DLL1/NOTCH1 signaling pathway maintain angiogenesis in meniscus development and degeneration.

OBJECTIVES: The decline in vascular capacity within the meniscus is a well-documented phenomenon during both development and degeneration. Maintaining vascular integrity has been proposed as a potential therapeutic strategy for osteoarthritis. Therefore, our study aims to investigate the characteristics of endothelial cells and blood vessels in embryonic and degenerated meniscus tissues. METHODS: Human embryonic and mature menisci were used for histological analyses. Single-cell RNA sequencing was used to identify cell clusters and their significant genes in embryo meniscus to uncover characteristic of endothelial cells. Computer analysis and various staining techniques were used to characterize vessels in development and osteoarthritis meniscus. RESULTS: Vessels structure first observed in E12w and increasing in E14w. Vessels were veins majorly and arteries growth in E35w. Endothelial cells located not only perivascular but also in the surface of meniscus. The expression of DLL1 was observed to be significantly altered in endothelial cells within the vascular network that failed to form. Meniscus tissues affected by osteoarthritis, characterized by diminished vascular capacity, displayed reduced levels of DLL1 expression. Experiment in vitro confirmed DLL1/NOTCH1 be vital to angiogenesis. CONCLUSION: Lack of DLL1/NOTCH1 signaling pathway was mechanism of vascular declination in development and degenerated meniscus.

Gliotoxin elicits immunotoxicity in the early innate immune system of ducks.

Gliotoxin (GT) belongs to the epipolythiodioxopiperazine (ETP) family, which is considered a crucial virulence determinant among the secondary metabolites produced by Aspergillus fumigatus. The metabolites are commonly found in food and feed, contributing to the invasion and immune escape of Aspergillus fumigatus, thereby posing a significant threat to the health of livestock, poultry, and humans. Heterophil extracellular traps (HETs), a novel form of innate immune defense, have been documented in the chicken's innate immune systems for capturing and eliminating invading microbes. However, the effects and mechanisms of GT on the production of duck HETs in vitro remain unknown. In this study, we first confirmed the presence of HETs in duck innate immune systems and further investigated the molecular mechanism underlying GT-induced HETs release. Our results demonstrate that GT can trigger typical release of HETs in duck. The structures of GT-induced HETs structures were characterized by DNA decoration, citrullinated histones 3, and elastase. Furthermore, NADPH oxidase, glycolysis, ERK1/2 and p38 signaling pathway were found to regulate GT-induced HETs. In summary, our findings reveal that gliotoxin activates HETs release in the early innate immune system of duck while providing new insights into the immunotoxicity of GT towards ducks.

Additively manufactured bioceramic scaffolds based on triply periodic minimal surfaces for bone regeneration.

The study focused on the effects of a triply periodic minimal surface (TPMS) scaffolds, varying in porosity, on the repair of mandibular defects in New Zealand white rabbits. Four TPMS configurations (40%, 50%, 60%, and 70% porosity) were fabricated with ß-tricalcium phosphate bioceramic via additive manufacturing. Scaffold properties were assessed through scanning electron microscopy and mechanical testing. For proliferation and adhesion assays, mouse bone marrow stem cells (BMSCs) were cultured on these scaffolds. In vivo, the scaffolds were implanted into rabbit mandibular defects for 2 months. Histological staining evaluated osteogenic potential. Moreover, RNA-sequencing analysis and RT-qPCR revealed the significant involvement of angiogenesis-related factors and Hippo signaling pathway in influencing BMSCs behavior. Notably, the 70% porosity TPMS scaffold exhibited optimal compressive strength, superior cell proliferation, adhesion, and significantly enhanced osteogenesis and angiogenesis. These findings underscore the substantial potential of 70% porosity TPMS scaffolds in effectively promoting bone regeneration within mandibular defects.

Follow-up study of isolated calf muscular vein thrombosis for anticoagulant therapy after primary hip and knee arthroplasty.

