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Explicitly sharing individual level data in genomics studies has many merits comparing to sharing summary statistics, including more strict QCs, common statistical analyses, relative identification and improved statistical power in GWAS, but it is hampered by privacy or ethical constraints. In this study, we developed encG-reg, a regression approach that can detect relatives of various degrees based on encrypted genomic data, which is immune of ethical constraints. The encryption properties of encG-reg are based on the random matrix theory by masking the original genotypic matrix without sacrificing precision of individual-level genotype data. We established a connection between the dimension of a random matrix, which masked genotype matrices, and the required precision of a study for encrypted genotype data. encG-reg has false positive and false negative rates equivalent to sharing original individual level data, and is computationally efficient when searching relatives. We split the UK Biobank into their respective centers, and then encrypted the genotype data. We observed that the relatives estimated using encG-reg was equivalently accurate with the estimation by KING, which is a widely used software but requires original genotype data. In a more complex application, we launched a finely devised multi-center collaboration across 5 research institutes in China, covering 9 cohorts of 54,092 GWAS samples. encG-reg again identified true relatives existing across the cohorts with even different ethnic backgrounds and genotypic qualities. Our study clearly demonstrates that encrypted genomic data can be used for data sharing without loss of information or data sharing barrier.
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Estudio de Asociación del Genoma Completo , Privacidad , Humanos , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Programas Informáticos , GenómicaRESUMEN
Splicing factors (SFs) are the major RNA-binding proteins (RBPs) and key molecules that regulate the splicing of mRNA molecules through binding to mRNAs. The expression of splicing factors is frequently deregulated in different cancer types, causing the generation of oncogenic proteins involved in cancer hallmarks. In this study, we investigated the genes that encode RNA-binding proteins and identified potential splicing factors that contribute to the aberrant splicing applying a random forest classification model. The result suggested 56 splicing factors were related to the prognosis of 13 cancers, two SF complexes in liver hepatocellular carcinoma, and one SF complex in esophageal carcinoma. Further systematic bioinformatics studies on these cancer prognostic splicing factors and their related alternative splicing events revealed the potential regulations in a cancer-specific manner. Our analysis found high ILF2-ILF3 expression correlates with poor prognosis in LIHC through alternative splicing. These findings emphasize the importance of SFs as potential indicators for prognosis or targets for therapeutic interventions. Their roles in cancer exhibit complexity and are contingent upon the specific context in which they operate. This recognition further underscores the need for a comprehensive understanding and exploration of the role of SFs in different types of cancer, paving the way for their potential utilization in prognostic assessments and the development of targeted therapies.
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Empalme Alternativo , Biología Computacional , Regulación Neoplásica de la Expresión Génica , Aprendizaje Automático , Neoplasias , Factores de Empalme de ARN , Humanos , Factores de Empalme de ARN/genética , Factores de Empalme de ARN/metabolismo , Pronóstico , Empalme Alternativo/genética , Neoplasias/genética , Biología Computacional/métodos , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Empalme del ARN/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/genéticaRESUMEN
A-to-I RNA editing diversifies human transcriptome to confer its functional effects on the downstream genes or regulations, potentially involving in neurodegenerative pathogenesis. Its variabilities are attributed to multiple regulators, including the key factor of genetic variants. To comprehensively investigate the potentials of neurodegenerative disease-susceptibility variants from the view of A-to-I RNA editing, we analyzed matched genetic and transcriptomic data of 1596 samples across nine brain tissues and whole blood from two large consortiums, Accelerating Medicines Partnership-Alzheimer's Disease and Parkinson's Progression Markers Initiative. The large-scale and genome-wide identification of 95 198 RNA editing quantitative trait loci revealed the preferred genetic effects on adjacent editing events. Furthermore, to explore the underlying mechanisms of the genetic controls of A-to-I RNA editing, several top RNA-binding proteins were pointed out, such as EIF4A3, U2AF2, NOP58, FBL, NOP56 and DHX9, since their regulations on multiple RNA-editing events were probably interfered by these genetic variants. Moreover, these variants may also contribute to the variability of other molecular phenotypes associated with RNA editing, including the functions of 3 proteins, expressions of 277 genes and splicing of 449 events. All the analyses results shown in NeuroEdQTL (https://relab.xidian.edu.cn/NeuroEdQTL/) constituted a unique resource for the understanding of neurodegenerative pathogenesis from genotypes to phenotypes related to A-to-I RNA editing.
