Abstract “The rancher of Irapuato/ [as stated on the cover of the typed copy in prose, the only one preserved to this day from an original titled Natural and figure] Comedy of manners. Written in magnificent verses in / two acts by the Mexican poet / Don José T. de Cuéllar /. -1868-.” The comedy, according to the transcription made ad litterae pedem of that prose, does not lead to considering, as someone who was able to read it in its original said, that it was "written in magnificent verses", because it is one thing to think and write in verse and another. very different, thinking and writing in prose what was in verse. Therefore, this prose copy, based on the verses of the original comedy, did not have to respect the rhythm or the numerical form or the rhyme of the verse. And thus, the said verses rescued from that prose, which will now be published in a faithful version, will irremediably alter these factors and in a large part of them there will be neither the syllabic rhythm nor the rhymes appropriate to the versatile modalities developed by the author of the comedy, who wrote in eight-syllable verses, in the form of romances and redondillas.

Resumen “El ranchero de Irapuato/ [como lo consigna la portada de la copia mecanográfica en prosa, única que hasta hoy se conserva de un original titulado Natural y figura] Comedia de costumbres. Escrita en magníficos versos en/ dos actos por el poeta mexicano/ Don José T. de Cuéllar/. -1868-.” La comedia, acorde a la transcripción hecha ad litterae pedem de esa prosa, no lleva a considerar, como dijera quien acaso pudo leerla en su original, que estaba “escrita en magníficos versos”, porque una cosa es pensar y escribir en verso y otra muy diferente, pensar y escribir en prosa lo que estaba en verso. Por tanto, esa copia en prosa, basada en los versos de la comedia original no tenía por qué respetar el ritmo ni la forma numérica ni la rima del verso. Y así, los dichos versos rescatados de esa prosa, que ahora se editará en una versión fiel, van a alterar sin remedio esos factores y no habrá en una gran parte de ellos ni el ritmo silábico ni las rimas apropiadas a las modalidades versátiles desarrolladas por el autor de la comedia, que escribió en versos octosílabos, en la modalidad de romances y redondillas.

Abstract Introduction: In clinical settings, nursing practices are more focused on the dependent person than on the caregiver, which may be related to the complexity of the informal caregiver training process. Objective: To explore and understand the phenomenon of nurses' avoidance of the informal caregiver training process and identify the underlying factors. Methods: This is an exploratory and descriptive study with a qualitative approach. Semi-structured interviews were carried out with nine nurses from a central hospital in Portugal. After transcription, content analysis was performed according to Bardin using the NVivo10® software. Ethical requirements were met, and a favorable opinion was obtained from the ethics committee. Results: Three thematic units emerged that were organized into categories and subcategories: Recognition of the phenomenon (2 categories); Intrinsic factors that condition nurses in training informal caregivers (4 categories and 2 subcategories); and Extrinsic factors that condition nurses in training informal caregivers (6 categories and 6 subcategories). Conclusion: A comprehensive approach is needed to preparing caregivers, from training nurses to identify and assess caregivers’ needs to coordinating and managing the therapeutic regime and planning for discharge. Healthcare organizations and communities should commit to creating the conditions for caregivers to achieve a healthy and safe transition.

Resumen Introducción: En contextos clínicos, las prácticas de enfermería se centran más en la persona dependiente que en el cuidador, lo que puede estar relacionado con la complejidad del proceso de empoderamiento del cuidador. Objetivo: Explorar y comprender el fenómeno de la evitación del empoderamiento del cuidador por parte de las enfermeras, identificando los factores subyacentes. Métodos: Se trata de un estudio exploratorio y descriptivo con enfoque cualitativo. Se realizaron entrevistas semiestructuradas a 9 enfermeras de un hospital central y tras su transcripción, se llevó a cabo el análisis de contenido según Bardin con el apoyo de NVivo10®. Se cumplieron los requisitos éticos y se obtuvo el dictamen favorable del comité de ética. Resultados: Surgieron tres unidades temáticas con sus respectivas categorías y subcategorías: reconocimiento del fenómeno (2 categorías); factores intrínsecos que condicionan la capacitación del cuidador (4 categorías y 2 subcategorías); y factores (6 categorías y 6 subcategorías). Conclusión: Es necesario un enfoque integral para preparar al cuidador, que abarque desde la formación del personal de enfermería en la identificación y evaluación de las necesidades del cuidador, hasta la conciliación y gestión del régimen terapéutico y la planificación del alta. También debe existir un compromiso por parte de las organizaciones sanitarias y de toda la comunidad para crear las condiciones necesarias para que el cuidador logre una transición saludable y segura.