BACKGROUND: Although isolated calf muscular vein thrombosis (ICMVT) is commonly seen after hip and knee arthroplasty, no treatment guidelines for ICMVT after joint replacement are available. The purpose of this study was to evaluate the outcomes of patients with ICMVT for anticoagulant therapy at different time points after primary hip and knee arthroplasty. METHODS: Patients with ICMVT after primary hip and knee arthroplasty were included in the study. Diagnosis was established with Doppler ultrasound. Patients were followed up clinically and with Doppler ultrasound at 1, 2, and 3 months. The outcomes were efficacy (complete resolution) and acceptability (hemorrhagic events). Anticoagulant therapy at curative dosage was prescribed for 1 month and was extended for 2 additional months in case of incomplete resolution at 1 month or if propagation was present. The chi-square test was used to compare the outcomes at different time points. RESULTS: 302 patients were taken hip and knee arthroplasty from January 2021 to May 2022, in which 51 patients presented with 51 ICMVTs postoperatively. The incidence of ICMVT was about 16.89%. Resolution of ICMVT was considered complete at 1, 2, and 3 months at 36.73%, 61.22%, and 91.84%, respectively, with significant differences among the time points (P < 0.05). All patients with ICMVT receiving anticoagulant therapy remained free of propagations and hemorrhagic events within 3 months. CONCLUSION: Our findings provide new insights into the anticoagulant therapy for ICMVT after primary hip and knee arthroplasty, taking oral Rivaroxaban for 3 months is effective and safe, which contributes to provide the reference for clinical practice.

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.

Comparative Efficacy and Safety of Measures for the Treatment of Adults with Isolated Calf Muscular Vein Thrombosis: A Systematic Review and Network Meta-analysis.

BACKGROUND: Isolated calf muscular vein thrombosis (ICMVT) can result in pulmonary embolism, but the treatment of ICMVT remains controversial. Therefore, the purpose of the present study was to investigate the optimal treatment for the ICMVT by comparing the efficacy and safety of different treatments. METHODS: A network meta-analysis was conducted to search for studies published from database inception to April 30, 2022, that compared the outcomes of 2 or more treatments for ICMVT. The primary outcomes were efficacy (resolution rate) and safety (adverse reactions). Data were extracted following predefined hierarchy and the Cochrane Collaboration risk of bias tool was used to evaluate the methodological quality of the included studies. We estimated summary odds ratios with 95% credibility intervals using Bayesian network meta-analysis with random effects. RESULTS: A total of 16 studies were enrolled in the study. In terms of efficacy and safety, urokinase thrombolysis combined with low-molecular-weight heparin (LMWH) was most effective but had the lowest safety, while physical therapy was safest but had the lowest efficacy. More important, direct oral factor Xa inhibitors were most likely to be second most effective and safe compared with other treatments. For the duration of treatment, anticoagulant therapy for at least 3 months could effectively increase the resolution rate of ICMVT. CONCLUSIONS: Considering both efficacy and safety, taking direct oral factor Xa inhibitors for at least 3 months was the optimal treatment compared to LMWH, urokinase thrombolysis combined LMWH, physical therapy and warfarin for patients with ICMVT.

Toxoplasma gondii-induced neutrophil extracellular traps are relevant to glycolysis, TLR2, and TLR4 MAPK signaling pathway in goats.

Toxoplasma gondii (T. gondii) exhibits a significantly high prevalence of infection in goats, leading to adverse consequences such as abortion and stillbirth in ewes, thereby posing a substantial challenge to the goat farming industry. Neutrophil extracellular traps (NETs) have been shown to capture T. gondii in goats; however, the precise mechanisms underlying NET release in goats remain poorly understood. Therefore, the aim of our research was to elucidate the involved mechanism. We assessed the cytotoxicity of T. gondii on neutrophils using CCK-8 assay, visualized the structure of T. gondii-induced goat NETs through immunofluorescence, quantified ROS release during T. gondii-induced NET formation using fluorescence microplate analysis, and employed inhibitors targeting TLR 2, TLR4, NADPH oxidase, ERK1/2, and P38 MAPK signaling pathways as well as glycolysis to dissect the mechanisms underlying T. gondii-induced NET release. Within 1 h, T. gondii did not exhibit significant cytotoxicity towards neutrophils in our findings. The formation of typical NET structures induced by T. gondii involved DNA, citrullinated histone 3 (citH3), and neutrophil elastase (NE). Additionally, T. gondii significantly stimulated the release of NETs in goats. The process was accompanied by the production of reactive oxygen species (ROS) mediated through NADPH oxidase, p38, and ERK1/2 signaling pathways. Inhibition of these pathways resulted in a decrease in NET release. Moreover, inhibition of TLR 2, TLR4, and glycolysis also led to a reduction in T. gondii-induced NET release. Overall, our study demonstrates that T. gondii can induce characteristic NET structures and elucidates the involvement of various mechanisms including TLR2/TLR4 signaling pathway activation, NADPH oxidase activity modulation via ROS production regulation through p38 MAPK and ERK1/2 signaling pathways, and glycolysis regulation during the innate immune response against T. gondii infection in goats.

