ABSTRACT
Compared to nanozymes with single enzyme activity, those with multiple enzyme activities possess broader application potential due to their diversified enzymatic functionalities. However, the multienzyme nanozymes currently face challenges of interference among different enzymatic activities during practical applications. In this study, we report the synthesis of a light-responsive YbGd-carbon quantum dots nano-hybrid, termed YbGd-CDs, which exhibits controllable enzyme-mimicking activities. This light-responsive behavior enables selective control of the enzymatic activities. Under visible light irradiation, YbGd-CDs demonstrate robust oxidase-like activity. Conversely, under dark conditions, they primarily exhibit peroxidase-like activity. Leveraging the dual-enzyme-mimicking capabilities of YbGd-CDs, we developed colorimetric assays for sensitive detection of total antioxidant capacity (TAC) in both normal and cancer cells as well as d-amino acids in human saliva. This study not only advances the synthesis of carbon-based nanozymes but also highlights their potential in biosensing applications.
Subject(s)
Biosensing Techniques , Carbon , Light , Quantum Dots , Quantum Dots/chemistry , Biosensing Techniques/methods , Humans , Carbon/chemistry , Saliva/chemistry , Saliva/enzymology , Colorimetry , Antioxidants/analysis , Antioxidants/chemistry , Antioxidants/metabolismABSTRACT
CD44 is associated with a high risk of metastasis, recurrence, and drug resistance in various cancers. Here we report that platelet endothelial aggregation receptor 1 (PEAR1) is a CD44 chaperone protein that protected CD44 from endocytosis-mediated degradation and enhances cleavage of the CD44 intracellular domain (CD44-ICD). Furthermore, we found that lysyl oxidase-like protein 2 (LOXL2), an endogenous ligand of PEAR1, bound to the PEAR1-EMI domain and facilitated the interaction between PEAR1 and CD44 by inducing PEAR1 Ser891 phosphorylation in a manner that was independent of its enzyme activity. Levels of PEAR1 protein and PEAR1 phosphorylation at Ser891 were increased in patients with triple-negative breast cancer (TNBC), were positively correlated with expression of LOXL2 and CD44, and were negatively correlated with overall survival. The level of PEAR1 Ser891 phosphorylation was identified as the best independent prognostic factor in TNBC patients. The prognostic efficacy of the combination of PEAR1 phosphorylation at Ser891 and CD44 expression was superior to that of PEAR1 phosphorylation at Ser891 alone. Blocking the interaction between LOXL2 and PEAR1 with monoclonal antibodies significantly inhibited TNBC metastasis, representing a promising therapeutic strategy for TNBC.
Subject(s)
Amino Acid Oxidoreductases , Hyaluronan Receptors , Neoplasm Metastasis , Receptors, Cell Surface , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/genetics , Hyaluronan Receptors/metabolism , Hyaluronan Receptors/genetics , Female , Phosphorylation , Receptors, Cell Surface/metabolism , Receptors, Cell Surface/genetics , Amino Acid Oxidoreductases/metabolism , Amino Acid Oxidoreductases/genetics , Animals , Cell Line, Tumor , Mice , Proteolysis , Neoplasm Proteins/metabolism , Neoplasm Proteins/geneticsABSTRACT
PURPOSE: Nontraditional lipid parameters are associated with intracranial atherosclerotic stenosis (ICAS) progression. This study aimed to investigate the association of nontraditional lipid parameters with the risk of restenosis in patients with ICAS after endovascular treatment (EVT). METHODS: This study retrospectively enrolled consecutive patients with symptomatic ICAS after successful EVT followed by at least 3 months of angiography. Participants were divided into restenosis or non-restenosis groups based on the angiographic follow-up results. The nontraditional lipid parameters were calculated from conventional lipid parameters. The COX regression models and restricted cubic splines (RCS) were used to explore the association between nontraditional lipid parameters and