Resumo Introdução: Nos contextos clínicos verifica-se que as práticas de enfermagem estão mais centradas na pessoa dependente do que no cuidador, o que pode estar relacionado com a complexidade do processo de capacitação do cuidador informal. Objetivo: Explorar e conhecer o fenómeno do evitamento dos enfermeiros à capacitação do cuidador informal, com identificação dos fatores subjacentes. Métodos: Estudo exploratório e descritivo, com abordagem qualitativa. Foram realizadas entrevistas semiestruturadas a 9 enfermeiros de um hospital central de Portugal e após transcrição, efetuada a análise de conteúdo segundo Bardin e apoio do NVivo10®. Cumpridos os pressupostos éticos e obtido parecer favorável da comissão de ética. Resultados: Emergiram três unidades temáticas com as respetivas categorias e subcategorias: reconhecimento do fenómeno (2 categorias); fatores intrínsecos que condicionam a capacitação do cuidador (4 categorias e 2 subcategorias); e fatores extrínsecos (6 categorias e 6 subcategorias). Conclusão: É necessária uma abordagem abrangente na preparação do cuidador informal, tendo por base a formação dos enfermeiros, a identificação e avaliação das suas necessidades, a implementação/gestão de cuidados e o planeamento da alta. Deve haver também um compromisso das organizações de saúde e de toda a comunidade na criação de condições para que se consiga uma transição saudável e segura.

Abstract Background ST-segment elevation myocardial infarction (STEMI) is one of the leading causes of fatal cardiovascular diseases, which have been the prime cause of mortality worldwide. Diagnosis in the early phase would benefit clinical intervention and prognosis, but the exploration of the biomarkers of STEMI is still lacking. Objectives In this study, we conducted a bioinformatics analysis to identify potential crucial biomarkers in the progress of STEMI. Methods We obtained GSE59867 for STEMI and stable coronary artery disease (SCAD) patients. Differentially expressed genes (DEGs) were screened with the threshold of |log2fold change| > 0.5 and p <0.05. Based on these genes, we conducted enrichment analysis to explore the potential relevance between genes and to screen hub genes. Subsequently, hub genes were analyzed to detect related miRNAs and DAVID to detect transcription factors for further analysis. Finally, GSE62646 was utilized to assess DEGs specificity, with genes demonstrating AUC results exceeding 75%, indicating their potential as candidate biomarkers. Results 133 DEGs between SCAD and STEMI were obtained. Then, the PPI network of DEGs was constructed using String and Cytoscape, and further analysis determined hub genes and 6 molecular complexes. Functional enrichment analysis of the DEGs suggests that pathways related to inflammation, metabolism, and immunity play a pivotal role in the progression from SCAD to STEMI. Besides, related-miRNAs were predicted, has-miR-124, has-miR-130a/b, and has-miR-301a/b regulated the expression of the largest number of genes. Meanwhile, Transcription factors analysis indicate that EVI1, AML1, GATA1, and PPARG are the most enriched gene. Finally, ROC curves demonstrate that MS4A3, KLRC4, KLRD1, AQP9, and CD14 exhibit both high sensitivity and specificity in predicting STEMI. Conclusions This study revealed that immunity, metabolism, and inflammation are involved in the development of STEMI derived from SCAD, and 6 genes, including MS4A3, KLRC4, KLRD1, AQP9, CD14, and CCR1, could be employed as candidate biomarkers to STEMI. STsegment ST segment (STEMI diseases worldwide prognosis lacking GSE GSE5986 (SCAD patients (DEGs log2fold logfold log fold change 05 0 5 0. 005 <0.05 Subsequently Finally GSE6264 75 75% 13 Then Cytoscape complexes metabolism Besides relatedmiRNAs predicted hasmiR124, hasmiR124 hasmiR has miR 124, 124 has-miR-124 hasmiR130a/b, hasmiR130ab hasmiRab 130a/b, 130a b has-miR-130a/b hasmiR301a/b hasmiR301ab 301a/b 301a Meanwhile EVI1 EVI AML1 AML GATA1 GATA gene MS4A3 MSA MS A KLRC4 KLRC KLRD1 KLRD AQP9 AQP CD CD1 CCR1 CCR GSE598 00 <0.0 GSE626 7 1 hasmiR12 12 has-miR-12 hasmiR130a hasmiR130a/b ab 130ab 130a/b hasmiR301a 301ab MS4A GSE59 <0. GSE62 hasmiR1 has-miR-1 hasmiRa GSE5 <0 GSE6 has-miR- < has-miR