Using Rasch Wright map to identify hospital employee satisfaction during and before COVID-19.

During the surge of the COVID-19 outbreak, medical personnel attended to countless patients, which adversely affected their mental well-being. To support their staff, hospitals implemented guidelines that focused on promoting mental health among medical professionals. The hypothesis that employee satisfaction declined during the COVID-19 pandemic needs confirmation. Several findings were derived from a series of visualizations using Rasch Wright map. The research sample was taken from a medical center in southern Taiwan based on satisfaction survey data from 2017 to 2022 (n = 1222). Perceptions on job satisfaction perceptions during and prior to COVID-19 in 2 stages of 2017 to 2019 and 2020 to 2022 were compared using Rasch Wright map. Through a series of visualizations, including the dimension with the highest satisfaction, the demographical category of hospital employees with the lowest satisfaction during the pandemic, and Rasch Wright map displaying employs' perfections on 4 domains over years. The results indicated: Employee satisfaction was significantly lower during the COVID-19 period in 2 domains: compensation and benefits, work atmosphere; among the 23 questions, Question 5 (regarding meals provided by the hospital to staff) scored the lowest, while Question 23 (regarding the hospital emergency response and disaster prevention capabilities) scored the highest. Among the 4 domains, organizational leadership had the highest satisfaction; out of 104 demographic variables, 21 groups showed that employee satisfaction during the pandemic was significantly (P < .05) lower than before the pandemic; the selection of specific demographic variables is for top-tier supervisors, and they showed that employee satisfaction during the pandemic was significantly (P < .05) lower than before the pandemic across all 4 dimensions. Therefore, this study accepts the hypothesis that employee satisfaction was negatively affected during the COVID-19 period on 2 domains only: compensation and benefits, work atmosphere. The study visual examination, especially using Rasch Wright map, offers a comparative perspective on hospital staff satisfaction and serves as a methodological guide for subsequent satisfaction research.

Development and psychometric testing of a Chinese version of the postnatal care experience scale for postpartum women.

BACKGROUND: Postnatal period is a critical transitional phase in the lives of mothers and newborn babies. In recent years the importance on promoting a positive experience of care following childbirth is increasingly emphasized. Yet published evidence of the methodological and psychometric quality of instruments to evaluate women's experience of comprehensive postnatal care is still lacking. OBJECTIVE: This study aimed to develop and validate a unique scale (the Chinese version of the Postnatal Care Experience Scale, PCES) to measure women's overall experience of care during postnatal periods. METHODS: The PCES instrument was developed and validated over three phases, including item development, scale development, and scale evaluation. The item pool of the PCES was generated through existing literature and in-depth semi-structured interviews, followed by assessment of content validity and rating of importance and feasibility of items through two-round Delphi surveys. Psychometric properties were examined in a convenience sample of 736 postpartum women. Both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to assess the construct validity of the developed PCES. The relationship between the total PCES score and the global item construct was estimated using Pearson product-moment coefficient. Reliability was assessed using Cronbach's alpha and Spearman Brown coefficients. RESULTS: The content validity index of the Chinese version PCES was 0.867. Following item reduction analysis, this instrument consisted of 30 five-point Likert items. The Kaiser-Meyer-Olkin statistic was 0.964 and the chi-square value of the Bartlett spherical test was 11665.399 (P < .001). The scale explained 75.797% of the total variance and consisted of three subscales, including self-management, social support, and facility- and community-based care. The Pearson correlation coefficient between the total PCES score and the global item construct was 0.909. The CFA showed that the 3-factor model had suitable fitness for the data. Cronbach's alpha value and Spearman-Brown Split-half reliability for the total scale were 0.979 and 0.941, respectively. CONCLUSIONS: The newly developed 30-item PCES is a psychometrically reliable and valid instrument that assesses women's overall experience of postnatal care. Future research should aim to use the PCES in various populations to obtain further evidence for its validity and reliability.