restenosis. RESULTS: This study recruited 222 cases with 224 lesions eligible for our study, of which 56 (25%) had restenosis. Compared with the non-restenosis group, patients in the restenosis group had higher levels of the atherogenic index of plasma (AIP) (0.211, interquartile range, IQR, 0.065-0.404 vs. 0.083, IQR, -0.052-0.265, Pâ¯= 0.001), remnant cholesterol (RC) (0.55, IQR, 0.33-0.77 vs. 0.30, IQR, 0.18-0.49, Pâ¯< 0.001) and Castelli's indexI (CRI-I) (4.13, IQR, 3.39-5.34 vs. 3.74, IQR, 2.94-4.81, Pâ¯= 0.030). In the multivariable COX regression analysis, a 0.1 unit increase of AIP was an independent risk factor for restenosis (hazard ratio, HRâ¯= 1.20, 95% confidence interval, CI 1.05-1.35, Pâ¯= 0.005) whereas such an association was not observed for RC (HRâ¯= 1.01, 95% CI 0.90-1.15, Pâ¯= 0.835). The restricted cubic spline (RCS) plot revealed a linear relationship between AIP and restenosis (P for nonlinearâ¯= 0.835) but a nonlinear relationship for RC (P for nonlinearâ¯= 0.012). Patients were stratified according to tertiles (T) of AIP and RC and the risk of restenosis increased in T3 compared to T1 (HRâ¯= 3.21, 95% CI 1.35-7.62, Pâ¯= 0.008 and HRâ¯= 2.99, 95% CI 1.11-8.03, Pâ¯= 0.030, respectively). Furthermore, this association remained stable within each LDLC level subgroup. CONCLUSION: The AIP and RC were positively and independently associated with restenosis in patients with ICAS after EVT.
ABSTRACT
The nature always offers amazing inspiration, where it is highly desirable to endow coatings on marine equipment with powerful functions. An excellent example is slippery zone of Nepenthes pitcher, which possesses novel liquid-repellent and self-cleaning performance. Therefore, this study presents an efficient fabrication method to prepare a novel coating. The coatings were fabricated by designing biomimetic textures extracted from the lunate bodies of slippery zone on polydimethylsiloxane (PDMS) and then grafting Dictyophora indusiata polysaccharide (DIP) modifier. The as-prepared slippery coatings exhibited outstanding antifouling properties against kinds of daily life pollutants such as Chlorella and coffee. This synergistic strategy was proposed combined with environmentally friendly modifier grafting and heterogeneous microstructure on the surface to broaden new probabilities for manufacturing slippery coatings with incredible protective functionality.
ABSTRACT
Introduction: Bispecific antibodies (BsAbs) can simultaneously target two epitopes of different antigenic targets, bringing possibilities for diversity in antibody drug design and are promising tools for the treatment of cancers and other diseases. T-cell engaging bsAb is an important application of the bispecific antibody, which could promote T cell-mediated tumor cell killing by targeting tumor-associated antigen (TAA) and CD3 at the same time. Methods: This study comprised antibodies purification, Elisa assay for antigen binding, cytotoxicity assays, T cell activation by flow cytometry in vitro and xenogenic tumor model in vivo. Results: We present a novel bsAb platform named PHE-Ig technique to promote cognate heavy chain (HC)-light chain (LC) pairing by replacing the CH1/CL regions of different monoclonal antibodies (mAbs) with the natural A and B chains of PHE1 fragment of Integrin ß2 based on the knob-in-hole (KIH) technology. We had also verified that PHE-Ig technology can be effectively used as a platform to synthesize different desired bsAbs for T-cell immunotherapy. Especially, BCMA×CD3 PHE-Ig bsAbs exhibited robust anti-multiple myeloma (MM) activity in vitro and in vivo. Discussion: Moreover, PHE1 domain was further shortened with D14G and R41S mutations, named PHE-S, and the PHE-S-based BCMA×CD3 bsAbs also showed anti BCMA+ tumor effect in vitro and in vivo, bringing more possibilities for the development and optimization of different bsAbs. To sum up, PHE1-based IgG-like antibody platform for bsAb construction provides a novel strategy for enhanced T-cell immunotherapy.
