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Mucociliary clearance through coordinated ciliary beating is a major innate defense removing pathogens from the lower airways, but the pathogen sensing and downstream signaling mechanisms remain unclear. We identified virulence-associated formylated bacterial peptides that potently stimulated ciliary-driven transport in the mouse trachea. This innate response was independent of formyl peptide and taste receptors but depended on key taste transduction genes. Tracheal cholinergic chemosensory cells expressed these genes, and genetic ablation of these cells abrogated peptide-driven stimulation of mucociliary clearance. Trpm5-deficient mice were more susceptible to infection with a natural pathogen, and formylated bacterial peptides were detected in patients with chronic obstructive pulmonary disease. Optogenetics and peptide stimulation revealed that ciliary beating was driven by paracrine cholinergic signaling from chemosensory to ciliated cells operating through muscarinic M3 receptors independently of nerves. We provide a cellular and molecular framework that defines how tracheal chemosensory cells integrate chemosensation with innate defense.
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Acetilcolina/inmunología , Proteínas Bacterianas/farmacología , Cilios/inmunología , Depuración Mucociliar/inmunología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Canales Catiónicos TRPM/inmunología , Tráquea/inmunología , Acetilcolina/metabolismo , Animales , Proteínas Bacterianas/inmunología , Transporte Biológico , Cilios/efectos de los fármacos , Cilios/metabolismo , Femenino , Formiatos/metabolismo , Expresión Génica , Humanos , Inmunidad Innata , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Optogenética/métodos , Comunicación Paracrina/inmunología , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/patología , Receptor Muscarínico M3/genética , Receptor Muscarínico M3/inmunología , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/inmunología , Canales Catiónicos TRPM/deficiencia , Canales Catiónicos TRPM/genética , Papilas Gustativas/inmunología , Papilas Gustativas/metabolismo , Tráquea/efectos de los fármacos , Tráquea/patología , VirulenciaRESUMEN
Real-time detection and effective degradation of toxic gases have attracted considerable attention in environmental monitoring and human health. Here, we demonstrate a solvent-assisted dynamic assembly strategy to strongly enhance the detection and degradation performance for 2-chloroethyl ethyl sulfide (CEES, as a sulfur mustard simulant) via confinement of a conjugated polymer in metal-organic frameworks (MOFs). The conjugated polymer poly(9,9-di-n-octylfluorene-altbenzothiadiazole) (F8BT) is infiltrated into one-dimensional nanochannels of the Zr-based topological MOF NU-1000 in a single-chain manner, which is caused by the nanoconfinement effect and the steric hindrance between 9,9-dioctylfluorene units and benzothiadiazole units. The obtained F8BTâNU-1000 composites provide a high specific surface area and abundant active sites. Based on the cooperative effect of F8BT and NU-1000, rapid and sensitive detection of CEES has been achieved. Moreover, the F8BTâNU-1000 composites can selectively oxidize CEES into 2-chloroethyl ethyl sulfoxide (CEESO) under mild photooxidation conditions. Overall, this study opens a new avenue for the fabrication of conjugated polymer/MOF hybrid materials that show great potential for the sensitive detection and effective removal of hazardous chemicals.
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The immune system of bony fish closely resembles that of mammals, comprising both specific (adaptive) and non-specific (innate) components. Notably, the mucosa-associated lymphoid tissue (MALT) serves as the first line of defense within the non-specific immune system, playing a critical role in protecting these aquatic organisms against invading pathogens. MALT encompasses a network of immune cells strategically distributed throughout the gills and intestines, forming an integral part of the mucosal barrier that interfaces directly with the surrounding aquatic environment. Spring Viremia of Carp Virusï¼SVCVï¼, a highly pathogenic agent causing substantial harm to common carp populations, has been designated as a Class 2 animal disease by the Ministry of Agriculture and Rural Affairs of China. Utilizing a comprehensive array of research techniques, including Hematoxylin and Eosin (HE)ãAlcian Blue Periodic Acid-Schiff (AB-PAS)ãtranscriptome analysis for global gene expression profiling and Reverse Transcription-Polymerase Chain Reaction (RT-qPCR), this study uncovered several key findings: SVCV is capable of compromising the mucosal architecture in the gill and intestinal tissues of carp, and stimulate the proliferation of mucous cells both in gill and intestinal tissues. Critically, the study revealed that SVCV's invasion elicits a robust response from the carp's mucosal immune system, demonstrating the organism's capacity to resist SVCV invasion despite the challenges posed by the pathogen.