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Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/genética , Edición de ARN , Transcriptoma , Perfilación de la Expresión Génica , Sitios de Carácter Cuantitativo , Factor 4A Eucariótico de Iniciación/genética , ARN Helicasas DEAD-box/genéticaRESUMEN
AIMS: Gastrointestinal paresthesia and dysmotility are common side effects of vincristine (VCR) chemotherapy, which have become one of the factors for dose reduction, therapy delay or discontinuation. However, the mechanism is not entirely clear, whether it is related to autonomic nerves injury remains unknown. Therefore, we aimed to study whether VCR-induced gastrointestinal toxicity is related to changes in mesenteric afferent activity. METHODS: The effects of a single VCR stimulation and long-term systemic VCR treatment on mesenteric afferent activity were investigated by directly recording mesenteric afferent discharge in vitro. RESULTS: Our results showed that a single VCR (0.001-1 µmol/L) stimulation obviously increased the spontaneous, chemically evoked and mechanically evoked discharge of jejunal and colonic mesenteric afferents. This kind of hypersensitivity of VCR could be blocked by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist. For the mice treated with VCR (0.1 mg/kg/d, i.p.) for 14 days, the abdominal withdrawal reflex and writhing response scores were reduced. Meanwhile, the spontaneous discharge of colonic mesenteric afferents and the afferent response to VCR was downregulated, and the afferent sensitivity to chemical and mechanical stimulation was reduced. Moreover, the expression of TRPV1 in colon was decreased. CONCLUSIONS: These results suggest that the direct stimulation by VCR increases the mesenteric afferent sensitivity by activating TRPV1, which may be the reason of VCR-induced abdominal pain; the long-term systemic treatment of VCR decreases mesenteric afferent sensitivity by reducing TRPV1, which may be the reason of VCR-induced constipation.
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Canales Catiónicos TRPV , Ratones , Animales , Vincristina/toxicidad , Regulación hacia Abajo , Canales Catiónicos TRPV/metabolismoRESUMEN
Pseudotime analysis from scRNA-seq data enables to characterize the continuous progression of various biological processes, such as the cell cycle. Cell cycle plays an important role in cell fate decisions and differentiation and is often regarded as a confounder in scRNA-seq data analysis when analyzing the role of other factors. Therefore, accurate prediction of cell cycle pseudotime and identification of cell cycle stages are important steps for characterizing the development-related biological processes. Here, we develop CCPE, a novel cell cycle pseudotime estimation method to characterize cell cycle timing and identify cell cycle phases from scRNA-seq data. CCPE uses a discriminative helix to characterize the circular process of the cell cycle and estimates each cell's pseudotime along the cell cycle. We evaluated the performance of CCPE based on a variety of simulated and real scRNA-seq datasets. Our results indicate that CCPE is an effective method for cell cycle estimation and competitive in various applications compared with other existing methods. CCPE successfully identified cell cycle marker genes and is robust to dropout events in scRNA-seq data. Accurate prediction of the cell cycle using CCPE can also effectively facilitate the removal of cell cycle effects across cell types or conditions.
