RESUMEN
INTRODUCTION: The structures of the skull and the brain are related to each other. Prior work in individuals with isolated congenital anosmia (ICA) showed that these individuals were characterized by olfactory bulb (OB) defects. The aim of this study was to compare the morphological pattern of the anterior skull base surrounding the OB between individuals with ICA and normosmic controls. We meant to investigate whether these features can help distinguish abnormalities from normal variation. METHODS: We conducted a retrospective study to acquire T2-weighted magnetic resonance images from individuals diagnosed with ICA (n = 31) and healthy, normosmic controls matched for age and gender (n = 62). Between both groups, we compared the depth and width of the olfactory fossa, the angle of the ethmoidal fovea, as well as the angle of the lateral lamella of the cribriform plate. Within the ICA group, we further performed subgroup analyses based on the presence or absence of the OB, to investigate whether the morphology of the anterior skull base relates to the presence of OBs. The diagnostic performance of these parameters was evaluated using receiver operating characteristic analysis. RESULTS: Individuals with ICA exhibited a flattened ethmoid roof and shallower olfactory fossa when compared to controls. Further, the absence of the OB was found to be associated with a higher degree of flattening of the ethmoid roof and a shallow olfactory fossa. We reached the results in the following areas under the receiver operating characteristic curves: 0.80 - angle of fovea ethmoidalis, 0.76 - depth of olfactory fossa, 0.70 - angle of lateral lamella of the cribriform plate for significant differentiation between individuals with ICA and normosmic controls. CONCLUSION: Individuals with ICA exhibited an unusual anterior skull base surrounding the OB. This study supports the idea of an integrated development of OB and anterior skull base. Hence, the morphological pattern of the anterior skull base surrounding the OB helps distinguish individuals with ICA from normosmic controls and may therefore be useful for the diagnosis of ICA, although it is certainly not an invariable sign of congenital anosmia.
Asunto(s)
Hueso Etmoides , Trastornos del Olfato , Trastornos del Olfato/congénito , Humanos , Estudios Retrospectivos , Hueso Etmoides/patología , Base del Cráneo/diagnóstico por imagen , Trastornos del Olfato/diagnóstico por imagenRESUMEN
AIM: This trial was designed to assess the efficacy and safety of cetagliptin added to metformin in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy. METHODS: In total, 446 patients with type 2 diabetes on metformin monotherapy were randomized to receive the addition of once-daily cetagliptin 100 mg, cetagliptin 50 mg and placebo in a 2:2:1 ratio for 24-week double-blind treatment. At week 24, patients initially randomized to cetagliptin 50 mg and placebo were switched to cetagliptin 100 mg for 28 weeks open-label treatment. The primary endpoint was the change in haemoglobin A1c (HbA1c) from baseline, and the efficacy analyses were based on an all-patients-treated population using an analysis of co-variance. RESULTS: After 24 weeks, both add-on therapies led to greater glycaemic control. Reductions in HbA1c from baseline were -1.17 ± 0.794%, -1.23 ± 0.896% in cetagliptin 100 mg and 50 mg plus metformin group, respectively. No difference was observed between the cetagliptin 100 mg and 50 mg plus metformin group. Patients with higher baseline HbA1c levels (≥8.5%) experienced greater reductions in HbA1c. A significantly greater proportion of patients achieved an HbA1c <7.0% with cetagliptin 100 mg (49.4%) and cetagliptin 50 mg (51.1%) plus metformin than metformin monotherapy (14.4%). Both combination therapies also improved the homeostasis model assessment ß-function index and decreased systolic blood pressure. There was no increased risk of adverse effects with combination therapy, and both combination therapies were generally well tolerated. CONCLUSIONS: The addition of cetagliptin once daily to metformin was more efficacious and well tolerated than metformin monotherapy in Chinese patients with type 2 diabetes who had inadequate glycaemic control with metformin monotherapy.
