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1.
Cereb Cortex ; 34(4)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38566508

RESUMEN

Physical activity and sedentary behavior, both distinct lifestyle behaviors associated with brain health, have an unclear potential relationship with brain cortical structure. This study aimed to determine the causal link between physical activity, sedentary behavior, and brain cortical structure (cortical surface area and thickness) through Mendelian randomization analysis. The inverse-variance weighted method was primarily utilized, accompanied by sensitivity analyses, to confirm the results' robustness and accuracy. Analysis revealed nominally significant findings, indicating a potential positive influence of physical activity on cortical thickness in the bankssts (ß = 0.002 mm, P = 0.043) and the fusiform (ß = 0.002 mm, P = 0.018), and a potential negative association of sedentary behavior with cortical surface area in the caudal middle frontal (ß = -34.181 mm2, P = 0.038) and the pars opercularis (ß = -33.069 mm2, P = 0.002), alongside a nominally positive correlation with the cortical surface area of the inferior parietal (ß = 58.332 mm2, P = 0.035). Additionally, a nominally significant negative correlation was observed between sedentary behavior and cortical thickness in the paracentral (ß = -0.014 mm, P = 0.042). These findings offer insights into how lifestyle behaviors may influence brain cortical structures, advancing our understanding of their interaction with brain health.


Asunto(s)
Encéfalo , Análisis de la Aleatorización Mendeliana , Encéfalo/diagnóstico por imagen , Ejercicio Físico , Área de Broca , Estudio de Asociación del Genoma Completo
2.
J Transl Med ; 22(1): 240, 2024 03 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443933

RESUMEN

BACKGROUND: Mitochondria produce adenosine triphosphate through respiratory activities to power sperm differentiation and motility, and decreased mitochondrial respiratory activity can result in poor sperm motility and asthenospermia. The mitochondrial sheath is a component of the mid-piece of the sperm flagellum, and dysfunction of the sheath can reduce sperm motility and cause male infertility. The membrane occupation and recognition nexus-motif protein 2 (MORN2) is testis enriched in mice, and the MORN motif was reported to play a role in the regulation of bioelectrical signal homeostasis in cardiomyocytes. METHODS: We generated Morn2-/- mice using CRISPR/Cas9 and evaluated the potential functions of MORN2 in spermiogenesis through histological analysis, fertility examination, RT-PCR, CASA, immunofluorescence, TUNEL, electron microscopy analysis, mitochondrial energy metabolism analysis, etc. RESULTS: The Morn2-/- mice were infertile, and their sperm showed severe motility defects. Morn2-/- sperm also had abnormal morphology characterized by bent heads, aberrant mitochondrial sheath formation, lower mitochondrial membrane potential, higher levels of reactive oxygen species, and decreased mitochondrial respiratory activity. CONCLUSIONS: Our study demonstrates that MORN2 is essential for male fertility and indicates that MORN2 functions in mitochondrial sheath formation and regulates mitochondrial respiratory activity.


Asunto(s)
Semen , Motilidad Espermática , Animales , Masculino , Ratones , Metabolismo Energético , Fertilidad , Mitocondrias
3.
Fish Shellfish Immunol ; 149: 109593, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38697374

RESUMEN

A type of fermented bile acids (FBAs) has been produced through a biological method, and its effects on growth performance, metabolism, and intestinal microbiota in largemouth bass were investigated. The results demonstrated that incorporating 0.03 %-0.05 % FBAs diet could improve the final weight, weight gain and specific growth rate, and decrease the feed conversion ratio. Dietary FBAs did not significantly affect the levels of high-density lipoprotein, low-density lipoprotein, and triglycerides, but decreased the activities of α-amylase in most groups. Adding FBAs to the diet significantly increased the integrity of the microscopic structure of the intestine, thickened the muscular layer of the intestine, and notably enhanced its intestinal barrier function. The addition of FBAs to the diet increased the diversity of the gut microbiota in largemouth bass. At the phylum level, there was an increase in the abundance of Proteobacteria, Firmicutes, Tenericutes and Cyanobacteria and a significant decrease in Actinobacteria and Bacteroidetes. At the genus level, the relative abundance of beneficial bacteria Mycoplasma in the GN6 group and Coprococcus in the GN4 group significantly increased, while the pathogenic Enhydrobacter was inhibited. Meanwhile, the highest levels of AKP and ACP were observed in the groups treated with 0.03 % FBAs, while the highest levels of TNF-α and IL-10 were detected in the group treated with 0.04 % FBAs. Additionally, the highest levels of IL-1ß, IL-8T, GF-ß, IGF-1, and IFN-γ were noted in the group treated with 0.06 % FBAs. These results suggested that dietary FBAs improved growth performance and intestinal wall health by altering lipid metabolic profiles and intestinal microbiota in largemouth bass.