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Ciclo Celular/genética , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , RNA-Seq , Análisis de la Célula Individual , Algoritmos , Bases de Datos Genéticas , Regulación de la Expresión Génica , RNA-Seq/métodos , Análisis de la Célula Individual/métodosRESUMEN
The long non-coding RNAs associating with other molecules can coordinate several physiological processes and their dysfunction can impact diverse human diseases. To date, systematic and intensive annotations on diverse interaction regulations of lncRNAs in human cancer were not available. Here, we built lncRNAfunc, a knowledgebase of lncRNA function in human cancer at https://ccsm.uth.edu/lncRNAfunc, aiming to provide a resource and reference for providing therapeutically targetable lncRNAs and intensive interaction regulations. To do this, we collected 15 900 lncRNAs across 33 cancer types from TCGA. For individual lncRNAs, we performed multiple interaction analyses of different biomolecules including DNA, RNA, and protein levels. Our intensive studies of lncRNAs provide diverse potential mechanisms of lncRNAs that regulate gene expression through binding enhancers and 3'-UTRs of genes, competing for miRNA binding sites with mRNAs, recruiting the transcription factors to gene promoters. Furthermore, we investigated lncRNAs that potentially affect the alternative splicing events through interacting with RNA binding Proteins. We also performed multiple functional annotations including cancer stage-associated lncRNAs, RNA A-to-I editing event-associated lncRNAs, and lncRNA expression quantitative trait loci. lncRNAfunc is a unique resource for cancer research communities to help better understand potential lncRNA regulations and therapeutic lncRNA targets.
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Bases de Datos Genéticas , Bases del Conocimiento , Neoplasias/genética , ARN Largo no Codificante/genética , Empalme Alternativo/genética , Humanos , Neoplasias/clasificación , ARN Largo no Codificante/clasificación , ARN Mensajero/genéticaRESUMEN
BACKGROUND: Although the extreme environmental adaptation of organisms is a hot topic in evolutionary biology, genetic adaptation to high-altitude environment remains poorly characterized in ectothermic animals. Squamates are among the most diverse terrestrial vertebrates, with tremendous ecological plasticity and karyotype diversity, and are a unique model system to investigate the genetic footprints of adaptation. RESULTS: We report the first chromosome-level assembly of the Mongolian racerunner (Eremias argus) and our comparative genomics analyses found that multiple chromosome fissions/fusions events are unique to lizards. We further sequenced the genomes of 61 Mongolian racerunner individuals that were collected from altitudes ranging from ~ 80 to ~ 2600 m above sea level (m.a.s.l.). Population genomic analyses revealed many novel genomic regions under strong selective sweeps in populations endemic to high altitudes. Genes embedded in those genomic regions are mainly associated with energy metabolism and DNA damage repair pathways. Moreover, we identified and validated two substitutions of PHF14 that may enhance the lizards' tolerance to hypoxia at high altitudes. CONCLUSIONS: Our study reveals the molecular mechanism of high-altitude adaptation in ectothermic animal using lizard as a research subject and provides a high-quality lizard genomic resource for future research.
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Altitud , Lagartos , Animales , Metagenómica , Lagartos/genética , Evolución Biológica , Adaptación Fisiológica/genética , CromosomasRESUMEN
BACKGROUND: Rice wine (RW) fermentation is limited by its long fermentation time, weak taste and unpleasant flavors such as oil and odor. In this study, a novel ultrasound technology of Saccharomyces cerevisiae was used with the aim of improving fermentation efficiency and volatile flavor quality of RW. RESULTS: The results showed that fixed-frequency ultrasonic treatment (28 kHz, 45 W L-1, 20 min) of S. cerevisiae seed culture at its logarithmic metaphase significantly increased the biomass and alcohol yield by 31.58% and 26.45%, respectively, and reduced fermentation time by nearly 2 days. Flavor analysis indicated that the flavor compounds in RW, specifically the esters and alcohols, were also increased in quantity after the ultrasonic treatment of S. cerevisiae seed liquid. Isobutyl acetate, ethyl butyrate, ethyl hexanoate and phenethyl acetate contents were increased by 78.92%, 129.19%, 7.79% and 97.84%, respectively, as compared to the control. CONCLUSION: Ultrasonic treatment of S. cerevisiae reduced fermentation time and enhanced the flavor profile of RW. This study could provide a theoretical and/or technological basis for the research and development of RW. © 2024 Society of Chemical Industry.
