ABSTRACT
Metacestodiasis is an infectious disease caused by the larval stage of cestode parasites. This disease poses a serious health hazard to wildlife, livestock, and humans, and it incurs substantial economic losses by impacting the safety of the livestock industry, the quality of meat production, and public health security. Unfortunately, there is currently no available molecular diagnostic method capable of distinguishing cysticercus- and Echinococcus-derived microRNAs (miRNAs) from other helminthes and hosts in the plasma of metacestode-infected animals. This study aims to develop a specific, sensitive, and cost-efficient molecular diagnostic method for cysticercosis and echinococcosis, particularly for early detection. The study developed a rolling circular amplification (RCA)-assisted CRISPR/Cas9 detection method based on parasite-derived miRNA let-7-5p. Using a series of dilutions of the let-7 standard, the limit of detection (LOD) of the qPCR, RCA, and RCA-assisted CRISPR/Cas9 methods was compared. The specificity of qPCR and CRISPR/Cas9 was evaluated using four artificially synthesized let-7 standards from different species. A total of 151 plasma samples were used to evaluate the diagnostic performance. Additionally, the study also assessed the correlation between plasma levels of let-7-5p, the number of Taenia pisiformis cysticerci, and the weight of Echinococcus multilocularis cysts. The results demonstrated that the RCA-assisted CRISPR/Cas9 assay could significantly distinguish let-7 from cestodes and other species, achieving a LOD of 10 aM; the diagnostic sensitivity and specificity for rabbit cysticercosis and mouse E. multilocularis were 100% and 97.67%, and 100% and 100%, respectively. Notably, let-7-5p gradually increased in the plasma of T. pisiformis-infected rabbits from 15 days post infection (dpi), peaked at 60 dpi, and persisted until 120 dpi. In E. multilocularis-infected mice, let-7-5p gradually increased from 15 dpi and persisted until 90 dpi. Furthermore, the expression of let-7-5p positively correlated with the number of cysticerci and cyst weight. These results indicated that the let-7-5p-based RCA-assisted CRISPR/Cas9 assay is a sensitive and specific detection method that can be used as a universal diagnostic method for metacestodiasis, particularly for early diagnosis (15 dpi).
Subject(s)
CRISPR-Cas Systems , Cysticercosis , MicroRNAs , Animals , MicroRNAs/genetics , MicroRNAs/blood , Mice , Cysticercosis/diagnosis , Cysticercosis/veterinary , Cysticercosis/parasitology , Echinococcosis/diagnosis , Nucleic Acid Amplification Techniques/methods , Sensitivity and Specificity , HumansABSTRACT
Resolution control and expansibility have always been challenges to the fabrication of structural color materials. Here, a facile strategy to print cholesteric liquid crystal elastomers (CLCEs) into complex structural color patterns with variable resolution and enhanced expansibility is reported. A volatile solvent is introduced into the synthesized CLC oligomers, modifying its rheological properties and allowing direct-ink-writing (DIW) under mild conditions. The combination of printing shear flow and anisotropic deswelling of ink drives the CLC molecules into an ordered cholesteric arrangement. The authors meticulously investigate the influence of printing parameters to achieve resolution control over a wide range, allowing for the printing of multi-sized 1D or 2D patterns with constant quality. Furthermore, such solvent-cast direct-ink-writing (DIW) strategy is highly expandable and can be integrated easily into the DIW of bionic robots. Multi-responsive bionic butterfly and flower are printed with biomimetic in both locomotion and coloration. Such designs dramatically reduced the processing difficulty of precise full-color printing and expanded the capability of structural color materials to collaborate with other systems.
ABSTRACT
Cationic lipids play a pivotal role in developing novel drug delivery systems for diverse biomedical applications, owing to the success of mRNA vaccines against COVID-19 and the Phase III antitumor agent EndoTAG-1. However, the therapeutic potential of these positively charged liposomes is limited by dose-dependent toxicity. While an increased content of cationic lipids in the formulation can enhance the uptake and cytotoxicity toward tumor-associated cells, it is crucial to balance these advantages with the associated toxic side effects. In this work, we synthesized the cationic lipid HC-Y-2 and incorporated it into sialic acid (SA)-modified cationic liposomes loaded with paclitaxel to target tumor-associated immune cells efficiently. The SA-modified cationic liposomes exhibited enhanced binding affinity toward both RAW264.7 cells and 4T1 tumor cells in vitro due to the increased ratios of cationic HC-Y-2 content while effectively inhibiting 4T1 cell lung metastasis in vivo. By leveraging electrostatic forces and ligand-receptor interactions, the SA-modified cationic liposomes specifically target malignant tumor-associated immune cells such as tumor-associated macrophages (TAMs), reduce the proportion of cationic lipids in the formulation, and achieve dual objectives: high cellular uptake and potent antitumor efficacy. These findings highlight the potential advantages of this innovative approach utilizing cationic liposomes.
