immune defense against pathogen infection but also involved in pathophysiological mechanisms of several diseases. However, the immunotoxicity of T-2 on HET formation in vitro has not yet been reported. In this study, heterophils were exposed to T-2 at doses of 20, 40, and 80 ng/mL for 90 min. Observation of the structure of HETs by immunofluorescence staining and the mechanism of HET formation was analyzed by inhibitors and PicoGreen. These results showed that T-2-triggered HET formation consisted of DNA, elastase, and citH3. Furthermore, T-2 increased reactive oxygen species (ROS) generation, and the formation of T-2-triggered HETs was also decreased by the inhibitors of glycolysis, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p38 and extracellular signal-regulated kinase (ERK)1/2 signaling pathways, suggesting that T-2-induced HETs are associated with glycolysis, ROS production, ERK1/2 and p38 signaling pathways, and NADPH oxidase. Taken together, this study elucidates the mechanism of T-2-triggered HET formation, and it may provide new insight into understanding the immunotoxicity of T-2 to early innate immunity in chickens.

Baicalin protects against zearalenone-induced chicks liver and kidney injury by inhibiting expression of oxidative stress, inflammatory cytokines and caspase signaling pathway.

Zearalenone (ZEA) is a secondary metabolite produced by fungi such as Fusarium and Fusarium flavum, which is classified as a mycotoxin. Crops and feed in a humid surrounding are widely polluted by ZEA, which further endangering the healthful aquaculture of poultry and even human health. Up to now, prevention and cure of mycotoxicosis is still a crucial subject of poultry husbandry. Baicalin (BAI) is a flavonoid refined from dried roots of Scutellaria baicalensis possessing the function of hepatoprotective, anti-inflammatory, anti-oxidant, and anti-atherosclerotic efficacies.etc. But whether Baicalin also has a protective effect against ZEA intoxication is unclear. Therefore, the aim of this study was to establish a model of ZEA-induced toxic injury in chicks, and then to investigate the way in which Baicalin plays a protective role in the mechanism of ZEA-induced liver and kidney injury in chicks. The results exhibit that Baicalin could not only significantly decrease aspartate aminotransferase (AST) , alanine aminotransferase (ALT) and creatinine (Cre) levels in serum, but also ameliorate ZEA-induced pathologic changes of liver and kidney. Baicalin could also significantly regulate ZEA-induced the changes of catalase (CAT) , malondialdehyde (MDA) , total sulfhydryl group , except for glutathione peroxidase (GSH-px) , and inhibit the mRNA levels of inflammatory cytokines tumor necrosis factor-α (TNF-α) , interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2) with caspase-3 and caspase-11 in the caspase signaling pathway , meanwhile inhibit the cell apoptosis in immunohistochemistry. In summary, we successfully established a model of ZEA-induced liver injury in chicks, and confirm that Baicalin can reduce ZEA-induced liver and kidney injury in chicks. The mechanism of these effects is via inhibiting inflammation, oxidative stress and apoptosis, which also indicates the potential applicability of Baicalin for the prevention and treatment of ZEA-induced toxicity in chicks.

Sodium Butyrate Alleviates Lipopolysaccharide-Induced Inflammatory Responses by Down-Regulation of NF-κB, NLRP3 Signaling Pathway, and Activating Histone Acetylation in Bovine Macrophages.

Sodium butyrate is the sodium salt of butyric acid, which possesses many biological functions including immune system regulation, anti-oxidant and anti-inflammatory ability. The present study was designed to elucidate the anti-inflammatory effects and mechanisms of sodium butyrate on lipopolysaccharide (LPS)-stimulated bovine macrophages. The effect of sodium butyrate on the cell viability of bovine macrophages was assayed by using the CCK-8 kit. Quantitative real-time PCR (qRT-PCR) was used to detect the gene expression of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), cyclooxygenase-2 (COX-2), and inducible Nitric Oxide Synthase (iNOS). NF-κB, NLRP3 signaling pathway, and histone deacetylase were detected by western blotting. The results showed that sodium butyrate had no significant effect on cell viability at 0-1 mM, and inhibited LPS-induced IL-6, IL-1ß, COX-2, and iNOS expression. Moreover, sodium butyrate suppressed LPS (5 µg/ml)-stimulated the phosphorylation of IκB and p65, inhibited the deacetylation of histone H3K9, and has also been found to inhibit protein expression in NLRP3 inflammasomes. Thus, our finding suggested that sodium butyrate relieved LPS-induced inflammatory responses in bovine macrophage by inhibiting the canonical NF-κB, NLRP3 signaling pathway, and histone decetylation, which might be helpful to prevent cow mastitis.