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Carpas , Enfermedades de los Peces , Perfilación de la Expresión Génica , Branquias , Intestinos , Infecciones por Rhabdoviridae , Rhabdoviridae , Animales , Branquias/inmunología , Branquias/virología , Rhabdoviridae/fisiología , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/virología , Carpas/inmunología , Carpas/genética , Perfilación de la Expresión Génica/veterinaria , Infecciones por Rhabdoviridae/inmunología , Infecciones por Rhabdoviridae/veterinaria , Infecciones por Rhabdoviridae/virología , Intestinos/inmunología , Intestinos/virología , Inmunidad Innata/genética , Transcriptoma/inmunología , Inmunidad MucosaRESUMEN
Metabarcoding analysis has been demonstrated to be an effective technology for monitoring diversity and dynamics of phytoplankton including Skeletonema species. Although molecular diversity uncovered in metabarcoding projects has generally been interpreted as sum of interspecies diversity and intraspecies diversity, accumulating evidence suggests that it also harbors unprecedentedly high levels of intra-genomic variations (IGVs). As up to thousands of amplicon sequence variants (ASVs) identified in a typical metabarcoding project can be annotated to be Skeletonema species, we hypothesize that substantial portions of these ASVs are contributed by IGVs. Here, the nature of IGVs in Skeletonema species was quantitatively analyzed by carrying out single-strain metabarcoding analysis of 18S rDNA V4 in 49 strains belonging to seven Skeletonema species. Results showed that each Skeletonema strain harbored a high level of IGVs as expected. While many Skeletonema strains each contained one dominant ASV and a substantial number of ASVs displaying much lower relative abundance, other Skeletonema strains each contained multiple ASVs with comparable or nearly equally abundances. Thus the co-existence of multiple dominant ASVs in a single cell indicated a tug-of-war of these variants in evolution, which may eventually result in harmonized coexistence of multiple dominant ASVs. A total of nine dominant ASVs and 652 non-dominant ASVs were found in 49 strains of seven Skeletonema species, indicating rich interspecies and intraspecies variations, and complex evolution of IGVs in genus of Skeletonema. The results confirmed that the extensive degree of IGVs was the main contributor to the high molecular diversity revealed by metabarcoding analysis. This study highlights the importance of quantitative characterization of IGVs in Skeletonema species for accurate interpretation of species diversity in metabarcoding analysis.
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OBJECTIVES: The objective of this study is to preoperatively investigate the value of multiphasic contrast-enhanced computed tomography (CT)-based radiomics signatures for distinguishing high-risk thymic epithelial tumors (HTET) from low-risk thymic epithelial tumors (LTET) compared with conventional CT signatures. MATERIALS AND METHODS: Pathologically confirmed 305 thymic epithelial tumors (TETs), including 147 LTET (Type A/AB/B1) and 158 HTET (Type B2/B3/C), were retrospectively analyzed, and were randomly divided into training (n = 214) and validation cohorts (n = 91). All patients underwent nonenhanced, arterial contrast-enhanced, and venous contrast-enhanced CT analysis. The least absolute shrinkage and selection operator regression with 10-fold cross-validation was performed for radiomic models building, and multivariate logistic regression analysis was performed for radiological and combined models building. The performance of the model was evaluated by the area under the receiver operating characteristic curve (AUC of ROC), and the AUCs were compared using the Delong test. Decision curve analysis was used to evaluate the clinical value of each model. Nomogram and calibration curves were plotted for the combined model. RESULTS: The AUCs for radiological model in the training and validation cohorts were 0.756 and 0.733, respectively. For nonenhanced, arterial contrast-enhanced, venous contrast-enhanced CT and 3-phase images combined radiomics models, the AUCs were 0.940, 0.946, 0.960, and 0.986, respectively, in the training cohort, whereas 0.859, 0.876, 0.930, and 0.923, respectively, in the validation cohort. The combined model, including CT morphology and radiomics signature, showed AUCs of 0.990 and 0.943 in the training and validation cohorts, respectively. Delong test and decision curve analysis showed that the predictive performance and clinical value of the 4 radiomics models and combined model were greater than the radiological model ( P < 0.05). CONCLUSIONS: The combined model, including CT morphology and radiomics signature, greatly improved the predictive performance for distinguishing HTET from LTET. Radiomics texture analysis can be used as a noninvasive method for preoperative prediction of the pathological subtypes of TET.
