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This study aimed to establish a novel noninvasive model based on the serum N-glycan spectrum for providing an objective value for determining the stage of liver necroinflammation related to chronic hepatitis B (CHB) patients. N-glycan profiles of the sera of 295 treatment-naïve CHB patients were analyzed. N-glycan profiles were tested for different liver necroinflammation stages using DNA sequence-assisted fluorophore-assisted carbohydrate electrophoresis. A serum N-glycan model named N-glycan-LI (NGLI) using support vector machine was selected to evaluate the classification of liver necroinflammation (G < 2 and G ≥ 2). The area under the receiver operating characteristic curves (AUROCs) was 0.898 (training set, n = 236) and 0.911 (validation set, n = 59) regardless of the stage of liver fibrosis (AUROC = 0.886 and 0.926, respectively, in S < 2 and S ≥ 2 group). The NGLI correspondingly had the highest specificity (SP) of 90.79% and negative predictive value of 92.00% in an inactive stage (including immune-tolerant [IT] and inactive-carrier [IC] stage), had the highest positive predictive value of 95.18% in stage immune-active, and had the highest SP of 93.94% in grey zone IT + IC. N-glycan profiles appear to correlate well with hepatic necroinflammation in CHB when compared with liver biopsy. The newly developed model appears to reliably predict liver damage in naïve-treatment patients with CHB.
Subject(s)
Biomarkers , Hepatitis B, Chronic , Liver , Polysaccharides , Humans , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/pathology , Polysaccharides/blood , Male , Female , Adult , Biomarkers/blood , Liver/pathology , Middle Aged , ROC Curve , Necrosis , Young Adult , Inflammation/blood , Liver Cirrhosis/blood , Liver Cirrhosis/pathology , Liver Cirrhosis/diagnosis , Sensitivity and SpecificityABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Euonymus alatus (Thunb.) Siebold. (EA), a traditional Chinese medicine, is widely used in the treatment of diabetes. Our group has previously found that EA could treat diabetic retinopathy (DR) and stigmast-4-en-3-one (Numbered E6) is the active substance responsible for inhibiting angiogenesis in vitro by EA. However, the effects and mechanisms of E6 in the treatment of DR is still unknown. AIM OF THE STUDY: The aim of this study was to investigate the effects and mechanisms of E6 in EA on DR. Additionally, a comparison was made between the effects of E6 and triamcinolone acetonide (TA), as well as the side effects of E6 and dexamethasone. MATERIALS AND METHODS: Ocular affinity assessment and pharmacokinetic parameter prediction were conducted to evaluate the potential of E6 to treat DR. Retinal endothelial cells were used to investigate the in vitro inhibitory effect of E6 on vascular proliferation. Additionally, chicken embryos, zebrafish, and mice were used to investigate the in vivo anti-vascular proliferation effect of E6. Finally, diabetic mice were used to investigate whether E6 improves diabetic retinopathy and to compare its efficacy with that of TA. We then used network pharmacology to study the targets of E6 and performed molecular docking; followed by immunofluorescence experiments, ELISA, Western blot, and tube formation experiments to further investigate its mechanism. Finally, we compared the side effects of E6 with those of dexamethasone. RESULTS: E6 was found to have an affinity for the eye and to inhibit vascular proliferation both in vivo and in vitro. Moreover, E6 was found to be more efficacious than TA in the treatment of DR. Molecular docking experiments predicted that the glucocorticoid receptor (GR) is a potential target of E6, and immunofluorescence analyses confirmed that E6 upregulated the expression of the GR in the retina of hyperglycemic mice. In addition, western blotting results and tube formation experiments showed that E6 also attenuated angiogenesis by inhibiting the Hippo and VEGF pathways. Finally, by comparing the effects of E6 and dexamethasone on glucose regulation and osteoporosis, E6 was found to have fewer side effects. CONCLUSIONS: E6 is a highly effective drug for the treatment of DR, superior to TA and with fewer side effects than dexamethasone. Its mechanism involves the activation of glucocorticoid receptor and inhibition of Hippo and VEGF pathways to alleviate angiogenesis and inflammation. This study is the first to investigate the role and mechanism of E6 in improving DR. The findings suggest that E6 has unique advantages in the treatment of DR.