Neuroprotective effects of etanercept on diabetic retinopathy via regulation of the TNF-α/NF-κB signaling pathway

Purpose: To study the influence of etanercept on diabetic retinopathy in rats via tumor necrosis factor alpha (TNF-α)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. Methods: Thirty-six Sprague-Dawley (SD) rats were randomly divided into normal, model and etanercept groups. The expression of Caspase-3 was determined by immunohistochemistry, while the relative protein and mRNA expression levels of TNF-α and NF-κB were determined by Western blotting and quantitative polymerase chain reaction, respectively. Besides, the contents of TNF-α and interleukin-1 beta (IL-1β) were evaluated using enzyme-linked immunosorbent assay (ELISA), while cell apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Results: Immunohistochemical studies showed that the mean optical density of tissues positive for caspase-3 in both the model and etanercept groups were significantly higher than in the normal group (p < 0.05), while the mean optical density in the etanercept group was significantly lower than that in the model group (p < 0.05). The protein expression levels of TNF-α and NF-κB in the etanercept group were significantly lower than those in the model group (p < 0.05). Furthermore, mRNA expressions of TNF-α and NF-κB declined in the etanercept group (p < 0.05); in addition, TNF-α, and IL-1β levels in the etanercept group were lower than in the model group (p < 0.05). Cell apoptosis in the etanercept group was also lower than in the model group. Conclusion: Etanercept suppresses TNF-α/NF-κB signaling pathway thereby repressing inflammation and cell apoptosis in diabetic retinopathy rats. Therefore, etenercept’s neuroprotective effect may potentially be useful in developing a suitable therapy for diabetic neuropathy

Baiji genomes reveal low genetic variability and new insights into secondary aquatic adaptations

The baiji, or Yangtze River dolphin (Lipotes vexillifer), is a flagship species for the conservation of aquatic animals and ecosystems in the Yangtze River of China; however, this species has now been recognized as functionally extinct. Here we report a high-quality draft genome and three re-sequenced genomes of L. vexillifer using Illumina short-read sequencing technology. Comparative genomic analyses reveal that cetaceans have a slow molecular clock and molecular adaptations to their aquatic lifestyle. We also find a significantly lower number of heterozygous single nucleotide polymorphisms in the baiji compared to all other mammalian genomes reported thus far. A reconstruction of the demographic history of the baiji indicates that a bottleneck occurred near the end of the last deglaciation, a time coinciding with a rapid decrease in temperature and the rise of eustatic sea level

Activation of GSDME by Lithospermum erythrorhizon drives pyroptotic cell death

Objective: To reveal GSDME-executed pyroptosis in cancer cells induced by the Chinese traditional herbal medicine plant Lithospermum erythrorhizon (L. erythrorhizon, Zi Cao) and to investigate the potential mechanism. Methods: L. erythrorhizon was extracted by ultrasonication in 95% ethanol, and determined using high-performance liquid chromatography (HPLC). HeLa, A549, SW620, HEK-293 T, THP-1, K562, Raw264.7 and MDA-MB-231 cell lines were used to investigate the morphology and mechanism of pyroptosis induced by L. erythrorhizon. The lactate dehydrogenase (LDH) release, propidium iodide (PI)/Hoechst double-staining, and pyroptosis reconstitution experiments were performed to study L. erythrorhizon -induced cell pyroptosis. Results: Compared with the death inhibitor, PI/Hoechst and LDH release experiments, we found that L. erythrorhizon induced pyroptosis. Recombination and western blot experiments confired that L. erythrorhizon induced GSDME cleavage, which drives pyroptosis. This phenomenon is conserved in several cancer cell lines that might be triggered by caspase family proteases. The mechanism of L. erythrorhizon inducing pyroptosis is widely found in tumor cells. Conclusion: Our findings not only explain how L. erythrorhizon triggers cancer cell pyroptosis, but also provide mechanistic insights to guide its clinical application in the future