Resumo Fundamento O infarto do miocárdio com elevação do segmento ST (IAMCSST) é uma das principais causas de doenças cardiovasculares fatais, que têm sido a principal causa de mortalidade em todo o mundo. O diagnóstico na fase inicial beneficiaria a intervenção clínica e o prognóstico, mas ainda falta a exploração dos biomarcadores do IAMCSST. Objetivos Neste estudo, conduzimos uma análise bioinformática para identificar potenciais biomarcadores cruciais no progresso do IAMCSST. Métodos Obtivemos GSE59867 para pacientes com IAMCSST e doença arterial coronariana estável (DACE). Genes diferencialmente expressos (GDEs) foram selecionados com o limiar de |log2fold change| > 0,5 e p < 0,05. Com base nesses genes, conduzimos análises de enriquecimento para explorar a relevância potencial entre genes e para rastrear genes centrais. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Posteriormente, os genes centrais foram analisados para detectar miRNAs relacionados e DAVID para detectar fatores de transcrição para análise posterior. Finalmente, o GSE62646 foi utilizado para avaliar a especificidade dos GDEs, com genes demonstrando resultados de AUC superiores a 75%, indicando seu potencial como candidatos a biomarcadores. Resultados 133 GDEs entre DACE e IAMCSST foram obtidos. Em seguida, a rede PPI de GDEs foi construída usando String e Cytoscape, e análises posteriores determinaram genes centrais e 6 complexos moleculares. A análise de enriquecimento funcional dos GDEs sugere que as vias relacionadas à inflamação, metabolismo e imunidade desempenham um papel fundamental na progressão de DACE para IAMCSST. Além disso, foram previstos miRNAs relacionados, has-miR-124, has-miR-130a/b e has-miR-301a/b regularam a expressão do maior número de genes. Enquanto isso, a análise dos fatores de transcrição indica que EVI1, AML1, GATA1 e PPARG são os genes mais enriquecidos. Finalmente, as curvas ROC demonstram que MS4A3, KLRC4, KLRD1, AQP9 e CD14 exibem alta sensibilidade e especificidade na previsão de IAMCSST. Conclusões Este estudo revelou que imunidade, metabolismo e inflamação estão envolvidos no desenvolvimento de IAMCSST derivado de DACE, e 6 genes, incluindo MS4A3, KLRC4, KLRD1, AQP9, CD14 e CCR1, poderiam ser empregados como candidatos a biomarcadores para IAMCSST. (IAMCSST fatais mundo prognóstico GSE GSE5986 DACE. . (DACE) (GDEs log2fold logfold log fold change 05 0 5 0, 005 0,05 Posteriormente posterior Finalmente GSE6264 75 75% 13 obtidos seguida Cytoscape moleculares disso hasmiR124, hasmiR124 hasmiR has miR 124, 124 has-miR-124 hasmiR130a/b hasmiR130ab hasmiRab 130a/b 130a b hasmiR301a/b hasmiR301ab 301a/b 301a isso EVI1 EVI AML1 AML GATA enriquecidos MS4A3 MSA MS KLRC4 KLRC KLRD1 KLRD AQP CD CD1 CCR1 CCR GSE598 (DACE 00 0,0 GSE626 7 1 hasmiR12 12 has-miR-12 hasmiR130a ab 130ab hasmiR301a 301ab MS4A GSE59 GSE62 hasmiR1 has-miR-1 hasmiRa GSE5 GSE6 has-miR- has-miR

ABSTRACT Purpose: The regulatory effect of microRNA on diseases has been confirmed. This study aimed to evaluate the expression of microRNA-210-3p in age-related cataracts and assess the effect of abnormal miR-210-3p expressions on H2O2-induced SAR01/04 cells. Methods: Reverse-transcription quantitative polymerase chain reaction method was performed to assess the levels of miR-210-3p in aqueous humor samples. Receiver operating characteristic analysis was employed to assess the discrimination ability of miR-210-3p between patients with age-related cataracts and healthy people, and Pearson correlation analysis was used to identify the correlation between miR-210-3p and oxidative stress indices such as superoxide dismutase, glutathione peroxidase, malonaldehyde. Cell counting kit-8 assay and Transwell assay were used to estimate the biological function of H2O2-induced age-related cataract cell model. The levels of oxidative stress indices such as superoxide dismutase, glutathione peroxidase, and malonaldehyde were measured to evaluate the degree of oxidative stress damage in the age-related cataract cell model. The relationship between miR-210-3p and its target gene was verified by luciferase reporter gene analysis. Results: The miR-210-3p expression was elevated in the aqueous humor of patients with age-related cataracts. A high miR-210-3p expression showed a high diagnostic value for age-related cataracts and was significantly associated with the level of oxidative stress markers in patients with age-related cataracts. The inhibition of miR-210-3p can reverse oxidative stress stimulation and adverse effects on H2O2-induced cell function. Conclusions: The results suggested that miR-210-3p could promote cell viability, cell migration, and oxidative stress by targeting autophagy-related gene 7 in in vitro age-related cataract cell model. Purpose confirmed microRNA2103p microRNAp 210 3p p agerelated age related miR2103p miRp miR H2O2induced HOinduced H2O2 induced H O SAR0104 SAR SAR01 04 SAR01/0 cells Methods Reversetranscription Reverse transcription samples people dismutase peroxidase kit8 kit 8 kit- model Results Conclusions viability migration autophagyrelated autophagy 21 HO H2O SAR010 SAR0 0 SAR01/ 2