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Retinopathy , Euonymus , Receptors, Glucocorticoid , Zebrafish , Animals , Diabetic Retinopathy/drug therapy , Mice , Receptors, Glucocorticoid/metabolism , Chick Embryo , Diabetes Mellitus, Experimental/drug therapy , Euonymus/chemistry , Male , Molecular Docking Simulation , Dexamethasone/pharmacology , Mice, Inbred C57BL , Cell Proliferation/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Angiogenesis Inhibitors/pharmacology , Triamcinolone Acetonide/pharmacology , AngiogenesisABSTRACT
Background: Angiogenesis plays a pivotal role in colorectal cancer (CRC), yet its underlying mechanisms demand further exploration. This study aimed to elucidate the significance of angiogenesis-related genes (ARGs) in CRC through comprehensive multi-omics analysis. Methods: CRC patients were categorized according to ARGs expression to form angiogenesis-related clusters (ARCs). We investigated the correlation between ARCs and patient survival, clinical features, consensus molecular subtypes (CMS), cancer stem cell (CSC) index, tumor microenvironment (TME), gene mutations, and response to immunotherapy. Utilizing three machine learning algorithms (LASSO, Xgboost, and Decision Tree), we screen key ARGs associated with ARCs, further validated in independent cohorts. A prognostic signature based on key ARGs was developed and analyzed at the scRNA-seq level. Validation of gene expression in external cohorts, clinical tissues, and blood samples was conducted via RT-PCR assay. Results: Two distinct ARC subtypes were identified and were significantly associated with patient survival, clinical features, CMS, CSC index, and TME, but not with gene mutations. Four genes (S100A4, COL3A1, TIMP1, and APP) were identified as key ARCs, capable of distinguishing ARC subtypes. The prognostic signature based on these genes effectively stratified patients into high- or low-risk categories. scRNA-seq analysis showed that these genes were predominantly expressed in immune cells rather than in cancer cells. Validation in two external cohorts and through clinical samples confirmed significant expression differences between CRC and controls. Conclusion: This study identified two ARG subtypes in CRC and highlighted four key genes associated with these subtypes, offering new insights into personalized CRC treatment strategies.
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Immune therapy has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients, yet its efficacy remains limited, underscoring the urgency to identify new therapeutic targets and biomarkers. Here, we investigated the pathological and physiological roles of KIF20A and assess its potential in enhancing HCC treatment efficacy when combined with PD-1 inhibitors. We initially assess KIF20A's oncogenic function using liver-specific KIF20A knockout (Kif20a CKO) mouse models and orthotopic xenografts. Subsequently, we establish a regulatory axis involving KIF20A, FBXW7, and c-Myc, validated through construction of c-Myc splicing mutants. Large-scale clinical immunohistochemistry (IHC) analyses confirm the pathological relevance of the KIF20A-FBXW7-c-Myc axis in HCC. We demonstrate that KIF20A overexpression correlates with poor prognosis in HCC by competitively inhibiting FBXW7-mediated degradation of c-Myc, thereby promoting glycolysis and enhancing tumor proliferation. Conversely, KIF20A downregulation suppresses these effects, impairing tumor growth through c-Myc downregulation. Notably, KIF20A inhibition attenuates c-Myc-induced MMR expression, associated with improved prognosis in HCC patients receiving PD-1 inhibitor therapy. Furthermore, in Kif20a CKO HCC mouse models, we observe synergistic effects between Kif20a knockout and anti-PD-1 antibodies, significantly enhancing immunotherapeutic efficacy against HCC. Our findings suggest that targeting the KIF20A-c-Myc axis could identify HCC patients likely to benefit from anti-PD-1 therapy. In conclusion, we propose that combining KIF20A inhibitors with anti-PD-1 treatment represents a promising therapeutic strategy for HCC, offering new avenues for clinical development and patient stratification.
