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Xylan is one of the major hemicelluloses in plant cell walls and its xylosyl backbone is often decorated at O-2 with glucuronic acid (GlcA) and/or methylglucuronic acid (MeGlcA) residues. The GlcA/MeGlcA side chains may be further substituted with 2-O-arabinopyranose (Arap) or 2-O-galactopyranose (Gal) residues in some plant species, but the enzymes responsible for these substitutions remain unknown. During our endeavor to investigate the enzymatic activities of Arabidopsis MUR3-clade members of the GT47 glycosyltransferase family, we found that one of them was able to transfer Arap from UDP-Arap onto O-2 of GlcA side chains of xylan, and thus it was named xylan 2-O-arabinopyranosyltransferase 1 (AtXAPT1). The function of AtXAPT1 was verified in planta by its T-DNA knockout mutation showing a loss of the Arap substitution on xylan GlcA side chains. Further biochemical characterization of XAPT close homologs from other plant species demonstrated that while the poplar ones had the same catalytic activity as AtXAPT1, those from Eucalyptus, lemon-scented gum, sea apple, 'Ohi'a lehua, duckweed and purple yam were capable of catalyzing both 2-O-Arap and 2-O-Gal substitutions of xylan GlcA side chains albeit with differential activities. Sequential reactions with XAPTs and glucuronoxylan methyltransferase 3 (GXM3) showed that XAPTs acted poorly on MeGlcA side chains, whereas GXM3 could efficiently methylate arabinosylated or galactosylated GlcA side chains of xylan. Furthermore, molecular docking and site-directed mutagenesis analyses of Eucalyptus XAPT1 revealed critical roles of several amino acid residues at the putative active site in its activity. Together, these findings establish that XAPTs residing in the MUR3 clade of family GT47 are responsible for 2-O-arabinopyranosylation and 2-O-galactosylation of GlcA side chains of xylan.
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Explicit logical reasoning, like transitive inference, is a hallmark of human intelligence. This study investigated cortical oscillations and their interactions in transitive inference with EEG. Participants viewed premises describing abstract relations among items. They accurately recalled the relationship between old pairs of items, effectively inferred the relationship between new pairs of items, and discriminated between true and false relationships for new pairs. First, theta (4-7 Hz) and alpha oscillations (8-15 Hz) had distinct functional roles. Frontal theta oscillations distinguished between new and old pairs, reflecting the inference of new information. Parietal alpha oscillations changed with serial position and symbolic distance of the pairs, representing the underlying relational structure. Frontal alpha oscillations distinguished between true and false pairs, linking the new information with the underlying relational structure. Second, theta and alpha oscillations interacted through cross-frequency and inter-regional phase synchronization. Frontal theta-alpha 1:2 phase locking appeared to coordinate spectrally diverse neural activity, enhanced for new versus old pairs and true versus false pairs. Alpha-band frontal-parietal phase coherence appeared to coordinate anatomically distributed neural activity, enhanced for new versus old pairs and false versus true pairs. It suggests that cross-frequency and inter-regional phase synchronization among theta and alpha oscillations supports human transitive inference.
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Recuerdo Mental , Solución de Problemas , Humanos , Electroencefalografía , Sincronización CorticalRESUMEN
The human brain is distinguished by its ability to perform explicit logical reasoning like transitive inference. This study investigated the functional role of the inferior parietal cortex in transitive inference with functional MRI. Participants viewed premises describing abstract relations among items. They accurately recalled the relationship between old pairs of items, effectively inferred the relationship between new pairs of items, and discriminated between true and false relationships for new pairs. First, the inferior parietal cortex, but not the hippocampus or lateral prefrontal cortex, was associated with transitive inference. The inferior parietal activity and functional connectivity were modulated by inference (new versus old pairs) and discrimination (true versus false pairs). Moreover, the new/old and true/false pairs were decodable from the inferior parietal representation. Second, the inferior parietal cortex represented an integrated relational structure (ordered and directed series). The inferior parietal activity was modulated by serial position (larger end versus center pairs). The inferior parietal representation was modulated by symbolic distance (adjacent versus distant pairs) and direction (preceding versus following pairs). It suggests that the inferior parietal cortex may flexibly integrate observed relations into a relational structure and use the relational structure to infer unobserved relations and discriminate between true and false relations.