RESUMO Objetivo: O efeito regulador do microRNA em doenças tem sido confirmado, e este artigo tentou avaliar a expressão do microRNA-210-3p na catarata relacionada à idade e avaliar o efeito da expressão anormal do miR-210-3p em células SAR01/04 induzidas por H2O2. Métodos: O método de transcrição reversa seguida de reação em cadeia da polimerase (RT-PCR) quantitativa foi realizado para avaliar os níveis de miR-210-3p em amostras de humor aquoso. Análise de características operacionais do receptor foi feita para avaliar a capacidade de discriminação do miR-210-3p entre pacientes com catarata relacionada à idade e pessoas saudáveis. A análise de correlação de Pearson identificou a correlação do miR-210-3p e índices de estresse oxidativo, como superóxido dismutase, glutationa peroxidase, malonaldeído. O ensaio de contagem de células kit-8 (cck-8) e o ensaio no sistema Transwell foram utilizados para estimar a função biológica do formato de células de catarata relacionada com a idade induzida por H2O2. Os níveis de índices de estresse oxidativo como superóxido dismutase, glutationa peroxidase e malonaldeído foram detectados para avaliar o grau de dano do estresse oxidativo em formato de células de catarata relacionada à idade. A relação entre miR-210-3p e seu gene alvo foi verificada por análise do gene repórter luciferase. Resultados: A expressão miR-210-3p foi elevada no humor aquoso de pacientes com catarata relacionada à idade. A expressão miR-210-3p altamente expressiva mostrou alto valor diagnóstico para catarata relacionada à idade e foi significativamente associado ao nível de marcadores de estresse oxidativo em pacientes com catarata relacionada à idade. A inibição de miR-210-3p pode reverter a estimulação do estresse oxidativo e os efeitos adversos da função celular induzida por H2O2. Conclusões: Esses dados sugeriram que a expressão miR-210-3p poderia promover a viabilidade celular, migração celular e estresse oxidativo ao direcionar genes ATG 7 relacionados à autofagia em modelo in vitro de células de catarata relacionadas à idade. Objetivo confirmado microRNA2103p microRNAp 210 3p p miR2103p miRp miR SAR0104 SAR SAR01 04 SAR01/0 H2O2 HO H Métodos RTPCR RT PCR (RT-PCR saudáveis dismutase kit8 kit 8 kit- cck8 cck (cck-8 luciferase Resultados Conclusões 21 SAR010 SAR0 0 SAR01/ H2O (cck- 2 (cck

Abstract Monkeypox (MPX), an orthopoxviral disease endemic in Africa, is now a public health emergency of international concern (PHEIC) as declared by the World Health Organization in July 2023. Although it is generally mild, the overall case fatality rate was reported to be 3%, and the basic reproduction number (R0) is > 1 in men who have sex with men (MSM, i.e., Portugal (1.4), the United Kingdom (1.6), and Spain (1.8)). However, R0 is < 1 in other settings. In concordance with the smallpox virus, it is also expected to increase the risk of adverse outcomes for both the mother and the fetus. The outcomes of the disease in an immunocompromised state of pregnancy are scary, showing high mortality and morbidity of both mother and fetus, with up to a 75% risk of fetal side effects and a 25% risk of severe maternal diseases. Therefore, it warrants timely diagnosis and intervention. The reverse transcription polymerase chain reaction (RT PCR) test is the standard approach to diagnosis. We summarized the recent findings of MPX on pregnancy, and the associated risk factors. We also give recommendations for active fetal surveillance, perinatal care, and good reporting to improve outcomes. The available vaccines have shown promise for primary disease prevention. MPX, , (MPX) Africa PHEIC (PHEIC 2023 mild 3 3% R (R0 MSM, MSM (MSM ie i e i.e. 1.4, 14 1.4 4 (1.4) 1.6, 16 1.6 6 (1.6) 1.8. 18 1.8 . 8 (1.8)) However settings virus fetus scary 75 25 diseases Therefore intervention RT PCR factors surveillance care prevention (MPX 202 (R i.e 1. (1.4 (1.6 (1.8) 7 2 20 (1. (1.8 (1 (

