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 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 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 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 (

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 Terpenoids are one of the secondary metabolites of plants and are the most widely distributed in nature with a diverse skeleton and significant biological activity, among which sesquiterpenoids are the most abundant. Sesquiterpenoids and triterpenoids are mainly synthesized by the mevalonate pathway, and the processes involve a variety of key enzymes and are regulated by transcription factors. They play important roles in plant growth and development, environmental adaptation, and resistance to pests and diseases. It is important to understand the gene functions of key enzymes to increase the production of sesquiterpenoids and triterpenoids to meet the market demand and to study the mevalonate biosynthesis pathway in depth. In this paper, the progress of gene cloning and transcription factor regulation of sesquiterpenes, triterpenoids and key enzymes of mevalonate synthesis pathway will be briefly reviewed. activity abundant factors development adaptation diseases depth paper sesquiterpenes reviewed

Abstract Objective: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. Method: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People’s Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. Result: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3′UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122. Objective miRNA122 miRNA 122 miRNA-12 diagnosis severity (ACI Method 6 Peoples People s 1 2019 selected collected age sex history CReactive C Reactive CRP , [CRP] Interleukin6 Interleukin Interleukin- IL6, IL6 IL [IL-6] PCT, PCT [PCT] GelatinaseAssociated Gelatinase Associated NGAL. . [NGAL]) (NIHSS shortterm short term [mRS] recorded reversetranscription reverse transcription RealTime Real Time RTQPCR, RTQPCR RT QPCR (RT-QPCR) analyzed people (HUVECs apoptosisrelated related Bcl2, Bcl2 Bcl 2, 2 Caspase3, Caspase3 Caspase 3, angiogenesisrelated angiogenesis Hes1 Hes Notch1 Notch VEGF (VEGF) CCNG blot miRNA122, 122, dualluciferase Result 0929 0 929 0.929 95 08750983 875 983 0.875‒0.983 cutoff cut off 1397 397 1.397 6, IL-6 0.05 005 05 CPR h 72h proapoptotic pro apoptotic caspase3 caspase caspase- antiapoptotic anti Bcl- Caspase- 3UTR UTR miRNA122. 122. miRNA12 12 miRNA-1 201 [CRP [IL-6 [PCT [NGAL] [mRS (RT-QPCR (VEGF 092 92 0.92 9 0875098 87 98 0.875‒0.98 139 39 1.39 IL- 0.0 00 miRNA1 miRNA- 20 [IL- [NGAL 09 0.9 087509 8 0.875‒0.9 13 1.3 0. [IL 08750 0.875‒0. 1. 0875 0.875‒0 087 0.875‒ 08 0.875 0.87 0.8

Abstract NAC transcription factors are plant-specific proteins involved in many processes during the plant life cycle and responses to biotic and abiotic stresses. Previous studies have shown that stress-induced OsNAC5 from rice (Oryza sativa L.) is up-regulated by senescence and might be involved in control of iron (Fe) and zinc (Zn) concentrations in rice seeds. Aiming a better understanding of the role of OsNAC5 in rice plants, we investigated a mutant line carrying a T-DNA insertion in the promoter of OsNAC5, which resulted in enhanced expression of the transcription factor. Plants with OsNAC5 enhanced expression were shorter at the seedling stage and had reduced yield at maturity. In addition, we evaluated the expression level of OsNAC6, which is co-expressed with OsNAC5, and found that enhanced expression of OsNAC5 leads to increased expression of OsNAC6, suggesting that OsNAC5 might regulate OsNAC6 expression. Ionomic analysis of leaves and seeds from the OsNAC5 enhanced expression line revealed lower Fe and Zn concentrations in leaves and higher Fe concentrations in seeds than in WT plants, further suggesting that OsNAC5 may be involved in regulating the ionome in rice plants. Our work shows that fine-tuning of transcription factors is key when aiming at crop improvement. plantspecific specific stresses stressinduced stress induced OsNAC Oryza L. L upregulated up regulated (Fe (Zn plants TDNA T DNA factor maturity addition coexpressed co expressed finetuning fine tuning improvement