A prediction nomogram for deep venous thrombosis risk in patients undergoing primary total hip and knee arthroplasty: a retrospective study.

INTRODUCTION: Deep venous thrombosis (DVT) prediction after total hip and knee arthroplasty remains challenging. Early diagnosis and treatment of DVT are crucial. This research aimed to develop a nomogram for early DVT prediction. METHODS: A total of 317 patients undergoing primary total hip and knee arthroplasty in Sun Yat-sen Memorial Hospital were enrolled between May 2020 and September 2022. Data from May 2020 to February 2022 were used as the development datasets to build the nomogram model (n = 238). Using multivariate logistic regression, independent variables and a nomogram for predicting the occurrence of DVT were identified. Datasets used to validate the model for internal validation ranged from March 2022 to September 2022 (n = 79). The nomogram's capacity for prediction was also compared with the Caprini score. RESULTS: For both the development and validation datasets, DVT was found in a total of 38 (15.97%) and 9 patients (11.39%) on post-operative day 7 (pod7), respectively. 59.6% patients were symptomatic DVT (leg swelling). The multivariate analysis revealed that surgical site (Knee vs. Hip), leg swelling and thrombin-antithrombin complex (TAT) were associated with DVT. The previously indicated variables were used to build the nomogram, and for the development and validation datasets, respectively. In development and validation datasets, the area under the receiver operating characteristic curve was 0.836 and 0.957, respectively. In both datasets, the predictive value of the Nomogram is greater than the Caprini score. CONCLUSIONS: A proposed nomogram incorporating surgical site (Knee vs. Hip), leg swelling, and thrombin antithrombin complex (TAT) may facilitate the identification of patients who are more prone to develop DVT on pod7.

Trans-acting aptazyme for conditional gene knockdown in eukaryotic cells.

Trans-acting hammerhead ribozyme inherits the advantages of being the smallest and best-characterized RNA-cleaving ribozyme, offering high modularity and the ability to cleave any desired sequence without the aid of any protein, as long as the target sequence contains a cleavage site. However, achieving precise control over the trans-acting hammerhead ribozyme would enable safer and more accurate regulation of gene expression. Herein, we described an intracellular selection of hammerhead aptazyme that contains a theophylline aptamer on stem II based on toxin protein IbsC. Based on the intracellular selection, we obtained three new cis-acting hammerhead aptazymes. Moreover, the corresponding trans-acting aptazymes could be efficiently induced by theophylline to knock down different targeted genes in eukaryotic cells. Notably, the best one, T195, exhibited a ligand-dependent and dose-dependent response to theophylline, and the cleavage efficiency could be enhanced by incorporating multiplex aptazymes.

Pathological characteristics and congenital immunological responses of pigeons-infected with Neospora caninum.

Pigeons are natural intermediate host of Neospora caninum (N. caninum). In comparison to ruminants, N. caninum causes milder clinical symptoms and less financial loss to pigeons. Natural infectious rates and high prevalence of N. caninum in pigeons, and death cases of N. caninum-infected pigeons under experimental conditions have been reported, but the detailed pathological characteristics and congenital immunological responses of pigeons-infected with N. caninum remain not well described. In this study, pigeons were infected intraperitoneally with 107 N. caninum tachyzoites. N. caninum in tissues was detected by qPCR. Pathological changes of tissues were examined by hematoxylin-eosin staining. Blood smears were prepared for counting eosinophils changes in blood. Heterophil extracellular traps (HETs) in vivo and in vitro were quantified by Pico Green. N. caninum-induced HETs structures were observed by immunofluorescence staining. The model of pigeons-infected with N. caninum was successfully established. Lung and duodenum were the main target organs of pigeons-infected with N. caninum. N. caninum caused hemorrhage, edema and inflammatory cell infiltration in liver, pulmonary congestion and hemorrhage, organizational destruction in lung, and shorter villi or even disappear in duodenum. N. caninum also increased the number of eosinophils in blood of pigeons. Moreover, N. caninum-induced HETs release in the congenital immunological system of pigeons were first demonstrated, and the HETs structures were consisted of DNA as the skeleton and modified with citH3 and elastase. N. caninum-induced HETs release was related with NADPH oxidase, TLR 2 and 4, ERK1/2 and p38 MAPK signaling pathways, and glycolysis. In summary, it is the first report on the detailed pathological characteristics and congenital immunological responses of pigeons-infected with N. caninum, which may provide theoretical basis for the prevention and control of Neosporosis in pigeons.