Subject(s)
Breast Neoplasms , Lung Neoplasms , Humans , Female , Liposomes/chemistry , N-Acetylneuraminic Acid/chemistry , Breast Neoplasms/drug therapy , COVID-19 Vaccines , Paclitaxel/therapeutic use , Lung Neoplasms/drug therapy , Lipids , Cations , Cell Line, TumorABSTRACT
OBJECTIVE: To investigate the feasibility and effectiveness of applying intraoperative ultrasound (IOUS) to evaluate spinal canal expansion in patients undergoing French-door cervical laminoplasty (FDCL). MATERIALS AND METHODS: Twenty-five patients who underwent FDCL for multilevel degenerative cervical myelopathy were prospectively recruited. Formulae describing the relationship between laminoplasty opening angle (LOA) and laminoplasty opening size, the increase in sagittal canal diameter and the spinal canal area were deduced with trigonometric functions. The LOA was measured with IOUS imaging during surgery, and other spinal canal parameters were assessed. Actual spinal canal enlargement was verified on postoperative CT images. Linear correlation analysis and BlandâAltman analysis were used to evaluate correlation and agreement between the intraoperative and postoperative measurements. RESULTS: The LOA at C5 measured with IOUS was 27.54 ± 3.12°, and it was 27.23 ± 3.02° on postoperative CT imaging. Linear correlation analysis revealed a significant correlation between IOUS and postoperative CT measurements (r = 0.88; p < 0.01). Bland-Altman plots showed good agreement between these two methods, with a mean difference of 0.30°. For other spinal canal expansion parameter measurements, correlation analysis showed a moderate to a high degree of correlation (p < 0.01), and Bland-Altman analysis indicated good agreement. CONCLUSION: In conclusion, during the French-door cervical laminoplasty procedure, application of IOUS can accurately evaluate spinal canal expansion. This innovative method may be helpful in improving surgical accuracy by enabling the operator to measure and determine canal enlargement during surgery, leading to ideal clinical outcomes and fewer postoperative complications. CLINICAL RELEVANCE STATEMENT: The use of intraoperative ultrasonography to assess spinal canal expansion following French-door cervical laminoplasty may improve outcomes for patients undergoing this procedure by providing more accurate measurements of spinal canal expansion. KEY POINTS: ⢠Spinal canal expansion after French-door cervical laminoplasty substantially influences operative prognosis; insufficient or excessive lamina opening may result in unexpected outcomes. ⢠Prediction of spinal canal expansion during surgery was previously impracticable, but based on this study, intraoperative ultrasonography offers an innovative approach and strongly agrees with postoperative CT measurement. ⢠Since this is the first research to offer real-time canal expansion guidance for cervical laminoplasty, it may improve the accuracy of the operation and produce ideal clinical outcomes with fewer postoperative complications.