Asunto(s)
Alimentación Animal , Lubina , Ácidos y Sales Biliares , Dieta , Microbioma Gastrointestinal , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ácidos y Sales Biliares/metabolismo , Alimentación Animal/análisis , Lubina/crecimiento & desarrollo , Lubina/inmunología , Dieta/veterinaria , Intestinos/microbiología , Fermentación , Metaboloma , Suplementos Dietéticos/análisis , Distribución Aleatoria
4.
Dig Dis Sci ; 69(5): 1674-1690, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38507125

RESUMEN

BACKGROUND: Esophageal cancer (ESCA) is a common malignant tumor of the digestive tract, and its poor prognosis is mainly attributed to the occurrence of invasion and metastasis. Z-DNA binding protein 1 (ZBP1), as a mRNA regulatory factor, plays an important role in the occurrence and development of various tumors. However, the role of ZBP1 in ESCA is not yet understood. AIMS: This study aims to explore the expression of ZBP1 in ESCA and its role in the development of ESCA. METHODS: Using bioinformatics analysis and immunohistochemistry staining, we detected the expression of ZBP1 in ESCA and normal tissues. The potential mechanism of ZBP1 in ESCA was analyzed from the aspects of genetic mutations, protein interaction networks, and pathway enrichment. We performed functional experiments in vitro to elucidate the effect of ZBP1 on ESCA cells. RESULTS: ZBP1 was found to be significantly upregulated in ESCA compared to adjacent noncancerous tissues, and its expression is closely related to gender, age, and lymph node metastasis. In ESCA, the genetic variation rate of ZBP1 is 8%, and its expression is positively correlated with immune cell infiltration. The ZBP1 co-expressed gene is mainly involved in processes such as lymph node proliferation and intercellular adhesion. In vitro experiments have confirmed that downregulation of ZBP1 significantly inhibited the proliferation, migration, and invasion of ESCA cells. CONCLUSION: This research proves that downregulation of ZBP1 can inhibit the progression of ESCA. This finding indicates that ZBP1 may be a novel biomarker to improve the diagnosis and treatment of ESCA.


Asunto(s)
Neoplasias Esofágicas , Proteínas de Unión al ARN , Femenino , Humanos , Masculino , Línea Celular Tumoral , Proliferación Celular , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica , Metástasis Linfática , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética , Regulación hacia Arriba
5.
Alzheimers Dement ; 20(4): 2329-2339, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38284799

RESUMEN

INTRODUCTION: Various associations between social factors and motoric cognitive risk syndrome (MCR) have been reported. However, whether social frailty (integrated from multiple social factors) is associated with MCR is still unclear. METHODS: We included 4657 individuals without MCR at Round 1 of the NHATS as the discovery sample, and 3075 newly recruited individuals from Round 5 of the NHATS as the independent validation sample. Social frailty was assessed by five social items. MCR was defined as the presence of both subjective cognitive complaints and slow gait speed in individuals without dementia or mobility disability. RESULTS: Compared with normal individuals, those with social frailty had higher risk of incident MCR (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.34-1.84). Each additional unfavorable social item was associated with an increased risk of MCR (HR: 1.32, 95% CI: 1.22-1.43). DISCUSSION: Social frailty was associated with an increased risk of incident MCR in older adults. HIGHLIGHTS: Various associations between social factors and motoric cognitive risk syndrome (MCR) have been reported. Social frailty that integrated from multiple social factors was associated with an increased risk of incident MCR. Social frailty should be included in the early screening of individuals to identify those at higher risk of MCR.


