ABSTRACT
Leaf rust is a widespread foliar wheat disease causing substantial yield losses worldwide. Slow rusting is "adult plant" resistance that significantly slows epidemic development and thereby reduces yield loss. Wheat accession CI 13227 was previously characterized as having slow-rusting resistance. To validate the quantitative trait loci (QTLs) and develop diagnostic markers for slow rusting resistance in CI 13227, a new population of recombinant inbred lines of CI 13227 × Everest was evaluated for latent period, final severity, area under the disease progress curve, and infection type in greenhouses and genotyped using genotyping-by-sequencing. Four QTLs were identified on chromosome arms 2BL, 2DS, 3BS, and 7BL, explaining 6.82 to 28.45% of the phenotypic variance for these traits. Seven kompetitive allele-specific polymorphism markers previously reported to be linked to the QTLs in two other CI 13227 populations were validated. In addition, the previously reported QLr.hwwg-7AL was remapped to 2BL (renamed QLr.hwwg-2BL) after adding new markers in this study. Phenotypic data showed that the recombinant inbred lines harboring two or three of the QTLs had a significantly longer latent period. QLr.hwwg-2DS on 2DS showed a major effect on all rust resistance traits and was finely mapped to a 2.7-Mb interval by two newly developed flanking markers from exome capture. Three disease-resistance genes and two transporter genes were identified as the putative candidates for QLr.hwwg-2DS. The validated QTLs can be used as slow-rusting resistance resources, and the markers developed in this study will be useful for marker-assisted selection.
Subject(s)
Basidiomycota , Disease Resistance , Plant Diseases , Quantitative Trait Loci , Triticum , Quantitative Trait Loci/genetics , Triticum/genetics , Triticum/microbiology , Triticum/immunology , Plant Diseases/microbiology , Plant Diseases/genetics , Plant Diseases/immunology , Disease Resistance/genetics , Basidiomycota/physiology , Phenotype , Chromosome Mapping , Puccinia , Genetic Markers/genetics , Genotype , Chromosomes, Plant/genetics , AllelesABSTRACT
BACKGROUND: Perihematomal edema (PHE) after post-intracerebral hemorrhage (ICH) has complex pathophysiological mechanisms that are poorly understood. The complicated immune response in the post-ICH brain constitutes a crucial component of PHE pathophysiology. In this study, we aimed to characterize the transcriptional profiles of immune cell populations in human PHE tissue and explore the microscopic differences between different types of immune cells. METHODS: 9 patients with basal ganglia intracerebral hemorrhage (hematoma volume 50-100 ml) were enrolled in this study. A multi-stage profile was developed, comprising Group1 (n = 3, 0-6 h post-ICH, G1), Group2 (n = 3, 6-24 h post-ICH, G2), and Group3 (n = 3, 24-48 h post-ICH, G3). A minimal quantity of edematous tissue surrounding the hematoma was preserved during hematoma evacuation. Single cell RNA sequencing (scRNA-seq) was used to map immune cell populations within comprehensively resected PHE samples collected from patients at different stages after ICH. RESULTS: We established, for the first time, a comprehensive landscape of diverse immune cell populations in human PHE tissue at a single-cell level. Our study identified 12 microglia subsets and 5 neutrophil subsets in human PHE tissue. What's more, we discovered that the secreted phosphoprotein-1 (SPP1) pathway served as the basis for self-communication between microglia subclusters during the progression of PHE. Additionally, we traced the trajectory branches of different neutrophil subtypes. Finally, we also demonstrated that microglia-produced osteopontin (OPN) could regulate the immune environment in PHE tissue by interacting with CD44-positive cells. CONCLUSIONS: As a result of our research, we have gained valuable insight into the immune-microenvironment within PHE tissue, which could potentially be used to develop novel treatment modalities for ICH.