Subject(s)
Antibodies, Bispecific , T-Lymphocytes , Antibodies, Bispecific/immunology , Animals , Humans , T-Lymphocytes/immunology , Mice , Immunoglobulin G/immunology , Immunotherapy/methods , Cell Line, Tumor , Multiple Myeloma/immunology , Multiple Myeloma/therapy , Xenograft Model Antitumor Assays , Lymphocyte Activation/immunology , CD3 Complex/immunology , Antigens, Neoplasm/immunologyABSTRACT
Impaired differentiation of megakaryocytes constitutes the principal etiology of thrombocytopenia. The signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor in regulating megakaryocyte differentiation, yet the precise mechanism of its activation remains unclear. PALLD, an actin-associated protein, has been increasingly recognized for its essential functions in multiple biological processes. This study revealed that megakaryocyte/plateletspecific knockout of PALLD in mice exhibited thrombocytopenia due to diminished platelet biogenesis. In megakaryocytes, PALLD deficiency led to impaired proplatelet formation and polyploidization, ultimately weakening their differentiation for platelet production. Mechanistic studies demonstrated that PALLD bound to STAT3 and interacted with its DNA-binding domain (DBD) and Src homology 2 (SH2) domain via Immunoglobulin domain 3 (Ig3). Moreover, the absence of PALLD attenuated STAT3 Y705 phosphorylation and impeded STAT3 nuclear translocation. Based on the PALLD-STAT3 binding sequence, we designed a peptide C-P3, which can facilitate megakaryocyte differentiation and accelerate platelet production in vivo. In conclusion, this study highlights the pivotal role of PALLD in megakaryocyte differentiation and proposes a novel approach for treating thrombocytopenia by targeting the PALLD-STAT3 interaction.
ABSTRACT
Naphthoquine is a promising candidate for antimalarial combination therapy. Its combination with artemisinin has demonstrated excellent efficacy in clinical trials conducted across various malaria-endemic areas. A co-formulated combination of naphthoquine and azithromycin has also shown high clinical efficacy for malaria prophylaxis in Southeast Asia. Developing new combination therapies using naphthoquine will provide additional arsenal responses to the growing threat of artemisinin resistance. Furthermore, due to its long half-life, the possible interaction of naphthoquine with other drugs also needs attention. However, studies on its pharmacodynamic interactions with other drugs are still limited. In this study, the in vitro interactions of naphthoquine with ivermectin, atovaquone, curcumin, and ketotifen were evaluated in the asexual stage of Plasmodium falciparum 3D7. By using the combination index analysis and the SYBR Green I-based fluorescence assay, different interaction patterns of selected drugs with naphthoquine were revealed. Curcumin showed a slight but significant synergistic interaction with naphthoquine at lower effect levels, and no antagonism was observed across the full range of effect levels for all tested ratios. Atovaquone showed a potency decline when combined with naphthoquine. For ivermectin, a significant antagonism with naphthoquine was observed at a broad range of effect levels below 75% inhibition, although no significant interaction was observed at higher effect levels. Ketotifen interacted with naphthoquine similar to ivermectin, but significant antagonism was observed for only one tested ratio. These findings should be helpful to the development of new naphthoquine-based combination therapy and the clinically reasonable application of naphthoquine-containing therapies. IMPORTANCE: Pharmacodynamic interaction between antimalarials is not only crucial for the development of new antimalarial combination therapies but also important for the appropriate clinical use of antimalarials. The significant synergism between curcumin and naphthoquine observed in this study suggests the potential value for further development of new antimalarial combination therapy. The finding of a decline in atovaquone potency in the presence of naphthoquine alerts to a possible risk of treatment or prophylaxis failure for atovaquone-proguanil following naphthoquine-containing therapies. The observation of antagonism between naphthoquine and ivermectin raised a need for concern about the applicability of naphthoquine-containing therapy in malaria-endemic areas with ivermectin mass drug administration deployed. Considering the role of atovaquone-proguanil as a major alternative when first-line artemisinin-based combination therapy is ineffective and the wide implementation of ivermectin mass drug administration in malaria-endemic countries, the above findings will be important for the appropriate clinical application of antimalarials involving naphthoquine-containing therapies.