Subject(s)
Carcinoma, Hepatocellular , F-Box-WD Repeat-Containing Protein 7 , Kinesins , Liver Neoplasms , Proto-Oncogene Proteins c-myc , Ubiquitination , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Liver Neoplasms/immunology , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Animals , Humans , Mice , Kinesins/genetics , Kinesins/antagonists & inhibitors , Kinesins/metabolism , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , F-Box-WD Repeat-Containing Protein 7/genetics , F-Box-WD Repeat-Containing Protein 7/metabolism , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Cell Line, Tumor , Mice, Knockout , Xenograft Model Antitumor Assays , Cell Proliferation , Immunotherapy/methods , Male , Prognosis , Gene Expression Regulation, NeoplasticABSTRACT
The global meridional overturning circulation (GMOC) is important for redistributing heat and, thus, determining global climate, but what determines its strength over Earth's history remains unclear. On the basis of two sets of climate simulations for the Paleozoic characterized by a stable GMOC direction, our research reveals that GMOC strength primarily depends on continental configuration while climate variations have a minor impact. In the mid- to high latitudes, the volume of continents largely dictates the speed of westerly winds, which in turn controls upwelling and the strength of the GMOC. At low latitudes, open seaways also play an important role in the strength of the GMOC. An open seaway in one hemisphere allows stronger westward ocean currents, which support higher sea surface heights (SSH) in this hemisphere than that in the other. The meridional SSH gradient drives a stronger cross-equatorial flow in the upper ocean, resulting in a stronger GMOC. This latter finding enriches the current theory for GMOC.
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N-glycosylation is a highly conserved glycan modification that plays crucial roles in various physiological processes, including protein folding, trafficking, and signal transduction. Porcine deltacoronavirus (PDCoV) poses a newly emerging threat to the global porcine industry. The spike protein of PDCoV exhibits a high level of N-glycosylation; however, its role in viral infection remains poorly understood. In this study, we applied a lentivirus-based entry reporter system to investigate the role of N-glycosylation on the viral spike protein during PDCoV entry stage. Our findings demonstrate that N-glycosylation at positions 652 and 661 of the viral spike protein significantly reduces the infectivity of PDCoV pseudotyped virus. Overall, our results unveil a novel function of N-glycosylation in PDCoV infection, highlighting its potential for facilitating the development of antiviral strategies.
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The amyloid states of proteins are implicated in several neurodegenerative diseases and bioadhesion processes. However, the classical amyloid fibrillization mechanism fails to adequately explain the formation of polymorphic aggregates and their adhesion to various surfaces. Herein, we report a non-fibril amyloid aggregation pathway, with disulfide-bond-reduced lysozyme (R-Lyz) as a model protein under quasi-physiological conditions. Very different from classical fibrillization, this pathway begins with the air-water interface (AWI) accelerated oligomerization of unfolded full-length protein, resulting in unique plate-like oligomers with self-adaptive ability, which can adjust their conformations to match various interfaces such as the asymmetric AWI and amyloid-protein film surface. The pathway enables a stepwise packing of the plate-like oligomers into a 2D Janus nanofilm, exhibiting a divergent distribution of hydrophilic/hydrophobic residues on opposite sides of the nanofilm. The resulting Janus nanofilm possesses a top-level Young's modulus (8.3 ± 0.6 GPa) among amyloid-based materials and exhibits adhesive strength two times higher (145 ± 81 kPa) than that of barnacle cement. Furthermore, we found that such an interface-directed pathway exists in several amyloidogenic proteins with a similar self-adaptive 2D-aggregation process, including bovine serum albumin, insulin, fibrinogen, hemoglobin, lactoferrin, and ovalbumin. Thus, our findings on the non-fibril self-adaptive mechanism for amyloid aggregation may shed light on polymorphic amyloid assembly and their adhesions through an alternative pathway.
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This paper studies the dynamic response characteristics of the scanning angle in a liquid crystal cladding waveguide beam scanner. Based on liquid crystal dynamic theory, finite element analysis and vectorial refraction law, a dynamic response calculation model of scanning angle is constructed. The simulation results show that the dynamic responses of the scanning angle during the electric field-on and field-off processes are asymmetric, and exhibit "S"-shape and "L"-shape changing trends, respectively. In addition, by comparing with the bulk phase modulation response process of traditional liquid crystal devices, the intrinsic physical reason for the rapid light regulation of the liquid crystal cladding waveguide beam scanner is clarified to be that the liquid crystal close to the core layer has a faster rotation speed during the electric field-off process. Moreover, the liquid crystal cladding waveguide beam scanner is experimentally tested, and the experiment results are in good agreement with theoretical simulations.