Abstract Objectives The mid-palatal expansion technique is commonly used to correct maxillary constriction in dental clinics. However, there is a tendency for it to relapse, and the key molecules responsible for modulating bone formation remain elusive. Thus, this study aimed to investigate whether signal transducer and activator of transcription 3 (STAT3) activation contributes to osteoblast-mediated bone formation during palatal expansion and relapse. Methodology In total, 30 male Wistar rats were randomly allocated into Ctrl (control), E (expansion only), and E+Stattic (expansion plus STAT3-inhibitor, Stattic) groups. Micro-computed tomography, micromorphology staining, and immunohistochemistry of the mid-palatal suture were performed on days 7 and 14. In vitro cyclic tensile stress (10% magnitude, 0.5 Hz frequency, and 24 h duration) was applied to rat primary osteoblasts and Stattic was administered for STAT3 inhibition. The role of STAT3 in mechanical loading-induced osteoblasts was confirmed by alkaline phosphatase (ALP), alizarin red staining, and western blots. Results The E group showed greater arch width than the E+Stattic group after expansion. The differences between the two groups remained significant after relapse. We found active bone formation in the E group with increased expression of ALP, COL-I, and Runx2, although the expression of osteogenesis-related factors was downregulated in the E+stattic group. After STAT3 inhibition, expansive force-induced bone resorption was attenuated, as TRAP staining demonstrated. Furthermore, the administration of Stattic in vitro partially suppressed tensile stress-enhanced osteogenic markers in osteoblasts. Conclusions STAT3 inactivation reduced osteoblast-mediated bone formation during palatal expansion and post-expansion relapse, thus it may be a potential therapeutic target to treat force-induced bone formation. midpalatal mid clinics However relapse elusive Thus STAT (STAT3 osteoblastmediated osteoblast mediated total control, control , (control) only, only only) EStattic STAT3inhibitor, STAT3inhibitor STATinhibitor inhibitor, inhibitor STAT3-inhibitor Microcomputed Micro computed tomography 14 10% 10 (10 magnitude 05 0 5 0. frequency 2 duration inhibition loadinginduced loading induced ALP (ALP) blots COLI, COLI COL I, I COL-I Runx2 Runx osteogenesisrelated osteogenesis related Estattic stattic forceinduced force attenuated demonstrated Furthermore stressenhanced enhanced postexpansion post (STAT (control 1 (1 (ALP (

Abstract Objectives: The incidence of cerebellar Glioblastoma Multiforme (cGBM) is rare. Database like TCGA have not distinguish cGBM from GBM, our knowledge on cGBM gene expression characteristics is limited. The expression status of Oligodendrocyte Lineage Transcription factor 2 (OLIG2) and its clinical significance in cGBM is still unclear. Methods: The clinical data and tissue specimens of 73 cGBM patients were retrospectively studied. The association between OLIG2 expression level and the demographic characteristics of cGBM patients was identified by the Chi-Square test. The survival curves were drawn by Kaplan-Meier analysis. The independent prognostic factors was calculated according to Cox regression analysis. Results: The OLIG2 high expression was observed in about 57.5% (42/73) of the cGBM patients. Patients with high OLIG2 expression levels had a higher alive ratio at the end of follow-up (alive ratio: 70.6% vs. 29.4%, p = 0.04). The median survival time was 21 months and 13 months for high and low expression of OLIG2 (p < 0 .05). Univariate analysis and Multivariate analysis indicated that EOR (HR = 3.89, 95% CI 1.23−12.26, p = 0.02), low OLIG2 expression (HR = 5.26, 95% CI 1.13−24.59, p = 0.04), and without adjuvant therapy (HR = 4.95, 95% CI 1.22−20.00, p = 0.03) were independent risk factors for the OS of cGBM patients. Conclusion: High expression level of OLIG2 could be used as an independent favorable prognosis indicator in cGBM patients and be recognized as a characteristic biomarker of cGBM. Objectives (cGBM rare GBM limited OLIG (OLIG2 unclear Methods 7 studied ChiSquare Chi Square test KaplanMeier Kaplan Meier Results 575 57 5 57.5 42/73 4273 42 (42/73 followup follow up 706 70 6 70.6 vs 294 29 4 29.4% 0.04. 004 0.04 . 04 0.04) 1 .05. 05 .05 .05) HR 389 3 89 3.89 95 1231226 23 12 26 1.23−12.26 0.02, 002 0.02 , 02 0.02) 526 5.26 1132459 24 59 1.13−24.59 0.04, 495 4.95 1222000 22 20 00 1.22−20.00 0.03 003 03 Conclusion (OLIG 57. 42/7 427 (42/7 70. 29.4 0.0 .0 38 8 3.8 9 123122 1.23−12.2 52 5.2 113245 1.13−24.5 49 4.9 122200 1.22−20.0 42/ (42/ 29. 0. 3. 12312 1.23−12. 5. 11324 1.13−24. 4. 12220 1.22−20. (42 1231 1.23−12 1132 1.13−24 1222 1.22−20 (4 123 1.23−1 113 1.13−2 122 1.22−2 ( 1.23− 11 1.13− 1.22− 1.23 1.13 1.22 1.2 1.1 1.