ABSTRACT
It is not clear as to whether weight bearing and ambulation may affect bone growth. Our goal was to study the role of mechanical loading (one of the components of ambulation) on endochondral ossification and longitudinal bone growth. Thus, we applied cyclical, biologically relevant strains for a prolonged time period (4 weeks) to one tibia of juvenile mice, while using the contralateral one as an internal control. By the end of the 4-week loading period, the mean tibial growth of the loaded tibiae was significantly greater than that of the unloaded tibiae. The mean height and the mean area of the loaded tibial growth plates were greater than those of the unloaded tibiae. In addition, in female mice we found a greater expression of PTHrP in the loaded tibial growth plates than in the unloaded ones. Lastly, microCT analysis revealed no difference between loaded and unloaded tibiae with respect to the fraction of bone volume relative to the total volume of the region of interest or the tibial trabecular bone volume. Thus, our findings suggest that intermittent compressive forces applied on tibiae at mild-moderate strain magnitude induce a significant and persistent longitudinal bone growth. PTHrP expressed in the growth plate appears to be one growth factor responsible for stimulating endochondral ossification and bone growth in female mice.
Subject(s)
Growth Plate , Parathyroid Hormone-Related Protein , Tibia , Weight-Bearing , Animals , Female , Parathyroid Hormone-Related Protein/metabolism , Parathyroid Hormone-Related Protein/genetics , Tibia/metabolism , Tibia/growth & development , Tibia/diagnostic imaging , Growth Plate/metabolism , Growth Plate/growth & development , Mice , Weight-Bearing/physiology , Stress, Mechanical , Mice, Inbred C57BL , Bone Development , Osteogenesis/physiologyABSTRACT
Chemodynamic therapy (CDT) is an emerging therapeutic modality triggered by endogenous substances in the tumor microenvironment (TME) to generate reactive oxygen species. However, the mild acid pH, low H2O2 concentration, and overexpressed glutathione can suppress the CDT efficiency. Herein, ultrasound (US)-triggered Cu2+-based single-atom nanoenzymes (FA-NH2-UiO-66-Cu, FNUC) are constructed with the performance of target and glutathione depletion. In the TME, the single-atom Cu sites of FNUC consume glutathione and the FNUC:Cu+ generates â¢OH via peroxidase-like activity. The US-activated FNUC exhibits a fast â¢OH generation rate, a low Michaelis constant, and a large â¢OH concentration, indicating the cavitation effect of US promotes the â¢OH generation. Meanwhile, the tumor target of FNUC is confirmed by NIR-II fluorescence imaging, in which it is modified with IR-1061. Combined with the antitumor performance of FNUC in vitro and in vivo, the novel Cu-based SAzymes can achieve efficient and precise cancer treatment.
Subject(s)
Copper , Metal-Organic Frameworks , Tumor Microenvironment , Copper/chemistry , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacology , Humans , Animals , Tumor Microenvironment/drug effects , Mice , Catalysis , Neoplasms/diagnostic imaging , Neoplasms/therapy , Cell Line, Tumor , Glutathione/chemistry , Ultrasonic Waves , Reactive Oxygen Species/metabolismABSTRACT
The Jing-Mi Diversion Canal is a large-scale water diversion project in Beijing. Routine monitoring is crucial for the reliability and stability of urban water supply. Compared with traditional monitoring methods, interferometric synthetic aperture radar (InSAR) has the advantages of large scale and high accuracy. Based on the small baseline subset InSAR, 187 ascending and 102 descending SAR images obtained from Sentinel-1 were used to detect the deformation along the diversion canal from 2017 to 2023. The results show that there was a sinking trend along the diversion canal. The subsidence was serious in the first half of the canal, and continued to sink from 2019 to 2020. The subsidence was alleviated in 2023. Combined with leveling measurements, the InSAR deformation monitoring results of important pumping station buildings were verified. The measurement accuracy of InSAR can reach the millimeter level. We extracted the groundwater level time series and subsidence for risky canal segments. Through pixel-by-pixel comparison, it was found that fluctuations in groundwater level would have some impact on surface deformation. Severe local subsidence or uplift deformation occasionally occurred. To ensure the safety of water diversion, the monitoring and maintenance of relevant pump station buildings in risky areas should be increased in the future.