Asunto(s)
Trastornos del Conocimiento , Disfunción Cognitiva , Fragilidad , Humanos , Anciano , Trastornos del Conocimiento/epidemiología , Incidencia , Fragilidad/epidemiología , Fragilidad/complicaciones , Factores de Riesgo , Cognición , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/complicaciones
6.
J Sci Food Agric ; 2024 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-39444325

RESUMEN

BACKGROUND: Metal nanoparticles are widely used in agricultural production. As a new type of molybdenum fertilizer, MoO3NPs have the properties of nanomaterials and the characteristics of molybdenum nutrition. Previous studies have focused on their role in promoting crop growth. However, it is unknown whether excessive MoO3NPs will affect crop quality and nutritional value. In this study, the effects of different concentrations of MoO3NPs (0, 0.15, 0.5, 1.0, 5.0, 10, 50, 100 mg kg-1) on the growth and quality of soybean were investigated by pot experiments to analyze the plant effects caused by MoO3NPs. RESULTS: The results showed that the effects of MoO3NPs treatment on plant biomass and nodule number were promoted at low concentrations (0.15-5 mg kg-1) and inhibited at high concentrations (10-100 mg kg-1). According to the logistic distribution model, it was predicted that MoO3NPs would have the strongest toxic effect on soybean flowering stage. The contents of MoO3NPs which reduced the yield of soybean by 10% and 20% were 12.38 and 30.81 mg kg-1. NP0.15 could significantly improve the total amount of amino acids in grains, while NP100 reduced the total amount of amino acids in grains, both of them significantly increasing the contents of linolenic acid and linoleic acid in soybean seeds. CONCLUSION: A change of MoO3NPs concentration had no negative effect on the nutritional value of soybean grains. The research could lead to a better understanding of the potential impact of nutritional changes caused by MoO3NPs on human health. © 2024 Society of Chemical Industry.

7.
BMC Bioinformatics ; 24(1): 480, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38102537

RESUMEN

BACKGROUND: Spatial mapping of transcriptional states provides valuable biological insights into cellular functions and interactions in the context of the tissue. Accurate 3D cell segmentation is a critical step in the analysis of this data towards understanding diseases and normal development in situ. Current approaches designed to automate 3D segmentation include stitching masks along one dimension, training a 3D neural network architecture from scratch, and reconstructing a 3D volume from 2D segmentations on all dimensions. However, the applicability of existing methods is hampered by inaccurate segmentations along the non-stitching dimensions, the lack of high-quality diverse 3D training data, and inhomogeneity of image resolution along orthogonal directions due to acquisition constraints; as a result, they have not been widely used in practice. METHODS: To address these challenges, we formulate the problem of finding cell correspondence across layers with a novel optimal transport (OT) approach. We propose CellStitch, a flexible pipeline that segments cells from 3D images without requiring large amounts of 3D training data. We further extend our method to interpolate internal slices from highly anisotropic cell images to recover isotropic cell morphology. RESULTS: We evaluated the performance of CellStitch through eight 3D plant microscopic datasets with diverse anisotropic levels and cell shapes. CellStitch substantially outperforms the state-of-the art methods on anisotropic images, and achieves comparable segmentation quality against competing methods in isotropic setting. We benchmarked and reported 3D segmentation results of all the methods with instance-level precision, recall and average precision (AP) metrics. CONCLUSIONS: The proposed OT-based 3D segmentation pipeline outperformed the existing state-of-the-art methods on different datasets with nonzero anisotropy, providing high fidelity recovery of 3D cell morphology from microscopic images.