Subject(s)
Laminoplasty , Spinal Cord Diseases , Humans , Laminoplasty/adverse effects , Laminoplasty/methods , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Spinal Canal/diagnostic imaging , Spinal Canal/surgery , Ultrasonography , Postoperative Complications/etiology , Treatment Outcome , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/surgery , Spinal Cord Diseases/complications , Retrospective StudiesABSTRACT
OBJECTIVES: To evaluate the ability of intraoperative CEUS to predict neurological recovery in patients with degenerative cervical myelopathy (DCM). METHODS: Twenty-six patients with DCM who underwent laminoplasty and intraoperative ultrasound (IOUS) were included in this prospective study. The modified Japanese Orthopaedic Association (mJOA) scores and MRI were assessed before surgery and 12 months postoperatively. The anteroposterior diameter (APD), maximum spinal cord compression (MSCC), and area of signal changes in the cord at the compressed and normal levels were measured and compared using MRI and IOUS. Conventional blood flow and CEUS indices (time to peak, ascending slope, peak intensity (PI), and area under the curve (AUC)) at different levels during IOUS were calculated and analysed. Correlations between all indicators and the neurological recovery rate were evaluated. RESULTS: All patients underwent IOUS and intraoperative CEUS, and the total recovery rate was 50.7 ± 33.3%. APD and MSCC improved significantly (p < 0.01). The recovery rate of the hyperechoic lesion group was significantly worse than that of the isoechoic group (p = 0.016). 22 patients were analysed by contrast analysis software. PI was higher in the compressed zone than in the normal zone (24.58 ± 3.19 versus 22.43 ± 2.39, p = 0.019). ΔPI compress-normal and ΔAUC compress-normal of the hyperechoic lesion group were significantly higher than those of the isoechoic group (median 2.19 versus 0.55, p = 0.017; 135.7 versus 21.54, p = 0.014, respectively), and both indices were moderately negatively correlated with the recovery rate (r = - 0.463, p = 0.030; r = - 0.466, p = 0.029). CONCLUSIONS: Signal changes and microvascular perfusion evaluated using CEUS during surgery are valuable predictors of cervical myelopathy prognosis. CLINICAL RELEVANCE STATEMENT: In the spinal cord compression area of degenerative cervical myelopathy, especially in the hyperechoic lesions, intraoperative CEUS showed more significant contrast agent perfusion than in the normal area, and the degree was negatively correlated with the neurological prognosis. KEY POINTS: ⢠Recovery rates in patients with hyperechoic findings were lower than those of patients without lesions detected during intraoperative ultrasound. ⢠The peak intensity of CEUS was higher in compressed zones than in the normal parts of the spinal cord. ⢠Quantitative CEUS comparisons of the peak intensity and area under the curve at the compressed and normal levels of the spinal cord revealed differences that were inversely correlated to the recovery rate.
Subject(s)
Cervical Cord , Spinal Cord Compression , Spinal Cord Diseases , Humans , Spinal Cord Compression/pathology , Prospective Studies , Cervical Cord/diagnostic imaging , Cervical Cord/surgery , Cervical Cord/pathology , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Cervical Vertebrae/pathology , Spinal Cord/pathology , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/surgery , Spinal Cord Diseases/pathology , Magnetic Resonance Imaging , Treatment OutcomeABSTRACT
We formerly reported that EZH2 inhibitors sensitized HIF-1 inhibitor-resistant cells and inhibited HIF-1α to promote SUZ12 transcription, leading to enhanced EZH2 enzyme activity and elevated H3K27me3 levels, and conversely, inhibition of EZH2 promoted HIF-1α transcription. HIF-1α and EZH2 interacted to form a negative feedback loop that reinforced each other's activity. In this paper, a series of 2,2- dimethylbenzopyran derivatives containing pyridone structural fragments were designed and synthesized with DYB-03, a HIF-1α inhibitor previously reported by our group, and Tazemetostat, an EZH2 inhibitor approved by FDA, as lead compounds. Among these compounds, D-01 had significant inhibitory activities on HIF-1α and EZH2. In vitro experiments showed that D-01 significantly inhibited the migration of A549 cells, clone, invasion and angiogenesis. Moreover, D-01 had good pharmacokinetic profiles. All the results about compound D-01 could lay a foundation for the research and development of HIF-1α and EZH2 dual-targeting compounds.