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ETHNOPHARMACOLOGICAL RELEVANCE: Potentilla Anserina Linnaeus, a traditional Chinese herb with ethnic characteristics, is considered a superior material by the people of Qinghai and Tibet. Traditionally, it has been used to invigorate the spleen, quench thirst, tonify the blood, astringing to stop bleeding, and relieve diarrhea. This is the reason for its frequent usage in treating spleen deficiency, diarrhea, and various bleeding disorders. At the same time, P. anserina is often consumed as food by the Tibetan people to obtain nourishment and health benefits. AIM OF THE REVIEW: The present review provides a systematic description of P. anserina, covering its botany, ethnopharmacology, phytochemical constituents, and various pharmacological activities of extracts. This overview aims to provide insights into research directions and potential applications of P. anserina. MATERIALS AND METHODS: Information on P. anserina was gathered through various sources, including Google Scholar, PubMed, Elsevier, CNKI, and Web of Science. In addition, information was available from native texts and prominent ethnopharmacologists. RESULTS: So far, 154 different chemical substances have been isolated and identified from P. anserina, with tannins, flavonoids, and triterpenes accounting for the majority. Polysaccharides and triterpenes are the main material components responsible for the pharmacological activity of P. anserina. Research shows that P. anserina exhibits rich pharmacological activities, including antioxidant, antiviral, blood tonic, immune regulation, cardiovascular system treatment, diabetes treatment, and liver protection. CONCLUSIONS: Some traditional applications of P. anserina have been confirmed. However, due to incomplete evaluation indicators and other reasons, further in vitro and in vivo studies are needed to clarify its pharmacological evaluation, which remains a focus of future research. Additionally, we recommend that future studies concentrate on the quality control and safety evaluation of P. anserina to address research gaps and offer theoretical support for the plant's potential functions and clinical applications.
Subject(s)
Ethnopharmacology , Phytochemicals , Potentilla , Humans , Potentilla/chemistry , Phytochemicals/pharmacology , Phytochemicals/therapeutic use , Animals , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Phytotherapy , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic useABSTRACT
Objective: To analyse clinical manifestations of unexplained abnormal liver function and perform hepatobiliary histopathology procedures on patients to evaluate the value of liver biopsy in diagnosing the aetiology of unexplained abnormal liver function. Methods: A convenience sampling method was used to retrospectively collect the data of patients who were diagnosed with unexplained abnormal liver function and who received liver biopsy in the Pathology Department of Tianjin Second People's Hospital, China, between March 2022 and July 2023 to analyse liver pathology and clinical manifestations. Results: A total of 1302 patients were included in this study, which mainly included 11 diseases: autoimmune liver disease (74 cases, 5.68%), drug-induced liver injury (DILI) (204 cases, 15.67%), cancer (237 cases, 18.20%), non-alcoholic fatty liver disease (104 cases, 7.99%), non-alcoholic steatohepatitis (74 cases, 5.68%), viral hepatitis (490 cases, 37.63%), other types of hepatitis (30 cases, 2.30%), cholestatic liver disease (17 cases, 1.31%), alcoholic liver disease (15 cases, 1.15%), hepatic cyst (5 cases, 0.38%) and Gilbert syndrome (4 cases, 0.31%). The success rate of liver biopsy sampling was 100%, and (1.52 ± 0.130) tissue strips were sampled. The average operating time was 11.52 minutes. The percutaneous liver biopsy did not significantly increase short-term liver function index values (serum γ-glutamyl transpeptidase, total bilirubin, alanine transaminase, aspartate aminotransferase, alkaline phosphatase). Ninety-two patients had a small amount of liver subcapsular fluid, but there was no progress after medical treatment. Conclusion: Ultrasound-guided percutaneous liver biopsy has value in the diagnosis of unexplained abnormal liver function. Viral hepatitis, cancer and DILI are the most common causes of unexplained abnormal liver function. Liver biopsy does not aggravate the organic and functional impairment of the liver.