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Encéfalo , Solución de Problemas , Humanos , Corteza Prefrontal/diagnóstico por imagen , Lóbulo Parietal/diagnóstico por imagen , Mapeo EncefálicoRESUMEN
Members of the domain of unknown function 231 (DUF231)/trichome birefringence-like (TBL) family have been shown to be O-acetyltransferases catalyzing the acetylation of plant cell wall polysaccharides, including pectins, mannan, xyloglucan and xylan. However, little is known about the origin and evolution of plant cell wall polysaccharide acetyltransferases. Here, we investigated the biochemical functions of TBL homologs from Klebsormidium nitens, a representative of an early divergent class of charophyte green algae that are considered to be the closest living relatives of land plants, and Marchantia polymorpha, a liverwort that is an extant representative of an ancient lineage of land plants. The genomes of K. nitens and M. polymorpha harbor two and six TBL homologs, respectively. Biochemical characterization of their recombinant proteins expressed in human embryonic kidney (HEK) 293 cells demonstrated that the two K. nitens TBLs exhibited acetyltransferase activities acetylating the pectin homogalacturonan (HG) and hence were named KnPOAT1 and KnPOAT2. Among the six M. polymorpha TBLs, five of them (MpPOAT1 to 5) possessed acetyltransferase activities toward pectins and the remaining one (MpMOAT1) catalyzed 2-O- and 3-O-acetylation of mannan. While MpPOAT1,2 specifically acetylated HG, MpPOAT3,4,5 could acetylate both HG and rhamnogalacturonan-I (RG-I). Consistent with the acetyltransferase activities of these TBLs, pectins isolated from K. nitens and both pectins and mannan from M. polymorpha were shown to be acetylated. These findings indicate that the TBL genes were recruited as cell wall polysaccharide O-acetyltransferases as early as in charophyte green algae with activities toward pectins and they underwent expansion and functional diversification to acetylate various cell wall polysaccharides during evolution of land plants.
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Grass xylan consists of a linear chain of ß-1,4-linked xylosyl residues that often form domains substituted only with either arabinofuranose (Araf) or glucuronic acid (GlcA)/methylglucuronic acid (MeGlcA) residues, and it lacks the unique reducing end tetrasaccharide sequence found in dicot xylan. The mechanism of how grass xylan backbone elongation is initiated and how its distinctive substitution pattern is determined remains elusive. Here, we performed biochemical characterization of rice xylan biosynthetic enzymes, including xylan synthases, glucuronyltransferases and methyltransferases. Activity assays of rice xylan synthases demonstrated that they required short xylooligomers as acceptors for their activities. While rice xylan glucuronyltransferases effectively glucuronidated unsubstituted xylohexaose acceptors, they transferred little GlcA residues onto (Araf)-substituted xylohexaoses and rice xylan 3-O-arabinosyltransferase could not arabinosylate GlcA-substituted xylohexaoses, indicating that their intrinsic biochemical properties may contribute to the distinctive substitution patterns of rice xylan. In addition, we found that rice xylan methyltransferase exhibited a low substrate binding affinity, which may explain the partial GlcA methylation in rice xylan. Furthermore, immunolocalization of xylan in xylem cells of both rice and Arabidopsis showed that it was deposited together with cellulose in secondary walls without forming xylan-rich nanodomains. Together, our findings provide new insights into the biochemical mechanisms underlying xylan backbone elongation and substitutions in grass species.