Subject(s)
Antineoplastic Agents , Drug Screening Assays, Antitumor , Enhancer of Zeste Homolog 2 Protein , Hypoxia-Inducible Factor 1, alpha Subunit , Lung Neoplasms , Pyridones , Humans , Enhancer of Zeste Homolog 2 Protein/antagonists & inhibitors , Enhancer of Zeste Homolog 2 Protein/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Pyridones/chemistry , Pyridones/pharmacology , Pyridones/chemical synthesis , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Structure-Activity Relationship , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Molecular Structure , Dose-Response Relationship, Drug , Cell Proliferation/drug effects , Animals , Benzopyrans/chemistry , Benzopyrans/pharmacology , Benzopyrans/chemical synthesis , Cell Movement/drug effectsABSTRACT
Alzheimer's disease, the commonest cause of dementia, is a growing global health concern with huge implications for individuals and society. Stroke has still been a significant challenge in clinics for a long time, which is the second leading cause of death in the world, especially ischemic stroke. Both Alzheimer's disease and stroke are closely related to oxidative stress and HIF-1 signaling pathways in nerve cells. Herein, we describe our structure-based design, synthesis, and biological evaluation of a new class of 8-biaryl-2,2-dimethylbenzopyranamide derivatives as natural product derivatives. Our efforts have resulted in the discovery of highly potent neuroprotective agents, as exemplified by compound D13 as a HIF-1α inhibitor, which significant improvement in the behavior of Alzheimer's disease mice and shows great potential improvement of brain infarct volume in pMCAO model rats, improves the increase of blood-brain barrier permeability after cerebral ischemia in rats, neuroprotective effect, reduce the level of apoptotic cells in rats after cerebral ischemia, better than Edaravone.
Subject(s)
Alzheimer Disease , Benzopyrans , Brain Ischemia , Ischemic Stroke , Neuroprotective Agents , Stroke , Animals , Mice , Rats , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Blood-Brain Barrier , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Ischemic Stroke/drug therapy , Ischemic Stroke/metabolism , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , Neuroprotective Agents/metabolism , Stroke/drug therapy , Stroke/metabolism , Benzopyrans/chemistry , Benzopyrans/pharmacologyABSTRACT
AIMS: Microtubule inhibitors are widely used in first line cancer therapy, though drug resistance often develops and causes treatment failure. Colchicine binds to tubulins and inhibits tumor growth, but is not approved for cancer therapy due to systemic toxicity. In this study, we aim to improve the therapeutic index of colchicine through structural modification. METHODS: The methoxyl group of the tropolonic ring in colchicine was replaced with amino groups. The cross-resistance of the derivatives with paclitaxel and vincristine was tested. Antitumor effects of target compounds were tested in vivo in A549 and paclitaxel-resistant A549/T xenografts. The interaction of target compounds with tubulins was measured using biological and chemical methods. RESULTS: Methylamino replacement of the tropolonic methoxyl group of colchicine increases, while demethylation loses, selective tubulin binding affinity, G2/M arrest and antiproliferation activity. Methylaminocolchicine is more potent than paclitaxel and vincristine to inhibit tumor growth in vitro and in vivo without showing cross-resistance to paclitaxel. Methylaminocolchicine binds to tubulins in unique patterns and inhibits P-gp with a stable pharmacokinetic profile. CONCLUSION: Methylanimo replacement of the tropolonic methoxyl group of colchicine increases antitumor activity with improved therapeutic index. Methylaminocolchicine represents a new type of mitotic inhibitor with the ability of overcoming paclitaxel and vincristine resistance.
Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Paclitaxel/pharmacology , Paclitaxel/chemistry , Paclitaxel/therapeutic use , Colchicine/pharmacology , Colchicine/chemistry , Colchicine/metabolism , Tubulin , Vincristine/pharmacology , Vincristine/therapeutic use , Neoplasms/drug therapy , Cell Line, Tumor , Antineoplastic Agents/therapeutic useABSTRACT
Infection of Taenia pisiformis cysticercus is very frequently found in lagomorphs and causes serious economic losses to rabbit breeding industry. T. pisiformis cysticercus has evolved numerous strategies to manipulate their hosts. The release of exosomes is of importance in the interaction between host and parasite. However, the mechanism by which T. pisiformis cysticercus evades the host immune system for long-term survival within the host remains unclear. Using small RNA sequencing and TMT labelling proteomic, we profiled the expression patterns of miRNAs and proteins in rabbit peritoneal macrophages treated with T. pisiformis cysticercus exosomes. Seven differentially expressed (DE)-miRNAs and six DE-proteins were randomly selected to validate the accuracy of the sequencing data by qRT-PCR or western blot. Functions of DE-miRNAs and proteins were analyzed using public data bases. And DE-miRNAs-DE-proteins correlation network were established. CCK-8 assay was used to evaluate the effect of exosomes on macrophages proliferation. Cell cycle of macrophages, isolated from T. pisiformis-infected rabbits, was determined using flow cytometry. A total of 21 miRNAs were significantly differentially expressed, including three worm-derived miRNAs. The expressions of miRNAs and proteins were consistent with the sequencing results. DE-miRNAs targets were related to cell proliferation and apoptosis. Exosomes treatment resulted in a decrease of macrophages proliferation. In vivo, T. pisiformis cysticercus significantly induced S phase cell arrest. Moreover, DE-proteins were related to production of interferon-gamma and interleukin-12, and immunoregulation. Correlation network analysis revealed a negative correlation relationship between DE-miRNAs and DE-proteins. Among them, novel334 and tpi-let-7-5p have potential regulatory effects on IL1ß and NFκB2 respectively, which imply that novel334-IL1ß/tpi-let-7-5p-NFκB2 axis may be an important way that T. pisiformis cysticercus modulates host immune response through exosomes. Further understanding of these potential regulatory mechanisms will contribute to clarify the mechanism of escape mediated by T. pisiformis exosomes.