Abstract Background: To comprehensively analyze the clinical significance of Immune Checkpoint-Related Genes (ICRGs) in Pancreatic Adenocarcinoma (PAAD). Method: PAAD tissues and normal pancreatic tissues were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, and 283 ICRGs were integrated by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome datasets. Unsupervised clustering was used to obtain potential ICRGs-based PAAD subtypes. Wilcoxon test was performed to screen Differentially Expressed ICRGs (DEICRGs), while cox regression analyses were utilized to identify prognosis-related ICRGs and clinicopathological factors, and construct the corresponding models. The Tumor Immune Microenvironment (TIME) was evaluated. Moreover, the authors performed enrichment analysis, Gene Set Enrichment Analysis (GSEA), and transcription factor regulatory networks to realize underlying mechanisms. Results: Three ICRGs-based PAAD subtypes were identified, and they were associated with three ESTIMATE scores, a Tumor Microenvironment (TMB) score, 14 therapeutic immune checkpoints, and infiltration levels of seven immune cells. On top of that, the authors constructed two signatures based on DEICRGs to predict the Overall Survival (OS) (Area Under the ROC Curve [AUC: 0.741-0.778]) and Progression-Free Survival (PFS) (AUC: 0.746~0.831) of patients. Two nomograms were established by combining clinical variables and signatures. In addition, the authors found higher infiltration of naïve B cells and CD8+ T-cells in low-risk PAAD patients, and higher infiltration of suppressive immune cells and cancer-related signaling pathways in high-risk PAAD patients. Conclusion: The present study suggested that ICRGs were associated with TIME formation and prognosis of PAAD patients, which may serve as novel clinical biomarkers and therapeutic targets. Background CheckpointRelated Checkpoint Related (ICRGs PAAD. . (PAAD) Method TCGA (TCGA GenotypeTissue Genotype Tissue GTEx (GTEx databases 28 KEGG (KEGG datasets ICRGsbased DEICRGs, , (DEICRGs) prognosisrelated related factors models (TIME evaluated Moreover analysis GSEA, GSEA (GSEA) mechanisms Results identified scores TMB (TMB score 1 checkpoints OS (OS Area AUC [AUC 0.7410.778 07410778 0.741 0.778 0 741 778 0.741-0.778] ProgressionFree Progression Free PFS (PFS (AUC 0.746~0.831 07460831 746 831 patients addition CD8 CD Tcells T lowrisk low risk cancerrelated cancer highrisk high Conclusion targets (PAAD 2 (DEICRGs (GSEA 7410 0.7410.77 0741077 0741 0.74 0778 0.77 74 77 0.741-0.778 0.746~0.83 0746083 83 0.7410.7 074107 074 0.7 077 7 0.741-0.77 0.746~0.8 074608 8 0.7410. 07410 07 0. 0.741-0.7 0.746~0. 07460 0.7410 0.741-0. 0.746~0 0746 0.741-0 0.746~ 0.741- 0.746

This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 μg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 μg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 μg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment. mechanism (DePDLSCs confirmed viability (LPS 0100 0 100 (0-10 μgmL μg mL kit8 kit 8 kit- CCK8 CCK (CCK-8 assay realtime real time PCR, PCR , PCR) (ALP staining addition osteogenicinduced induced 1 highthroughput throughput data PI3KAKT PIKAKT PI3K AKT PI K activator 740YP. 740YP YP 740Y P. P Y LPSinduced treatment conclusion manner antiinflammatory anti inflammatory 010 (0-1 (CCK- KAKT PIK 01 (0- (CCK (0 (

Abstract We aimed to find new therapeutic targets related to Cancer Stem Cell alterations in recurrent patients from two TCGA cohorts: Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC). Raw sequencing data were downloaded from the TCGA database. Datasets containing RNA expression and Methylation files were directly downloaded from cBioportal. Variant Call Format files (VCFs) were downloaded from the GDC portal. Gene enrichment analysis was performed using GSEA (Gene Set Enrichment Analysis) software. Transcriptome profiling, coexpression co-occurrence, networks, and survival analyses were performed using cBioportal tools, while mutational analysis of patients was processed using UNIX scripts. We found that cancer stem cell transcription factors were highly expressed in Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC) cohorts, compared to the other 29 cancer cohorts in TCGA. Patients presented a poorer diagnosis when the genes (POU5F1, NANOG, SOX2, SALL4, ABCB1, ABCC1, and ABCG2) were altered. In UCEC cohorts, recurrent patients showed the ABCG2 potentially phosphorylated by the PIM1 kinase. In the TGCT cohort, genes ABCB1 and ABCG2 only appeared in the phosphonetwork in recurrent patients potentially phosphorylated by the same kinase, PIM1, but also by PRKACA. Our data indicate that PRKACA and PIM1 may modulate POU5F1 phosphorylation. (TGCT UCEC. . database VCFs (VCFs portal Analysis software profiling cooccurrence, cooccurrence co occurrence, occurrence co-occurrence networks tools scripts (UCEC 2 POU5F1, POUF POU F (POU5F1 NANOG SOX2 SOX SALL4 SALL ABCB ABCC1 ABCC ABCG altered PIM kinase cohort POU5F phosphorylation (POU5F