Subject(s)
Brain Edema , Cerebral Hemorrhage , Disease Progression , Sequence Analysis, RNA , Single-Cell Analysis , Humans , Brain Edema/immunology , Brain Edema/pathology , Brain Edema/genetics , Brain Edema/metabolism , Brain Edema/etiology , Cerebral Hemorrhage/immunology , Cerebral Hemorrhage/pathology , Cerebral Hemorrhage/genetics , Male , Female , Middle Aged , Sequence Analysis, RNA/methods , Aged , Hematoma/pathology , Hematoma/immunology , Hematoma/geneticsABSTRACT
Amino acid formula (AAF) is increasingly consumed in infants with cow's milk protein allergy; however, the long-term influences on health are less described. In this study, we established a mouse model by subjecting neonatal mice to an amino acid diet (AAD) to mimic the feeding regimen of infants on AAF. Surprisingly, AAD-fed mice exhibited dysbiotic microbiota and increased neuronal activity in both the intestine and brain, as well as gastrointestinal peristalsis disorders and depressive-like behavior. Furthermore, fecal microbiota transplantation from AAD-fed mice or AAF-fed infants to recipient mice led to elevated neuronal activations and exacerbated depressive-like behaviors compared to that from normal chow-fed mice or cow's-milk-formula-fed infants, respectively. Our findings highlight the necessity to avoid the excessive use of AAF, which may influence the neuronal development and mental health of children.
Subject(s)
Microbiota , Milk Hypersensitivity , Humans , Infant , Female , Cattle , Child , Animals , Mice , Infant Formula/chemistry , Amino Acids , DysbiosisABSTRACT
The NOD-like receptor (NLR) family pyrin domain containing 6 (NLRP6) serves as a sensor for microbial dsRNA or lipoteichoic acid (LTA) in intestinal epithelial cells (IECs), and initiating multiple pathways including inflammasome pathway and type I interferon (IFN) pathway, or regulating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. NLRP6 can exert its function in both inflammasome-dependent and inflammasome-independent manners. However, there is no tool to distinguish the contribution of individual NLRP6-mediated pathway to the physiology and pathology in vivo. Here, we validated that Arg39 and Trp50 residues in the pyrin domain (PYD) of murine NLRP6 are required for ASC recruitment and inflammasome activation, but are not important for the RNA binding and PYD-independent NLRP6 oligomerization. We further generated the Nlrp6R39E&W50E mutant mice, which showed reduced inflammasome activation in either steady state intestine or during viral infection. However, the type I IFN production in cells or intestine tissue from Nlrp6R39E&W50E mutant mice remain normal. Interestingly, NLRP6-mediated inflammasome activation or the IFN-I production seems to play distinct roles in the defense responses against different types of RNA viruses. Our work generated a useful tool to study the inflammasome-dependent role of NLRP6 in vivo, which might help to understand the complexity of multiple pathways mediated by NLRP6 in response to the complicated and dynamic environmental cues in the intestine.
Subject(s)
Inflammasomes , NF-kappa B , Mice , Animals , Inflammasomes/genetics , Inflammasomes/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Intestines , Mitogen-Activated Protein Kinases , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolismABSTRACT
Objective: This study evaluated the regulatory effect of Tetramethylpyrazine (TMP) on the spinal cord injury (SCI) rat model and clarified the neuroprotective mechanism of TMP on SCI. Methods: An SCI rat model was generated and treated with TMP injections for two weeks. miR-497-5p and EGFL7 expression changes were evaluated, motor function recovery after SCI was assessed by BBB score test and footprint analysis, lesions of rat spinal cord were assessed by HE staining and TUNEL staining; angiogenesis was assessed by immunoblotting for CD31; inflammatory factor levels were detected by ELISA. EGFL7 was verified as a target of miR-497-5p by bioinformatics website analysis and luciferase reporter gene assay. H2O2-injured neurons were cultured in vitro to explore the effect of TMP. Results: After SCI, miR-497-5p was upregulated while EGFL7 was downregulated in rats. TMP inhibited apoptosis and promoted angiogenesis, nerve regeneration, and repair of nerve defects by reducing miR-497-5p and increasing EGFL7 expression. miR-497-5p targeted EGFL7. In addition, TMP hindered neuronal inflammation and apoptosis induced by H2O2in vitro. Conclusion: TMP promotes angiogenesis by downregulating miR-497-5p to target EGFL7, and promotes nerve regeneration and repair of nerve defects in rats with SCI.