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Fermentación , Oryza , Saccharomyces cerevisiae , Gusto , Vino , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/crecimiento & desarrollo , Vino/análisis , Vino/microbiología , Oryza/metabolismo , Oryza/química , Oryza/microbiología , Oryza/crecimiento & desarrollo , Aromatizantes/metabolismo , Aromatizantes/química , Ultrasonido/métodos , Etanol/metabolismo , Etanol/análisis , Odorantes/análisisRESUMEN
BACKGROUND: Eggs represent important sources of protein and are widely loved by consumers. Egg yolk taste is an important index for egg selection, and the moisture content of the egg yolk affects the taste. To understand the molecular mechanism underlying egg yolk moisture content, this study determined the phenotype and heritability of egg yolk water content and conducted a genome-wide association study (GWAS) using a mixed linear model. RESULTS: We determined the phenotype and heritability of thermogelled egg yolk water content (TWC) and found that the average TWC was 47.73%. Moreover, significant variations occurred (41.06-57.12%), and the heritability was 0.11, which indicates medium-low heritability. Through the GWAS, 48 single nucleotide polymorphisms (SNPs) related to TWC (20 significantly, 28 suggestively) were obtained, and they were mainly located on chromosomes 10 and 13. We identified 36 candidate genes based on gene function and found that they were mainly involved in regulating fat, protein, and water content and embryonic development. FGF9, PIAS1, FEM1B, NOX5, GLCE, VDAC1, IGFBP7, and THOC5 were involved in lipid formation and regulation; AP3S2, GNPDA1, HSPA4, AP1B1, CABP7, EEF1D, SYTL3, PPP2CA, SKP1, and UBE2B were involved in protein folding and hydrolysis; and CSF2, SOWAHA, GDF9, FSTL4, RAPGEF6, PAQR5, and ZMAT5 were related to embryonic development and egg production. Moreover, MICU2, ITGA11, WDR76, BLM, ANPEP, TECRL, EWSR1, and P4HA2 were related to yolk quality, while ITGA11, WDR76, BLM, and ANPEP were potentially significantly involved in egg yolk water content and thus deserve further attention and research. In addition, this study identified a 19.31-19.92 Mb genome region on GGA10, and a linkage disequilibrium analysis identified strong correlations within this region. Thus, GGA10 may represent a candidate region for TWC traits. CONCLUSION: The molecular genetic mechanism involved in TWC was revealed through heritability measurements and GWAS, which identified a series of SNPs, candidate genes, and candidate regions related to TWC. These results provide insights on the molecular mechanism of egg yolk moisture content and may aid in the development of new egg traits.
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Yema de Huevo , Estudio de Asociación del Genoma Completo , Animales , Estudio de Asociación del Genoma Completo/métodos , Pollos/genética , Genómica , Proteínas/genética , Fenotipo , Agua , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Eggshell speckle phenotype is an important trait in poultry production because they affect eggshell quality. However, the genetic architecture of speckled eggshells remains unclear. In this study, we determined the heritability of eggshell speckles and conducted a genome-wide association study (GWAS) on purebred Rhode Island Red (RIR) hens at 28 weeks to detect potential genomic loci and candidate genes associated with eggshell speckles. RESULTS: The heritability of eggshell speckles was 0.35 at 28 weeks, and the speckle level is not related to other eggshell quality traits in terms of phenotypic correlation. We detected 311 SNPs (6 significantly, and 305 suggestively associated) and 39 candidate genes associated with eggshell speckles. Based on the pathway analysis, the 39 candidate genes were mainly involved in alpha-linolenic acid metabolism, linoleic acid metabolism, ether lipid metabolism, GnRH signaling pathway, vascular smooth muscle contraction, and MAPK signaling pathway. Ultimately, ten genes, LOC423226, SPTBN5, EHD4, LOC77155, TYRO3, ITPKA, DLL4, PLA2G4B, PLA2G4EL5, and PLA2G4EL6 were considered the most promising genes associated with eggshell speckles that were implicated in immunoregulation, calcium transport, and phospholipid metabolism, while its function in laying hens requires further studies. CONCLUSIONS: This study provides new insights into understanding the genetic basis of eggshell speckles and has practical application value for the genetic improvement of eggshell quality.