Recognition of Areca Leaf Yellow Disease Based on PlanetScope Satellite Imagery

Areca yellow leaf disease is a major attacker of the planting and production of arecanut. The continuous expansion of arecanut (Areca catechu L.) planting areas in Hainan has placed a great need to strengthen the monitoring of this disease. At present, there is little research on the monitoring of areca yellow leaf disease. PlanetScope imagery can achieve daily global coverage at a high spatial resolution (3 m) and is thus suitable for the high-precision monitoring of plant pest and disease. In this paper, PlanetScope images were employed to extract spectral features commonly used in disease, pest and vegetation growth monitoring for primary models. In this paper, 13 spectral features commonly used in vegetation growth and pest monitoring were selected to form the initial feature space, followed by the implementation of the Correlation Analysis (CA) and independent t-testing to optimize the feature space. Then, the Random Forest (RF), Backward Propagation Neural Network (BPNN) and AdaBoost algorithms based on feature space optimization to construct double-classification (healthy, diseased) monitoring models for the areca yellow leaf disease. The results indicated that the green, blue and red bands, and plant senescence reflectance index (PSRI) and enhanced vegetation index (EVI) exhibited highly significant differences and strong correlations with healthy and diseased samples. The RF model exhibits the highest overall recognition accuracy for areca yellow leaf disease (88.24%), 2.95% and 20.59% higher than the BPNN and AdaBoost models, respectively. The commission and omission errors were lowest with the RF model for both healthy and diseased samples. This model also exhibited the highest Kappa coefficient at 0.765. Our results exhibit the feasible application of PlanetScope imagery for the regional large-scale monitoring of areca yellow leaf disease, with the RF method identified as the most suitable for this task. Our study provides a reference for the monitoring, a rapid assessment of the area affected and the management planning of the disease in the agricultural and forestry industries

Factors influencing the bone mineral density in Duroc boars

Abstract Background Leg weakness affects animal welfare and is one of the primary reasons for culling of boars. Low bone mineral density (BMD) is one of the primary factors contributing to leg weakness. Low BMD also appeared to be associated with severe bone pain and has the highest risk of skeletal fragility. Surprisingly, few studies have been performed on the factors influencing BMD in pigs. Therefore, the primary aim of this study was to identify the influencing factors on boar BMD. Herein, the BMD data were determined through the use of ultrasonography from 893 Duroc boars. Logistic regression model was utilized in the analysis of BMD, in which the explanatory variables in the model were lines, ages, body weights, backfat thicknesses and serum mineral element concentrations (Ca, P, Mg, Cu, Fe, Zn, Mn, Se, Pb and Cd). Results Results showed that factors significantly influencing BMD included serum Ca, P concentrations, ages and backfat thicknesses (P < 0.05), in which serum Ca concentrations were positively correlated with BMD (P < 0.01), whereas increasing concentrations of serum P decreased BMD (P < 0.01). The serum Ca/P ratio showed significant quadratic effects on BMD (r = 0.28, P < 0.01), and the Ca/P ratio to achieve the best BMD was determined to be 3.7. Furthermore, BMD also changed with age quadratically (r = 0.40, P < 0.01), and reached a peak value around 47 months. Interestingly, a quadratic (r = 0.26, P < 0.01) increase in the BMD was observed as backfat thickness increased, and the inflection point was calculated at around 17 mm. Conclusion In conclusion, BMD characteristics of boars could be detected by ultrasonic method, and serum Ca, serum P, age, and backfat thickness contributed to the greatest effect on BMD

A case of Cardiobacterium valvarum endocarditis with cerebral hemorrhage after MVR, TVP and vegetation removal operation

Abstract Background Cardiobacterium is a fastidious Gram-negative bacillus, and is a rare human pathogen in clinical settings. Herein, we describe a case of Cardiobacterium valvarum (C. valvarum) endocarditis with a rare complication of cerebral hemorrhage after mitral valve replacement (MVR), tricuspid valve prosthesis (TVP) and vegetation removal operation. Case presentation A 41-year-old woman who had a history of gingivitis developed into infective endocarditis due to the infection of C. valvarum. Then, she was hospitalized to receive MVR, TVP and vegetation removal operation. The indicators of patient tended to be normal until the abrupt cerebral hemorrhage occurred on day 15 after operation. This is the first well-described case of C. valvarum infection in China, and the first report of C. valvarum endocarditis with cerebral hemorrhage after MVR, TVP and vegetation removal operation worldwide. Conclusions We reported the first case of C. valvarum infection in China clinically, with a rare complication of cerebral hemorrhage after MVR, TVP and vegetation removal operation