ABSTRACT
In order to ensure the normal operation of rotating equipment, it is very important to quickly and efficiently diagnose the faults of anti-friction bearings. Hereto, fault diagnosis of anti-friction bearings based on Bi-dimensional ensemble local mean decomposition and optimized dynamic least square support vector machine (LSSVM) is presented in this paper. Bi-dimensional ensemble local mean decomposition, an extension of ensemble local mean decomposition from one-dimensional signal processing to Bi-dimensional signal processing, is used to extract the features of anti-friction bearings. Moreover, an optimized dynamic LSSVM is used to fault diagnosis of anti-friction bearings. The experimental results show that Bi-dimensional ensemble local mean decomposition is superior to Bi-dimensional local mean decomposition, optimized dynamic LSSVM is superior to traditional LSSVM, and the proposed Bi-dimensional ensemble local mean decomposition and optimized dynamic LSSVM method is effective for fault diagnosis of anti-friction bearings.
ABSTRACT
Periodontitis is a common public health problem worldwide and an inflammatory disease with irregular defect of alveolar bone caused by periodontal pathogens. Both antibacterial therapy and bone regeneration are of great importance in the treatment of periodontitis. In this study, injectable and thermosensitive hydrogels with 3D networks were used as carriers for controlled release of osteo-inductive agent (BMP-2) and Near Infrared Region-II (NIR-II) phototherapy agents (T8IC nano-particles). T8IC nano-particles were prepared by reprecipitation and acted as photosensitizer under 808 nm laser irradiation. Besides, we promoted photodynamic therapy (PDT) through adding H2O2 to facilitate the antibacterial effect instead of increasing the temperature of photothermal therapy (PTT). Hydrogel + T8IC + Laser + BMP-2 + H2O2 incorporated with mild PTT (45 °C), enhanced PDT and sustained release of BMP-2. It was present with excellent bactericidal effect, osteogenic induction and biosafety both in vitro and in vivo. Besides, immunohistochemistry staining and micro-CT analyses had confirmed that PTT and PDT could promote bone regeneration through alleviating inflammation state. Altogether, this novel approach with synergistic antibacterial effect, anti-inflammation and bone regeneration has a great potential for the treatment of periodontitis in the future.
Subject(s)
Hydrogels , Periodontitis , Humans , Hydrogels/pharmacology , Hydrogen Peroxide/pharmacology , Phototherapy , Bone Regeneration , Anti-Bacterial Agents/pharmacology , Periodontitis/drug therapyABSTRACT
Enhanced recognition ability, cell uptake capacity, and biostability are characteristics attributed to aptamer-based targeted anticancer agents, and are possibly associated with increased accumulation at the tumor site, improved therapeutic efficacy and reduced negative side effects. Herein, a phosphorothioate backbone modification strategy was applied to regulate the biomedical properties of pancreatic cancer cell-targeting aptamer for efficient in vivo drug delivery. Specifically, the CD71- targeting aptamer XQ-2d was modified into a fully thio-substituted aptamer S-XQ-2d, improving the plasma stability of S-XQ-2d and mitomycin C (MMC)-functionalized S-XQ-2d (MFSX), thus considerably prolonging their half-life in mice. Moreover, the binding and uptake capacities of S-XQ-2d were significantly enhanced. MFSX showed the same level of cytotoxicity as that of MMC against targeted cancer cells, but lower toxicity to non-targeted cells, highlighting its specificity and biosafety. Brief mechanistic studies demonstrated that XQ-2d and S-XQ-2d had different interaction modes and internalization pathways with the targeted cells.