Asunto(s)
Imagenología Tridimensional , Redes Neurales de la Computación , Anisotropía , Imagenología Tridimensional/métodos , Procesamiento de Imagen Asistido por Computador/métodos
8.
Anal Chem ; 95(16): 6490-6495, 2023 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-37053522

RESUMEN

There is a high demand to develop chemical tools to control the property and function of RNA. Current methods mainly rely on ultraviolet light-based caging strategies, which may cause phototoxicity in live cell-based experiments. We herein report an endogenous stimulus-responsive RNA acylation approach by introducing boronate ester (BE) groups to 2'-hydroxyls through postsynthetic modification. Treatment with hydrogen peroxide (H2O2) yields a phenol derivative which undergoes a 1,6-eliminaton for the traceless release of 2'-hydroxyl. We demonstrated that the acylation of crRNA enabled conditional regulation of CRISPR/Cas13a activity for activatable detection of target RNA. We also showed that the highly specific acylation of the single RNA in 8-17 DNAzyme allowed reversible control of the catalytic activity of DNAzyme, which was further applied to the cell-selective imaging of metal ions in cancer cells. Thus, our strategy provides a simple, general, and cell-selective method to control RNA activity, affording great potential in the construction of activatable RNA sensors and pre-RNA medicines.


Asunto(s)
ADN Catalítico , ARN , Acilación , Peróxido de Hidrógeno , Metales , ARN/química , Técnicas Biosensibles
9.
Anal Chem ; 95(7): 3551-3555, 2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36774652

RESUMEN

Nucleic acids are valuable tools for intracellular biomarker detection and gene regulation. Here we propose a new type of protein (avidin)-scaffolded DNA nanostructure (ADN) for imaging the activity of apurinic/apyrimidinic endonuclease 1 (APE1) in live cells. ADN is designed by assembling an avidin-displayed abasic site containing DNA strands labeled with a fluorophore or a quencher via a complementary linker strand. ADN is nonemissive due to the close proximity of fluorophores and quenchers. APE1-mediated cleavage separates the fluorophores from the quenchers, delivering activated fluorescence. In vitro assays show that ADN is responsive to APE1 with high sensitivity and high specificity. ADN can efficiently enter the cells, and its capability to visualize and detect intracellular APE1 activities is demonstrated in drug-treated cells and different cell lines. The modular and easy preparation of our nanostructures would afford a valuable platform for imaging and detecting APE1 activities in live cells.


Asunto(s)
Avidina , ADN-(Sitio Apurínico o Apirimidínico) Liasa , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , ADN/química , Reparación del ADN , Diagnóstico por Imagen , Endonucleasas/metabolismo , Daño del ADN
10.
Small ; 19(40): e2303466, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37267936

RESUMEN

Void volume fraction (VVF) is a global measurement frequently used to characterize the void space of granular scaffolds, yet there is no gold standard by which to measure VVF in practice. To study the relationship  between VVF and particles of varying size, form, and composition, a library of 3D simulated scaffolds is used. Results reveal that relative to particle count, VVF is a less predictable metric across replicate scaffolds. Simulated scaffolds are used to explores the relationship between microscope magnification and VVF, and recommendations are offered for optimizing the accuracy of approximating VVF using 2D microscope images. Lastly, VVF of hydrogel granular scaffolds is measured while varying four input parameters: image quality, magnification, analysis software, and intensity threshold. Results show that VVF is highly sensitive to these parameters. Overall, random packing produces variation in VVF among granular scaffolds comprising the same particle populations. Furthermore, while VVF is used to compare the porosity of granular materials within a study, VVF is a less reliable metric across studies that use different input parameters. VVF, a global measurement, cannot describe the dimensions of porosity within granular scaffolds, and the work supports the notion that more descriptors are necessary to sufficiently characterize void space.