BACKGROUND Human immunodeficiency virus (HIV)-1 infection can activate the expression of human endogenous retroviruses (HERVs), particularly HERV-K (HML-2). HIV controllers (HICs) are rare people living with HIV (PLWHs) who naturally control HIV-1 replication and overexpress some cellular restriction factors that negatively regulate the LTR-driven transcription of HIV-1 proviruses. OBJECTIVES To understand the ability of HICs to control the expression of endogenous retroviruses. METHODS We measured endogenous retrovirus type K6 (ERVK-6) RNA expression in peripheral blood mononuclear cells (PBMCs) of HICs (n = 23), antiretroviral (ART)-suppressed subjects (n = 8), and HIV-1-negative (NEG) individuals (n = 10) and correlated the transcript expression of ERVK-6 with multiple HIV-1 cellular restriction factors. FINDINGS Our study revealed that ERVK-6 RNA expression in PBMCs from HICs was significantly downregulated compared with that in both the ART and NEG control groups. Moreover, we detected that ERVK-6 RNA levels in PBMCs across all groups were negatively correlated with the expression levels of p21 and MCPIP1, two cellular restriction factors that limit the activation of macrophages and T cells by downregulating the activity of NF-kB. MAIN CONCLUSIONS These findings support the hypothesis that HICs activate innate antiviral mechanisms that may simultaneously downregulate the transcription of both exogenous (HIV-1) and endogenous (ERVK-6) retroviruses. Future studies with larger cohorts should be performed to confirm this hypothesis and to explore the role of p21 and MCPIP1 in regulating HERV-K expression in physiological and pathological conditions. HIV1 1 (HIV)- HERVs, HERVs , (HERVs) HERVK HERV K HML2. HML2 HML 2 . (HML-2) (HICs PLWHs (PLWHs HIV- LTRdriven LTR driven proviruses ERVK6 ERVK 6 (ERVK-6 (PBMCs n 23, 23 23) ARTsuppressed suppressed 8, 8 8) HIV1negative HIVnegative negative (NEG 10 ERVK- Moreover p p2 MCPIP NFkB. NFkB NF kB. kB NF-kB (HIV-1 conditions (HIV) (HERVs (HML-2 (ERVK- (HIV- (HIV (HML- (ERVK (HML

ABSTRACT Craniofacial microsomia (CFM) is a complex congenital condition that affects approximately one in 5,000 live births. It was initially described by Carl Ferdinand Von Arlt in 1881, and over time, various synonymous terms have been used to refer to this condition. The pathophysiology of CFM revolves around the disruption of embryonic craniofacial development, primarily stemming from abnormalities in the first and second pharyngeal arches. Both genetic and non-genetic factors play a role in impacting the development of the ear and jaw. These factors encompass a range of elements, including: variants of transcription factors responsible for neural crest cell migration and patterning, chromatin modifiers, growth factors and their receptors, DNA pre-replication complexes, ribosome assembly, and the spliceosome. Although there is currently a better understanding of the pathophysiology of this entity, it is still necessary to continue with more specific research on the related etiological factors. The aim of this review is to compile the most pertinent genetic factors associated with craniofacial microsomia as reported in the last decade.

RESUMEN La microsomía craneofacial (CFM) es una malformación congénita compleja que afecta aproximadamente a uno de cada 5.000 nacidos vivos. En 1881, la CFM fue descrita por primera vez por Carl Ferdinand Von Arlt. A lo largo de la historia, han surgido términos sinónimos que han descrito esta malformación dentro del gran espectro clínico que abarca. El eje central de la fisiopatología es la alteración del desarrollo embrionario de las estructuras craneofaciales derivadas del primer y segundo arco faríngeos. El desarrollo del oído y la mandíbula se ve afectado por factores no genéticos y genéticos, los cuales son: variantes de los factores de transcripción implicados en la migración y el patrón de las células de la cresta neural, modificadores de la cromatina, factores de crecimiento y sus receptores, complejos de prereplicación de ADN, ensamblaje de ribosomas y el spliceosoma. Aunque actualmente existe una mejor comprensión de la fisiopatología de esta entidad, aún es necesario continuar con investigaciones más específicas sobre los factores etiológicos relacionados. El objetivo de esta revisión es realizar un recuento de los factores genéticos más relevantes relacionados con la microsomía craneofacial reportados en los últimos 10 años.

Abstract Background: CTHRC1 is highly expressed in various cancers. Objectives: The aim of the study was to study the role of CTHRC1 played in lung adenocarcinoma (LUAD) development and its underlying biological functions. Methods: Enriched pathways and upstream transcription factors of CTHRC1 were explored by bioinformatics analysis. Dual-luciferase assay and Chromatin immunoprecipitation assay were used to verify the binding relationship between CTHRC1 and HOXB9. CCK-8 was utilized to detect cell viability. Expression levels of CTHRC1, HOXB9, and angiogenesis-related genes were assessed by quantitative real time-polymerase chain reaction. Angiogenesis assay was used to detect angiogenesis ability. Quantitative analysis of metabolites were used to detect the accumulation of neutral lipids, the levels of free fatty acids (FAs), and glycerol. Western blot was conducted to measure expression of metabolic enzymes of FA. Results: CTHRC1 was enriched in FA metabolic pathway, which was positively correlated and bound with HOXB9. CTHRC1 and HOXB9 expression was remarkably up-regulated in LUAD cells. Overexpression of CTHRC1 promoted FA metabolic pathway and angiogenesis, and FA inhibitor Orlistat restored it to NC group level. Meanwhile, CTHRC1 affected LUAD angiogenesis by activating HOXB9 to regulate FA metabolism. Conclusions: This study found that activation of CTHRC1 by HOXB9 induces angiogenesis by mediating FA metabolism. CTHRC1 may be a potential target for LUAD diagnosis.