ABSTRACT
Chemiluminescent probes have become increasingly popular in various research areas including precise tumor imaging and immunofluorescence analysis. Nevertheless, previously developed chemiluminescence probes are mainly limited to studying oxidation reaction-associated biological events. This study presents the first example of bioimaging applicable bicyclic dioxetane chemiluminescent probes with tunable emission wavelengths that range from 525 to 800 nm. These newly developed probes were able to detect the analytes of ß-Gal, H2O2, and superoxide with high specificity and a limit of detection of 77 mU L-1, 96, and 28 nM, respectively. The bioimaging application of the probes was verified in ovarian and liver cancer cells and macrophage cells, allowing the detection of the content of ß-Gal, H2O2, and superoxide inside the cells. The high specificity allowed us to image the xenografted tumor in mice. We expect that our probes will receive extensive applications in recording complex biomolecular events using noninvasive imaging techniques.
Subject(s)
Hydrogen Peroxide , Superoxides , Animals , Mice , Diagnostic Imaging , Cell Line , HeterograftsABSTRACT
Cell membrane proteins play a crucial role in the development of early cancer diagnosis strategies and precision medicine techniques. However, the application of aptamers in cell membrane protein-based biomedical research is limited by their inherent drawbacks, such as sensitivity to the recognition environment and susceptibility to enzymatic degradation, which leads to the loss of recognition ability. To address these challenges, this study presents a subzero-temperature-enabled molecule stacking strategy for the on-demand tailoring of aptamer glues for the precision recognition and efficient degradation of membrane protein. Mechanistic studies revealed that nucleic acid molecule stacking occurred during the freezing and melting processes, facilitating a rapid click reaction by bringing two reactive groups together. In vitro investigations demonstrated that the strategy confers aptamer glues with significantly enhanced specific recognition ability and binding affinity, allowing the distinction of a targeted cell line from a nontargeted cell line. Moreover, the engineered aptamer glue exhibited impressive targeted cell membrane protein degradation ability; around 74% of the c-Met protein was degraded in 24 h. These findings hold great potential for advancing cancer diagnosis and targeted therapy through the development of more stable and reliable aptamer probes.
Subject(s)
Aptamers, Nucleotide , Neoplasms , Humans , Membrane Proteins/metabolism , Proteolysis , Aptamers, Nucleotide/chemistry , Neoplasms/diagnosis , Cell LineABSTRACT
KEY MESSAGE: Two QTLs with major effects on rolled leaf trait were consistently detected on chromosomes 1A (QRl.hwwg-1AS) and 5A (QRl.hwwg-5AL) in the field experiments. Rolled leaf (RL) is a morphological strategy to protect plants from dehydration under stressed field conditions. Identification of quantitative trait loci (QTLs) underlining RL is essential to breed drought-tolerant wheat cultivars. A mapping population of 154 recombinant inbred lines was developed from the cross between JagMut1095, a mutant of Jagger, and Jagger to identify quantitative trait loci (QTLs) for the RL trait. A linkage map of 3106 cM was constructed with 1003 unique SNPs from 21 wheat chromosomes. Two consistent QTLs were identified for RL on chromosomes 1A (QRl.hwwg-1AS) and 5A (QRl.hwwg-5AL) in all field experiments. QRl.hwwg-1AS explained 24-56% of the phenotypic variation and QRl.hwwg-5AL explained up to 20% of the phenotypic variation. The combined percent phenotypic variation associated with the two QTLs was up to 61%. Analyses of phenotypic and genotypic data of recombinants generated from heterogeneous inbred families of JagMut1095 × Jagger delimited QRl.hwwg-1AS to a 6.04 Mb physical interval. This work lays solid foundation for further fine mapping and map-based cloning of QRl.hwwg-1AS.