Subject(s)
Exosomes , MicroRNAs , Taenia , Animals , Rabbits , Cysticercus/genetics , Taenia/genetics , MicroRNAs/genetics , Macrophages, Peritoneal , Exosomes/genetics , ProteomicsABSTRACT
Thrombosis plays an important role in the occurrence and development of cardiovascular and cerebrovascular diseases that contribute to high mortality and morbidity in patients. L-(-)-Quebrachitol (QCT), a natural product, was first isolated from quebracho bark. It can inhibit PAF receptor and decrease gastric damage induced by indomethacin, as a drug against platelet aggregation. Here, five QCT derivatives were synthesized and investigated for their inhibitory effects on platelet aggregation. Among them, compound 3a showed anticoagulant effects comparable to aspirin, while compound 4b showed dose-independent inhibitory activities in rats that were stronger than aspirin.
Subject(s)
Platelet Aggregation Inhibitors , Platelet Aggregation , Animals , Platelet Aggregation/drug effects , Rats , Molecular Structure , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation Inhibitors/chemistry , Aspirin/pharmacology , Anticoagulants/pharmacology , Anticoagulants/chemistry , Anticoagulants/chemical synthesis , Plant Bark/chemistry , MaleABSTRACT
PURPOSE: A fracture of the posterior talar process is easily missed because of its hidden position. Inappropriate treatment is likely to result in complications, such as nonunion of the fracture and traumatic arthritis. This study evaluated the outcomes of arthroscopy-assisted reduction combined with robotic-assisted screw placement in the treatment of fractures of the posterior talar process. METHODS: The clinical data for nine patients who underwent surgical treatment of a fracture of the posterior talar process at our institution between September 2017 and January 2021 were retrospectively reviewed. Arthroscopy-assisted reduction of the fracture was performed, and a cannulated screw was placed using three-dimensional orthopedic robotic-assisted navigation. RESULTS: The patients (seven men, two women) had a mean age of 36.33 ± 9.77 years and were followed up for 21 ± 5.43 months. The operation time was 106.67 ± 24.5 min with blood loss of 47.78 ± 9.05 ml. Primary healing was obtained in all cases, and no patient sustained a nerve or tendon injury, had fracture nonunion, or developed talar osteonecrosis. One patient developed subtalar arthritis, for which subtalar joint fusion was performed; pain was markedly less severe after cleaning. CONCLUSION: Arthroscopy-assisted reduction and robotic-assisted screw placement have the advantages of visualization of fracture reduction, minimal injury, and precise screw placement in the treatment of fractures of the posterior talar process.