11.
Genomics ; 114(1): 351-360, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34929287

RESUMEN

Circular RNA (circRNA) is a non-coding RNA molecule that lacks polyadenylated tails and is highly stable, abundant, and conserved in human cells. CircRNAs can serve as a competing endogenous RNA (ceRNA) to sponge microRNAs (miRNA) and block their effects on target mRNA expression. CircRNAs also have possible relevance to cancer and therefore may be considered as ideal biomarkers for monitoring cancer progression. Of the about 300,000 predicted human circRNAs, only a few have validated biological functions related to cancer. To better understand the ceRNA role of circRNAs in colorectal cancer (CRC), we performed genome-wide circRNA-based RNA-sequencing (RNA-Seq) on nine CRC tumor samples and their paired histologically normal adjacent tissue samples. By profiling the mRNA expression in the same patients, we further explored the expression correlation between circRNAs and mRNAs generated from the same parental gene. Focusing on the concordant differential expression between circRNAs and mRNAs, we substantially reduced the regulatory noise. In total, we identified 694 circRNA-mRNA pairs that were consistently up or downregulated between tumor and normal tissues. These 694 circRNA-mRNA pairs are from 182 protein-coding genes associated with hormone responses and chemotaxis. Of these 182 genes, 43 are downstream targets of three highly conserved miRNAs (miR-410-3p, miR-135a, and miR-30a). Interestingly, these 43 genes are highly mutated in another cohort from eight independent CRC studies, which have significant effects on patient survival time. Focusing on miR-410-3p and its target oncogene MET, we experimentally validated the ceRNA regulatory motif of circMET. Notably, circMET is substantially upregulated in CRC cell lines and could promote cell proliferation and growth. By confirming the regulatory relationship between miR-410-3p and circMET, we propose a new mechanism for the observed sustained activation of MET in CRC. In conclusion, our work identifies a novel regulatory role of circMET and provides a potential diagnostic biomarker for CRC.


Asunto(s)
Neoplasias Colorrectales , MicroARNs , Proteínas Proto-Oncogénicas c-met , ARN Circular , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Perfilación de la Expresión Génica , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-met/genética , ARN Circular/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo
12.
Cell Mol Neurobiol ; 42(7): 2031-2053, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33886036

RESUMEN

Central nervous system injuries and diseases, such as ischemic stroke, spinal cord injury, neurodegenerative diseases, glioblastoma, multiple sclerosis, and the resulting neuroinflammation often lead to death or long-term disability. MicroRNAs are small, non-coding, single-stranded RNAs that regulate posttranscriptional gene expression in both physiological and pathological cellular processes, including central nervous system injuries and disorders. Studies on miR-124, one of the most abundant microRNAs in the central nervous system, have shown that its dysregulation is related to the occurrence and development of pathology within the central nervous system. Herein, we review the molecular regulatory functions, underlying mechanisms, and effective delivery methods of miR-124 in the central nervous system, where it is involved in pathological conditions. The review also provides novel insights into the therapeutic target potential of miR-124 in the treatment of human central nervous system injuries or diseases.


Asunto(s)
Enfermedades del Sistema Nervioso Central , MicroARNs , Enfermedades Neurodegenerativas , Traumatismos de la Médula Espinal , Traumatismos del Sistema Nervioso , Sistema Nervioso Central , Humanos
13.
Med Sci Monit ; 28: e937498, 2022 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-36203334

RESUMEN

BACKGROUND Preeclampsia (PE) is a serious pregnancy disorder associated with immune tolerance imbalance. The etiology of preeclampsia has not been fully elucidated. The aim of this study was to clarify the possible role of the lymphocyte activation gene 3 (LAG-3)/fibrinogen-like protein 1 (FGL-1) signaling pathway in the immune imbalance of early-onset PE. MATERIAL AND METHODS We enrolled 34 women with early-onset PE and 34 age-matched normal pregnancies (NPs). Flow cytometry was performed to determine the expression of LAG-3 on peripheral T cell subsets (CD3+, CD4+, and CD8+ T cells). We measured LAG-3 expression on decidual T cells to determine whether there was a difference in the expression of LAG-3 between decidual and peripheral T cells. Maternal plasma levels of FGL-1 were measured by ELISA. RESULTS There was no significant difference in LAG-3 expression on peripheral CD3+ T cells between NP and early-onset PE. Compared to NP, the significant decrease expression of LAG-3 by peripheral CD4+ and CD8+T cells was found in early-onset PE. The LAG-3 expression was higher on decidual T cells than peripheral counterparts in all pregnancies. The plasma level of FGL-1 was significantly elevated in early-onset PE compared with NP. CONCLUSIONS Abnormal expression of LAG-3/FGL-1 signaling pathway may be associated with immune activation of effector T cells and impaired immune tolerance in early-onset PE.