Subject(s)
Antimalarials , Atovaquone , Curcumin , Drug Interactions , Ivermectin , Ketotifen , Naphthoquinones , Plasmodium falciparum , Plasmodium falciparum/drug effects , Atovaquone/pharmacology , Antimalarials/pharmacology , Naphthoquinones/pharmacology , Humans , Curcumin/pharmacology , Ivermectin/pharmacology , Ketotifen/pharmacology , Drug Synergism , Aminoquinolines/pharmacology , Malaria, Falciparum/drug therapy , Malaria, Falciparum/parasitology , 1-Naphthylamine/analogs & derivativesABSTRACT
OBJECTIVE: The objective of this study was to evaluate the safety and effectiveness of radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE) in the treatment of large hepatic hemangiomas (LHH) (5-9.9 cm in diameter). METHODS AND MATERIALS: This study retrospectively collected data from 82 patients with LHH treated at Chaoyang Central Hospital. The study analyzed the differences in postoperative efficacy, operative time, blood routine, liver and kidney function on the first day after surgery, postoperative hospitalization time and postoperative complications. RESULTS: There were statistically significant differences in indicators such as white blood cell count, alanine aminotransferase, aspartate aminotransferase and total bilirubin on the first day after surgery between the RFA group (39 cases) and the TACE group (43 cases) ( P < 0.001). Compared to RFA, LHH patients treated with TACE had a general complication rate of 39.5% (vs. 43.6%; P = 0.7), a procedure-related complication rate of 30.2% (vs. 59.0%; P = 0.009), an effective rate at 6-12 months postoperatively of 55.8% (vs. 82.1%; P = 0.01), an operating-time of 41.2 ± 14.9 min (vs. 100.8 ± 35.5 min; P < 0.001) and hospitalization costs of 17052.7 ± 1364.8 yuan (vs. 30952.1 ± 4327.6 yuan; P < 0.001). CONCLUSION: This study indicates that the efficacy of RFA in treating LHH is significantly superior to TACE. Microwave ablation and RFA appear to be safe treatments for LHH. The TACE group exhibited shorter operating-time, lower hospitalization costs and lower demands on cardiopulmonary function.
Subject(s)
Chemoembolization, Therapeutic , Hemangioma , Liver Neoplasms , Operative Time , Humans , Male , Female , Liver Neoplasms/therapy , Middle Aged , Retrospective Studies , Treatment Outcome , Hemangioma/therapy , Adult , Chemoembolization, Therapeutic/methods , Chemoembolization, Therapeutic/adverse effects , Radiofrequency Ablation/adverse effects , Radiofrequency Ablation/methods , Length of Stay , Aged , Postoperative Complications/etiology , Catheter Ablation/methods , Catheter Ablation/adverse effects , Time Factors , Tumor BurdenABSTRACT
Recent strides in nanotechnology have given rise to nanozymes, nanomaterials designed to emulate enzymatic functions. Despite their promise, challenges such as batch-to-batch variability and limited atomic utilization persist. This study introduces Pt(Glu)2, a platinum glutamic acid complex, as a versatile small-molecule peroxidase mimic. Synthesized through a straightforward method, Pt(Glu)2 exhibits robust catalytic activity and stability. Steady-state kinetics reveal a lower Km value compared to that of natural enzymes, signifying strong substrate affinity. Pt(Glu)2 was explored for controllable chemical modification and integration into cascade reactions with natural enzymes, surpassing other nanomaterials. Its facile synthesis and seamless integration enhance cascade reactions beyond the capabilities of nanozymes. In biosensing applications, Pt(Glu)2 enabled simultaneous detection of cholesterol and alkaline phosphatase in human serum with high selectivity and sensitivity. These findings illustrate the potential of small molecule mimetics in catalysis and biosensing, paving the way for their broader applications.