Leveraging Small Molecule-Induced Aptazyme Cleavage for Directed A-to-I RNA Editing.

As a promising therapeutic approach for the correction of pathogenic mutations, the RNA editing process is reversible and tunable without permanently altering the genome. RNA editing mediated by human ADAR proteins offers distinct advantages, including high specificity and low propensity to cause immunogenicity. Herein, we describe a small molecule-inducible RNA editing strategy by incorporating aptazymes into the guide RNA of ADAR-based RNA editing technology. Once small molecules are added or removed, aptazymes trigger self-cleavage to release the guide RNA, achieving small molecule-controlled RNA editing. To satisfy different RNA editing applications, both turn-on and turn-off A-to-I RNA editing of target mRNA have been realized by using on/off-switch aptazymes. Theoretically speaking, this strategy can be applied to various ADAR-based editing systems, which could improve the safety and potential clinical applications of RNA editing technology.

Toxoplasma gondii triggers heterophil extracellular traps via NADPH oxidase, ERK1/2 and P38 signalling pathways, glycolysis and autophagy in chickens.

Toxoplasma gondii is a zoonotic parasite with a global distribution. Heterophil extracellular traps (HETs) are a novel innate immune mechanism of chickens against pathogens, but whether T. gondii can induce HETs release in chickens has not been reported. The effects of T. gondii on heterophils viability were assessed by using Cell Counting Kit-8. T. gondii-induced HETs were observed and analysed by the immunofluorescence method. T. gondii-induced reactive oxygen species (ROS) was determined by the DCFH-DA method. The mechanisms underlying T. gondii-triggered HETs were investigated by inhibitors and fluorescence microplate reader. T. gondii did not significantly affect heterophils viability at a 1:1 ratio within 1 h. It was demonstrated for the first time that T. gondii could induce HETs release in chicken, and the structure of HETs was comprised of DNA, elastase and citrullinated histone 3 (citH3). T. gondii increased ROS production in a dose-dependent manner. Inhibitors of NADPH oxidase, extracellular signal-regulated kinase 1/2 (ERK1/2 ) and P38 signalling pathways, glycolysis and autophagy significantly decreased the release of T. gondii-induced HETs. Taken together, T. gondii can induce HETs release in chickens, and ROS, NADPH oxidase, ERK1/2 and P38 signalling pathways, glycolysis and autophagy participate in the process of HETs release, which provides new insights into the innate immune mechanism of chickens against T. gondii infection.

Reliability and validity of the functional combined anteversion measurement method using standing lateral radiography after total hip arthroplasty.

Background: The functional safe zone of combined anteversion (CA) shows a superior predictive value for dislocation after total hip arthroplasty (THA) compared to that of the Lewinnek safe zone. Thus, it is necessary to establish a feasible and accurate method for assessing CA for the evaluation of dislocation risk. We aimed to evaluate the reliability and validity of using standing lateral (SL) radiographs for determining CA. Methods: Sixty-seven patients who underwent SL radiography and computed tomography (CT) scans after THA were included. Radiographic CA values were obtained via the calculation of the sum of the acetabular cup and femoral stem anteversion (FSA) measurements as obtained from the SL radiographs. Acetabular cup anteversion (AA) was measured based on the tangential line to the face of the cup, whereas FSA was calculated using the developed formula based on the neck-shaft angle. The intra-observer and inter-observer reliabilities for each measurement were examined. Radiological CA values were compared with the CT scan measurements to evaluate their validity. Results: The intra-observer and inter-observer agreements of the SL radiography were excellent [intraclass correlation coefficient (ICC) ≥0.90]. The radiographic measurements correlated well with the CT scan measurements (r=0.869, P<0.001). The mean difference between the radiographic and CT scan measurements was -0.55°±4.68° and ranged from 0.3° to 2.2° in terms of the 95% confidence interval (CI). Conclusions: SL radiography is a reliable and valid imaging tool for the assessment of functional CA.

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.

Post-operative complications of total knee arthroplasty in patients with hypertension.