Asunto(s)
Preeclampsia , Antígenos CD/metabolismo , Linfocitos T CD8-positivos , Femenino , Fibrinógeno/metabolismo , Humanos , Embarazo , Transducción de Señal , Subgrupos de Linfocitos T , Proteína del Gen 3 de Activación de Linfocitos
14.
Nucleic Acids Res ; 48(3): 1572-1582, 2020 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-31919512

RESUMEN

BCDIN3 domain containing RNA methyltransferase, BCDIN3D, monomethylates the 5'-monophosphate of cytoplasmic tRNAHis with a G-1:A73 mispair at the top of an eight-nucleotide-long acceptor helix, using S-adenosyl-l-methionine (SAM) as a methyl group donor. In humans, BCDIN3D overexpression is associated with the tumorigenic phenotype and poor prognosis in breast cancer. Here, we present the crystal structure of human BCDIN3D complexed with S-adenosyl-l-homocysteine. BCDIN3D adopts a classical Rossmann-fold methyltransferase structure. A comparison of the structure with that of the closely related methylphosphate capping enzyme, MePCE, which monomethylates the 5'-γ-phosphate of 7SK RNA, revealed the important residues for monomethyl transfer from SAM onto the 5'-monophosphate of tRNAHis and for tRNAHis recognition by BCDIN3D. A structural model of tRNAHis docking onto BCDIN3D suggested the molecular mechanism underlying the different activities between BCDIN3D and MePCE. A loop in BCDIN3D is shorter, as compared to the corresponding region that forms an α-helix to recognize the 5'-end of RNA in MePCE, and the G-1:A73 mispair in tRNAHis allows the N-terminal α-helix of BCDIN3D to wedge the G-1:A73 mispair of tRNAHis. As a result, the 5'-monophosphate of G-1 of tRNAHis is deep in the catalytic pocket for 5'-phosphate methylation. Thus, BCDIN3D is a tRNAHis-specific 5'-monomethylphosphate capping enzyme that discriminates tRNAHis from other tRNA species, and the structural information presented in this study also provides the molecular basis for the development of drugs against breast cancers.


Asunto(s)
Metiltransferasas/ultraestructura , ARN de Transferencia de Histidina/ultraestructura , ARN de Transferencia/genética , S-Adenosilhomocisteína/química , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Cristalografía por Rayos X , Citoplasma/química , Citoplasma/genética , Femenino , Regulación Enzimológica de la Expresión Génica/genética , Humanos , Metilación , Metiltransferasas/química , Metiltransferasas/genética , Conformación Proteica en Hélice alfa , Pliegue de Proteína , ARN de Transferencia/química , ARN de Transferencia de Histidina/química , ARN de Transferencia de Histidina/genética
15.
BMC Biol ; 19(1): 122, 2021 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-34134716