ABSTRACT
In this work, a double-end diffusion bonded Nd:YVO4 self-Raman laser was designed to drive an intracavity, noncritically-phase-matched KTiOAsO4 (KTA) optical parametric oscillator (OPO). Both conversion efficiency and output power at 1.7â µm (the wavelength of the OPO signal field) were improved by effectively reducing the thermal lens effect and increasing the effective length of self-Raman medium. At an incident pump power of 15.4 W, the output power for 1742 nm output laser reached 2.16 W with a conversion efficiency of 14%, and the output having a pulse width of 10.5â ns and a pulse repetition frequency of 90 kHz. The competition between the OPO and cascaded Raman laser was observed when the incident pump power was above 12.4 W. The results highlight that in order to improve output power at 1742 nm, it is critical that both the cascaded, second-Stokes field at 1313â nm and the signal field generated at 1534â nm from the 1064â nm field driving the KTA-OPO be minimized, if not completely suppressed. This laser system combining the processes of stimulated Raman scattering and optical parametric oscillation for the generation of laser emission at 1742 nm may find significant application across a broad range of fields including biological engineering, laser therapy, optical coherence tomography and for the generation of mid-infrared laser wavelengths.
ABSTRACT
Avian leukosis virus (ALV) is an avian oncogenic retrovirus that can impair immunological function, stunt growth and decrease egg production in avian flocks. The capsid protein (P27) is an attractive candidate for ALV diagnostics. In the present study, a new hybridoma cell (1F8) stably secreting an anti-P27 monoclonal antibody (mAb) was developed. The mAb exhibited a high affinity constant (Ka) of 8.65 × 106.0 L/mol, and it could be used for the detection of ALV-A/B/J/K strains. Moreover, a total of eight truncated recombinant proteins and five synthetic polypeptides were utilized for the identification of the B-cell epitopes present on P27. The results revealed that 218IIKYVLDRQK227 was the minimal epitope recognized by 1F8, which had never been reported before. Additionally, the epitopes could strongly react with different ALV subgroup's specific positive serum and had a complete homology among all the ALV subgroups strains. Finally, a new sandwich ELISA method was created for the detection of ALV antigens, demonstrating increased sensitivity compared to a commercially available ELISA kit. These results offer essential knowledge for further characterizing the antigenic composition of ALV P27 and will facilitate the development of diagnostic reagents for ALV.
ABSTRACT
Ischemic stroke is a common cerebrovascular disease with high mortality, high morbidity, and high disability. Cerebral ischemia/reperfusion injury seriously affects the quality of life of patients. Luteolin-7-O-ß-d-glucuronide (LGU) is a major active flavonoid compound extracted from Ixeris sonchifolia (Bge.) Hance, a Chinese medicinal herb mainly used for the treatment of coronary heart disease, angina pectoris, cerebral infarction, etc. In the present study, the protective effect of LGU on cerebral ischemia/reperfusion injury was investigated in an oxygen-glucose deprivation/reoxygenation (OGD/R) neuronal model and a transient middle cerebral artery occlusion (tMCAO) rat model. In in vitro experiments, LGU was found to improve the OGD/R-induced decrease in neuronal viability effectively by the MTT assay. In in vivo experiments, neurological deficit scores, infarction volume rates, and brain water content rates were improved after a single intravenous administration of LGU. These findings suggest that LGU has significant protective effects on cerebral ischemia/reperfusion injury in vitro and in vivo. To further explore the potential mechanism of LGU on cerebral ischemia/reperfusion injury, we performed a series of tests. The results showed that a single administration of LGU decreased the content of EB and S100B and ameliorated the abnormal expression of tight junction proteins ZO-1 and occludin and metalloproteinase MMP-9 in the ischemic cerebral cortex of the tMCAO 24-h injury model. In addition, LGU also improved the tight junction structure between endothelial cells and the degree of basement membrane degradation and reduced the content of TNF-α and IL-1ß in the brain tissue. Thereby, LGU attenuated cerebral ischemia/reperfusion injury by improving the permeability of the blood-brain barrier. The present study provides new insights into the therapeutic potential of LGU in cerebral ischemia.