Asunto(s)
Diabetes Mellitus Tipo 2 , Metformina , Humanos , Metformina/efectos adversos , Hipoglucemiantes/efectos adversos , Hemoglobina Glucada , Resultado del Tratamiento , Quimioterapia CombinadaRESUMEN
PURPOSE: The aim of this prospective study was to examine the characteristics of a clinical test for the assessment of nasal trigeminal sensitivity to mechanical stimuli and its association with the perception of nasal patency. METHODS: Thirty-two normosmic healthy subjects participated (17 women and 15 men; age = 26 ± 3 years). Precisely defined air puffs were used with a flow rate of 2L/min for mechanical stimulation. They were presented to the nasal vestibule, nasal septum, and inferior turbinate with various stimulus durations. Thresholds were measured by single-staircase stimuli with changes in stimulus duration in steps of 10 ms. Trigeminal suprathreshold intensity was rated by subjects for stimulus durations of 200, 300, 400, and 500 ms. Test-retest reliability was examined by intraclass correlations (ICCs) and Bland-Altman plot with limits of agreement. Pearson's correlations were calculated between self-rated nasal patency and nasal trigeminal sensitivity. RESULTS: As indicated by trigeminal threshold and suprathreshold intensities, the nasal vestibule is the most sensitive area among the three locations, followed by the nasal septum and the inferior turbinate (p < 0.001). Coefficients of correlations between test and retest were 0.76 for thresholds, and 0.56 suprathreshold intensities (p < 0.001). The Bland-Altman analysis showed a good agreement between test-retest values. In addition, significant positive associations between trigeminal suprathreshold intensities and self-rated nasal obstruction were found at the inferior turbinate (r = 0.4, p < 0.05). CONCLUSION: Reliable assessment of nasal trigeminal sensitivity for air puffs appears to be possible. Nasal trigeminal suprathreshold sensitivity to mechanical stimuli is associated with the perception of nasal patency at the inferior turbinate. This opens a window into the assessment of the perception of nasal airflow in various clinical purposes, especially for patients with sinonasal diseases.
Asunto(s)
Cavidad Nasal , Obstrucción Nasal , Masculino , Humanos , Femenino , Adulto Joven , Adulto , Estudios Prospectivos , Reproducibilidad de los Resultados , Cavidad Nasal/fisiología , Obstrucción Nasal/diagnóstico , Tabique Nasal , Percepción/fisiología , Nervio Trigémino/fisiologíaRESUMEN
Porcine deltacoronavirus (PDCoV) and porcine sapelovirus (PSV) are two viruses that can cause diarrhoea in pigs and bring great economic loss to the pig industry. In this research, a duplex real-time quantitative polymerase chain reaction (qPCR) assay based on SYBR Green I was developed to simultaneously detect PDCoV and PSV. No specific melting peaks were found in other porcine diarrhoea-associated viruses, indicating that the method developed in this study had good specificity. The detection limits of PDCoV and PSV were 1.0 × 101 copies µl-1 and 1.0 × 102 copies µl-1, respectively. The duplex real-time qPCR assay tested two hundred and three (203) intestinal and faecal samples collected from diarrhoeal and asymptomatic pigs. The positive rates of PDCoV and PSV were 20.2% and 23.2%, respectively. The co-infection rate of PDCoV and PSV was 13.8%. To evaluate the accuracy of the developed method, conventional PCR and singular TaqMan real-time qPCR assays for PDCoV/PSV were also used to detect the samples. The results showed that the duplex real-time qPCR assay was consistent with the singular assays, but its sensitivity was higher than conventional PCR methods. This duplex real-time qPCR assay provides a rapid, sensitive and reliable method in a clinic to simultaneously detect PDCoV and PSV.
RESUMEN
MAIN CONCLUSION: Two sesquiterpene synthases were identified through comparative transcriptome analysis of Leonurus sibiricus. LsSqTPS2 could produce high titer of δ-cadinene in vivo which suggests the terpene specificity of L. sibiricus. Leonurus sibiricus L., a medicinal herb, is widely used in China due to its pharmacological activities. Cadinene type sesquiterpenes, one of major bioactive components mainly present in aerial parts of L. sibiricus, showed antibacterial, anti-inflammatory, antioxidant and antiproliferative properties. However, there is no report about the sesquiterpene biosynthesis in L. sibiricus. This study identified L. sibiricus sesquiterpene synthases (LsSqTPSs) through comparative transcriptome analysis of L. sibiricus leaf and root samples using the BGISEQ-500 sequencing technique. A total of 83,244 unigenes were obtained with an average length of 1025 bp. Among them, 50,356 unigenes (60.49%) acquired annotations according to the BLAST searching results. A total of 68 differentially expressed genes (DEGs) were potentially involved in the sesquiterpene biosynthesis. Furthermore, four candidate DEGs encoding LsSqTPSs were characterized. The enzymatic characterization in engineered yeast showed that LsSqTPS1 produced α-farnesene as the single product and LsSqTPS2 mainly produced 76.23 mg/L of δ-cadinene, which constituted the major component of L. sibiricus leaf essential oil. This work contributes to the investigation of sesquiterpene biosynthesis in L. sibiricus.