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Oryza , Proteínas de Plantas , Xilanos , Xilanos/metabolismo , Oryza/genética , Oryza/enzimología , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Pentosiltransferasa/metabolismo , Pentosiltransferasa/genética , Metiltransferasas/metabolismo , Metiltransferasas/genética , Xilema/metabolismo , Arabidopsis/enzimología , Arabidopsis/genética , Arabidopsis/metabolismo , Glucuronosiltransferasa/metabolismo , Glucuronosiltransferasa/genéticaRESUMEN
Varicella-zoster virus (VZV), a common pathogen with humans as the sole host, causes primary infection and undergoes a latent period in sensory ganglia. The recurrence of VZV is often accompanied by severe neuralgia in skin tissue, which has a serious impact on the life of patients. During the acute infection of VZV, there are few related studies on the pathophysiological mechanism of skin tissue. In this study, transcriptome sequencing data from the acute response period within 2 days of VZV antigen stimulation of the skin were used to explore a model of the trajectory of skin tissue changes during VZV infection. It was found that early VZV antigen stimulation caused activation of mainly natural immune-related signaling pathways, while in the late phase activation of mainly active immune-related signaling pathways. JAK-STAT, NFκB, and TNFα signaling pathways are gradually activated with the progression of infection, while Hypoxia is progressively inhibited. In addition, we found that dendritic cell-mediated immune responses play a dominant role in the lesion damage caused by VZV antigen stimulation of the skin. This study provides a theoretical basis for the study of the molecular mechanisms of skin lesions during acute VZV infection.
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Herpesvirus Humano 3 , Transducción de Señal , Piel , Infección por el Virus de la Varicela-Zóster , Herpesvirus Humano 3/genética , Piel/patología , Piel/virología , Piel/inmunología , Animales , Infección por el Virus de la Varicela-Zóster/virología , Infección por el Virus de la Varicela-Zóster/inmunología , Infección por el Virus de la Varicela-Zóster/genética , Infección por el Virus de la Varicela-Zóster/patología , Humanos , Ratones , Células Dendríticas/inmunología , Herpes Zóster/virología , Herpes Zóster/patología , Herpes Zóster/genética , Herpes Zóster/inmunología , Transcriptoma , Modelos Animales de Enfermedad , Antígenos Virales/inmunología , Antígenos Virales/genética , FN-kappa B/metabolismo , FN-kappa B/genéticaRESUMEN
MAIN CONCLUSION: A member of the rice GT61 clade B is capable of transferring both 2-O-xylosyl and 2-O-arabinosyl residues onto xylan and another member specifically catalyses addition of 2-O-xylosyl residue onto xylan. Grass xylan is substituted predominantly with 3-O-arabinofuranose (Araf) as well as with some minor side chains, such as 2-O-Araf and 2-O-(methyl)glucuronic acid [(Me)GlcA]. 3-O-Arabinosylation of grass xylan has been shown to be catalysed by grass-expanded clade A members of the glycosyltransferase family 61. However, glycosyltransferases mediating 2-O-arabinosylation of grass xylan remain elusive. Here, we performed biochemical studies of two rice GT61 clade B members and found that one of them was capable of transferring both xylosyl (Xyl) and Araf residues from UDP-Xyl and UDP-Araf, respectively, onto xylooligomer acceptors, whereas the other specifically catalysed Xyl transfer onto xylooligomers, indicating that the former is a xylan xylosyl/arabinosyl transferase (named OsXXAT1 herein) and the latter is a xylan xylosyltransferase (named OsXYXT2). Structural analysis of the OsXXAT1- and OsXYXT2-catalysed reaction products revealed that the Xyl and Araf residues were transferred onto O-2 positions of xylooligomers. Furthermore, we demonstrated that OsXXAT1 and OsXYXT2 were able to substitute acetylated xylooligomers, but only OsXXAT1 could xylosylate GlcA-substituted xylooligomers. OsXXAT1 and OsXYXT2 were predicted to adopt a GT-B fold structure and molecular docking revealed candidate amino acid residues at the predicted active site involved in binding of the nucleotide sugar donor and the xylohexaose acceptor substrates. Together, our results establish that OsXXAT1 is a xylan 2-O-xylosyl/2-O-arabinosyl transferase and OsXYXT2 is a xylan 2-O-xylosyltransferase, which expands our knowledge of roles of the GT61 family in grass xylan synthesis.