Subject(s)
Biosensing Techniques , Peroxidase , Humans , Glutamic Acid , Platinum/chemistry , Peroxidases/chemistry , Biosensing Techniques/methods , Coloring AgentsABSTRACT
Soluble pea protein isolate-curcumin nanoparticles were successfully prepared at a novel pH combination, with encapsulation efficiency and drug loading amount of 95.69 ± 1.63 % and 32.73 ± 0.56 µg/mg, respectively, resulting in >4000-fold increase in the water solubility of curcumin. The encapsulation propensity and interaction mechanism of pea protein isolates with curcumin and colchicine were comparatively evaluated by structural characterization, molecular dynamics simulations and molecular docking. The results showed that the nanoparticles formed by curcumin and colchicine with pea protein isolates were mainly driven by hydrogen bonding and hydrophobic interactions, and the binding process did not alter the secondary structure of pea protein. In contrast, pea protein isolate-curcumin nanoparticles exhibited smaller particle size, lower RMSD value, lower binding Gibbs free energy and greater structural stability. Therefore, pea protein isolate is a suitable encapsulation material for hydrophobic compounds. Furthermore, the pea protein isolate-curcumin nanoparticles showed remarkably enhanced antitumor activity, as evidenced by a significant reduction in IC50, and the anti-tumor mechanism of it involved the ROS-induced mitochondria-mediated caspase cascade apoptosis pathway. These findings provide insights into the development of pea protein-based delivery systems and the possibility of a broader application of curcumin in antitumor activity.
Subject(s)
Curcumin , Nanoparticles , Pea Proteins , Curcumin/chemistry , Molecular Docking Simulation , Nanoparticles/chemistry , Hydrogen-Ion Concentration , Colchicine , Particle Size , Drug Carriers/chemistryABSTRACT
Metformin has shown great promise in the treatment of HCC. Radiofrequency ablation (RFA) deficiency results in recurrence and metastasis of remaining HCC tumors. Here, we aimed to investigate the role and mechanism of metformin in HCC after RFA deficiency. HCC cell line Hep-G2 was selected to simulate RFA deficiency and named HepG2-H cells. After treating cells with different concentrations of metformin (2.5, 5, 10 µM) or transfecting related plasmids, cell proliferation, migration, invasion, apoptosis and angiogenesis were detected, in vitro permeability test was performed, and an angiogenesis-related protein VEGFA was analyzed. The residual HCC model after RFA deficiency was established in mice. Metformin was administered by gavage to detect changes in tumor volume and weight, and CD31 staining was used to observe microvessels. The targeting relationship between miR-302b-3p and TXNIP was demonstrated by the bioinformatics website, dual-luciferase reporter assay, and RNA pull-down assay. The results found that metformin inhibited RFA deficiency-induced growth and angiogenesis of HCC cells in vitro. miR-302b-3p counteracted the therapeutic effect of metformin on RFA deficiency. miR-302b-3p targeted regulation of TXNIP. The up-regulation of TXNIP reversed the effects of overexpression of miR-302b-3p on RFA-deficient HCC cells. Metformin inhibited RFA-deficiency-induced HCC growth and tumor vascular abnormalities in vivo. Overall, metformin promotes the normalization of abnormal blood vessels after RFA deficiency in HCC by miR-302b-3p targeting TXNIP, which can be used to prevent the progression of HCC after RFA.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Metformin , MicroRNAs , Radiofrequency Ablation , Animals , Mice , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Liver Neoplasms/drug therapy , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Metformin/pharmacology , Metformin/therapeutic use , Cell Line, Tumor , Cell Proliferation/genetics , Thioredoxins/genetics , Gene Expression Regulation, NeoplasticABSTRACT
Pulmonary fibrosis (PF) is a lethal disease characterized by a progressive decline in lung function. Currently, lung transplantation remains the only available treatment for PF. However, both artemisinin (ART) and hydroxychloroquine (HCQ) possess potential antifibrotic properties. This study aimed to investigate the effects and mechanisms of a compound known as Artemisinin-Hydroxychloroquine (AH) in treating PF, specifically by targeting the TGF-ß1/Smad2/3 pathway. To do this, we utilized an animal model of PF induced by a single tracheal drip of bleomycin (BLM) in Sprague-Dawley (SD) rats. The PF animal models were administered various doses of AH, and the efficacy and safety of AH were evaluated through pulmonary function testing, blood routine tests, serum biochemistry tests, organ index measurements, and pathological examinations. Additionally, Elisa, western blotting, and qPCR techniques were employed to explore the potential molecular mechanisms of AH in treating PF. Our findings reveal that AH effectively and safely alleviate PF by inhibiting BLM-induced specific inflammation, reducing extracellular matrix (ECM) deposition, and interfering with the TGF-ß1/Smad2/3 signaling pathway. Notably, the windfall for this study is that the inhibition of ECM may initiate self-healing in the BLM-induced PF animal model. In conclusion, AH shows promise as a potential therapeutic drug for PF, as it inhibits disease progression through the TGF-ß1/Smad2/3 signaling pathway.