Asunto(s)
Leonurus , Sesquiterpenos , China , Perfilación de la Expresión Génica , Sesquiterpenos/análisis , Transcriptoma/genéticaRESUMEN
Mylia taylorii is an ancient nonseed land plant that accumulates various sesquiterpenes with insecticidal and antibacterial activities. Recently, microbial-type sesquiterpene synthases (STSs) with atypical aspartate-rich metal ion binding motifs have been identified in some liverworts. Here, transcriptome analysis of M. taylorii was performed to identify M. taylorii sesquiterpene synthases (MtSTSs) that are potentially involved in sesquiterpene biosynthesis and diversity. A total of 255,669 unigenes were obtained with an average length of 963 bp in the transcriptome data of M. taylorii, among which 148,093 (57.92%) unigenes had BLAST results. Forty-eight unigenes were related to the sesquiterpene backbone biosynthesis according to KEGG annotation. In addition, MtSTS1, MtSTS2 and MtSTS3 identified from putative MtSTSs display sesquiterpene catalytic activities on the basis of functional characterizations in yeast. Interestingly, MtSTSs exhibit a noncanonical metal ion binding motif and the structural composition of a single α-domain, which are features of microbial STSs instead of archetypical plant STSs. This study revealed new microbial-type STS members of nonseed plants, and functionally identified that MtSTSs may contribute to the investigation of the biosynthesis and biological role of sesquiterpenes in M. taylorii.
Asunto(s)
Hepatophyta/genética , Proteínas de Plantas/análisis , Transcriptoma , Transferasas/análisis , Secuencia de Aminoácidos , Biocatálisis , Perfilación de la Expresión Génica , Aceites Volátiles/análisis , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Alineación de Secuencia , Sesquiterpenos/análisis , Transferasas/química , Transferasas/genéticaRESUMEN
OBJECTIVE: Functional magnetic resonance imaging (fMRI) allows the measurement of changes in blood flow in association with changes in brain activity. This technique has been used frequently to study brain activation in response to odorous stimuli. The aim of this study was to evaluate the effects of odor delivery conditions on brain responses obtained with fMRI. STUDY DESIGN: Prospective cohort study SETTING: Academic institution. METHODS: Twenty healthy volunteers (mean age = 29.5 years; 9 women, 11 men) participated. Three odor delivery methods were used: "tube" (odor presented intranasally with separate tubing for each nostril), "mask" (odor presented in a face mask covering the subject's nose) and "vacuum" (odor presented into the ambient air). Presentation of the pleasant "peach" odor was performed using a computer-controlled olfactometer. Subjects were asked to evaluate the intensity of the odors after each fMRI run. RESULTS: "Tube" showed higher self-rated odor intensity compared to "mask" and "vacuum" (F = 18.4, p < 0.001). Odor intensity had a positive correlation (r = 0.6, p < 0.05) with percent signal change extracted from the secondary olfactory cortex region in the mask condition. In the tube condition, several selected regions of interest (Amygdala, Insula, Thalamus) showed lower activations compared to the other two conditions (puncorrected < 0.001, mask > tube, vacuum > tube). CONCLUSION: Activations of region of interests (ROIs) in response to the odorous stimuli showed differences under the three conditions (mask, tube, vacuum). In this passive fMRI paradigm, this may partly reflect the differences in odor intensity, but also in attention and contextual variables related to odor perception.