Subject(s)
Arthritis , Fractures, Bone , Robotic Surgical Procedures , Talus , Male , Humans , Female , Adult , Middle Aged , Fracture Fixation, Internal/adverse effects , Fracture Fixation, Internal/methods , Robotic Surgical Procedures/adverse effects , Arthroscopy/adverse effects , Retrospective Studies , Fractures, Bone/surgery , Bone Screws , Talus/diagnostic imaging , Talus/surgery , Talus/injuries , Treatment OutcomeABSTRACT
BACKGROUND: An issue of pressing concern is the manganese contamination in farmland soils adjacent to industrial areas. To address this, intercropping hyperaccumulator plants with crops emerges as a sustainable approach to ensuring food security. This study aims to investigate the influence of intercropping Sedum alfredii with maize or soybean on their growth and the dynamics of manganese accumulation through field experiments. RESULTS: The results showed that compared with monoculture, the Sedum alfredii-maize intercropping system exhibited a land equivalent ratio (LER) of 1.89, signifying a 71.13% augmentation in bioaccumulation amount (BCA). Additionally, it led to a significant reduction in manganese content in various organs, ranging from 17.05% to 25.50%. However, the Sedum alfredii-soybean intercropping system demonstrated a LER of 1.94, accompanied by a 66.11% increase in BCA, but did not significantly reduce the manganese content in the roots, stems, and pods of soybeans. Furthermore, manganese accumulation in maize and soybean grains was primarily attributed to the aboveground translocation of manganese. The intercropping effect on blocking manganese absorption of maize during growth and maturity is primarily attributed to the earlier manganese accumulation in intercropped maize by 2.63 to 4.35 days, and a reduction of 21.95% in the maximum manganese accumulation rate. CONCLUSIONS: The study found that manganese accumulation dynamics vary significantly depending on the crop family. Intercropping Sedum alfredii with maize enhances land-use efficiency and reduces manganese uptake by crops, making it a promising strategy for remediating manganese-contaminated farmland near industrial areas. © 2024 Society of Chemical Industry.
ABSTRACT
Replication factor C 5 (RFC5) is involved in a variety of biological functions of cancer. However, the expression pattern of RFC5 and the underlying mechanisms in colorectal cancer (CRC) remain elusive. Here, we show that RFC5 is significantly upregulated in CRC tissues and cells. Patients with CRC and increased RFC5 levels have an unfavorable prognosis. RFC5 can promote the proliferation, migration, and invasion of CRC cells and inhibit the apoptosis of CRC cells. Additionally, upstream of RFC5, we constructed the competing endogenous RNA network and confirmed that RFC5 in this network was inhibited by miR-3614-5p by directly targeting its 3'-untranslated regions. We verified that circ_0038985, which is positively correlated with RFC5, directly targeted miR-3614-5p. Overexpression of circ_0038985 promoted CRC cell migration and invasion, and these effects were partially reversed by the reintroduction of miR-3614-5p. Moreover, we found that RFC5 may promote the vascular endothelial growth factor A (VEGFa)/vascular endothelial growth factor receptor 2 (VEGFR2)/extracellular signal-regulated protein kinase (ERK) pathway. The knockdown of RFC5 reduced CRC tumorigenesis in vivo. Collectively, these data demonstrate that the circ_0038985/miR-3614-5p/RFC5 axis plays a critical role in the progression of CRC, and RFC5 may promote CRC progression by affecting the VEGFa/VEGFR2/ERK pathway.
Subject(s)
Colorectal Neoplasms , MicroRNAs , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Vascular Endothelial Growth Factor A/metabolism , Replication Protein C/genetics , Replication Protein C/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , OncogenesABSTRACT
Barley yellow dwarf virus (BYDV) has caused considerable losses in the global production of grain crops such as wheat, barley and maize. We investigated the phylodynamics of the virus by analysing 379 and 485 nucleotide sequences of the genes encoding the coat protein and movement protein, respectively. The maximum clade credibility tree indicated that BYDV-GAV and BYDV-MAV, BYDV-PAV and BYDV-PAS share the same evolutionary lineage, respectively. The diversification of BYDV arises from its adaptability to vector insects and geography. Bayesian phylogenetic analyses showed that the mean substitution rates of the coat and movement proteins of BYDV ranged from 8.327 × 10- 4 (4.700 × 10- 4-1.228 × 10- 3) and 8.671 × 10- 4 (6.143 × 10- 4-1.130 × 10- 3) substitutions/site/year, respectively. The time since the most recent common BYDV ancestor was 1434 (1040-1766) CE (Common Era). The Bayesian skyline plot (BSP) showed that the BYDV population experienced dramatic expansions approximately 8 years into the 21st century, followed by a dramatic decline in less than 15 years. Our phylogeographic analysis showed that the BYDV population originating in the United States was subsequently introduced to Europe, South America, Australia and Asia. The migration pathways of BYDV suggest that the global spread of BYDV is associated with human activities.