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Neoplasias Glandulares y Epiteliales , Radiología , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Neoplasias Glandulares y Epiteliales/diagnóstico por imagenRESUMEN
Current therapeutic strategies for Alzheimer's disease (AD) mainly focus on amyloid ß oligomer (AßO) formation or clearance. However, most of them have failed to yield good clinical results. There is an urgent need to explore an alternative therapeutic target for AD treatments. Recent studies have indicated that the cellular prion protein (PrPC) is one of the cell-surface receptors of AßO that mediates related neurotoxicity. Besides, as a neuroprotective protein, the dimerization of PrPC seems to be critical for its trophic activity. We presume that modulating PrPC receptor activity could be another potential approach to abrogate AßO toxicity. In the present work, using an aptamer-induced dimerization (AID) strategy, we enforce PrPC dimerization and modulate its neurotrophic signaling. The AID strategy can attenuate AßO toxic action by (i) interfering with AßO-PrPC interaction and promoting neuroprotective shedding of PrPC; (ii) preventing the AßO-induced mitochondrial dysfunction and the caspase-3-induced apoptosis; and (iii) reducing the secretion of inflammatory cytokines and relieving the neuroinflammation microenvironment. Our findings suggest that the strategy targeting PrPC signaling may shed light on validating new therapeutic strategies in AD.
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Enfermedad de Alzheimer , Proteínas PrPC , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/toxicidad , Dimerización , Humanos , Proteínas PrPC/metabolismo , Proteínas PriónicasRESUMEN
BACKGROUND: Regenerative endodontic procedures (REPs) have achieved clinical success on the immature permanent teeth with pulp necrosis, and can promote root development. However, preoperative factors and their effects on root development of REPs have not been definitely concluded. The aim of this study was to investigate the preoperative factors that may influence the root development of REPs. METHODS: A total of 116 teeth in 110 patients treated with REPs in the Paediatric Dentistry Department and Endodontics Department from 2013 to 2017 were included in this study. Preoperative factors including aetiology, age, diagnosis and initial root morphology were collected retrospectively, and the associations between these factors and root development after REPs were analysed by Fisher's exact test and multivariate logistic regression model. RESULTS: The overall rate of root development after REPs was 89.7%. The dens evaginatus group showed a higher rate (98.8%) in root development than the trauma group (67.6%) (P < 0.01). There was no significant difference among the different age groups (7-13 years old) or among different diagnoses groups (P > 0.05). And it showed in the trauma group that the teeth with apical foramen sizes larger than 3 mm significantly promoted root development than those smaller than 3 mm (P < 0.01). Multivariate logistic regression indicated that aetiology was significantly correlated with root development of REPs (OR: 0.07, 95% CI 0.007, 0.627, P < 0.05). CONCLUSIONS: The REPs promoted more root developments in the dens evaginatus group than the trauma group, indicating that aetiology may be correlated with the root development of REPs.