Asunto(s)
Encéfalo , Odorantes , Adulto , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Emociones , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Estudios Prospectivos , OlfatoRESUMEN
Sesquiterpenes are important defense and signal molecules for plants to adapt to the environment, cope with stress, and communicate with the outside world, and their evolutionary history is closely related to physiological functions. In this study, the information of plant sesquiterpene synthases (STSs) with identified functions were collected and sorted to form a dataset containing about 500 members. The phylogeny of spermatophyte functional STSs was constructed based on the structural comparative analysis to reveal the sequence-structure-function relationships. We propose the evolutionary history of plant sesquiterpene skeletons, from chain structure to small rings, followed by large rings for the first time and put forward a more detailed function-driven hypothesis. Then, the evolutionary origins and history of spermatophyte STSs are also discussed. In addition, three newly identified STSs CaSTS2, CaSTS3, and CaSTS4 were analyzed in this functional evolutionary system, and their germacrene D products were consistent with the functional prediction. This demonstrates an application of the structure-based phylogeny in predicting STS function. This work will help us to understand evolutionary patterns and dynamics of plant sesquiterpenes and STSs and screen or design STSs with specific product profiles as functional elements for synthetic biology application.
Asunto(s)
Transferasas Alquil y Aril/genética , Evolución Molecular , Plantas/enzimología , Sesquiterpenos/metabolismo , Transferasas Alquil y Aril/química , Secuencia de Aminoácidos , Filogenia , Sesquiterpenos/químicaRESUMEN
MAIN CONCLUSION: A BAHD terpene alcohol acyltransferase, CaAT20, was identified from Celastrus angulatus Maxim, expressed in E. coli and functionally characterized. S405A mutant of CaAT20 increased the enzyme activity. Acylation is a diversely physiological process in the biosynthesis of plant secondary metabolites. Plant BAHD acyltransferases play an important role in the modification of volatile esters with biological activities. In this research, a BAHD acyltransferase (CaAT20) was identified from Celastrus angulatus Maxim and the function of this enzyme was characterized. CaAT20 could convert geraniol to geranyl esters by using benzoyl-CoA and acetyl-CoA as the acyl donors respectively. Furthermore, the catalytic activity of CaAT20 for benzoyl-CoA was higher than that of acetyl-CoA. Site-directed mutation of CaAT20 was carried out based on the results of molecular simulation. In vitro site-directed mutant S405A of CaAT20 increased the volume of binding cavity so as to facilitate the entry of geraniol, indicating a more efficient acylation for geraniol and benzoyl-CoA. Our research provides new insight for the catalytic functions of CaAT20.
Asunto(s)
Aciltransferasas/metabolismo , Celastrus/enzimología , Acilcoenzima A/metabolismo , Aciltransferasas/genética , Celastrus/genética , Escherichia coli/enzimología , Escherichia coli/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
BACKGROUND: Celastrus angulatus Maxim is a kind of crucial and traditional insecticidal plant widely distributed in the mountains of southwest China. Celangulin V is the efficient insecticidal sesquiterpenoid of C. angulatus and widely used in pest control in China, but the low yield and discontinuous supply impeded its further popularization and application. Fortunately, the development of synthetic biology provided an opportunity for sustainable supply of Celangulin V, for which understanding its biosynthetic pathway is indispensable. RESULTS: In this study, six cDNA libraries were prepared from leaf and root of C. angulatus before global transcriptome analyses using the BGISEQ-500 platform. A total of 104,950 unigenes were finally obtained with an average length of 1200 bp in six transcriptome databases of C. angulatus, in which 51,817 unigenes classified into 25 KOG classifications, 39,866 unigenes categorized into 55 GO functional groups, and 48,810 unigenes assigned to 135 KEGG pathways, 145 of which were putative biosynthetic genes of sesquiterpenoid and triterpenoid. 16 unigenes were speculated to be related to Celangulin V biosynthesis. De novo assembled sequences were verified by Quantitative Real-Time PCR (qRT-PCR) analysis. CONCLUSIONS: This study is the first report on transcriptome analysis of C. angulatus, and 16 unigenes probably involved in the biosynthesis of Celangulin V were finally collected. The transcriptome data will make great contributions to research for this specific insecticidal plant and the further gene mining for biosynthesis of Celangulin V and other sesquiterpene polyol esters.