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BACKGROUND: Interferon-induced transmembrane protein 2 (IFITM2) is involved in repressing viral infection. This study aim to investigate the expression of IFITM2 in colorectal cancer (CRC) and explore its effect on cell proliferation, migration, and invasion. METHODS: We analyzed The Cancer Genome Atlas (TCGA) database for IFITM2 expression in colorectal cancer and used western blots to detect IFITM2 protein in specimens and cell lines of colorectal cancers. To assess the association between IFITM2 and clinical features, both univariate and multivariate cox regression analysis were conducted. Kaplan-Meier plots were used in the TCGA database to assess IFITM2 gene expression's prognostic significance. Silencing IFITM2 in SW480 and HCT116 cells was achieved by transient transfection with siRNA. Proliferation of CRCs was examined using Cell Counting Kit-8. The effect of IFITM2 on the migration and invasion of CRC cells was studied using wound healing and transwell assays. Gene set enrichment analysis (GSEA) was used to examine IFITM2-associated pathways and Western blotting was used to confirm it. RESULTS: IFITM2 was over-expressed in the CRC tissues and cells, with high IFITM2 expression related to the tumor N, M, and pathologic stages. The presence of IFITM2 significantly impacted patient survival in CRC. The proliferation of SW480 and HCT116 cells was suppressed when IFITM2 was silenced, resulting in weakened migration and invasion of CRC cells. GSEA analysis showed that IFITM2 was positively related to the phosphoinositide 3-kinase (PI3K)/AKT pathway, and western blot results confirmed that IFITM2 activated it. CONCLUSIONS: IFITM2 was over-expressed in CRC and modulated the PI3K/AKT pathway to promote CRC cells proliferation and metastasis.
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Chelidonium majus L. contained alkaloids as its main component, exhibiting various biological activities, particularly antibacterial activity. This study aimed to extract alkaloids from C. majus L. (total alkaloids) and evaluate their antibacterial activity both in vitro and in vivo. Reflux extraction was carried out on C. majus L., and the extract was purified with HPD-600 macroporous resin and 732 cation exchange resin columns. Infection modeling of Caenorhabditis elegans (C. elegans) was established to investigate the impact of Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-sensitive Staphylococcus aureus (MSSA) on the motility, longevity, and reactive oxygen species (ROS) levels of wild-type worms (N2 strain). The effects of total alkaloids on longevity and ROS were further evaluated in infected N2 worms. Additionally, the effect of total alkaloids on the stress resistance of C. elegans and the mechanism of action were investigated. By utilizing CB1370, DR26 and CF1038 transgenic strains of C. elegans to identify whether the antibacterial activity of total alkaloids was dependent on DAF-2/DAF-16 pathway. The results showed that total alkaloids exhibited a significant antibacterial activity against both MRSA and MSSA (MIC 31.25 µg/mL). Compared with MSSA, the MRSA exhibited a stronger inhibitory effect on the movement behavior and development of worms, along with faster pathogenicity and unique virulence factors. Total alkaloids also displayed the ability to extend the lifespan of C. elegans under oxidative stress and heat stress, and reduce the expression of ROS. The antibacterial activity of total alkaloids was primarily dependent on the DAF-2/DAF-16 pathway, and the presence of functional DAF-2 was deemed essential in total alkaloids mediated immune response against MRSA. Moreover, the antibacterial and anti-infection effects of total alkaloids were found to be associated with the daf-16 gene fragment.
Subject(s)
Alkaloids , Anti-Bacterial Agents , Caenorhabditis elegans , Chelidonium , Methicillin-Resistant Staphylococcus aureus , Caenorhabditis elegans/drug effects , Animals , Alkaloids/pharmacology , Alkaloids/isolation & purification , Methicillin-Resistant Staphylococcus aureus/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , Chelidonium/chemistry , Reactive Oxygen Species/metabolism , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Longevity/drug effects , Caenorhabditis elegans Proteins , Plant Extracts/pharmacology , Plant Extracts/chemistry , Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Chelidonium majusABSTRACT
Dysphagia is a common complication of various clinical conditions, with an increased incidence as age advances. Complications such as aspiration, malnutrition, and aspiration pneumonia caused by dysphagia significantly affect the overall treatment outcomes of patients. Scholars both domestically and internationally are increasingly focusing on early rehabilitation for dysphagia. This article summarizes common conditions causing dysphagia, clinical manifestations, complications, screening assessment, diagnosis, rehabilitation, and nutritional support related to dysphagia. It emphasizes the arrival at a multidisciplinary collaborative diagnosis and formulation of a rehabilitation management plan for dysphagia in general hospitals in order to provide strategic suggestions for establishing a multidisciplinary collaborative model for swallowing disorder management in general hospitals.