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Endodoncia , Endodoncia Regenerativa , Adolescente , Niño , Necrosis de la Pulpa Dental/terapia , Dentición Permanente , Humanos , Estudios Retrospectivos , Tratamiento del Conducto Radicular/efectos adversos , Tratamiento del Conducto Radicular/métodosRESUMEN
This study uses the daily product data of the concentration of ozone in the atmospheric column (ozone column concentration) collected by the Aura satellite's Ozone Monitoring Instrument (OMI), to evaluate the ozone pollution status of the Fenwei Plain in east-central China, by employing pixel-based spatial analysis, an θslope trend index, a Hurst index, and grey correlation. The following results were found. (1) The spatial distribution of ozone in the atmosphere of the Fenwei Plain was higher in the north and lower in the south, with high values appearing in Jinzhong, Lvliang, and other cities. (2) The changes in ozone column concentration periodically and seasonally in the Fenwei Plain. Seasonally, the ozone column concentration was highest in spring, followed by summer, winter, and autumn. (3) The pixel-based trend change of the ozone slope (θslope) indicated that the ozone concentration in the region was in a downward trend, while the long-term correlation of the time series trend Hurst index found that the region should expect to see a weak rebound in the ozone column concentration in the future, so that routine monitoring should be strengthened. (4) The present study on the factors influencing the ozone concentration found that the concentration is relatively closely related to temperature, air pressure, humidity, grain sowing area, highway mileage, and secondary industry.
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Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Contaminantes Atmosféricos/análisis , Contaminación del Aire/análisis , China , Ciudades , Monitoreo del Ambiente/métodos , Ozono/análisis , Tecnología de Sensores Remotos , Estaciones del AñoRESUMEN
BACKGROUND: Skeletonema species are prominent primary producers, some of which can also cause massive harmful algal blooms (HABs) in coastal waters under specific environmental conditions. Nevertheless, genomic information of Skeletonema species is currently limited, hindering advanced research on their role as primary producers and as HAB species. Mitochondrial genome (mtDNA) has been extensively used as "super barcode" in the phylogenetic analyses and comparative genomic analyses. However, of the 21 accepted Skeletonema species, full-length mtDNAs are currently available only for a single species, S. marinoi. RESULTS: In this study, we constructed full-length mtDNAs for six strains of five Skeletonema species, including S. marinoi, S. tropicum, S. grevillei, S. pseudocostatum and S. costatum (with two strains), which were isolated from coastal waters in China. The mtDNAs of all of these Skeletonema species were compact with short intergenic regions, no introns, and no repeat regions. Comparative analyses of these Skeletonema mtDNAs revealed high conservation, with a few discrete regions of high variations, some of which could be used as molecular markers for distinguishing Skeletonema species and for tracking the biogeographic distribution of these species with high resolution and specificity. We estimated divergence times among these Skeletonema species using 34 mtDNAs genes with fossil data as calibration point in PAML, which revealed that the Skeletonema species formed the independent clade diverging from Thalassiosira species approximately 48.30 Mya. CONCLUSIONS: The availability of mtDNAs of five Skeletonema species provided valuable reference sequences for further evolutionary studies including speciation time estimation and comparative genomic analysis among diatom species. Divergent regions could be used as molecular markers for tracking different Skeletonema species in the fields of coastal regions.
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Diatomeas , Genoma Mitocondrial , ADN Mitocondrial , Diatomeas/genética , Floraciones de Algas Nocivas , FilogeniaRESUMEN
Gut microbial dysbiosis and alteration of gut microbiota composition in Parkinson's disease (PD) have been increasingly reported, no recognized therapies are available to halt or slow progression of PD and more evidence is still needed to illustrate its causative impact on gut microbiota and PD and mechanisms for targeted mitigation. Epidemiological evidence supported an association between milk intake and a higher incidence of Parkinson's disease (PD), questions have been raised about prospective associations between dietary factors and the incidence of PD. Here, we investigated the significance of casein in the development of PD. The mice were given casein (6.75 g/kg i.g.) for 21 days after MPTP (25 mg/kg i.p. × 5 days) treatment, the motor function, dopaminergic neurons, inflammation, gut microbiota and fecal metabolites were observed. The experimental results revealed that the mice with casein gavage after MPTP treatment showed a persisted dyskinesia, the content of dopamine in striatum and the expression of TH in midbrain and ileum were decreased, the expression of Iba-1, CD4, IL-22 in midbrain and ileum increased continuously with persisted intestinal histopathology and intestinal barrier injury. Decreased intestinal bile secretion in addition with abnormal digestion and metabolism of carbohydrate, lipids and proteins were found, whereas these pathological status for the MPTP mice without casein intake had recovered after 24 days, no significant differences were observed with regard to only treated with casein. Our study demonstrates that intestinal pathologic injury, intestinal dysbacteriosis and metabolism changes promoted by casein in MPTP mice ultimately exacerbated the lesions to dopaminergic neurons.