Asunto(s)
Celastrus/genética , Haptenos/genética , Anotación de Secuencia Molecular , Transcriptoma/genética , Alcaloides/genética , Vías Biosintéticas/genética , Celastrus/crecimiento & desarrollo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Genoma de Planta/genética , Haptenos/biosíntesis , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrolloRESUMEN
BACKGROUND Circular RNAs are important regulators in human cancers, including thyroid carcinoma. The circ_0067934 RNA is reported to participate in hepatocellular carcinoma, esophageal squamous cell carcinoma, and lung cancer. Whether it regulates thyroid carcinoma remains unclear. The purpose of this study was to research potential mechanisms of circ_0067934 in thyroid tumors to provide potential new diagnostic and treatment targets. MATERIAL AND METHODS The expression level of circ_0067934 in thyroid tumors, adjacent tissues, and cell lines was measured by qRT-PCR. The Kaplan-Meier survival curve analysis was used to explore the relationship between circ_0067934 level and survival time of patients. Circ_0067934 was knocked down to research its functional role in thyroid tumors. Cell proliferation was detected by CCK-8 (cell counting kit-8) assay. Migration and invasion were analyzed by Transwell assay. Western blot was applied to analyze the expression of epithelial-mesenchymal-transition (EMT) and PI3K/AKT related proteins. RESULTS Compared with adjacent tissue, circ_0067934 was highly expressed in thyroid tumors. Circ_0067934 expression level was highly expressed in thyroid tumor cell lines. Patients with high expression of circ_0067934 showed lower survival rates. Knockdown of circ_0067934 inhibited cell proliferation, migration, and invasion and also promoted apoptosis. In addition, circ_0067934 knockdown inhibited EMT and PI3K/AKT signaling pathways. CONCLUSIONS circ_0067934 could improve the development of thyroid carcinoma by promoting EMT and PI3K/AKT signaling pathways.
Asunto(s)
ARN/genética , Neoplasias de la Tiroides/genética , Adulto , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , China , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-akt , ARN/análisis , ARN Circular , Transducción de Señal , Transcriptoma/genéticaRESUMEN
PURPOSE: To investigate the correlation of tissue eosinophil count and chemosensory functions in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS). METHODS: This was a cross-sectional study including 40 patients with a history of ESS for CRSwNP recruited consecutively. Visual analog scale score and the Lund-Kennedy endoscopic score were recorded. Biopsies of the ethmoidal sinus mucosal were performed and evaluated. Chemosensory functions were measured by Sniffin' Sticks and chemosensory event-related potentials (CSERP). The associations between chemosensory functions and tissue eosinophil count were analyzed using Spearman correlation and partial correlation after adjusting the confounding factors. Kendall's tau-b correlation was performed between sneezing score and CSERP with ethyl alcohol (EAL) stimulation. RESULTS: Olfactory and trigeminal nerve function was successfully evaluated using CSERP. Postoperative tissue eosinophil count was correlated with threshold (T) score (partial correlation coefficient r = - 0.460, p = 0.012) and CSERP peak latency for olfactory (N1: partial r = 0.471, p = 0.010; P2: partial r = 0.487, p = 0.007) and mixed olfactory-trigeminal (N1: partial r = - 0.516, p = 0.008; P2: partial r = - 0.590, p = 0.002). There were also correlations between T score and N1 latency with phenyl ethyl alcohol (PEA) (partial r = - 0.560, p < 0.001), between sneezing score and N1 latency with EAL (Kendall's tau-b = - 0.40, p = 0.005). CONCLUSIONS: Postoperative tissue eosinophilia is significantly associated with postoperative olfactory disorders as assessed by Sniffin' Sticks and CSERP peak latency. Furthermore, olfaction as measured by T score correlates with olfactory ERP latency in inflammation-associated olfactory dysfunction. Trigeminal sensitivity also appears to relate to tissue eosinophilia, indicating mucosal inflammation can affect both sensory systems in the nose.