ABSTRACT
The silent information regulator T1 (SIRT1) is linked to longevity and is a crucial mediator of osteoblast function. We investigated the direct role of Sirt1 during bone modeling and remodeling stages in vivo using Tamoxifen-inducible osteoblast-specific Sirt1 conditional knockout (cKO) mice. cKO mice exhibited lower trabecular and cortical bone mass in the distal femur. These phenotypes were coupled with lower bone formation and bone resorption. Metabolomics analysis revealed that the metabolites involved in glycolysis were significantly decreased in cKO mice. Further analysis of the quantitative acetylome revealed 11 proteins with upregulated acetylation levels in both the femur and calvaria of cKO mice. Cross-analysis identified four proteins with the same upregulated lysine acetylation site in both the femur and calvaria of cKO mice. A combined analysis of the metabolome and acetylome, as well as immunoprecipitation, gene knockout, and site-mutation experiments, revealed that Sirt1 deletion inhibited glycolysis by directly binding to and increasing the acetylation level of Glutamine oxaloacetic transaminase 1 (GOT1). In conclusion, our study suggested that Sirt1 played a crucial role in regulating osteoblast metabolism to maintain bone homeostasis through its deacetylase activity on GOT1. These findings provided a novel insight into the potential targeting of osteoblast metabolism for the treatment of bone-related diseases.
Subject(s)
Glycolysis , Homeostasis , Mice, Knockout , Osteoblasts , Sirtuin 1 , Animals , Mice , Acetylation , Bone and Bones/metabolism , Femur/metabolism , Osteoblasts/metabolism , Osteogenesis , Sirtuin 1/metabolism , Sirtuin 1/geneticsABSTRACT
Bladder Urothelial Carcinoma (BLCA), a prevalent and lethal cancer, lacks understanding regarding the roles and prognostic value of cuproptosis-related lncRNAs (CRLs), a novel form of cell death induced by copper. We collected RNA-seq data, clinical information, and prognostic data for 414 BLCA samples and 19 matched controls from The Cancer Genome Atlas. Using multivariate and univariate Cox regression analyses, we identified CRLs to create a prognostic signature. Patients were then divided into low- and high-risk groups based on their risk scores. We analyzed overall survival using the Kaplan-Meier method, evaluated stromal and immune scores, and explored functional differences between these risk groups with gene set enrichment analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also conducted to understand the links between CRLs and BLCA development. We developed a prognostic signature using 4 independent CRLs: RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1. This signature independently predicted the prognosis of BLCA patients. High-risk patients had worse outcomes, with gene set enrichment analysis revealing enrichment in tumor- and immune-related pathways in the high-risk group. Notably, high-risk patients exhibited enhanced responses to immunotherapy and conventional chemotherapy drugs like sunitinib, paclitaxel, and gemcitabine. The independent prognostic signature variables RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1 predicted the prognoses of BLCA patients and provided a basis for the study of the mechanism of CRLs in BLCA development and progression, and the guidance of clinical treatments for patients with BLCA.
Subject(s)
RNA, Long Noncoding , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/mortality , RNA, Long Noncoding/genetics , Male , Prognosis , Female , Aged , Middle Aged , Biomarkers, Tumor/genetics , Kaplan-Meier Estimate , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/pathologyABSTRACT
BACKGROUND: Sirtuins (SIRTs) are NAD+-dependent deacetylases that play various roles in numerous pathophysiological processes, holding promise as therapeutic targets worthy of further investigation. Among them, the SIRT2 subtype is closely associated with tumorigenesis and malignancies. Dysregulation of SIRT2 activation can regulate the expression levels of related genes in cancer cells, leading to tumor occurrence and metastasis. METHODS: In this study, we used computer simulations to screen for novel SIRT2 inhibitors from the FDA database, based on which 10 compounds with high docking scores and good interactions were selected for in vitro anti-pancreatic cancer metastasis testing and enzyme binding inhibition experiments. The results showed that fluvastatin sodium may possess inhibitory activity against SIRT2. Subsequently, fluvastatin sodium was subjected to molecular docking experiments with various SIRT isoforms, and the combined results from Western blotting experiments indicated its potential as a SIRT2 inhibitor. Next, molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations were performed, revealing the binding mode of fluvastatin sodium at the SIRT2 active site, further validating the stability and interaction of the ligand-protein complex under physiological conditions. RESULTS: Overall, this study provides a systematic virtual screening workflow for the discovery of SIRT2 activity inhibitors, identifies the potential inhibitory effect of fluvastatin sodium as a lead compound on SIRT2, and opens up a new direction for developing highly active and selectively targeted SIRT2 inhibitors.