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Arabidopsis , Oryza , Glicosiltransferasas/análisis , Oryza/metabolismo , Xilanos/metabolismo , Arabidopsis/metabolismo , Simulación del Acoplamiento Molecular , UDP Xilosa Proteína Xilosiltransferasa , Poaceae/metabolismo , Pared Celular/metabolismoRESUMEN
The rhizotoxicity of protons (H+) in acidic soils is a fundamental constraint that results in serious yield losses. However, the mechanisms underlying H+-mediated inhibition of root growth are poorly understood. In this study, we revealed that H+-induced root growth inhibition in Arabidopsis depends considerably on excessive iron deposition in the root apoplast. Reducing such aberrant iron deposition by decreasing the iron supply or disrupting the ferroxidases LOW PHOSPHATE ROOT 1 (LPR) and LPR2 attenuates the inhibitory effect of H+ on primary root growth efficiently. Further analysis showed that excessive iron deposition triggers a burst of highly reactive oxygen species, consequently impairing normal root development. Our study uncovered a valuable strategy for improving the ability of plants to tolerate H+ toxicity by manipulating iron availability.
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Proteínas de Arabidopsis , Arabidopsis , Hierro , Raíces de Plantas , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Hierro/metabolismo , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Concentración de Iones de Hidrógeno , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Theory of mind (ToM), the ability to infer others' mental state, is essential for social interaction among human beings. It has been widely reported that both cognitive (inference of knowledge) and affective (inference of emotion) components of ToM are disrupted in Parkinson's disease (PD). Previous studies usually focused on the involvement of the prefrontal cortex. OBJECTIVE: This study investigated the causal role of the subthalamic nucleus (STN), a key hub of the fronto-basal ganglia loops, in ToM. METHODS: Thirty-four patients with idiopathic PD (15 women, aged 62.2 ± 8.3 years) completed a Yoni task with deep brain stimulation (DBS) ON and OFF. The Yoni task was designed to separate the cognitive and affective components of ToM. Volumes of tissue activated (VTA) were computed for three subregions of the STN. RESULTS: DBS showed insignificant effects on ToM inference costs at the group level, which may be due to the large interindividual variability. The associative VTA correlated with the cognitive inference cost change but not the affective inference cost change. Patients with greater associative STN stimulation infer more slowly on cognitive ToM. Stimulating associative STN can adversely affect cognitive ToM in PD patients, especially in patients with a wide range of stimulation (≥0.157) or cognitive decline (Montreal Cognitive Assessment < 26). CONCLUSIONS: The associative STN plays a causal role in cognitive ToM in patients with PD. However, stimulating the associative STN likely impairs cognitive ToM and potentially leads to social interaction deficits in PD. © 2024 International Parkinson and Movement Disorder Society.
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Cognición , Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Teoría de la Mente , Humanos , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/fisiopatología , Núcleo Subtalámico/fisiología , Femenino , Estimulación Encefálica Profunda/métodos , Teoría de la Mente/fisiología , Persona de Mediana Edad , Masculino , Anciano , Cognición/fisiología , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: The weight-adjusted-waist index (WWI) is a novel obesity index, and gallstones are associated with obesity. This study aimed to investigate the possible relationship between WWI and gallstones. METHODS: The datasets from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between WWI and gallstones incidence. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship. RESULTS: The study comprised 8004 participants over the age of 20, including 833 reported with gallstones. Participants in the higher WWI tertile tended to have a higher gallstones prevalence. In the final adjusted model, a positive association between WWI and gallstones prevalence was observed (OR = 1.34, 95% CI: 1.20â1.49). Participants in the highest WWI tertile had a significantly 71% higher risk of gallstones than those in the lowest WWI tertile (OR = 1.71, 95% CI: 1.35â2.17). A nonlinear correlation was found between the WWI and gallstones prevalence, with an inflection point of 12.7. CONCLUSIONS: Our study found that higher WWI levels connected with increased prevalence of gallstones. However, more prospective studies are needed to validate our findings.