Asunto(s)
Endoscopía/efectos adversos , Eosinófilos , Pólipos Nasales/cirugía , Trastornos del Olfato , Complicaciones Posoperatorias , Rinitis , Sinusitis , Adulto , Enfermedad Crónica , Correlación de Datos , Estudios Transversales , Endoscopía/métodos , Femenino , Humanos , Recuento de Leucocitos/métodos , Masculino , Persona de Mediana Edad , Trastornos del Olfato/sangre , Trastornos del Olfato/etiología , Trastornos del Olfato/fisiopatología , Senos Paranasales/cirugía , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/fisiopatología , Rinitis/sangre , Rinitis/fisiopatología , Sinusitis/sangre , Sinusitis/fisiopatologíaRESUMEN
Sesquiterpenes comprise a diverse group of natural products with a wide range of applications in cosmetics, food, medicine, agriculture, and biofuels. Heterologous biosynthesis is increasingly employed for sesquiterpene production, aiming to overcome the limitations associated with chemical synthesis and natural extraction. Sesquiterpene synthases (STSs) play a crucial role in the heterologous biosynthesis of sesquiterpene. Under the catalysis of STSs, over 300 skeletons are produced through various cyclization processes (C1-C10 closure, C1-C11 closure, C1-C6 closure, and C1-C7 closure), which are responsible for the diversity of sesquiterpenes. According to the cyclization types, we gave an overview of advances in understanding the mechanism of STSs cyclization from the aspects of protein crystal structures and site-directed mutagenesis. We also summarized the applications of engineering STSs in the heterologous biosynthesis of sesquiterpene. Finally, the bottlenecks and potential research directions related to the STSs cyclization mechanism and application of modified STSs were presented.
Asunto(s)
Transferasas Alquil y Aril , Sesquiterpenos , Sesquiterpenos/metabolismo , Ciclización , Catálisis , Transferasas Alquil y Aril/genética , Transferasas Alquil y Aril/metabolismoRESUMEN
Zealexin A1 is a nonvolatile sesquiterpene phytoalexin, which not only exhibits extensive antifungal and insecticidal activities but also has the ability to enhance the drought resistance of plants, and thus has potential applications in agricultural and food fields. In this study, the biosynthetic pathway of zealexin A1 was constructed in Saccharomyces cerevisiae for the first time, and the highest production of zealexin A1 reported to date was achieved. First, through screening of sesquiterpene synthases from various plants, BdMAS11 had a stronger (S)-ß-macrocarpene synthesis ability was obtained, and the heterologous synthesis of zealexin A1 was achieved by coexpressing BdMAS11 with cytochrome P450 oxygenase ZmCYP71Z18. Subsequently, after the site-directed mutagenesis of BdMAS11, fusion expression of farnesyl diphosphate synthase ERG20 and BdMAS11, and tailored truncation of BdMAS11 and ZmCYP71Z18, the strain coexpressing the manipulated BdMAS11 and original ZmCYP71Z18 produced 119.31 mg/L of zealexin A1 in shake-flask fermentation. Finally, the production of zealexin A1 reached 1.17 g/L through fed-batch fermentation in a 5 L bioreactor, which was 261.7-fold that of the original strain. This study lays the foundation for the industrial production of zealexin A1 and other terpenoids.
RESUMEN
The liverwort Jungermannia exsertifolia is one of the oldest terrestrial plants and rich in structurally specific sesquiterpenes. There are several sesquiterpene synthases (STSs) with non-classical conserved motifs that have been discovered in recent studies on liverworts; these motifs are rich in aspartate and bind with cofactors. However, more detailed sequence information is needed to clarify the biochemical diversity of these atypical STSs. This study mined J. exsertifolia sesquiterpene synthases (JeSTSs) through transcriptome analysis using BGISEQ-500 sequencing technology. A total of 257,133 unigenes was obtained, and the average length was 933 bp. Among them, a total of 36 unigenes participated in the biosynthesis of sesquiterpenes. In addition, the in vitro enzymatic characterization and heterologous expression in Saccharomyces cerevisiae showed that JeSTS1 and JeSTS2 produced nerolidol as the major product, while JeSTS4 could produce bicyclogermacrene and viridiflorol, suggesting a specificity of J. exsertifolia sesquiterpene profiles. Furthermore, the identified JeSTSs had a phylogenetic relationship with a new branch of plant terpene synthases, the microbial terpene synthase-like (MTPSL) STSs. This work contributes to the understanding of the metabolic mechanism for MTPSL-STSs in J. exsertifolia and could provide an efficient alternative to microbial synthesis of these bioactive sesquiterpenes.