Abstract Head and Neck Cancer (HNC) is a heterogeneous group of cancers, which includes cancers arising in the oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx. Epidemiological studies have revealed that several factors such as tobacco and alcohol use, exposure to environmental pollutants, viral infection, and genetic factors are risk factors for developing HNC. The squamous cell carcinoma of oral tongue (SCCOT), which is significantly more aggressive than the other forms of oral squamous cell carcinoma, presents a propensity for rapid local invasion and spread, and a high recurrence rate. Dysregulation in the epigenetic machinery of cancer cells might help uncover the mechanisms of SCOOT tumorigenesis. Here, we used DNA methylation changes to identify cancer-specific enhancers that were enriched for specific transcription factor binding sites (TFBS), and potential master regulator transcription factors (MRTF) associated with SCCOT. We identified the activation of MRTFs associated with increased invasiveness, metastasis, epithelial-to-mesenchymal transition, poor prognosis, and stemness. On the other hand, we found the downregulation of MRTFs associated with tumor suppression. The identified MRTFs should be further investigated to clarify their role in oral cancer tumorigenesis and for their potential use as biological markers. HNC (HNC cavity nasopharynx oropharynx hypopharynx larynx pollutants infection SCCOT, SCCOT , (SCCOT) spread rate Here cancerspecific TFBS, TFBS (TFBS) MRTF (MRTF invasiveness metastasis epithelialtomesenchymal epithelial mesenchymal transition prognosis stemness hand suppression markers (SCCOT (TFBS

Abstract Hepatocellular carcinoma (HCC) is the most common type of liver malignancy with high incidence and poor prognosis. Transmembrane protein 147 (TMEM147) has been implicated in the development of colon cancer. However, the role of TMEM147 in HCC remains unclear. In this study, data of 371 HCC tissues, 50 adjacent nontumor tissues, and 110 normal liver tissues were retrieved from the TCGA and GTEx databases. TMEM147 expression was found to be increased in HCC tissues. High expression of TMEM147 was related to poor prognosis, and TMEM147 was confirmed to be an independent prognostic factor for HCC patients. A receiver operating characteristics (ROC) analysis was performed and showed that the diagnostic efficacy of TMEM147 was significantly higher than that of AFP (0.908 versus 0.746, p < 0.001). Furthermore, TMEM147 promoted tumor immune infiltration, and macrophages were the immune cells that predominantly expressed TMEM147 in HCC. Further analysis revealed that TMEM147 mainly impacted the ribosome pathway, and CTCF, MLLT1, TGIF2, ZNF146, and ZNF580 were predicted to be the upstream transcription factors for TMEM147 in HCC. These results suggest that TMEM147 serves as a promising biomarker for diagnosis and prognosis and may potentially become a therapeutic target for HCC. (HCC 14 TMEM (TMEM147 cancer However TMEM14 unclear study 37 5 11 databases patients ROC (ROC 0.908 0908 0 908 (0.90 0746 746 0.746 0.001. 0001 0.001 . 001 0.001) Furthermore infiltration pathway CTCF MLLT1 MLLT TGIF2 TGIF ZNF146 ZNF ZNF58 1 (TMEM14 TMEM1 3 0.90 090 90 (0.9 074 74 0.74 000 0.00 00 ZNF14 ZNF5 (TMEM1 0.9 09 9 (0. 07 7 0.7 0.0 ZNF1 (TMEM 0. (0 (

Resumo Fatores de transcrição (FT) são uma ampla classe de genes em plantas e podem regular a expressão de outros genes em resposta a vários estresses ambientais (estresses bióticos e abióticos). No presente estudo, a atividade do fator de transcrição na cana-de-açúcar foi examinada durante o estresse pelo frio. Inicialmente, as leituras de transcrição de RNA de duas cultivares de cana-de-açúcar (ROC22 e GT08-1108) sob estresse frio foram baixadas do banco de dados SRA NCBI. As leituras foram alinhadas em um genoma de referência e as análises de expressão diferencial foram realizadas com o pacote R / Bioconductor edgeR. Com base em nossas análises no cultivar ROC22, 963 genes TF foram significativamente regulados positivamente sob estresse pelo frio entre um total de 5.649 genes regulados positivamente, enquanto 293 genes TF foram regulados negativamente entre um total de 3.289 genes regulados negativamente. No cultivar GT08-1108, 974 genes TF foram identificados entre 5.649 genes regulados positivamente e 283 genes TF foram encontrados entre 3.289 genes regulados negativamente. Os fatores de transcrição, em sua maioria, foram anotados com categorias GO relacionadas à ligação de proteína, ligação de fator de transcrição, ligação específica de sequência de DNA, complexo de fator de transcrição, atividade de fator de transcrição em RNA polimerase II, atividade de fator de transcrição de ligação de ácido nucleico, atividade de corepressor de transcrição, sequência específica da região reguladora, atividade do fator de transcrição da RNA polimerase II, atividade do cofator do fator de transcrição, atividade do fator de transcrição do promotor do plastídio, atividade do fator de transcrição do promotor da RNA polimerase I, polimerase II e RNA polimerase III. As descobertas dos resultados acima ajudarão a identificar fatores de transcrição expressos diferencialmente durante o estresse pelo frio. Ele também fornece uma análise abrangente da regulação da atividade de transcrição de muitos genes. Portanto, este estudo fornece base molecular para melhorar a tolerância ao frio em cana-de-açúcar e outras gramíneas economicamente importantes.