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Cálculos Biliares , Humanos , Cálculos Biliares/complicaciones , Encuestas Nutricionales , Índice de Masa Corporal , Estudios Transversales , Obesidad/epidemiología , Obesidad/complicacionesRESUMEN
In contemporary society, the conversion and efficient utilization of waste biomass and its derivatives are of great significance. Carbonized wood (CW) is an easily accessible and cost-effective green resource, but it has limitations as an electrode material due to its low specific surface area, limited active sites and poor conductivity. Therefore, it is crucial to improve the performance of biomass-based materials by using activation, heteroatom doping and modification methods to enhance the specific surface area and active sites. In this study, we developed acid-modified urea-doped activated carbonized wood (AUACW) with a three-dimensional (3D) porous structure and porosity, achieving a high specific surface area of 1321.3 m2 g-1. In addition, the degree of graphitization (ID/IG = 1.0) provides good conductivity and a large number of active sites, which are conducive to charge transfer and ion diffusion. The increase of nitrogen and oxygen elements enhances the surface wettability of the material and provides additional pseudocapacitance. The specific capacitance of AUACW reaches 435.84 F g-1 at 0.8 A g-1 with a 93.6% capacitance retention after 10 000 cycles in a 1 M KOH electrolyte. More attractively, a symmetrical supercapacitor (SSC) based on AUACW delivers an energy density of 22.61 W h kg-1 at a power density of 533.26 W kg-1. This work demonstrates the promising potential of utilizing waste biomass to develop green and valuable carbon materials for supercapacitors.
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BACKGROUND: This study aimed to evaluate the effect of sacubitril valsartan (SV) on heart failure (HF) hospitalization and cardiovascular mortality in patients on hemodialysis with HF with preserved ejection fraction (EF; HFpEF). METHODS: This single-center, prospective study enrolled 155 stable hemodialysis patients with EF > 40% who were followed up for 12 months. Fifty-nine patients were treated with SV; the others were matched for EF (57.89 ± 9.35 vs. 58.00 ± 11.82, P = 0.9) at a ratio of 1:1 and included as controls. The target dosage of SV was 200 mg/day. RESULTS: Twenty-three (23/155; 14.84%) had HF with mid-range EF (HFmrEF), while 132 (85.16%) had HFpEF. After SV treatment, the peak early diastolic transmitral flow velocity/peak early diastolic mitral annular tissue velocity(E/e') improved from 17.19 ± 8.74 to 12.80 ± 5.52 (P = 0.006), the left ventricular (LV) end-diastolic diameter decreased from 53.14 ± 7.67 mm to 51.56 ± 7.44 mm (P = 0.03), and the LV mass index decreased from 165.7 ± 44.6 g/m2 to 154.8 ± 24.0 g/m2 (P = 0.02). LVEF (P = 0.08) and LV global longitudinal strain (P = 0.7) did not change significantly. The composite outcome of first and recurrent HF hospitalization or cardiovascular death showed no difference between group. However, the Acute Dialysis Quality Initiative Workgroup (ADQI) HF class improved in 39 and 15 patients and worsened in 1 and 11 patients in the SV and control groups, respectively (P < 0.001). Age, diabetes mellitus, and pulmonary arterial pressure were independent risk factors for HF hospitalization and cardiovascular mortality in patients with HFpEF. CONCLUSIONS: SV improved LV hypertrophy, diastolic function, and the ADQI class for HF; however, it failed to reduce the composite endpoints of HF hospitalization and cardiovascular disease-related mortality over 12 months of follow-up in patients on maintenance hemodialysis with EF of > 40%.