RESUMEN

BACKGROUND: The anticancer drug camptothecin (CPT), first isolated from Camptotheca acuminata, was subsequently discovered in unrelated plants, including Ophiorrhiza pumila. Unlike known monoterpene indole alkaloids, CPT in C. acuminata is biosynthesized via the key intermediate strictosidinic acid, but how O. pumila synthesizes CPT has not been determined. RESULTS: In this study, we used nontargeted metabolite profiling to show that 3α-(S)-strictosidine and 3-(S), 21-(S)-strictosidinic acid coexist in O. pumila. After identifying the enzymes OpLAMT, OpSLS, and OpSTR as participants in CPT biosynthesis, we compared these enzymes to their homologues from two other representative CPT-producing plants, C. acuminata and Nothapodytes nimmoniana, to elucidate their phylogenetic relationship. Finally, using labelled intermediates to resolve the CPT biosynthesis pathway in O. pumila, we showed that 3α-(S)-strictosidine, not 3-(S), 21-(S)-strictosidinic acid, is the exclusive intermediate in CPT biosynthesis. CONCLUSIONS: In our study, we found that O. pumila, another representative CPT-producing plant, exhibits metabolite diversity in its central intermediates consisting of both 3-(S), 21-(S)-strictosidinic acid and 3α-(S)-strictosidine and utilizes 3α-(S)-strictosidine as the exclusive intermediate in the CPT biosynthetic pathway, which differs from C. acuminata. Our results show that enzymes likely to be involved in CPT biosynthesis in O. pumila, C. acuminata, and N. nimmoniana have evolved divergently. Overall, our new data regarding CPT biosynthesis in O. pumila suggest evolutionary divergence in CPT-producing plants. These results shed new light on CPT biosynthesis and pave the way towards its industrial production through enzymatic or metabolic engineering approaches.


Asunto(s)
Vías Biosintéticas , Evolución Biológica , Camptotecina , Humanos , Magnoliopsida , Filogenia
16.
J Acoust Soc Am ; 151(3): 2101, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35364965

RESUMEN

A multi-range vertical array data processing (MRP) method based on a convolutional neural network (CNN) is proposed to estimate geoacoustic parameters in shallow water. The network input is the normalized sample covariance matrices of the broadband multi-range data received by a vertical line array. Since the geoacoustic parameters (e.g., bottom sound speed, density, and attenuation) have different scales, the multi-task learning is used to estimate these parameters simultaneously. To reduce the influence of the uncertainty of the source position, the training and validation data are composed of the simulation data of different source depths. Simulation results demonstrate that compared with the conventional matched-field inversion (MFI), the CNN with MRP alleviates the coupling between the geoacoustic parameters and is more robust to different source depths in the shallow water environment. Based on the inversion results, better localization performance is achieved when the range-dependent environment is assumed to be a range-independent model. Real data from the East China Sea experiment are used to validate the MRP method. The results show that, compared with the MFI and the CNN with single-range vertical array data processing, the use of geoacoustic parameters from MRP achieves better localization performance.

17.
Transp Res D Transp Environ ; 105: 103226, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36570332

RESUMEN

The COVID-19 pandemic has induced significant transit ridership losses worldwide. This paper conducts a quantitative analysis to reveal contributing factors to such losses, using data from the Chicago Transit Authority's bus and rail systems before and after the COVID-19 outbreak. It builds a sequential statistical modeling framework that integrates a Bayesian structural time-series model, a dynamics model, and a series of linear regression models, to fit the ridership loss with pandemic evolution and regulatory events, and to quantify how the impacts of those factors depend on socio-demographic characteristics. Results reveal that, for both bus and rail, remote learning/working answers for the majority of ridership loss, and their impacts depend highly on socio-demographic characteristics. Findings from this study cast insights into future evolution of transit ridership as well as recovery campaigns in the post-pandemic era.