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Caseínas/farmacología , Disbiosis/metabolismo , Inflamación/metabolismo , Enfermedad de Parkinson Secundaria/metabolismo , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Animales , Caseínas/administración & dosificación , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Neuronas Dopaminérgicas/efectos de los fármacos , Disbiosis/inducido químicamente , Heces/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Íleon/efectos de los fármacos , Íleon/enzimología , Íleon/metabolismo , Íleon/patología , Inflamación/etiología , Mucosa Intestinal/efectos de los fármacos , Masculino , Metaboloma/efectos de los fármacos , Ratones Endogámicos C57BL , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/complicaciones , Porción Compacta de la Sustancia Negra/efectos de los fármacos , Porción Compacta de la Sustancia Negra/enzimología , Porción Compacta de la Sustancia Negra/metabolismo , Porción Compacta de la Sustancia Negra/patología , Uniones Estrechas/metabolismo , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
OBJECTIVE: To estimate the prognostic efficacy of several systemic hemato-immunological indices for the treatment of cervical cancer as well as to determine whether the systemic hemato-immunological indices are associated with an increased risk of cervical collision cancer. METHODS: A systematic search was conducted to identify studies that evaluated the prognostic impact of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), thrombocyte-to-lymphocyte ratio (TLR), C-reactive protein/albumin ratio (CAR), and systemic immune-inflammation index (SII) in cervical cancer patients. The endpoints were overall survival (OS) or progression-free survival (PFS) and clinicopathologic parameters. A meta-analysis using random-effect models was performed to calculate hazard ratios (HRs) or odds ratios with 95% confidence intervals. RESULTS: Twenty-two retrospective cohort studies involving 9558 patients were included. Our results show that high NLR, PLR, TLR, and CAR indicated poor prognosis for patients with cervical cancer (HRs = 2.46, 1.88, 3.70, and 3.94, respectively; all P ≤ 0.001). Subgroup analysis suggested that the highest NLR and PLR were more precise biomarkers in patients who were diagnosed with FIGO stage I-III cervical cancer after treatment with chemo-radiotherapy. High TLR and high LMR displayed significant prognostic value in late-FIGO stage III-IV cervical cancer (HRs = 4.33 and 2.032, respectively). Additionally, CAR was associated with poor survival in patients with advanced-FIGO stage cervical cancer and larger tumor size. According to the difference of NLR, the younger (43-51 years old) cervical cancer patients had a tendency of increased collision risk. However, cervical cancer patients in the 52-61 years age group were more vulnerable than their respective counterparts using the pooled estimate for PLR. CONCLUSION: Our findings support a prognostic role for elevated CAR and TLR besides that of NLR and PLR in advanced-FIGO stage cervical cancer.