Subject(s)
Hordeum , Luteovirus , Humans , Phylogeny , Bayes Theorem , Luteovirus/genetics , Evolution, MolecularABSTRACT
Point cloud-based retrieval for place recognition is essential in robotic applications like autonomous driving or simultaneous localization and mapping. However, this remains challenging in complex real-world scenes. Existing methods are sensitive to noisy, low-density point clouds and require extensive storage and computation, posing limitations for hardware-limited scenarios. To overcome these challenges, we propose LWR-Net, a lightweight place recognition network for efficient and robust point cloud retrieval in noisy, low-density conditions. Our approach incorporates a fast dilated sampling and grouping module with a residual MLP structure to learn geometric features from local neighborhoods. We also introduce a lightweight attentional weighting module to enhance global feature representation. By utilizing the Generalized Mean pooling structure, we aggregated the global descriptor for point cloud retrieval. We validated LWR-Net's efficiency and robustness on the Oxford robotcar dataset and three in-house datasets. The results demonstrate that our method efficiently and accurately retrieves matching scenes while being more robust to variations in point density and noise intensity. LWR-Net achieves state-of-the-art accuracy and robustness with a lightweight model size of 0.4M parameters. These efficiency, robustness, and lightweight advantages make our network highly suitable for robotic applications relying on point cloud-based place recognition.
ABSTRACT
Colorectal cancer (CRC) is the second most common cancer-related deaths throughout the world. Ferroptosis is a recently regulated form of cell death, lately gains attention. MicroRNA-15a-3p (miR-15a-3p) plays a regulatory role in various kinds of cancers. However, the role of miR-15a-3p in cellular ferroptosis is still unclear. Here, we aimed to clarify whether miR-15a-3p could regulate the ferroptosis of CRC. Here we identified miR-15a-3p positively regulates ferroptosis via directly targeting glutathione peroxidase glutathione peroxidase 4 (GPX4) in CRC. Overexpression of miR-15a-3p repressed GPX4 through binding to the 3'-untranslated region of GPX4, resulting in increased reactive oxygen species level, intracellular Fe2+ level, and malondialdehyde accumulation in vitro and in vivo. Correspondingly, suppression of miR-15a-3p reduced the sensitivity of CRC cells to erastin and GPX4. Taken together, these data demonstrate that miR-15a-3p regulates ferroptosis through targeting GPX4 in CRC cells, illustrating the novel role of microRNA in ferroptosis.
Subject(s)
Colorectal Neoplasms , Ferroptosis , MicroRNAs , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Ferroptosis/genetics , Glutathione Peroxidase/genetics , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Phospholipid Hydroperoxide Glutathione Peroxidase/geneticsABSTRACT
BACKGROUND AND PURPOSE: The spinal cord central echo complex (SCCEC) is a special ultrasonography-based intramedullary structure, but its clinical significance in degenerative cervical myelopathy (DCM) is undefined. This study aimed to explore the potential of the SCCEC in predicting postoperative neurological recovery in DCM. METHODS: Thirty-two DCM patients who underwent intraoperative ultrasonography-guided French-door laminoplasty were prospectively enrolled. The modified Japanese Orthopaedic Association (mJOA) score was evaluated preoperatively and 12 months postoperatively. SCCEC width (SCCEC-W), and anteroposterior diameter (APD) and transverse diameter (TD) of the spinal cord were measured on transverse ultrasonographic images, while the tissue widths from anterior and posterior borders of the spinal cord to the SCCEC were measured on sagittal ultrasonographic images. The APD of the spinal cord and occupying rate of the spinal canal were measured on preoperative magnetic resonance imaging (MRI). RESULTS: All patients achieved improvements in mJOA scores, with an average recovery rate (RR) of 68.69 ± 20.22%. Spearman correlation analysis revealed that SCCEC-W, and ratios between the SCCEC-W and APD/TD based on ultrasonography, correlated moderately with mJOA score RR, with coefficients of -0.527, -0.605 and -0.514, respectively. The ratio between SCCEC-W and ultrasonographic TD correlated moderately with preoperative APD of the spinal cord. The MRI measurements and ultrasonography-based tissue widths showed no significant correlation with mJOA score RR. CONCLUSIONS: The SCCEC may have predictive potential as an intraoperative indicator of neurological recovery in treating DCM. SCCEC-W may be related to spinal cord compression in DCM.