18.
BMC Oral Health ; 22(1): 532, 2022 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-36424588

RESUMEN

BACKGROUND: At present, there are still controversies about the influence of orthodontic treatment on the size of upper airway and the position of hyoid bone. We investigated the effect of orthodontic vertical control therapy on the size of the upper airway and position of the tongue and hyoid bone in adult patients with hyperdivergent skeletal Class II. METHODS: Overall, 15 adults with hyperdivergent skeletal Class II and normal occlusion, respectively, were selected as the experimental and control groups. The angle and line of the craniofacial structure, upper airway, hyoid bone position and three-dimensional (3D) upper airway indexes were measured using the Uceph 4.2.1 standard version and Mimics 21.0 software, respectively. The paired t-test, Wilcoxon symbol rank test, t-test of two independent samples, two independent sample nonparametric tests, Mann-Whitney U test, Pearson correlation analysis, the Univariate linear regression analysis and Multiple linear regression analysis were performed. RESULTS: After treatment, the S-Go/N-Me (%) and the MP-SN and XiPm-SN angles were significantly different (P < 0.01). The U-MPW and PAS significantly increased (P < 0.05), sagittal diameter L2 increased significantly, and transverse diameter L2 decreased significantly (P < 0.01). Although no significant correlation was observed between the vertical change in the jaw and that in U-MPW and PAS, the sagittal diameter L2 showed a significant correlation (P < 0.05). The Multiple linear regression analysis showed that there was a significant negative correlation between the variables MP-SN and sagittal diameter L2 and positive correlation between S-Go/N-Me(%) and H-MP (P < 0.05). Furthermore, significant differences between the Hv (P < 0.01) and sagittal diameter L1(P < 0.05) were observed before and after treatment. CONCLUSIONS: After the orthodontic vertical control therapy in patients with hyperdivergent skeletal Class II, the upper airway only underwent adaptive changes during treatment without substantial size changes, the position of tongue body and hyoid bone did not change significantly. Furthermore, compared with normal occlusion, the velopharyngeal segment airway of patients with hyperdivergent skeletal Class II remains narrow and long after treatment.


Asunto(s)
Hueso Hioides , Lengua , Adulto , Humanos , Cefalometría
19.
Can J Infect Dis Med Microbiol ; 2022: 6441339, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35178135

RESUMEN

BACKGROUND: Increased studies have revealed that asymptomatic carriers substantially impact the epidemic and that asymptomatic transmission is very common. Therefore, the asymptomatic transmission threat to the spread of the pandemic should not be neglected. METHODS: The local outbreak in Taiwan, especially in Taipei City, is unprecedented and paramount and has claimed hundreds of lives, tens of thousands of cases, and enormous economic costs. As care providers and gatekeepers of infectious diseases, Taipei City Hospital has to perform regular polymerase chain reaction (PCR) results of admitted patients and healthcare workers (HCWs) to achieve these goals. RESULTS: In this study, the results revealed a low positive rate of less than 1%, but the asymptomatic proportions could range from 42% to 46%, which bolsters that systematic screening was effective in controlling coronavirus disease-19 (COVID-19) of Novel Coronavirus or Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and might be an exemplar to other similar scenarios. Universal screening of admitted patients may be important and necessary, especially in asymptomatic patients. CONCLUSIONS: Regular screening for healthcare providers is also important during this pandemic, and it is recommended that admitted patients and healthcare providers undergo systemic PCR testing.

20.
BMC Genomics ; 22(1): 458, 2021 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-34144671

RESUMEN

BACKGROUND: Brain cancer is one of the eight most common cancers occurring in people aged 40+ and is the fifth-leading cause of cancer-related deaths for males aged 40-59. Accurate subtype identification is crucial for precise therapeutic treatment, which largely depends on understanding the biological pathways and regulatory mechanisms associated with different brain cancer subtypes. Unfortunately, the subtype-implicated genes that have been identified are scattered in thousands of published studies. So, systematic literature curation and cross-validation could provide a solid base for comparative genetic studies about major subtypes. RESULTS: Here, we constructed a literature-based brain cancer gene database (BCGene). In the current release, we have a collection of 1421 unique human genes gathered through an extensive manual examination of over 6000 PubMed abstracts. We comprehensively annotated those curated genes to facilitate biological pathway identification, cancer genomic comparison, and differential expression analysis in various anatomical brain regions. By curating cancer subtypes from the literature, our database provides a basis for exploring the common and unique genetic mechanisms among 40 brain cancer subtypes. By further prioritizing the relative importance of those curated genes in the development of brain cancer, we identified 33 top-ranked genes with evidence mentioned only once in the literature, which were significantly associated with survival rates in a combined dataset of 2997 brain cancer cases. CONCLUSION: BCGene provides a useful tool for exploring the genetic mechanisms of and gene priorities in brain cancer. BCGene is freely available to academic users at http://soft.bioinfo-minzhao.org/bcgene/ .


Asunto(s)
Neoplasias Encefálicas , Bases de Datos Genéticas , Encéfalo , Neoplasias Encefálicas/genética , Genómica , Humanos , Masculino , Oncogenes
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