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Cáscara de Huevo , Estudio de Asociación del Genoma Completo , Animales , Femenino , Cáscara de Huevo/metabolismo , Pollos/genética , Genoma , FenotipoRESUMEN
Exon skipping (ES), the most common alternative splicing event, has been reported to contribute to diverse human diseases due to the loss of functional domains/sites or frameshifting of the open reading frame (ORF) and noticed as therapeutic targets. Accumulating transcriptomic studies of aging brains show the splicing disruption is a widespread hallmark of neurodegenerative diseases such as Alzheimer's disease (AD). Here, we built ExonSkipAD, the ES annotation database aiming to provide a resource/reference for functional annotation of ES events in AD and identify therapeutic targets in exon units. We identified 16 414 genes that have ~156 K, ~ 69 K, ~ 231 K ES events from the three representative AD cohorts of ROSMAP, MSBB and Mayo, respectively. For these ES events, we performed multiple functional annotations relating to ES mechanisms or downstream. Specifically, through the functional feature retention studies followed by the open reading frames (ORFs), we identified 275 important cellular regulators that might lose their cellular regulator roles due to exon skipping in AD. ExonSkipAD provides twelve categories of annotations: gene summary, gene structures and expression levels, exon skipping events with PSIs, ORF annotation, exon skipping events in the canonical protein sequence, 3'-UTR located exon skipping events lost miRNA-binding sites, SNversus in the skipped exons with a depth of coverage, AD stage-associated exon skipping events, splicing quantitative trait loci (sQTLs) in the skipped exons, correlation with RNA-binding proteins, and related drugs & diseases. ExonSkipAD will be a unique resource of transcriptomic diversity research for understanding the mechanisms of neurodegenerative disease development and identifying potential therapeutic targets in AD. Significance AS the first comprehensive resource of the functional genomics of the alternative splicing events in AD, ExonSkipAD will be useful for many researchers in the fields of pathology, AD genomics and precision medicine, and pharmaceutical and therapeutic researches.
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Regiones no Traducidas 3' , Empalme Alternativo , Enfermedad de Alzheimer , Bases de Datos de Ácidos Nucleicos , Exones , Transcriptoma , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Humanos , MicroARNs , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
A-to-I RNA editing, contributing to nearly 90% of all editing events in human, has been reported to involve in the pathogenesis of Alzheimer's disease (AD) due to its roles in brain development and immune regulation, such as the deficient editing of GluA2 Q/R related to cell death and memory loss. Currently, there are urgent needs for the systematic annotations of A-to-I RNA editing events in AD. Here, we built ADeditome, the annotation database of A-to-I RNA editing in AD available at https://ccsm.uth.edu/ADeditome, aiming to provide a resource and reference for functional annotation of A-to-I RNA editing in AD to identify therapeutically targetable genes in an individual. We detected 1676 363 editing sites in 1524 samples across nine brain regions from ROSMAP, MayoRNAseq and MSBB. For these editing events, we performed multiple functional annotations including identification of specific and disease stage associated editing events and the influence of editing events on gene expression, protein recoding, alternative splicing and miRNA regulation for all the genes, especially for AD-related genes in order to explore the pathology of AD. Combing all the analysis results, we found 108 010 and 26 168 editing events which may promote or inhibit AD progression, respectively. We also found 5582 brain region-specific editing events with potentially dual roles in AD across different brain regions. ADeditome will be a unique resource for AD and drug research communities to identify therapeutically targetable editing events. Significance: ADeditome is the first comprehensive resource of the functional genomics of individual A-to-I RNA editing events in AD, which will be useful for many researchers in the fields of AD pathology, precision medicine, and therapeutic researches.