Subject(s)
Quantitative Trait Loci , Triticum , Triticum/genetics , Genetic Linkage , Plant Breeding , Phenotype , Plant Leaves/geneticsABSTRACT
BACKGROUND: Depression is the most common mental illness in postpartum mothers, and the etiology of postpartum depression remains poorly understood. Over the past several decades, studies have reported that postpartum depression is caused by multiple factors, such as genetic, psychological, pregnancy, and environmental factors, with the family environment being an important environmental factor. The theory of family cohesion and adaptability put forward by Olson is a classic model that describes the level of family function. However, to date, this model has not been examined regarding its applicability to patients with postpartum depression. AIM: To investigate the relationship between family cohesion and adaptability and the risk of postpartum depressive symptoms. METHODS: We retrospectively analyzed 1446 patients admitted to the postpartum healthcare clinic of the Affiliated Foshan Maternity and Child Healthcare Hospital from April 2021 to December 2021. Patients were grouped according to whether postpartum depression symptoms were reported (symptoms, n = 454; no symptoms, n = 992). All patients completed the Edinburgh Postpartum Depression Scale and the Chinese version of the Family Cohesion and Adapt-ability Assessment Scale II. Baseline and clinical data were compared between groups. Univariate regression analysis was used to investigate the association between different types of family cohesion and postpartum depressive symptoms and the association between different family adaptability types and postpartum depressive symptoms. RESULTS: After adjusting for age, education, occupation, gravidity, parity, and mode of delivery, disengaged [adjusted odds ratio (AOR) = 3.36, 95%CI: 1.91-5.91], and separated (AOR = 1.97, 95%CI: 1.34-2.90) family cohesion types showed a higher risk of postpartum depression than the connection type, whereas the enmeshed type (AOR = 0.38, 95%CI: 0.28-0.51) protected against postpartum depressive symptoms. Rigid (AOR = 4.41, 95%CI: 3.02-6.43) and structured families (AOR = 1.88, 95%CI: 1.34-2.63) had a higher risk of postpartum depressive symptoms than flexible families, whereas chaotic families (AOR = 0.35, 95%CI: 0.24-0.51) protected against postpartum depressive symptoms. CONCLUSION: Family cohesion and adaptability are influencing factors for postpartum depressive symptoms, with higher family cohesion and adaptability being associated with a lower risk of postpartum depressive symptoms.
ABSTRACT
RNA helicase DHX9 has been extensively characterized as a transcriptional regulator, which is consistent with its mostly nucleic localization. It is also involved in recognizing RNA viruses in the cytoplasm. However, there is no in vivo data to support the antiviral role of DHX9; meanwhile, as a nuclear protein, if and how nucleic DHX9 promotes antiviral immunity remains largely unknown. Here, we generated myeloid-specific and hepatocyte-specific DHX9 knockout mice and confirmed that DHX9 is crucial for host resistance to RNA virus infections in vivo. By additional knockout MAVS or STAT1 in DHX9-deficient mice, we demonstrated that nucleic DHX9 plays a positive role in regulating interferon-stimulated gene (ISG) expression downstream of type I interferon. Mechanistically, upon interferon stimulation, DHX9 is directly bound to STAT1 and recruits Pol II to the ISG promoter region to participate in STAT1-mediated transcription of ISGs. Collectively, these findings uncover an important role for nucleic DHX9 in antiviral immunity.
Subject(s)
Interferon Type I , Virus Replication , Animals , Mice , Antiviral Agents , Mice, Knockout , STAT1 Transcription Factor/genetics , Virus Replication/geneticsABSTRACT
This case series describes conservative orthodontic and multidisciplinary approaches for treating two patients diagnosed with cleidocranial dysplasia in late adolescence and young adulthood. Most of the impacted permanent teeth erupted spontaneously within 3 to 4 years after surgical extraction of the deciduous and supernumerary teeth. The remaining unerupted permanent teeth were facilitated with traction or extracted followed by implantation or restoration. Repositioning of the maxilla and mandible via orthognathic surgery was also applied to correct skeletal and occlusal discrepancies and lead to satisfying results.