Subject(s)
Fluvastatin , Molecular Docking Simulation , Molecular Dynamics Simulation , Sirtuin 2 , Fluvastatin/pharmacology , Fluvastatin/chemistry , Sirtuin 2/antagonists & inhibitors , Sirtuin 2/chemistry , Sirtuin 2/metabolism , Humans , Protein Binding , Catalytic Domain , Computer SimulationABSTRACT
Luteolin-7-O-ß-d-glucuronide (LGU) is a major active flavonoid glycoside compound that is extracted from Ixeris sonchifolia (Bge.) Hance, and it is a Chinese medicinal herb mainly used for the treatment of coronary heart disease, angina pectoris, cerebral infarction, etc. In the present study, the neuroprotective effect of LGU was investigated in an oxygen glucose deprivation (OGD) model and a middle cerebral artery occlusion (MCAO) rat model. In vitro, LGU was found to effectively improve the OGD-induced decrease in neuronal viability and increase in neuronal death by a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a lactate dehydrogenase (LDH) leakage rate assay, respectively. LGU was also found to inhibit OGD-induced intracellular Ca2+ overload, adenosine triphosphate (ATP) depletion, and mitochondrial membrane potential (MMP) decrease. By Western blotting analysis, LGU significantly inhibited the OGD-induced increase in expressions of receptor-interacting serine/threonine-protein kinase 3 (RIP3) and mixed lineage kinase domain-like protein (MLKL). Moreover, molecular docking analysis showed that LGU might bind to RIP3 more stably and firmly than the RIP3 inhibitor GSK872. Immunofluorescence combined with confocal laser analyses disclosed that LGU inhibited the aggregation of MLKL to the nucleus. Our results suggest that LGU ameliorates OGD-induced rat primary cortical neuronal injury via the regulation of the RIP3/MLKL signaling pathway in vitro. In vivo, LGU was proven, for the first time, to protect the cerebral ischemia in a rat middle cerebral artery occlusion (MCAO) model, as shown by improved neurological deficit scores, infarction volume rate, and brain water content rate. The present study provides new insights into the therapeutic potential of LGU in cerebral ischemia.
Subject(s)
Brain Injuries , Glucuronides , Luteolin , Animals , Rats , Infarction, Middle Cerebral Artery/drug therapy , Molecular Docking Simulation , Signal Transduction , Protein KinasesABSTRACT
This study aims to investigate the role and underlying mechanisms of Sirt1 in the pathophysiological process of OA. Safranine O and HE staining were utilized to identify pathological changes in the cartilage tissue. Immunohistochemistry was employed to evaluate the expression levels of proteins. IL-1ß treatment and TamCartSirt1flox/flox mice were utilized to induce OA model both in vitro and in vivo. Key autophagy-related transcription factors, autophagy-related genes, and chondrocyte extracellular matrix (ECM) breakdown enzyme markers were examined using multi assays. Immunofluorescence staining revealed subcellular localization and gene expression patterns. ChIP assay and Co-immunoprecipitation assay were conducted to investigate the interactions between FoxO1 and the promoter regions of Atg7 and Sirt1. Our results demonstrate that Sirt1 deficiency exhibited inhibitory effects on ECM synthesis and autophagy, as well as exacerbated angiogenesis. Moreover, Atg7, Foxo1, and Sirt1 could form a protein complex. Sirt1 was observed to facilitate nuclear translocation of FoxO1, enhancing its transcriptional activity. Furthermore, FoxO1 was found to bind to the promoter regions of Atg7 and Sirt1, potentially regulating their expression. This study provides valuable insights into the involvement of Sirt1-Atg7-FoxO1 loop in OA, opening new avenues for targeted therapeutic interventions aiming to mitigate cartilage degradation and restore joint function.