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Adenosina/metabolismo , Enfermedad de Alzheimer/genética , Amnesia/genética , Inosina/metabolismo , Proteínas del Tejido Nervioso/genética , Edición de ARN , Transcriptoma , Adenosina/genética , Empalme Alternativo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Amnesia/metabolismo , Amnesia/patología , Encéfalo/metabolismo , Encéfalo/patología , Mapeo Encefálico , Bases de Datos Genéticas , Ontología de Genes , Humanos , Inosina/genética , MicroARNs/clasificación , MicroARNs/genética , MicroARNs/metabolismo , Anotación de Secuencia Molecular , Proteínas del Tejido Nervioso/clasificación , Proteínas del Tejido Nervioso/metabolismo , Receptores AMPA/genética , Receptores AMPA/metabolismoRESUMEN
PURPOSE: In this study, we explored the relationship of genes in HIF-1 signaling pathway with preeclampsia and establish a logistic regression model for diagnose preeclampsia using bioinformatics analysis. METHOD: Two microarray datasets GSE75010 and GSE35574 were downloaded from the Gene Expression Omnibus database, which was using for differential expression analysis. DEGs were performed the Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene set enrichment analysis (GSEA). Then we performed unsupervised consensus clustering analysis using genes in HIF-1 signaling pathway, and clinical features and immune cell infiltration were compared between these clusters, as well as the least absolute shrinkage and selection operator (LASSO) method to screened out key genes to constructed logistic regression model, and receiver operating characteristic (ROC) curve was plotted to evaluate the accuracy of the model. RESULTS: 57 DEGs were identified, of which GO, KEGG and analysis GSEA showed DEGs were mostly involved in HIF-1 signaling pathway. Two subtypes were identified of preeclampsia and 7 genes in HIF1-signaling pathway were screened out to establish the logistic regression model for discrimination preeclampsia from controls, of which the AUC are 0.923 and 0.845 in training and validation datasets respectively. CONCLUSION: Seven genes (including MKNK1, ARNT, FLT1, SERPINE1, ENO3, LDHA, BCL2) were screen out to build potential diagnostic model of preeclampsia.
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Preeclampsia , Femenino , Humanos , Embarazo , Análisis por Conglomerados , Bases de Datos Factuales , Péptidos y Proteínas de Señalización Intracelular , Modelos Logísticos , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismoRESUMEN
BACKGROUND: There is conclusive evidence of a multifaceted and bidirectional relationship between loneliness and depression and anxiety. Nonetheless, more extensive research is needed to examine their relationships at a more granular level. This study employed a network analysis approach to identify the pathological mechanisms underpinning those relationships and to identify important bridge nodes as potential targets for intervention. METHODS: 941 University students were included in this study. The ULS-6 (the short-form UCLA Loneliness Scale) was used to assess loneliness, the PHQ-9 (Patient Health questionnaire-9) and GAD-7 (Generalized anxiety disorder 7-item) scales were used to assess the symptoms of depression and anxiety. We constructed two network structures of loneliness-anxiety and loneliness-depression and computed bridge expected influence for each symptom. In addition, we showed a flow network of "Suicide" containing symptoms of depression and loneliness. RESULTS: All edges were positive in both networks constructed and the strongest edges were present within disorder communities. The overall connection between loneliness and depression was stronger compared to anxiety. The results demonstrated that the loneliness item "People are around me but not with me" was identified as bridge symptom in both networks. Furthermore, "Suicide" was directly connected to five symptoms of depression and four items of loneliness, with the strongest connections being between it and "Feeling of worthlessness" and "Psychomotor agitation/retardation". CONCLUSIONS: Our findings provide a more nuanced explanation of the link between loneliness and depression and anxiety. The results identified the bridge symptom "People are around me but not with me", which had the strongest effect on enhancing symptoms of depression and anxiety. Clinical improvements based on the findings of this study and the impact of the intervention are discussed.