Subject(s)
Deglutition Disorders , Hospitals, General , Humans , Deglutition Disorders/rehabilitation , Deglutition Disorders/diagnosis , Deglutition Disorders/therapy , Patient Care Team/organization & administrationABSTRACT
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a new nomenclature proposed in 2023. We aimed to compare the diagnostic efficacy of noninvasive tests (NITs) for advanced fibrosis under different nomenclatures in patients with chronic hepatitis B (CHB). A total of 844 patients diagnosed with CHB and concurrent steatotic liver disease (SLD) by liver biopsy were retrospectively enrolled and divided into four groups. The performances of fibrosis-4 (FIB-4), gamma-glutamyl transpeptidase to platelet ratio index (GPRI), aspartate aminotransferase to platelet ratio index (APRI), and liver stiffness measurement (LSM) were compared among the four groups. The four NITs showed similar diagnostic efficacy for nonalcoholic fatty liver disease (NAFLD), MASLD, and metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with CHB with advanced fibrosis. LSM showed the most stable accuracy for NAFLD (AUC = 0.842), MASLD (AUC = 0.846), and MAFLD (AUC = 0.863) compared with other NITs (p < 0.05). Among the four NITs, APRI (AUC = 0.841) and GPRI (AUC = 0.844) performed best in patients with CHB & MetALD (p < 0.05). The cutoff value for GPRI in patients with CHB & MetALD was higher than that in the other three groups, while further comparisons of NITs at different fibrosis stages showed that the median GPRI of CHB & MetALD (1.113) at F3-4 was higher than that in the CHB & MASLD group (0.508) (p < 0.05). Current NITs perform adequately in patients with CHB and SLD; however, alterations in cutoff values for CHB & MetALD need to be noted.
Subject(s)
Hepatitis B, Chronic , Non-alcoholic Fatty Liver Disease , Humans , Hepatitis B, Chronic/complications , Liver Cirrhosis/pathology , Retrospective Studies , Biomarkers , Biopsy , Aspartate Aminotransferases , ROC Curve , Liver/pathologyABSTRACT
In China, porcine reproductive and respiratory syndrome virus (PRRSV) vaccines are widely used. These vaccines, which contain inactivated and live attenuated vaccines (LAVs), are produced by MARC-145 cells derived from the monkey kidney cell line. However, some PRRSV strains in MARC-145 cells have a low yield. Here, we used two type 2 PRRSV strains (CH-1R and HuN4) to identify the genes responsible for virus yield in MARC-145 cells. Our findings indicate that the two viruses have different spread patterns, which ultimately determine their yield. By replacing the viral envelope genes with a reverse genetics system, we discovered that the minor envelope proteins, from GP2a to GP4, play a crucial role in determining the spread pattern and yield of type 2 PRRSV in MARC-145 cells. The cell-free transmission pattern of type 2 PRRSV appears to be more efficient than the cell-to-cell transmission pattern. Overall, these findings suggest that GP2a to GP4 contributes to the spread pattern and yield of type 2 PRRSV.
Subject(s)
Guanidines , Piperazines , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Vaccines , Swine , Animals , Porcine respiratory and reproductive syndrome virus/genetics , Cell LineABSTRACT
A real spatial continuous modeling of climate and carbon cycle is developed, and tested for early Cenozoic from 60 Ma to 40 Ma.
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Pelagic Sargassum in the Gulf of Mexico (GoM) plays an important role in ocean biology and ecology, yet our knowledge of its origins and transport pathways is limited. Here, using satellite observations of Sargassum areal density and ocean surface currents between 2000 and 2023, we show that large amounts of Sargassum in the GoM can either originate from the northwestern GoM or be a result of physical transport from the northwestern Caribbean Sea, both with specific transport pathways. Sargassum of the northwestern GoM can be transported to the eastern GoM by ocean currents and eddies, eventually entering the Sargasso Sea. Sargassum entering the GoM from the northwestern Caribbean Sea can be transported in three different directions, with the northward and eastward transports governed by the Loop Current System (LCS) and westward transport driven by the westward extension of the LCS, the propagation or relaying of ocean eddies, the wind-driven westward currents on the Campeche Bank with or without eddies, and the westward currents with/without currents associated with eddies in the northern/central GoM. Overall, the spatial distribution patterns of pelagic Sargassum in the GoM are strongly influenced by the LCS and relevant eddies.