Subject(s)
Osteoarthritis , Sirtuin 1 , Animals , Mice , Autophagy , Cartilage/metabolism , Chondrocytes , Osteoarthritis/metabolism , Sirtuin 1/genetics , Sirtuin 1/metabolismABSTRACT
The inhibition of transforming growth factor-ß1 (TGF-ß1) signaling by targeting TGF-ß receptor 1 (TßR1) has been considered as an ideal approach for the prevention of pancreatic cancer metastasis. Utilizing a pharmacophore model for TßR1 inhibitors, candidate compounds with the potential TßR1 binding ability were screened from the U.S. Food and Drug Administration (FDA) database, and riboflavin (RF) with a highest fit value was chosen to investigate its binding ability to TßR1 and effect on TGF-ß1 signaling in pancreatic cancer cells. Molecular docking and cellular thermal shift assay (CETSA) proved that RF at pharmacological concentrations could directly bind to TßR1. Further studies showed that pharmacological concentrations of RF in vitro could block TGF-ß1 signaling, suppress the migration and invasion, and prevent epithelial-mesenchymal transition (EMT) process of pancreatic cancer cells in the absence or presence of TGF-ß1 stimulation, indicating that RF presented anti-metastatic effect in pancreatic cancer cells. Knockdown of TßR1 could significantly attenuate the effects of RF on the migration and EMT process in pancreatic cancer cells, further confirming that the anti-metastatic effect of RF was achieved by blocking TGF-ß1 signaling after binding to TßR1. Moreover, in a mouse model of pancreatic cancer metastasis, it was certified that RF administration could block lung and liver metastases, TGF-ß1 signaling and EMT process of pancreatic cancer in vivo. In summary, our findings showed that RF could block TGF-ß1 signaling by directly binding to TßR1, thereby suppressing the metastasis of pancreatic cancer cells by inhibiting EMT process both in vitro and in vivo.
Subject(s)
Pancreatic Neoplasms , Transforming Growth Factor beta1 , Animals , Mice , Transforming Growth Factor beta1/metabolism , Molecular Docking Simulation , Cell Line, Tumor , Neoplasm Invasiveness/prevention & control , Pancreatic Neoplasms/drug therapy , Receptors, Transforming Growth Factor beta , Epithelial-Mesenchymal TransitionABSTRACT
Improving seed oil quality in peanut (Arachis hypogaea) has long been an aim of breeding programs worldwide. The genetic resources to achieve this goal are limited. We used an advanced recombinant inbred line (RIL) population derived from JH5 × KX01-6 to explore quantitative trait loci (QTL) affecting peanut oil quality and their additive effects, epistatic effects, and QTL × environment interactions. Gas chromatography (GC) analysis suggested seven fatty acids components were obviously detected in both parents and analyzed in a follow-up QTL analysis. The major components, palmitic acid (C16:0), oleic acid (C18:1), and linoleic acid (C18:2), exhibited considerable phenotypic variation and fit the two major gene and minor gene mixed-inheritance model. Seventeen QTL explained 2.57-38.72% of the phenotypic variation in these major components, with LOD values of 4.12-37.56 in six environments, and thirty-five QTL explained 0.94-32.21% of the phenotypic variation, with LOD values of 5.99-150.38 in multiple environments. Sixteen of these QTL were detected in both individual and multiple environments. Among these, qFA_08_1 was a novel QTL with stable, valuable and major effect. Two other major-effect QTL, qFA_09_2 and qFA_19_3, share the same physical position as FAD2A and FAD2B, respectively. Eleven stable epistatic QTL involving nine loci explained 1.30-34.97% of the phenotypic variation, with epistatic effects ranging from 0.09 to 6.13. These QTL could be valuable for breeding varieties with improved oil quality.