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Aminobutiratos , Compuestos de Bifenilo , Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Estudios Prospectivos , Volumen Sistólico , Tetrazoles/efectos adversos , Valsartán/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Diálisis Renal/efectos adversos , Función Ventricular IzquierdaRESUMEN
This study aimed to investigate ultrasound features of arteriovenous fistula stenosis and their relationship with primary patency after percutaneous transluminal angioplasty (post-intervention primary patency) and compare this classification with that using lesion location. Hemodialysis patients who underwent ultrasound-guided percutaneous transluminal angioplasty for arteriovenous fistula stenosis from July 2020 to December 2021 were retrospectively evaluated. Lesions (excluding inflow arteries) were categorized into five groups based on ultrasound features, and the clinical characteristics and risk factors affecting the post-intervention primary patency of the arteriovenous fistula were analyzed. Among 185 patients, 100 (54.05%), 36 (19.46%), 22 (11.89%), 11 (5.95%), and 16 (8.65%) were classified into the intima-dominant, non-intima-dominant, valve obstruction, vascular calcification, and mixed groups, respectively. The dialysis duration and arteriovenous fistula use time were the highest in the vascular calcification group at 86 (interquartile range: 49-140) and 77 (interquartile range: 49-110) months, respectively. Diabetes mellitus was most common in the intima-dominant group (42.0%). In Kaplan-Meier and univariate Cox analysis, type III lesion location (stenosis in the venous confluence site) was associated with the lower post-intervention primary patency. In the multivariate Cox analysis, percutaneous transluminal angioplasty times (the number of times patients were treated with percutaneous transluminal angioplasty for arteriovenous fistula stenosis dysfunction), vascular calcification, calcification at the lesion site requiring percutaneous transluminal angioplasty, and serum parathyroid hormone levels were independent risk factors for post-intervention primary patency. Ultrasound features showed that calcification of the arteriovenous fistula was detrimental to the post-intervention primary patency of arteriovenous fistula.
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Fístula Arteriovenosa , Calcificación Vascular , Humanos , Constricción Patológica , Estudios Retrospectivos , Ultrasonografía , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/terapia , Fístula Arteriovenosa/diagnóstico por imagen , Fístula Arteriovenosa/terapiaRESUMEN
Objective: To investigate the status quo and the needs of medical imaging technicians (MITs) in the radiology department of secondary and tertiary hospitals in China, so as to provide references and support for the development of the medical imaging technology industry and the relevant policymaking by health administrative departments. Methods: The questionnaire was developed by the Chinese Society of Imaging Technology. The radiology department of each hospital involved in the survey recommended one MIT to fill out the online questionnaire. The contents included: (a) the basic information of the hospital; (b) a general overview of the MITs in the hospital; (c) daily work; (d) career development and promotion; (e) research status and needs, etc. Differences in the number of MIT staff were compared using the Mann-Whitney U test and the chi-square test was used to compare the differences in the selected numbers of MITs in need between regions or between different levels of hospitals. Results: In this investigation, valid questionnaires were finally obtained from a total of 5403 hospitals in 31 provinces in China. The total number of MITs of the hospitals covered in the sample was 67481. The number of MITs in each hospital was 9 (5, 16). The male-to-female ratio was 1.41:1. MITs who were 20 to 40 years old accounted for 78%. The proportions of MITs who had completed doctorate, master's, undergraduate, junior college, and technical secondary school or lower level education were 0.6%, 3.3%, 60.7%, 30.8%, and 4.55%, respectively. The proportions of chief MITs, deputy chief MITs, supervisor MITs, primary MITs, assistant technician and those below were 1.0%, 4.21%, 22.1%, 51.8%, and 20.9%, respectively. The overall professional satisfaction of MITs was good. "Lack of opportunities for learning and communication" was quoted as the main problem MITs encountered in regard to improving their job-related competency. 59.2% of the respondents had not published any academic papers in the past five years, and only 7.0% of the respondents had published in journals included in the Science Citation Index (SCI) in the past five years. Conclusion: MITs in China are on average relatively young and the number of MITs has greatly increased. At this stage, more attention should be given to the cultivation of talents and continuing education of MITs and the construction of the discipline should be further strengthened, so as to provide strong support for the development of the medical imaging technology industry in China.