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Neoplasias del Cuello Uterino/sangre , Neoplasias del Cuello Uterino/inmunología , Plaquetas/inmunología , Plaquetas/patología , Estudios de Cohortes , Femenino , Humanos , Linfocitos/inmunología , Linfocitos/patología , Monocitos/inmunología , Monocitos/patología , Estudios Observacionales como Asunto , Pronóstico , Análisis de Regresión , Estudios RetrospectivosRESUMEN
Multiplex detection of tumor markers in blood with high specificity and high sensitivity is critical to cancer diagnosis, treatment, and prognosis. Herein, we demonstrate a strategy for simultaneous detection of multiple tumor markers in blood by functional liquid crystal (LC) sensors assisted with target-induced dissociation (TID) of an aptamer for the first time. Magnetic beads (MBs) coated with an aptamer (apt1) are employed to specifically capture target proteins in blood. After incubation of the obtained protein-coated MBs with duplexes of another aptamer (apt2) and signal DNA, sandwich complexes of apt1/protein/apt2 are formed on the MBs due to specific recognition of target proteins by apt2, which induces release of signal DNA into the aqueous solution. Subsequently, signal DNA is specifically recognized by highly sensitive DNA-laden LC sensors. Using this strategy, a 3D printed optical cell was employed to enable simultaneous detection of multiple tumor markers such as carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and prostate specific antigen (PSA) with high specificity and high sensitivity. Overall, this effective and low-cost multiplex approach takes advantage of the easy separation of MBs, high specificity of aptamer-based recognition, and high sensitivity of functional LC sensors. Plus, it offers a performance that is competitive to that of commercial ELISA kits without potential interference from hemolysis, which makes it very promising in multiplex detection of tumor markers in clinical applications.
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Aptámeros de Nucleótidos/química , Biomarcadores de Tumor/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Cristales Líquidos/química , Aptámeros de Nucleótidos/metabolismo , Antígeno Carcinoembrionario/sangre , Antígeno Carcinoembrionario/química , Antígeno Carcinoembrionario/metabolismo , Humanos , Magnetismo , Antígeno Prostático Específico/sangre , Antígeno Prostático Específico/química , Antígeno Prostático Específico/metabolismo , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/química , alfa-Fetoproteínas/metabolismoRESUMEN
Sonodynamic therapy (SDT) has the advantages of high penetration, non-invasiveness, and controllability, and it is suitable for deep-seated tumors. However, there is still a lack of effective sonosensitizers with high sensitivity, safety, and penetration. Now, ultrasound (US) and glutathione (GSH) dual responsive vesicles of Janus Au-MnO nanoparticles (JNPs) were coated with PEG and a ROS-sensitive polymer. Upon US irradiation, the vesicles were disassembled into small Janus Au-MnO nanoparticles (NPs) with promoted penetration ability. Subsequently, GSH-triggered MnO degradation simultaneously released smaller Au NPs as numerous cavitation nucleation sites and Mn2+ for chemodynamic therapy (CDT), resulting in enhanced reactive oxygen species (ROS) generation. This also allowed dual-modality photoacoustic imaging in the second near-infrared (NIR) window and T1 -MR imaging due to the released Mn2+ , and inhibited orthotopic liver tumor growth via synergistic SDT/CDT.
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Oro/química , Neoplasias Hepáticas/genética , Óxido de Magnesio/química , Ultrasonografía/métodos , Carcinógenos , Humanos , NanopartículasRESUMEN
Despite the observation of noncovalent interactions between chalcogen atoms in X-ray crystal structures, catalysis that harnesses the power of such chalcogen-chalcogen bonding interactions to produce advanced molecules remains an unresolved problem. Here, we show that a class of extraordinary chalcogen-bonding catalysts enables assembly of discrete small molecules including three ß-ketoaldehydes and one indole, leading to the construction of N-heterocycles in a highly efficient manner. The strong activation ability of these rationally designed catalysts provides a general solution to the intrinsic limitations of chalcogen bonding catalysis.
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Adenina/análogos & derivados , Glomeruloesclerosis Focal y Segmentaria , Péptidos y Proteínas de Señalización Intracelular , Leucemia Linfocítica Crónica de Células B , Proteínas de la Membrana , Síndrome Nefrótico , Piperidinas , Humanos , Glomeruloesclerosis Focal y Segmentaria/inducido químicamente , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/genética , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Mutación , Síndrome Nefrótico/genéticaRESUMEN
N-Heterocycles have been found in a large number of natural products, drug molecules, and bioactive compounds, and they thereby play a vital role in diverse research disciplines including drug discovery, organic synthesis, chemical biology, and material science. To this end, the development of new methods and strategies for the construction of N-heterocyclic frameworks is arguably one of the most dynamic and significant research areas in organic synthesis. One of these powerful approaches to the synthesis of N-heterocycles is to establish cyclization reactions based on the transformation of tertiary amines, which has emerged as an attractive research topic. In this Minireview, the significant achievements in the construction of N-heterocycles through cyclization of tertiary amines are highlighted and a comprehensive overview of the rational design, development, and application of these synthetic methods is presented.