Subject(s)
Arachis , Quantitative Trait Loci , Arachis/genetics , Plant Breeding , Fatty Acids/genetics , Plant OilsABSTRACT
Ulcerative colitis (UC) is one of the primary inflammatory bowel diseases (IBDs) and causes a serious threat to human public health around the world. Currently, there are no proven safe and effective treatment options to treat UC. Fraxetin (Fxt) is a widely recognized antioxidant and anti-inflammatory legume derived from ash bark. In the present study, we investigated the protective effect and mechanism of Fxt on UC. Our results showed that Fxt significantly attenuated the body weight, colon length reduction, tissue damage, and disease activity index induced by dextran sodium sulphate (DSS). Moreover, the DSS-induced activation of the NF-κB pathway and NLRP3 inflammasomes was inhibited, and the inflammatory response was reduced. Fxt restored gut barrier function by increasing the number of goblet cells and the levels of tight junction proteins (ZO-1 and occludin). In addition, Fxt can alter the intestinal microbiota by enhancing the diversity of the microbiota, increasing the relative abundance of beneficial bacteria and inhibiting the growth of harmful bacteria. These results revealed that Fxt alleviates DSS-induced colitis by modulating the inflammatory response, enhancing epithelial barrier integrity and regulating the gut microbiota. This study may provide a scientific basis for the potential therapeutic effect of Fxt in the prevention of colitis and other related diseases.
ABSTRACT
An efficient approach for the preparation of tetracyclic indeno[1,2-b]indoles via Rh(III)-catalyzed C-H cascade annulation between arylhydrazines and diazo indan-1,3-diones has been established. In addition, a series of indeno[1,2-b]indoles were obtained in up to 96% yield with a wide range of substrates and high functional group tolerance. Finally, the diverse transformations of the desired products demonstrate the synthetic utility and utilization of this protocol.
ABSTRACT
A microfluidic concentration gradient colorimetric detection system consisting of a microfluidic concentration gradient colorimetric detection chip, a self-built colorimetric signal acquisition box and a self-written smartphone APP was constructed for the rapid, in-field and visual quantitative detection of nitrite. Specifically, nitrite with initial concentration of C0 can be automatically diluted into 8 concentration gradients characterized by arithmetic series, and the concentrations are 0, 0.20 C0, 0.33 C0, 0.46 C0, 0.59 C0, 0.72 C0, 0.86 C0 and C0. The colorimetric signal acquisition box avoided the interference of light spots on data acquisition. Under the optimal experimental conditions, the quantitative detection of nitrite was achieved by the proposed two-step colorimetric method based on the inhibition of AuNPs signal amplification, and the limit of detection (LOD) was 0.14 mg/L. The microfluidic concentration gradient colorimetric detection system was able to detect nitrite as low as 0.43 mg/L and showed a good specificity. The practical application was investigated by analyzing 10 actual samples of river and lake water, pure water and tap water. The recoveries of the microfluidic concentration gradient colorimetric detection system ranged from 94.92% to 105.60%, which indicates that the method had a good application prospect in the detection of practical samples.
ABSTRACT
The design and synthesis of high-spin Mn(II)-based single-molecule magnets (SMMs) have not been well developed to a great extent, as compared with a large number of SMMs based on the other first row transition metal complexes. In light of our success in designing Fe(II), Co(II) and Fe(III)-based SMMs with a high coordination number of 8, it is of great interest to design Mn(II) analogues with such a strategy. In this contribution, four Mn(II) compounds, [MnII(Ln)2](ClO4)2 (1-4) were obtained from reactions of neutral tetradentate ligands, L1-L4, with hydrated MnII(ClO4)2 (L1 = 2,9-bis(carbomethoxy)-1,10-phenanthroline, L2 = 2,9-bis(carbomethoxy)-2,2'-dipyridine, L3 = N2,N9-dibutyl-1,10-phenanthroline-2,9-dicarboxamide, L4 = 6,6'-bis(2-(tert-butyl)-2H-tetrazol-5-yl)-2,2'-bipyridine). Their crystal structures have been determined by X-ray crystallography and it clearly shows that the Mn(II) centers in these compounds have an oversaturated coordination number of 8. Their magnetic properties have been investigated in detail; to our surprise, all of these Mn(II) compounds show interesting slow magnetic relaxation behaviors under an applied direct current field, although they have very small negative D values.