BACKGROUND: Hypertension is one of the most common comorbidities among patients undergoing surgery. However, few studies have focused on patients undergoing knee arthroplasty, and most of them had small sample sizes. This study aimed to analyze post-operative complications associated with hypertension in patients who underwent knee replacement surgery. METHODS: Data from the 2019 National Inpatient Sample (NIS) database were used. Patients who underwent primary total knee arthroplasty (pTKA) and those who underwent aseptic revision total knee arthroplasty (rTKA) were analyzed separately. Propensity score matching was performed to reduce the effects of demographic factors and comorbidities other than hypertension on post-operative complications. A multinomial logistic regression that included all significantly different demographics and comorbidities was performed to verify the results and evaluate the odds ratios. RESULTS: A total of 107,981 patients who underwent pTKA and 6571 who underwent rTKA owing to mechanical complications were identified in the 2019 NIS database. Compared with the non-hypertension group, patients with hypertension had a higher risk of developing acute renal failure and electrolyte disorders after TKA. Further analysis revealed that hyponatraemia and hypokalaemia were associated with hypertension. CONCLUSIONS: Hypertension was associated with the incidence of acute renal failure after TKA. It is important to identify patients with risk factors for acute renal failure (in addition to hypertension) and take careful measures to prevent acute renal failure in them.

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.

The impact of symmetry design of intangible cultural heritage souvenir on tourists' aesthetic pleasure.

Souvenirs play an important role in tourism development. They act not only as mementos, enabling tourists to relive and retain the memory of a particular journey, but also as main income sources for tourism destinations and stakeholders. Many intangible cultural heritages (ICH) have been developed into souvenirs, especially products made by traditional craftsmanship. ICH souvenirs facilitate cultural value that is understandable to tourists, who appreciate the design of the ICH souvenirs and their contributions to a pleasure and memorable journey. Based on the theory of beauty and the preference-for-prototypes theory, this study explored how symmetry design of ICH souvenirs influences tourist's aesthetic pleasure. As ICH souvenirs development is a commercialization process, and over-commodification would lead to cultures being lost and tourists' disappointment, the authenticity concept is applied in order to address over-commodification. Thus, this study analyzed the moderating role of tourists' authenticity perception of ICH souvenirs. Two lab-based between-subjects design experiments were employed to test the proposed hypotheses. Data analysis entailed multiple regression analysis, one-way ANOVA, and two-way ANOVA. The findings showed that symmetry of ICH souvenir design had a positive impact on tourists' aesthetic pleasure. Under the symmetric-design condition, tourists' typicality perception of ICH souvenirs positively mediated the main relationship, while under the asymmetric-design condition, tourists' novelty perception had a negative mediating effect. The moderated mediation effects were in accord with hypotheses to some extent; at a relatively high level of authenticity perception (above mean value), the indirect effect of symmetry on aesthetic pleasure via typicality perception increased as authenticity perception rose; at a relatively low level of authenticity perception (under mean value), the indirect effect of symmetry on aesthetic pleasure via novelty perception declined as authenticity perception rose. This study identified critical factors influencing tourists' aesthetic pleasure with ICH souvenirs, and it revealed the internal influencing mechanisms and moderating effects under different design conditions. These findings give some insights to ICH practitioners for using souvenir design to improve tourists' aesthetic pleasure.

Virome of Rhipicephalus ticks by metagenomic analysis in Guangdong, southern China.

Tick-borne viruses (TBVs) have increasingly caused a global public health concern. This study collected Rhipicephalus ticks in Guangdong, southern China to identify RNA viruses. Meta-transcriptome analysis revealed the virome in Rhipicephalus ticks, resulting in the discovery of 10 viruses, including Lihan tick virus, Brown dog tick phlebovirus 1 and 2 in the family Phenuiviridae, Mivirus and Wuhan tick virus 2 in the family Chuviridae, Wuhan tick virus 1 in the family Rhabdoviridae, bovine hepacivirus in the family Flaviviridae, Guangdong tick quaranjavirus (GTQV) in the family Orthomyxoviridae, Guangdong tick orbivirus (GTOV) in the family Reoviridae, and Guangdong tick Manly virus (GTMV) of an unclassified family. Phylogenetic analysis showed that most of these TBVs were genetically related to the strains in countries outside China, and GTQV, GTOV, and GTMV may represent novel viral species. These findings provided evidence of the long-distance spread of these TBVs in Guangdong, southern China, suggesting the necessity and importance of TBV surveillance.