SARS-CoV-2 spike host cell surface exposure promoted by a COPI sorting inhibitor

Via an insufficient coat protein complex I (COPI) retrieval signal, the majority of SARS-CoV-2 spike (S) is resident in host early secretory organelles and a tiny amount is leaked out in cell surface. Only surface-exposed S can be recognized by B cell receptor (BCR) or anti-S therapeutic monoclonal antibodies (mAbs) that is the trigger step for B cell activation after S mRNA vaccination or infected cell clearance by S mAbs. Now, a drug strategy to promote S host surface exposure is absent. Here, we first combined structural and biochemical analysis to characterize S COPI sorting signals. A potent S COPI sorting inhibitor was then invented, evidently capable of promoting S surface exposure and facilitating infected cell clearance by S antibody-dependent cellular cytotoxicity (ADCC). Importantly, with the inhibitor as a probe, we revealed Omicron BA.1 S is less cell surface exposed than prototypes because of a constellation of S folding mutations, possibly corresponding to its ER chaperone association. Our findings not only suggest COPI is a druggable target against COVID-19, but also highlight SARS-CoV-2 evolution mechanism driven by S folding and trafficking mutations

Synovium is a sensitive tissue for mapping the negative effects of systemic iron overload in osteoarthritis: identification and validation of two potential targets

Abstract Background The prevention and treatment of osteoarthritis (OA) pose a major challenge in its research. The synovium is a critical tissue in the systematic treatment of OA. The present study aimed to investigate potential target genes and their correlation with iron overload in OA patients. Methods The internal datasets for analysis included the microarray datasets GSE46750, GSE55457, and GSE56409, while the external datasets for validation included GSE12021 and GSE55235. The GSE176308 dataset was used to generate single-cell RNA sequencing profiles. To investigate the expression of the target genes in synovial samples, quantitative reverse transcription-PCR, western blotting, and immunohistochemical assay were conducted. ELISA was used to detect the levels of ferritin and Fe2+ in both serum and synovium. Results JUN and ZFP36 were screened from the differentially expressed genes, and their mRNA were significantly reduced in the OA synovium compared to that in normal synovium. Subsequently, complex and dynamically evolving cellular components were observed in the OA synovium. The mRNA level of JUN and ZFP36 differed across various cell clusters of OA synovium and correlated with immune cell infiltration. Moreover, ferritin and Fe2+ were significantly increased in the serum and synovium of OA patients. Further, we found that JUN elevated and ZFP36 decreased at protein level. Conclusions The synovium is a sensitive tissue for mapping the adverse effects of systemic iron overload in OA. JUN and ZFP36 represent potential target genes for attenuating iron overload during OA treatment. Some discrepancies between the transcription and protein levels of JUN suggest that post-transcriptional modifications may be implicated. Future studies should also focus on the roles of JUN and ZFP36 in inducing changes in cellular components in the synovium during OA pathogenesis

Exosomal U2AF2 derived from human bone marrow mesenchymal stem cells attenuates the intervertebral disc degeneration through circ_0036763/miR-583/ACAN axis

Intervertebral disc degeneration (IDD) is one of the major leading causes of back pain affecting the patient's quality of life. However, the roles of circular RNA (circRNA) in IDD remains unclear. This study aimed to explore the function and underlying mechanism of circ_0036763 in IDD. In this study, expressions of circ_0036763, U2 small nuclear RNA auxiliary factor 2 (U2AF2), miR-583 and aggrecan (ACAN) in primary human nucleus pulposus cells (HNPCs) derived from IDD patients and healthy controls were detected by quantitative real-time reverse transcription-PCR (qRT-PCR) or Western blot (WB). The relationship between pre-circ_0036763 and U2AF2, circ_0036763 and miR-583, miR-583 and ACAN mRNA was determined by bioinformatic analysis, miRNA pull down or RNA immunoprecipitation (RIP) assay. The expressions of Collagen I and Collagen II were evaluated by WB. Co-culture of bone marrow mesenchymal stem cells (bMSCs) or bMSCs-derived exosomes and HNPCs were performed to identify the effect of U2AF2 on the mature of circ_0036763 and ACAN. Results indicated that circ_0036763, U2AF2 and ACAN were downregulated while miR-583 was upregulated in HNPCs derived from IDD patients compared with that in normal HNPCs. Besides, overexpression of circ_0036763 elevated the expressions of ACAN and Collagen II whereas reduced Collagen I expression in HNPCs. Moreover, U2AF2 promoted the mature of circ_0036763, and circ_0036763 positively regulated ACAN by directly sponging miR-583. Furthermore, exosomal U2AF2 derived from bMSCs could increase U2AF2 levels in HNPCs and subsequently regulate the expression of ACAN by circ_0036763/miR-583 axis. In summary, circ_0036763 modified by exosomal U2AF2 derived from bMSCs alleviated IDD through regulating miR-583/ACAN axis in HNPCs. Thus, this study might provide novel therapeutic targets for IDD