Subject(s)
Cleidocranial Dysplasia , Tooth, Impacted , Tooth, Supernumerary , Humans , Adolescent , Young Adult , Adult , Cleidocranial Dysplasia/diagnosis , Cleidocranial Dysplasia/surgery , Tooth, Supernumerary/diagnosis , Tooth, Supernumerary/surgery , Maxilla , HeadABSTRACT
Tendinopathy has a high incidence in athletes and the aging population. It can cause pain and movement disorders, and is one of the most difficult problems in orthopedics. Animal models of tendinopathy provide potentially efficient and effective means to develop understanding of human tendinopathy and its underlying pathological mechanisms and treatments. The selection of preclinical models is essential to ensure the successful translation of effective and innovative treatments into clinical practice. Large animals can be used in both micro- and macro-level research owing to their similarity to humans in size, structure, and function. This article reviews the application of large animal models in tendinopathy regarding injuries to four tendons: rotator cuff, patellar ligament, Achilles tendon, and flexor tendon. The advantages and disadvantages of studying tendinopathy with large animal models are summarized. It is hoped that, with further development of animal models of tendinopathy, new strategies for the prevention and treatment of tendinopathy in humans will be developed.
ABSTRACT
Orally delivered antibiotics can reach the caecum and colon, and induce gut dysbiosis. Here we show that the encapsulation of antibiotics in orally administered positively charged polymeric nanoparticles with a glucosylated surface enhances absorption by the proximal small intestine through specific interactions of glucose and the abundantly expressed sodium-dependent glucose transporter 1. This improves bioavailability of the antibiotics, and limits their exposure to flora in the large intestine and their accumulation in caecal and faecal contents. Compared with the standard administration of the same antibiotics, the oral administration of nanoparticle-encapsulated ampicillin, chloramphenicol or vancomycin in mice with bacterial infections in the lungs effectively eliminated the infections, decreased adverse effects on the intestinal microbiota by protecting the animals from dysbiosis-associated metabolic syndromes and from opportunistic pathogen infections, and reduced the accumulation of known antibiotic-resistance genes in commensal bacteria. Glucosylated nanocarriers may be suitable for the oral delivery of other drugs causing gut dysbiosis.
Subject(s)
Gastrointestinal Microbiome , Nanoparticles , Animals , Anti-Bacterial Agents/pharmacology , Dysbiosis/chemically induced , Dysbiosis/prevention & control , Intestine, Small , MiceABSTRACT
Acute myeloid leukemia (AML) is a blood cancer with high heterogeneity and stratified as M0-M7 subtypes in the French-American-British (FAB) diagnosis system. Improved diagnosis with leverage of key molecular inputs will assist precisive medicine. Through deep-analyzing the transcriptomic data and mutations of AML, we report that a modern clustering algorithm, t-distributed Stochastic Neighbor Embedding (t-SNE), successfully demarcates M2, M3 and M5 territories while M4 bias to M5 and M0 & M1 bias to M2, consistent with the traditional FAB classification. Combining with mutation profiles, the results show that top recurrent AML mutations were unbiasedly allocated into M2 and M5 territories, indicating the t-SNE instructed transcriptomic stratification profoundly outperforms mutation profiling in the FAB system. Further functional data mining prioritizes several myeloid-specific genes as potential regulators of AML progression and treatment by Venetoclax, a BCL2 inhibitor. Among them two encode membrane proteins, LILRB4 and LRRC25, which could be utilized as cell surface biomarkers for monocytic AML or for innovative immuno-therapy candidates in future. In summary, our deep functional data-mining analysis warrants several unappreciated immune signaling-encoding genes as novel diagnostic biomarkers and potential therapeutic targets.