RESUMEN
The olfactory bulb (OB) plays a key role in the processing of olfactory information. A large body of research has shown that OB volumes correlate with olfactory function, which provides diagnostic and prognostic information in olfactory dysfunction. Still, the potential value of the OB shape remains unclear. Based on our clinical experience we hypothesized that the shape of the OB predicts olfactory function, and that it is linked to olfactory loss, age, and gender. The aim of this study was to produce a classification of OB shape in the human brain, scalable to clinical and research applications. Results from patients with the five most frequent causes of olfactory dysfunction (n = 192) as well as age/gender-matched healthy controls (n = 77) were included. Olfactory function was examined in great detail using the extended "Sniffin' Sticks" test. A high-resolution structural T2-weighted MRI scan was obtained for all. The planimetric contours (surface in mm2) of OB were delineated manually, and then all surfaces were added and multiplied to obtain the OB volume in mm3. OB shapes were outlined manually and characterized on a selected slice through the posterior coronal plane tangential to the eyeballs. We looked at OB shapes in terms of convexity and defined two patterns/seven categories based on OB contours: convex (olive, circle, and plano-convex) and non-convex (banana, irregular, plane, and scattered). Categorization of OB shapes is possible with a substantial inter-rater agreement (Cohen's Kappa = 0.73). Our results suggested that non-convex OB patterns were significantly more often observed in patients than in controls. OB shapes were correlated with olfactory function in the whole group, independent of age, gender, and OB volume. OB shapes seemed to change with age in healthy subjects. Importantly, the results indicated that OB shapes were associated with certain causes of olfactory disorders, i.e., an irregular OB shape was significantly more often observed in post-traumatic olfactory loss. Our study provides evidence that the shape of the OB can be used as a biomarker for olfactory dysfunction.
RESUMEN
Noncoding RNAs (ncRNAs) are crucial regulators in initiating and promoting thyroid cancer. Exploring the relationship between ncRNAs and thyroid cancer is essential for the diagnosis and treatment of thyroid cancer. Wet-lab experiments are costly and are difficult to conduct on a large scale. Although there are several ncRNA and cancer-related databases, there are few data related to thyroid cancer. There is a lack of computational approaches for predicting ncRNA-thyroid cancer associations. This work describes TCGCN, a linear residual graph convolution network to predict ncRNA-thyroid cancer associations. We collected a large amount of ncRNA-disease association data and constructed a bipartite graph. We use a simple linear embedding propagation at each convolutional layer and use the weighted sum of the embeddings on all graph convolutional layers to make the final prediction. In 5-fold cross-validation on the ncRNA-thyroid cancer dataset, TCGCN obtained significantly better performances with an AUC of 0.8162 and an AUPR of 0.8049, which are considerably better than those of other state-of-the-art approaches. We also demonstrate the usability of our method in the case studies.
Asunto(s)
Biología Computacional , Neoplasias de la Tiroides , Biología Computacional/métodos , Bases de Datos Factuales , Humanos , ARN no Traducido/genética , Neoplasias de la Tiroides/genéticaRESUMEN
The production and large-scale application of traditional chemical pesticides will bring environmental pollution and food safety problems. With the advantages of high safety and environmental friendliness, botanical biopesticides are in line with the development trend of modern agriculture and have gradually become the mainstream of modern pesticide development. However, the traditional production of botanical biopesticides has long been faced with prominent problems, such as limited source and supply, complicated production processes, and excessive consumption of resources. In recent years, the rapid development of synthetic biology will break through these bottlenecks, and many botanical biopesticides are produced using synthetic biology, such as emodin, celangulin, etc. This paper reviews the latest progress and application prospect of synthetic biology in the development of botanical pesticides so as to provide new ideas for the analysis of synthetic pathways and heterologous and efficient production of botanical biopesticides and accelerate the research process of synthetic biology of natural products.