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Diagnóstico por Imagen , China , Encuestas y Cuestionarios , Humanos , Femenino , Masculino , Diagnóstico por Imagen/estadística & datos numéricos , Servicio de Radiología en Hospital , Adulto , Recursos Humanos/estadística & datos numéricosRESUMEN
PTBP1 is an oncogene that regulates the splicing of precursor mRNA. However, the relationship between PTBP1 expression and gene methylation, cancer prognosis, and tumor microenvironment remains unclear. The expression profiles of PTBP1 across various cancers were derived from the TCGA, as well as the GTEx and CGGA databases. The CGGA mRNA_325, CGGA mRNA_301, and CGGA mRNA_693 datasets were utilized as validation cohorts. Immune cell infiltration scores were approximated using the TIMER 2.0 tool. Functional enrichment analysis for groups with high and low PTBP1 expression was conducted using Gene Set Enrichment Analysis (GSEA). Methylation data were predominantly sourced from the SMART and Mexpress databases. Linked-omics analysis was employed to perform functional enrichment analysis of genes related to PTBP1 methylation, as well as to conduct protein functional enrichment analysis. Single-cell transcriptome analysis and spatial transcriptome analysis were carried out using Seurat version 4.10. Compared to normal tissues, PTBP1 is significantly overexpressed and hypomethylated in various cancers. It is implicated in prognosis, immune cell infiltration, immune checkpoint expression, genomic variation, tumor neoantigen load, and tumor mutational burden across a spectrum of cancers, with particularly notable effects in low-grade gliomas. In the context of gliomas, PTBP1 expression correlates with WHO grade and IDH1 mutation status. PTBP1 expression and methylation play an important role in a variety of cancers. PTBP1 can be used as a marker of inflammation, progression and prognosis in gliomas.
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Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Glioma , Ribonucleoproteínas Nucleares Heterogéneas , Proteína de Unión al Tracto de Polipirimidina , Microambiente Tumoral , Humanos , Proteína de Unión al Tracto de Polipirimidina/genética , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/genética , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Pronóstico , Biomarcadores de Tumor/genética , Glioma/genética , Glioma/patología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Metilación de ADN , Perfilación de la Expresión Génica , Inflamación/genética , Transcriptoma , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/mortalidad , Progresión de la Enfermedad , MultiómicaRESUMEN
PURPOSE: Sequential working memory is the ability to maintain and manipulate sequential information at a second time scale. Patients with progressive supranuclear palsy (PSP) or Parkinson's disease (PD) perform poorly in tests that require the flexible arrangement of thoughts or actions. This study investigated whether sequential working memory is differently impaired in patients with PSP versus PD. METHOD: Twenty-nine patients with PSP Richardson's syndrome (PSP-RS), 36 patients with PD, and 36 healthy controls (HC) completed 3 well-established neuropsychological tests, including digit span forward (DST-F), digit span backward (DST-B), and adaptive digit ordering tests (DOT-A). The DST-F required maintaining digit sequences, and the DST-B and DOT-A required maintaining and manipulating digit sequences. FINDING: The PSP-RS group scored lower than the PD and HC groups in the DST-B and DOT-A but not in the DST-F, indicating that the ability to manipulate sequences was impaired, but the maintenance ability was preserved in PSP-RS patients. Moreover, in PSP-RS, the DST-B score negatively correlated with the severity of motor symptoms. The actual levodopa dose positively correlated with the DST-B ordering cost (DST-F score vs. DST-B score). The PSP patients who took a greater dose of levodopa tended to have higher DST-B ordering cost. There was no effect of levodopa on DST-B or DOT-A in PD. CONCLUSION: These results suggested that the ability to manipulate sequence was already reduced in patients with PSP-RS and was worse than in patients with PD.