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The visualization of glycosylation states of specific proteins in vivo is of great importance for uncovering their roles in disease development. However, the ubiquity of glycosylation makes probing the glycans on a certain protein as difficult as looking for a needle in a haystack. Herein, we demonstrate a proximity-induced hybridization chain reaction (HCR) strategy for amplified visualization of protein-specific glycosylation. The strategy relies on designing two kinds of DNA probes, glycan conversion probes and protein recognition probes, which are attached to glycans and target proteins, respectively. Upon sequential binding to the targets, the proximity-induced hybridization between two probes occurs, which leads to the structure-switching of protein recognition probes, followed by triggering of HCR assembly. This strategy has been used to visualize tyrosine-protein kinase 7-specific sialic acid in living CEM cells and zebrafish and to monitor its variation during drug treatment. It provides a potential tool for investigating protein-specific glycosylation and researching the relation between dynamic glycans state and disease process.
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Sondas de ADN/química , ADN/química , Glicoproteínas/análisis , Animales , Azidas/metabolismo , Carbocianinas/química , Línea Celular Tumoral , ADN/genética , Sondas de ADN/genética , Fluorescencia , Colorantes Fluorescentes/química , Glicoproteínas/química , Glicoproteínas/metabolismo , Glicosilación/efectos de los fármacos , Hexosaminas/metabolismo , Humanos , Microscopía Confocal , Microscopía Fluorescente , Hibridación de Ácido Nucleico , Polisacáridos/química , Tunicamicina/farmacología , Pez CebraAsunto(s)
Betacoronavirus/fisiología , Riñón/virología , Carga Viral , Tropismo Viral , Anciano , Anciano de 80 o más Años , Autopsia , Betacoronavirus/aislamiento & purificación , Encéfalo/virología , COVID-19 , Infecciones por Coronavirus , Femenino , Corazón/virología , Humanos , Hígado/virología , Pulmón/virología , Masculino , Persona de Mediana Edad , Pandemias , Faringe/virología , Neumonía Viral , SARS-CoV-2RESUMEN
The data and experiences in mitigating harmful algal blooms (HABs) by modified clay (MC) show that a bloom does not continue after the dispersal of the MC, even though the density of the residual cells in the water is still high, at 20-30% of the initial cell density. This interesting phenomenon indicates that in addition to flocculation, MC has an additional control mechanism. Here, transcriptome sequencing technology was used to study the molecular mechanism of MC in controlling HABs. In residual cells treated with MC, the photosynthetic light reaction was the most affected physiological process. Some genes related to the light harvesting complex, photosystem (PS) I and PS II, were significantly up-regulated ( p < 0.05), and several transcripts increased by as much as 6-fold. In contrast, genes associated with the dark reaction did not significantly change. In addition to genes associated with photosynthesis, numerous genes related to energy metabolism, stress adaptation, cytoskeletal functioning, and cell division also responded to MC treatment. These results indicated that following treatment with MC, the normal physiological processes of algal cells were disrupted, which inhibited cell proliferation and growth. Thus, these findings provide scientific proof that HABs are controlled by MC.
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Arcilla , Estramenopilos , Perfilación de la Expresión Génica , Floraciones de Algas Nocivas , Complejo de Proteína del Fotosistema IIRESUMEN
Described herein is a direct cyclization of simple tertiary aryl amines with iodonium ylides leading to a broad range of N-heterocycles. Completely different from the known reactivity of iodonium ylides, the finding reported herein is that an iodonium ylide is capable of cleaving a C(sp3 )-H bond and accepting two hydrogen atoms of a tertiary aryl amine, thus inducing a novel cyclization process. This transformation can proceed without the assistance of a transition-metal catalyst and eliminates the need for the premodification of the amine or the use of an additional initiator/oxidant.