ABSTRACT
Avian leukosis (AL), caused by avian leukosis virus (ALV), is a contagious tumor disease that results in significant economic losses for the poultry industry. Currently, ALV-A, B, J, and K subgroups are the most common in commercial poultry and cause possible coinfections. Therefore, close monitoring is necessary to avoid greater economic losses. In this study, a novel multiplex quantitative polymerase chain reaction (qPCR) assay was developed to detect ALV-A, ALV-B, ALV-J, and ALV-K with limits of detection of 40, 11, 13.7, and 96 copies/µL, respectively, and no cross-reactivity with other ALV subtypes and avian pathogens. We detected 852 cell cultures inoculated with clinical samples using this method, showing good consistency with conventional PCR and ELISA. The most prevalent ALV strain in Hubei Province, China, was still ALV-J (11.74%). Although single infections with ALV-A, ALV-B, and ALV-K were not found, coinfections with different subgroup strains were identified: 0.7% for ALV-A/J, 0.35% for ALV-B/J, 0.25% for ALV-J/K, and 0.12% for ALV-A/B/K and ALV-A/B/J. Therefore, our novel multiplex qPCR may be a useful tool for molecular epidemiology, clinical detection of ALV, and ALV eradication programs.
Subject(s)
Avian Leukosis Virus , Avian Leukosis , Coinfection , Animals , Avian Leukosis Virus/genetics , Coinfection/diagnosis , Coinfection/veterinary , Avian Leukosis/diagnosis , Cell Culture Techniques , Multiplex Polymerase Chain ReactionABSTRACT
Inkless and erasable printing (IEP) based on chromic materials holds great promise to alleviate environmental and sustainable problems. Metal-organic polymers (MOPs) are bright platforms for constructing IEP materials. However, it is still challenging to design target MOPs with excellent specific functions rationally due to the intricate component-structure-property relationships. Herein, an effective strategy was proposed for the rational design IEP-MOP materials. The stimuli-responsive viologen moiety was introduced into the construction of MOPs to give it potential chromic behaviors and two different coordination models (i. e. bilateral coordination model, M1 ; unilateral coordinated model, M2 ) based on the same viologen ligand were designed. Aided by theoretical calculations, model M1 was recommended secondarily as a more suitable system for IEP materials. Along this line, two representative viologen-ZnII MOPs 1 and 2 with models M1 and M2 were synthesized successfully. Experiments exhibit that 1 does have quicker stimuli response, stronger color contrast and longer radical lifetime compared to 2. Significantly, the obtained 1-IEP media brightly inherits the excellent chromic characteristics of 1 and the flexibility of the paper at the same time, which achieves most daily printing requirements, as well as enough resolution and durability to be used in identification by smart device.
ABSTRACT
Pseudorabies virus (PRV) can infect multiple hosts and lead to fatal encephalitis. There is a significant increase in the number of microglia in the brain of animals infected with PRV. However, whether and how microglia contribute to central nervous system damage in PRV infection remain unknown. In the present study, we elucidated that PRV infection can cause more severe inflammatory cell infiltration, thicker and more numerous vessel sleeve walls, and more severe inflammatory responses in the brains of natural hosts (pigs) than in those of nonnatural hosts (mice). In a mice infection model, activated microglia restricted viral replication in the early stage of infection. Acute neuroinflammation caused by microglia hyperactivation at late-stage of infection. Furthermore, in vitro experiments revealed that microglia restricted viral replication and decreased viral infectivity. This may be associated with the phagocytic ability of microglia because we observed a significant increase in the expression of the membrane receptor TREM2 in microglia, which is closely related to phagocytosis, we observed that depletion of microglia exacerbated neurological symptoms, blood-brain barrier breakdown, and peripheral lymphocyte infiltration. Taken together, we revealed the dual role of microglia in protecting the host and neurons from PRV infection.