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Depresión , Soledad , Humanos , Depresión/epidemiología , Depresión/diagnóstico , Universidades , Ansiedad/epidemiología , Ansiedad/diagnóstico , Trastornos de Ansiedad , EstudiantesRESUMEN
The current medical model has transitioned from the original biomedical treatment model to a bio-psycho-social model, where patients now have higher demands for service awareness. Consequently, doctor-patient relationships have become a crucial aspect of the contemporary medical process. Currently, psychological resilience among medical students in China tends to be at a moderately lower level. Medical students often exhibit poor psychological qualities in handling contradictions in doctor-patient relationships. Moreover, there is a lack of emphasis on the education of corresponding psychological qualities for medical students during the teaching process. This deficiency is highly disadvantageous for medical students in their future management of doctor-patient relationships. The article explores how to cultivate psychological resilience in medical students and enhance their ability to handle conflicts in doctor-patient relationships from the perspective of doctor-patient relationships. The author suggests that schools should place greater emphasis on the psychological resilience of medical students, change teaching methods, incorporate online education to enhance the mentalization level of medical students, and propose an eight-week mindfulness cognitive therapy program to improve psychological resilience. The intervention process should consider establishing positive coping mechanisms, promoting good interpersonal relationships among medical students, and regulating individual negative emotions. Through simulating doctor-patient scenarios, teachers should consciously train the psychological resilience of medical students, improve their cognition and thinking abilities, and accelerate their psychological health recovery.
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This study aimed to enhance the utilization value of sweet corn cob, an agricultural cereal byproduct. Sweet corn cob polysaccharide-ron (III) complexes were prepared at four different temperatures (40 °C, 50 °C, 60 °C, and 70 °C). It was demonstrated that the complexes prepared at different temperatures were successfully bound to iron (III), and there was no significant difference in chemical composition; and SCCP-Fe-C demonstrated the highest iron content. The structural characterization suggested that sweet corn cob polysaccharide (SCCP) formed stable ß-FeOOH iron nuclei with -OH and -OOH. All the four complexes' thermal stability was enhanced, especially in SCCP-Fe-C. In vitro iron (III) release experiments revealed that all four complexes were rapidly released and acted as iron (III) supplements. Moreover, in vitro antioxidant, α-glucosidase, and α-amylase inhibition studies revealed that the biological activities of all four complexes were enhanced compared with those of SCCP. SCCP-Fe-B and SCCP-Fe-C exhibited the highest in vitro antioxidant, α-glucosidase, and α-amylase inhibition abilities. This study will suggest using sweet corn cobs, a natural agricultural cereal byproduct, in functional foods. Furthermore, we proposed that the complexes prepared from agricultural byproducts can be used as a potential iron supplement.
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Antioxidantes , Zea mays , Zea mays/química , alfa-Glucosidasas , Hierro/química , Polisacáridos/farmacología , Polisacáridos/química , alfa-Amilasas , DigestiónRESUMEN
The health of living things and the ecosystem of the planet have both been negatively impacted by antibiotic residue in the water environment. There has been a lot of interest in the catalyst made of metal-carbon compounds from MOFs as a potential solution for activating peroxymonosulfate (PMS) to produce reactive oxygen species to catalyze the degradation of residual antibiotics. In this study, zeolitic imidazolate frameworks (ZIF-67) on bamboo fiber bundles (BFB) were pyrolyzed to produce magnetic Co/CoO nanoparticles with porous polyhedrons mounted on bamboo charcoal fiber bundles (BCFB)(BCFB@PCo/CoO). Specific surface area of obtained BCFB@PCo/CoO with abundant active sites arrives at 302.41 m2/g. The catalytic degradation efficiency of Tetracycline hydrochloride (TCH), a target contaminant, could reach up to 99.94% within 15 minutes (PMS = 0.4g/L, Cat. = 0.2g/L). The effects of potential factors, including PMS dosage, interference ions, and temperature, on catalytic degradation efficiencies were investigated. Magnetic recovery and antimicrobial properties of the BCFB@PCo/CoO were also evaluated and the possible degradation pathways were explored. Catalytic mechanism explorations of BCFB@PCo/CoO/PMS system reveal MOF-derived magnetic Co/CoO nanoparticles embedded in BCFB promote the synergistic interaction of both radicals and non-radical pathways for catalytic degradation of TCH. The novel BCFB@PCo/CoO provides an alternative to deal with wastewater containing antibiotics.