Subject(s)
Sargassum , Gulf of Mexico , Environment , Caribbean Region , EcologyABSTRACT
CONTEXT: 2,4,6,8,10, 12-hexanitro-2,4,6,8,10, 12-hexazepane (CL-20) is a new energetic material with high performance and low sensitivity. In-depth study of the thermal decomposition mechanism of CL-20 is a necessary condition to improve its performance, ensure its safety, and optimize its application. On the basis of a large number of empirical force fields used in molecular dynamics simulation in the past, the machine learning augmented first-principles molecular dynamics method was used for the first time to simulate the thermal decomposition reaction of CL-20 at 2200 K, 2500 K, 2800 K, and 3000 K isothermal temperature. The main stable resulting compounds are N2, CO2, CO, H2O, andH2, where CO2 and H2O continue to decompose at higher temperatures. The initial decomposition pathways are denitration by N-N fracture, ring-opening by C-N bond fracture, and redox reaction involving NO2 and CL-20. After ring opening, two main compounds, fused tricyclic pyrazine and azadicyclic, were formed, which were decomposed continuously to form monocyclic pyrazine and pyrazole ring structures. The most common fragments formed during decomposition are those containing two, three, four, and six carbons. The formation rule and quantity of main small molecule intermediates and resulting stable products under different simulated temperatures were analyzed. METHODS: Based on ab initio Bayesian active learning algorithm, efficient and accurate prediction of CL-20 is made using the dynamic machine learning function of Vienna Ab-Initio Simulation Package (VASP), which constructs the energy potential surface by learning a large number of data based on AIMD calculations. The result is a machine learning force field (MLFF). Then the molecular dynamics of CL-20 was simulated using the trained MLFF model. PAW pseudopotentials and generalized gradient approximation (GGA), namely, Perdew-Burke-Ernzerhof (PBE) functional, are used in the calculation. The plane wave truncation energy (ENCUT) is set to 550 eV, and using the Gaussian broadening, the thermal broadening size of the single-electron orbital is 0.05 eV. A van der Waals revision of the system with Grimme Version 3. The energy convergence accuracy (EDIFF) of electron self-consistent iteration is set to 1E-5 eV and 1E-6 eV, respectively. The two-step structure optimization is carried out using 1'1'1 k point grid and conjugate gradient method. The ENCUT was changed to 500 eV and EDIFF to 1E-5 eV, and NVT integration (ISIF = 2) of Langevin thermostat was used for machine learning force field training and AIMD simulation of the system.
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BACKGROUND: This study aimed to provide a comprehensive assessment of burden estimates and the secular trend of vision loss due to retinopathy of prematurity (ROP) among people younger than 20 years, at the global, regional and national levels. METHODS: Data were obtained from the Global Burden of Disease Study 2019 database. The average annual percentage change (AAPC) was calculated to quantify the temporal trends in the measures of vision loss. RESULTS: In 2019, the global age-standardised rates (ASRs) of prevalence per 100 000 population was 86.4 for vision loss, specifically, 35 for moderate vision loss, 19.9 for severe vision loss, 31.6 for blindness due to ROP among people younger than 20 years. Moreover, the ASR of years lived with disability per 100 000 was 10.6 for vision loss, specifically, 1.1 for moderate vision loss, 3.6 for severe vision loss, 5.9 for blindness, respectively. From 1990 to 2019, the ASR of prevalence of blindness and vision loss due to ROP significantly increased, while its burden slightly decreased. Males showed higher ASR of prevalence than females in 2019, whereas females have larger increasing trend than males from 1990 to 2019. The global highest ASR of disease burden was observed in South Asia and Southern sub-Saharan Africa, as well as low sociodemographic index (SDI) regions in 2019. CONCLUSIONS: Globally, although the burden decreased, the prevalence of childhood and adulthood vision loss due to ROP continues to increase. Reasonable resource allocation and advanced intervention are recommended to prevent and control the vision loss due to ROP.