Nickel-titanium arched shape-memory alloy connector combined with bone grafting in the treatment of scaphoid nonunion.

PURPOSE: To summarize the techniques and clinical effectiveness in treating scaphoid nonunion with nickel-titanium (Ni-Ti) arched shape-memory alloy connector in combination with autologous iliac bone grafts. METHODS: This study retrospectively analyzed 18 scaphoid nonunion cases treated with arched connectors with autologous iliac bone grafts. Based on scaphoid nonunion, 2 cases were classified as type II (fibrous union), 4 cases as type III (mild sclerotic union), 6 cases as type IV (moderate resorption and sclerosis), 5 cases as type V (severe bone resorption and sclerosis), and 1 case as type VI (pseudarthrosis formation). At the first 4, 8 and 12 weeks after the surgery, wrist anteroposterior, lateral X-ray were obtained, respectively, to evaluate bone healing. Patients who had not yet reached the standard of healing at 12 weeks after surgery would continue to receive additional appointments for follow-up visits, such as 14 weeks, 16 weeks, 18 weeks after surgery, until their imaging studies had achieved satisfactory bone healing. Clinical effectiveness was evaluated comprehensively, based on bone union time, Mayo wrist score, and visual analog pain score. RESULTS: All 18 patients achieved satisfactory reduction and fixation with a mean union time of 4.2 months. Preoperative Mayo wrist score averaged 57.4 and average final postoperative follow-up was 91.4. On the other hand, mean preoperative VAS score was 6.8, and final postoperative follow-up average was 1.6. Mayo wrist score of the overall treatment effectiveness was excellent (90-100) in 12 cases, good (80-90) in 5 cases, and acceptable (60-80) in 1 case with zero poor (below 60) cases observed. Statistical analysis suggested that a statistically significant improvement in fracture healing, wrist function recovery and visual analog pain after surgery when compared to the scores of the patients before surgery. CONCLUSION: Using Ni-Ti arched shape-memory alloy connector in combination with autologous bone grafting provided a new modality to treat scaphoid nonunions in a less traumatic, convenient to operate and satisfactory manner in treatment outcomes, and thus is worthy of further application.

G Protein-Coupled Receptor 109A and Host Microbiota Modulate Intestinal Epithelial Integrity During Sepsis.

The intestinal epithelial barrier is important to mucosal immunity, although how it is maintained after damage is unclear. Here, we show that G protein-coupled receptor 109A (GPR109A) supports barrier integrity and decreases mortality in a mouse cecum ligation and puncture (CLP) sepsis model. Data from 16S RNA sequencing showed that the intestinal microbiota of WT and Gpr109a-/- mice clustered differently and their compositions were disrupted after CLP surgery. GPR109A-deficient mice showed increased mortality, intestinal permeability, altered inflammation, and lower tight junction gene expression. After eliminating the intestinal flora with antibiotics, all experimental mice died within 48 h of CLP surgery. This demonstrates the critical role of the gut microbiota in CLP-induced sepsis. Importantly, mortality and other pathologies in the model were decreased after Gpr109a-/- mice received WT gut microbiota. These findings indicate that GPR109A regulates the gut microbiota, contributing to intestinal epithelial barrier integrity and decreased mortality in CLP-induced sepsis.

Peiminine Protects Dopaminergic Neurons from Inflammation-Induced Cell Death by Inhibiting the ERK1/2 and NF-κB Signalling Pathways.

Neuroinflammation, characterized marked by microglial activation, plays a very important role in the pathogenesis of Parkinson's disease (PD). Upon activation, pro-inflammatory mediators are produced by microglia, triggering excessive inflammatory responses and ultimately damaging dopaminergic neurons. Therefore, the identification of agents that inhibit neuroinflammation may be an effective approach for developing novel treatments for PD. In this study, we sought to investigate whether peiminine protects dopaminergic neurons by inhibiting neuroinflammation. We evaluated the effects of peiminine on behavioural dysfunction, microglial activation and the loss of dopaminergic neurons in a rat model of lipopolysaccharide (LPS)-induced PD. BV-2 cells were pretreated with peiminine for 1 h and then stimulated with LPS for different times. Then, inflammatory responses and the related signalling pathways were analysed. Peiminine markedly attenuated behavioural dysfunction and inhibited the loss of dopaminergic neurons and microglial activation in the LPS-induced PD rat model. In BV-2 cells, peiminine significantly decreased LPS-induced expression of the pro-inflammatory mediators TNF-α, IL-6 and IL-1ß, COX-2 and iNOS by inhibiting the phosphorylation of ERK1/2, AKT and NF-κB p65. Based on these results demonstrated that peiminine has a role in protecting dopaminergic neurons in the LPS-induced PD rat model by inhibiting neuroinflammation.