Abstract Transcription factors (TF) are a wide class of genes in plants, and these can regulate the expression of other genes in response to various environmental stresses (biotic and abiotic). In the current study, transcription factor activity in sugarcane was examined during cold stress. Initially, RNA transcript reads of two sugarcane cultivars (ROC22 and GT08-1108) under cold stress were downloaded from SRA NCBI database. The reads were aligned into a reference genome and the differential expression analyses were performed with the R/Bioconductor edgeR package. Based on our analyses in the ROC22 cultivar, 963 TF genes were significantly upregulated under cold stress among a total of 5649 upregulated genes, while 293 TF genes were downregulated among a total of 3,289 downregulated genes. In the GT08-1108 cultivar, 974 TF genes were identified among 5,649 upregulated genes and 283 TF genes were found among 3,289 downregulated genes. Most transcription factors were annotated with GO categories related to protein binding, transcription factor binding, DNA-sequence-specific binding, transcription factor complex, transcription factor activity in RNA polymerase II, the activity of nucleic acid binding transcription factor, transcription corepressor activity, sequence-specific regulatory region, the activity of transcription factor of RNA polymerase II, transcription factor cofactor activity, transcription factor activity from plastid promoter, transcription factor activity from RNA polymerase I promoter, polymerase II and RNA polymerase III. The findings of above results will help to identify differentially expressed transcription factors during cold stress. It also provides a comprehensive analysis of the regulation of the transcription activity of many genes. Therefore, this study provides the molecular basis for improving cold tolerance in sugarcane and other economically important grasses.

Resumo O crescimento populacional está aumentando rapidamente em todo o mundo, e para combater suas consequências precisamos produzir mais alimentos para suprir a demanda do aumento populacional. O mundo está enfrentando o aquecimento global devido à urbanização e industrialização e, nesse caso, plantas expostas continuamente a estresses abióticos, que é uma das principais causas do martelamento das safras todos os anos. Estresses abióticos consistem em seca, sal, calor, frio, oxidação e toxicidade de metais que prejudicam o rendimento da colheita continuamente. A seca e o estresse salino são afetados de maneira diversa pela planta e são a principal causa de redução da produtividade das culturas. As plantas respondem a vários estímulos sob condições de estresse abiótico ou biótico e expressam certos genes estruturais ou regulatórios que mantêm a integridade da planta. Os genes reguladores são principalmente os fatores de transcrição que exercem sua atividade ligando-se a certos elementos cis do DNA e, consequentemente, são regulados para cima ou para baixo para a expressão alvo. Esses fatores de transcrição são conhecidos como reguladores mestres porque sua única transcrição regula mais de um gene; nesse contexto, a palavra regulon é mais fascinante no âmbito dos fatores de transcrição. Progresso foi feito para entender melhor sobre o efeito dos regulons (AREB / ABF, DREB, MYB e NAC) sob estresses abióticos e uma série de regulons relatados como responsivos ao estresse e usados como uma melhor ferramenta transgênica de Arabidopsis e Rice.

Abstract Population growth is increasing rapidly around the world, in these consequences we need to produce more foods to full fill the demand of increased population. The world is facing global warming due to urbanizations and industrialization and in this concerns plants exposed continuously to abiotic stresses which is a major cause of crop hammering every year. Abiotic stresses consist of Drought, Salt, Heat, Cold, Oxidative and Metal toxicity which damage the crop yield continuously. Drought and salinity stress severally affected in similar manner to plant and the leading cause of reduction in crop yield. Plants respond to various stimuli under abiotic or biotic stress condition and express certain genes either structural or regulatory genes which maintain the plant integrity. The regulatory genes primarily the transcription factors that exert their activity by binding to certain cis DNA elements and consequently either up regulated or down regulate to target expression. These transcription factors are known as masters regulators because its single transcript regulate more than one gene, in this context the regulon word is fascinating more in compass of transcription factors. Progress has been made to better understand about effect of regulons (AREB/ABF, DREB, MYB, and NAC) under abiotic stresses and a number of regulons reported for stress responsive and used as a better transgenic tool of Arabidopsis and Rice.