Subject(s)
Spinal Cord Compression , Spinal Cord Diseases , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/pathology , Cervical Vertebrae/surgery , Humans , Magnetic Resonance Imaging/methods , Spinal Cord/diagnostic imaging , Spinal Cord/pathology , Spinal Cord/surgery , Spinal Cord Compression/pathology , Spinal Cord Compression/surgery , Spinal Cord Diseases/diagnostic imaging , Spinal Cord Diseases/pathology , Spinal Cord Diseases/surgery , Treatment Outcome , UltrasonographyABSTRACT
The interplay between virus and host has been one of the hot spot in virology, and it is also the important aspect of revealing the mechanism of virus infection. Increasing studies revealed that several key molecules took part in the process of virus-host interaction. White spot syndrome virus (WSSV) has been proved to affect several physiological processes of the host cells, especially apoptosis. While the relationship between them still remains unclear. In this study, a IFI27 gene (LvIFI27) of Litopenaeus vannamei was cloned. It is indicated that LvIFI27 was induced upon endoplasmic reticulum (ER)-stress and unfolded protein response activator Thapsigargin. Unlike human IFI27 locating to mitochondria, LvIFI27 lied to ER, and was involved in cell apoptosis process. Moreover, results of cumulative mortality analysis showed that LvIFI27 might contributed to WSSV proliferation by promoting apoptosis during the process of viral infection. Findings in this study enriched our understanding of the relationship between WSSV infection and ER-stress mediated apoptosis.
Subject(s)
Arthropod Proteins , DNA Virus Infections/veterinary , Endoplasmic Reticulum Stress , Membrane Proteins/genetics , Penaeidae , Animals , Apoptosis , Arthropod Proteins/genetics , Penaeidae/genetics , Penaeidae/virology , Unfolded Protein Response , White spot syndrome virus 1ABSTRACT
Numerous studies have proved that endoplasmic reticulum (ER)-stress is an important cause of aquatic animal diseases. Therefore, for effectively preventing and controlling aquatic animal diseases, a systematic and in-depth understanding of the environmental stress response in aquatic animals is necessary. In present study, the influence of ER-stress in Litopenaeus vannamei was investigated using Illumina HiSeq based RNA-Seq. Comparing to the cDNA library of hemocytes treated with DMSO in L. vannamei, 286 unigenes were significantly upregulated and 473 unigenes were significantly down-regulated in the Thapsigargin treated group. KEGG analysis indicated that the differentially expressed genes (DEGs) are mainly related to ER-stress, immune as well as metabolism. Besides the classical ER-stress response pathways, the regulation of cell cycle and DNA replication are also important measures of ER-stress response. It has been suggested that the influence of ER-stress on immune genes might be an important factor in environmental stress inducing shrimp disease. Our investigation exhibited that immune-related DEG Prophenoloxidase activating enzyme 2 (LvPPAE2) roled in anti-pathogen immunity of shrimp. This study provides a solid foundation for uncovering the environmental adaptation response and especially its relationship with L. vannamei immune system.
Subject(s)
Animal Diseases , Penaeidae , Animal Diseases/metabolism , Animals , Endoplasmic Reticulum , Gene Expression Profiling/veterinary , Hemocytes , TranscriptomeABSTRACT
Averaging amplitudes over consecutive time samples (i.e., time window) is widely used to calculate the peak amplitude of event-related potentials (ERPs). Cluster analysis of the spatio-temporal ERP data is a promising tool to determine the time window of an ERP of interest. However, determining an appropriate number of clusters to optimally represent ERPs is still challenging. Here, we develop a new method to estimate the optimal number of clusters utilizing consensus clustering. Various polarity dependent clustering methods, namely, k-means, hierarchical clustering, fuzzy c-means, self-organizing map, spectral clustering, and Gaussian mixture model, are used to configure consensus clustering after assessing them individually. When a range of clusters is applied many times, the optimal number of clusters should correspond to the expectation, which is the average of the obtained mean inner-similarities of estimated time windows across all conditions and groups converge in the satisfactory thresholds. In order to assess our method, the proposed method has been applied to simulated data and prospective memory experiment ERP data aimed to qualify N2 and P3, and N300 and prospective positivity components, respectively. The results of determining the optimal number of clusters meet at six cluster maps for both ERP data. In addition, our results revealed that the proposed method could be reliably applied to ERP data to determine the appropriate time window for the ERP of interest when the measurement interval is not accurately defined.