Subject(s)
Artemisinins , Pulmonary Fibrosis , Rats , Animals , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , Transforming Growth Factor beta1/metabolism , Bleomycin/toxicity , Hydroxychloroquine/adverse effects , Rats, Sprague-Dawley , Signal Transduction , Artemisinins/adverse effects , LungABSTRACT
Defect passivation of the perovskite surface and grain boundary (GBs) has become a widely adopted approach to reduce charge recombination. Research has demonstrated that functional groups with Lewis acid or base properties can successfully neutralize trap states and limit nonradiative recombination. Unlike traditional Lewis acid-base organic molecules that only bind to a single anionic or cationic defect, zwitterions can passivate both anionic and cationic defects simultaneously. In this work, zwitterions organic halide salt 1-amino pyridine iodine (AmPyI) is used as a perovskite for defect passivation. It is found that a pair of amino lone electrons in AmPyI can passivate defects surface and GBs through hydrogen bonding with perovskite, and the introduced I- can bind to uncoordinated Pb2+ while also controlling the surface morphology of the film and improving the crystallinity. In the presence of the AmPyI additive, we obtained about 1.24 µm of amplified perovskite grains and achieved an efficiency of 23.80% with minimal hysteresis.
ABSTRACT
Interindividual distances and orientations of laying hens provide quantitative measures to calculate and optimize space allocations for bird flocks. However, these metrics were often measured manually and have not been examined for different stocking densities of laying hens. The objectives of this study were to 1) integrate and develop several deep learning techniques to detect interindividual distances and orientations of laying hens; and 2) examine the 2 metrics under 8 stocking densities via the developed techniques. Laying hens (Jingfen breed, a popular hen breed in China) at 35 wk of age were raised in experimental compartments at 8 different stocking densities of 3,840, 2,880, 2,304, 1,920, 1,646, 1,440, 1,280, and 1,152 cm2â¢bird-1 (3-10 hens per compartment, respectively), and cameras on the top of the compartments recorded videos for further analysis. The designed deep learning image classifier achieved over 99% accuracy to classify bird's perching status and excluded frames with bird perching to ensure that all birds analyzed were on the same horizontal plane, reducing calculation errors. The YOLOv5m oriented object detection model achieved over 90% precision, recall, and F1 score in detecting birds in compartments and can output bird centroid coordinates and angles, from which interindividual distances and orientations were calculated based on pairs of birds. Laying hens maintained smaller minimum interindividual distances in higher stocking densities. They were in an intersecting relationship with conspecifics for over 90% of the time. The developed integrative deep learning techniques and behavior metrics provide animal-based measurement of space requirement for laying hens.
ABSTRACT
Insulin resistance (IR) is associated with a variety of cardiovascular diseases, but there are few studies on the correlation between IR and calcified aortic stenosis (CAS). In this study, the triglyceride-glucose (TyG) index, which reflects IR, was used to investigate the correlation between IR and CAS. The study included 183 elderly patients who were diagnosed with CAS by transthoracic echocardiography. The patients were matched 1:1 according to age and sex, and elderly patients who were hospitalized during the same period and underwent transthoracic echocardiography without aortic stenosis were included as the control group. The relationship between the TyG index and CAS was analyzed by a multivariable logistic regression model, curve fitting and trend test. Multivariate logistic regression analysis showed that the TyG index as a continuous variable was negatively associated with CAS (P < 0.001); trend tests and curve fitting further supported this association. Our study showed that the TyG index was negatively associated with CAS in elderly patients, which may be related to the impairment of insulin receptors and signaling pathways in IR.