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Carbón Orgánico , Tetraciclina , Ecosistema , Porosidad , Peróxidos/química , Fenómenos Magnéticos , AntibacterianosRESUMEN
The pathogenesis, clinical phenotype, treatment strategy, and family management of hereditary tumor syndromes are different from those of sporadic tumors. Nearly a quarter of patients with colorectal cancer show significant familial aggregation and genetic predisposition, and 5 to 10% are associated with definite genetic factors. According to the clinical phenotype, it can be divided into nonpolyposis syndrome and polyposis syndrome. Among the polyposis syndrome patients with definite clinical symptoms, there are still some patients with unknown etiology (especially attenuated familial adenomatous polyposis), which is a difficult problem in clinical diagnosis and treatment. Therefore, for this rare disease, it is urgent to carry out multicenter studies, complete the gene variation spectrum, explore new pathogenic factors, and accumulate clinical experience. This article mainly introduces the research progress and related work of colorectal polyposis syndrome in China.
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Exon skipping (ES) is reported to be the most common alternative splicing event due to loss of functional domains/sites or shifting of the open reading frame (ORF), leading to a variety of human diseases and considered therapeutic targets. To date, systematic and intensive annotations of ES events based on the skipped exon units in cancer and normal tissues are not available. Here, we built ExonSkipDB, the ES annotation database available at https://ccsm.uth.edu/ExonSkipDB/, aiming to provide a resource and reference for functional annotation of ES events in multiple cancer and tissues to identify therapeutically targetable genes in individual exon units. We collected 14 272 genes that have 90 616 and 89 845 ES events across 33 cancer types and 31 normal tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx). For the ES events, we performed multiple functional annotations. These include ORF assignment of exon skipped transcript, studies of lost protein functional features due to ES events, and studies of exon skipping events associated with mutations and methylations based on multi-omics evidence. ExonSkipDB will be a unique resource for cancer and drug research communities to identify therapeutically targetable exon skipping events.
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Empalme Alternativo/genética , Bases de Datos Genéticas , Exones/genética , Genoma Humano/genética , Mutación/genética , Neoplasias/genética , HumanosRESUMEN
HINTERGRUND: Die Chemotherapie ist die erste Behandlungsoption für das lokal fortgeschrittene oder metastasierte intrahepatische Cholangiokarzinom (ICC). Nach einer Erstlinien-Chemotherapie gibt es jedoch keine Standardzweitlinienbehandlung oder zielgerichtete Wirkstoffe für diese Patienten. FALLPRäSENTATION: Hier stellen wir einen fortgeschrittenen ICC-Patienten vor, der eine radikale Entfernung und eine adjuvante Chemotherapie (Gemcitabin + Cisplatin) erhalten hat. Aber der Patient bleibt nur 6 Monate frei von Krankheitsanzeichen (No Evidence of Disease) nach dem Ende der Chemotherapie. Dann erhielt er eine palliative Operation, Strahlentherapie und systemische Chemotherapie (Tegafur+Oxaliplatin (SOX) und Nab-Paclitaxel+Gemcitabin (AG)). Leider war die Krankheit immer noch nicht unter Kontrolle. Als eine BRAF-V600E-Mutation im Tumorgewebe durch eine Next Generation Sequencing Analyse (NGS) gezeigt wurde, begann dieser Patient mit der Einnahme von Vemurafenib in einer Dosierung von 720-960 mg zweimal täglich und erreichte ein progressionsfreies Überleben von 7 Monaten mit signifikanter Remission der klinischen Symptome. SCHLüSSELWöRTER: Die BRAF V600E Mutation ist bei ICC ziemlich selten, daher wird sie in der Klinik nicht routinemäßig untersucht. Allerdings kann Präzisionsmedizin durch die NGS-Technologie verwirklicht werden, sodass die Ärzte bei der Behandlung der auf Chemotherapie-refraktären ICC die personalisierten genomischen Informationen nutzen können.