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Memoria a Corto Plazo , Enfermedad de Parkinson , Parálisis Supranuclear Progresiva , Humanos , Parálisis Supranuclear Progresiva/fisiopatología , Parálisis Supranuclear Progresiva/tratamiento farmacológico , Masculino , Femenino , Anciano , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/tratamiento farmacológico , Persona de Mediana Edad , Memoria a Corto Plazo/fisiología , Pruebas Neuropsicológicas , Levodopa/administración & dosificación , Levodopa/farmacología , Levodopa/uso terapéuticoRESUMEN
Vascular cambium in tree species is a cylindrical domain of meristematic cells that are responsible for producing secondary xylem (also called wood) inward and secondary phloem outward. The poplar (Populus trichocarpa) WUSCHEL (WUS)-RELATED HOMEOBOX (WOX) family members, PtrWUSa and PtrWOX13b, were previously shown to be expressed in vascular cambium and differentiating xylem cells in poplar stems, but their functions remain unknown. Here, we investigated roles of PtrWUSa, PtrWOX13b and their close homologs in vascular organization and wood formation. Expression analysis showed that like PtrWUSa and PtrWOX13b, their close homologs, PtrWUSb, PtrWUS4a/b and PtrWOX13a/c, were also expressed in vascular cambium and differentiating xylem cells in poplar stems. PtrWUSa also exhibited a high level of expression in developing phloem fibers. Expression of PtrWUSa fused with the dominant EAR repression domain (PtrWUSa-DR) in transgenic poplar caused retarded growth of plants with twisted stems and curled leaves and a severe disruption of vascular organization. In PtrWUSa-DR stems, a drastic proliferation of cells occurred in the phloem region between vascular cambium and phloem fibers and they formed islands of ectopic vascular tissues or phloem fiber-like sclerenchyma cells. A similar proliferation of cells was also observed in PtrWUSa-DR leaf petioles and midveins. On the other hand, overexpression of PtrWOX4a-DR caused ectopic formation of vascular bundles in the cortical region, and overexpression of PtrWOX13a-DR and PtrWOX13b-DR led to a reduction in wood formation without affecting vascular organization in transgenic poplar plants. Together, these findings indicate crucial roles of PtrWUSa and PtrWOX13a/b in regulating vascular organization and wood formation, which furthers our understanding of the functions of WOX genes in regulating vascular cambium activity in tree species.
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Cámbium , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Plantas Modificadas Genéticamente , Populus , Madera , Xilema , Populus/genética , Populus/crecimiento & desarrollo , Populus/metabolismo , Madera/crecimiento & desarrollo , Madera/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Xilema/crecimiento & desarrollo , Xilema/metabolismo , Xilema/genética , Cámbium/genética , Cámbium/crecimiento & desarrollo , Plantas Modificadas Genéticamente/genética , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Genes Homeobox , Floema/genética , Floema/crecimiento & desarrollo , Floema/metabolismo , Tallos de la Planta/crecimiento & desarrollo , Tallos de la Planta/genética , Tallos de la Planta/metabolismoRESUMEN
BACKGROUND: The aim of this study is to identify risk factors associated with histological chorioamnionitis (HCA) and develop a predictive model for antepartum assessment of the risk of PPROM with HCA. METHODS: This study retrospectively analyzed pregnant women who experienced PPROM between 25 + 0 and 35 + 0 weeks of gestational age. The women were divided into two groups based on the presence or absence of HCA. Univariate and multivariate logistic regression analyses were conducted to identify maternal risk factors and develop a clinical prediction model for HCA. The model's discrimination and consistency were evaluated using receiver operating characteristic (ROC) and calibration curves. RESULTS: Seventeen thousand one hundred forty-six (17,146) pregnant women were screened, and 726 (4.23 %) had PPROM. Out of the 286 subjects with PPROM, 160 developed HCA. The maternal age of these subjects ranged from 18 to 43 years (30.0 ± 5.4), while their gestational age (GA) ranged from 25 + 0 to 35 + 0 weeks (31.6 ± 2.0). The average GA at delivery was 32.2 ± 2.0 (weeks).Compared with the non-HCA group, the expectant time > 48 h, GA at delivery > 32 weeks, twin pregnancy, HGB (<110 g/Lg/L), degree of LGB (IIb-III), and WBC (>9.5 × 109 /L) were significantly more than in the PPROM with HCA group. The results show that the best model was obtained by leave-one-out logistic regression (AUC = 0.785, CA = 0.741, F1 = 0.739, Precision = 0.740, Recall = 0.741). In the validation set, logistic regression also achieved good results (AUC = 0.710, CA = 0.671, F1 = 0.654, Precision = 0.683, Recall = 0.671). Combining the previous analysis, we found that the prognostic model constructed using the core six features had the best predictive effect. CONCLUSIONS: Six features were associated with the occurrence of chorioamnionitis. These features were used to construct a diagnostic model that can accurately predict the probability of chorioamnionitis occurrence and provide a beneficial tool for the prevention and management of PPROM with HCA.