Subject(s)
Aortic Valve Stenosis , Insulin Resistance , Aged , Humans , Cross-Sectional Studies , Aortic Valve Stenosis/diagnostic imaging , Glucose , TriglyceridesABSTRACT
The family Nidulariaceae, consisting of five genera including Cyathus, is a unique group of mushrooms commonly referred to as bird's nest fungi due to their striking resemblance to bird's nests. These mushrooms are considered medicinal mushrooms in Chinese medicine and have received attention in recent years for their anti-neurodegenerative properties. However, despite the interest in these mushrooms, very little is known about their mitochondrial genomes (mitogenomes). This study is the first comprehensive investigation of the mitogenomes of five Nidulariaceae species with circular genome structures ranging in size from 114,236 bp to 129,263 bp. Comparative analyses based on gene content, gene length, tRNA, and codon usage indicate convergence within the family Nidulariaceae and heterogeneity within the order Agaricales. Phylogenetic analysis based on a combined mitochondrial conserved protein dataset provides a well-supported phylogenetic tree for the Basidiomycetes, which clearly demonstrates the evolutionary relationships between Nidulariaceae and other members of Agaricales. Furthermore, phylogenetic inferences based on four different gene sets reveal the stability and proximity of evolutionary relationships within Agaricales. These results reveal the uniqueness of the family Nidulariaceae and its similarity to other members of Agaricales; provide valuable insights into the origin, evolution, and genetics of Nidulariaceae species; and enrich the fungal mitogenome resource. This study will help to expand the knowledge and understanding of the mitogenomes in mushrooms.
Subject(s)
Agaricales , Genome, Mitochondrial , Agaricales/genetics , Phylogeny , Genome, Mitochondrial/genetics , Introns/genetics , Gene Rearrangement , Mitochondrial ProteinsABSTRACT
BACKGROUND: Megakaryocyte differentiation and platelet production disorders are the main causes of thrombocythemia and thrombocytopenia and lead to thrombosis or hemorrhage. Branched-chain amino acids (BCAAs) are essential nutrients that regulate important metabolic signals. BCAA administration could also increase platelet activation and promote the risk of thrombosis. OBJECTIVES: To unveil the role of BCAAs in thrombocytopoiesis. METHODS: BCAA-fed mice and megakaryocyte/platelet-specific branched-chain α-keto acid dehydrogenase E1α subunit-deficient mice were used to study the role of BCAAs in thrombocytopoiesis. RESULTS: In this study, we found that BCAA diet could facilitate megakaryocyte differentiation and platelet production. Meanwhile, megakaryocyte/platelet-specific branched-chain α-keto acid dehydrogenase E1α subunit-deficient mice developed thrombocythemia, which was mainly caused by the excessive differentiation of megakaryocytes and proplatelet biogenesis. Moreover, the use of BT2, the agonist of BCAA catabolism, could affect proplatelet formation (PPF) and megakaryocyte polyploidization, as well as ameliorating the thrombocythemia of BCAA-fed mice. CONCLUSION: We found that deficiency in BCAA catabolism led to the activation of p70S6K/mammalian target of rapamycin (mTOR) signaling, megakaryocyte over differentiation, and the acceleration of PPF. Activating BCAA metabolism with BT2 could inhibit mTOR signaling, reduce PPF, and ameliorate thrombocythemia in BCAA-fed mice. Therefore, this study reveals a novel role of BCAAs in megakaryocyte differentiation and platelet production, suggesting that targeting BCAA-mediated p70S6K/mTOR signaling may be a potential strategy for the treatment of thrombocytopenia or thrombocythemia.