RESUMEN
Porcine epidemic diarrhoea virus (PEDV) and porcine deltacoronavirus (PDCoV) are the main enteric coronaviruses that cause acute diarrhoea and dehydration in pigs. The co-infection of PDCoV and PEDV is common in natural swine infections, but the clinical outcomes of the interaction between the co-circulating PDCoV and PEDV are unknown. In current study, we established a co-infection model by inoculating the cell culture-adapted PDCoV HNZK-02 strain and PEDV CV777 simultaneously or sequentially using 4-day-old piglets. The weight loss, clinical scores, viral load and titre, histopathological changes and serum cytokines expression were compared with piglets challenged by either virus. Our results indicated the piglets co-inoculated with PDCoV and PEDV showed more serious diarrhoeal symptoms, mainly characterized by longer diarrhoeal period when compared to those of the mono-infection piglets. Furthermore, we observed that PEDV could promote PDCoV replication in the co-inoculated piglets with evidence of prolonged faecal viral shedding, high viral titres in faeces and intestine tissues. Histological analysis indicated the co-infected piglets showed more extensive and serious pathological lesions in small intestine tissues than the mono-infection piglets. Our data also suggested that the co-infection of PDCoV and PEDV caused the excessive expression of pro-inflammatory cytokines (IL-6, IL-8 and TNF-α) in serum. These results proved there existed obvious synergistic pathogenic effects between PDCoV and PEDV co-infection, which provided new insights into the synergistic pathogenic mechanism caused by these two porcine coronaviruses.
Asunto(s)
Coinfección , Infecciones por Coronavirus , Coronavirus , Diarrea , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Animales , Coinfección/veterinaria , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/veterinaria , Citocinas , Deltacoronavirus , Diarrea/veterinaria , Índice de Severidad de la Enfermedad , PorcinosRESUMEN
The olfactory bulb (OB) has an essential role in the human olfactory pathway. A change in olfactory function is associated with a change of OB volume. It has been shown to predict the prognosis of olfactory loss and its volume is a biomarker for various neurodegenerative diseases, such as Alzheimer's disease. Thus far, obtaining an OB volume for research purposes has been performed by manual segmentation alone; a very time-consuming and highly rater-biased process. As such, this process dramatically reduces the ability to produce fair and reliable comparisons between studies, as well as the processing of large datasets. Our study aims to solve this by proposing a novel methodological framework for the unbiased measurement of OB volume. In this paper, we present a fully automated tool that successfully performs such a task, accurately and quickly. In order to develop a stable and versatile algorithm and to train the neural network, we used four datasets consisting of whole-brain T1 and high-resolution T2 MRI scans, as well as the corresponding clinical information of the subject's smelling ability. One dataset contained data of patients suffering from anosmia or hyposmia (N = 79), and the other three datasets contained data of healthy controls (N = 91). First, the manual segmentation labels of the OBs were created by two experienced raters, independently and blinded. The algorithm consisted of the following four different steps: (1) multimodal data co-registration of whole-brain T1 images and T2 images, (2) template-based localization of OBs, (3) bounding box construction, and lastly, (4) segmentation of the OB using a 3D-U-Net. The results from the automated segmentation algorithm were tested on previously unseen data, achieving a mean dice coefficient (DC) of 0.77 ± 0.05, which is remarkably convergent with the inter-rater DC of 0.79 ± 0.08 estimated for the same cohort. Additionally, the symmetric surface distance (ASSD) was 0.43 ± 0.10. Furthermore, the segmentations produced using our algorithm were manually rated by an independent blinded rater and have reached an equivalent rating score of 5.95 ± 0.87 compared to a rating score of 6.23 ± 0.87 for the first rater's segmentation and 5.92 ± 0.81 for the second rater's manual segmentation. Taken together, these results support the success of our tool in producing automatic fast (3-5 min per subject) and reliable segmentations of the OB, with virtually matching accuracy with the current gold standard technique for OB segmentation. In conclusion, we present a newly developed ready-to-use tool that can perform the segmentation of OBs based on multimodal data consisting of T1 whole-brain images and T2 coronal high-resolution images. The accuracy of the segmentations predicted by the algorithm matches the manual segmentations made by two well-experienced raters. This method holds potential for immediate implementation in clinical practice. Furthermore, its ability to perform quick and accurate processing of large datasets may provide a valuable contribution to advancing our knowledge of the olfactory system, in health and disease. Specifically, our framework may integrate the use of olfactory bulb volume (OBV) measurements for the diagnosis and treatment of olfactory loss and improve the prognosis and treatment options of olfactory dysfunctions.