Subject(s)
Thrombocytopenia , Thrombocytosis , Thrombosis , Mice , Animals , Amino Acids, Branched-Chain/metabolism , Ribosomal Protein S6 Kinases, 70-kDa , Thrombopoiesis , 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)/metabolism , TOR Serine-Threonine Kinases/metabolism , Mammals/metabolismABSTRACT
With the rapid development of large-scale and intensive swine production, the emission of aerosols from swine farms has become a growing concern, attracting extensive attention. While aerosols are found in various environments, those from swine farms are distinguished from human habitats, such as residential, suburban, and urban areas. In order to gain a comprehensive understanding of aerosols from swine farms, this paper reviewed relevant studies conducted between 2000 and 2022. The main components, concentrations, and size distribution of the aerosols were systematically reviewed. The differences between aerosols from swine farms and human living and working environments were compared. Finally, the sources, influencing factors, and reduction technologies for aerosols from swine farms were thoroughly elucidated. The results demonstrated that the concentrations of aerosols inside swine farms varied considerably, and most exceeded safety thresholds. However, further exploration is needed to fully understand the difference in airborne microorganism community structure and particles with small sizes (<1 µm) between swine farms and human living and working environments. More airborne bacterial and viruses were adhered to large particles in swine houses, while the proportion of airborne fungi in the respirable fraction was similar to that of human living and working environments. In addition, swine farms have a higher abundance and diversity of potential pathogens, airborne resistant microorganisms and resistant genes compared to the human living and working environments. The aerosols of swine farms mainly originated from sources such as manure, feed, swine hair and skin, secondary production, and waste treatment. According to the source analysis and factors influencing aerosols in swine farms, various technologies could be employed to mitigate aerosol emissions, and some end-of-pipe technologies need to be further improved before they are widely applied. Swine farms are advised not to increase aerosol concentration in human living and working environments, in order to decrease the impact of aerosols from swine farms on human health and restrain the spread of airborne potential pathogens. This review provides critical insights into aerosols of swine farms, offering guidance for taking appropriate measures to enhance air quality inside and surrounding swine farms.
Subject(s)
Air Pollution , Animals , Aerosols/analysis , Air Pollution/analysis , Bacteria , Farms , Manure , SwineABSTRACT
Non-invasive measures have a critical role in precision livestock and poultry farming as they can reduce animal stress and provide continuous monitoring. Animal activity can reflect physical and mental states as well as health conditions. If any problems are detected, an early warning will be provided for necessary actions. The objective of this study was to identify avian diseases by using thermal-image processing and machine learning. Four groups of 14-day-old Ross 308 Broilers (20 birds per group) were used. Two groups were infected with one of the following diseases: Newcastle Disease (ND) and Avian Influenza (AI), and the other two were considered control groups. Thermal images were captured every 8 h and processed with MATLAB. After de-noising and removing the background, 23 statistical features were extracted, and the best features were selected using the improved distance evaluation method. Support vector machine (SVM) and artificial neural networks (ANN) were developed as classifiers. Results indicated that the former classifier outperformed the latter for disease classification. The Dempster-Shafer evidence theory was used as the data fusion stage if neither ANN nor SVM detected the diseases with acceptable accuracy. The final SVM-based framework achieved 97.2% and 100% accuracy for classifying AI and ND, respectively, within 24 h after virus infection. The proposed method is an innovative procedure for the timely identification of avian diseases to support early intervention.
ABSTRACT
Knowledge, attitudes, and practices (KAP) surveys on malaria and antimalarial mass drug administration (MDA) have not received much attention in the Union of the Comoros. This study is a household-based cross-sectional survey using a multi-stage sampling technique aiming at investigating KAP toward malaria and antimalarial MDA with artemisinin-piperaquine among heads of households on Grande Comore Island, the largest island of the Comoros. A predefined structured questionnaire containing socio-demographic characteristics and questions about malaria and antimalarial MDA was administered to 1,368 randomly selected heads of households from 10 malaria-endemic villages on Grande Comore Island. The results showed that 81.4% of the heads of households knew that malaria is a transmissible disease, 77.6% recognized mosquitoes as the vectors of malaria, and 70.8% recognized fever as one of the frequent symptoms of malaria; 40.8% of respondents remembered the name of the antimalarial drug used for MDA, and 62.1% remembered the color of the antimalarial tablets; and 65.1% chose to go to a public health center to seek treatment as their first option within 24 hr of the onset of initial malaria symptoms. This study found that most heads of households had a reasonable level of knowledge about malaria and antimalarial MDA. However, only 7.3% obtained full points on all knowledge-related questions. Misconceptions about malaria cause, transmission, diagnostic method, and antimalarial MDA exist in the community of Grande Comore Island. As the Comoros continues to put great efforts to go toward malaria elimination, the community's KAP on malaria and antimalarial MDA is crucial to guarantee the community's long-term adherence to malaria elimination interventions and could become key to guaranteeing malarial elimination in the Comoros. Therefore, there is a great need to improve malaria prevention awareness through strengthening malaria education and promoting behavioral change. Heads of households should be the core target of malaria education and behavioral change for malaria elimination.