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1.
Genome Res ; 34(7): 1036-1051, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39134412

RESUMEN

Cell identity annotation for single-cell transcriptome data is a crucial process for constructing cell atlases, unraveling pathogenesis, and inspiring therapeutic approaches. Currently, the efficacy of existing methodologies is contingent upon specific data sets. Nevertheless, such data are often sourced from various batches, sequencing technologies, tissues, and even species. Notably, the gene regulatory relationship remains unaffected by the aforementioned factors, highlighting the extensive gene interactions within organisms. Therefore, we propose scHGR, an automated annotation tool designed to leverage gene regulatory relationships in constructing gene-mediated cell communication graphs for single-cell transcriptome data. This strategy helps reduce noise from diverse data sources while establishing distant cellular connections, yielding valuable biological insights. Experiments involving 22 scenarios demonstrate that scHGR precisely and consistently annotates cell identities, benchmarked against state-of-the-art methods. Crucially, scHGR uncovers novel subtypes within peripheral blood mononuclear cells, specifically from CD4+ T cells and cytotoxic T cells. Furthermore, by characterizing a cell atlas comprising 56 cell types for COVID-19 patients, scHGR identifies vital factors like IL1 and calcium ions, offering insights for targeted therapeutic interventions.


Asunto(s)
COVID-19 , Redes Reguladoras de Genes , RNA-Seq , Análisis de Expresión Génica de una Sola Célula , Humanos , Linfocitos T CD4-Positivos/metabolismo , COVID-19/genética , COVID-19/virología , Leucocitos Mononucleares/metabolismo , Anotación de Secuencia Molecular , RNA-Seq/métodos , SARS-CoV-2/genética , Transcriptoma
2.
Proc Natl Acad Sci U S A ; 121(37): e2411293121, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39236235

RESUMEN

The presaccadic preview of a peripheral target enhances the efficiency of its postsaccadic processing, termed the extrafoveal preview effect. Peripheral visual performance-and thus the quality of the preview-varies around the visual field, even at isoeccentric locations: It is better along the horizontal than vertical meridian and along the lower than upper vertical meridian. To investigate whether these polar angle asymmetries influence the preview effect, we asked human participants to preview four tilted gratings at the cardinals, until a central cue indicated which one to saccade to. During the saccade, the target orientation either remained or slightly changed (valid/invalid preview). After saccade landing, participants discriminated the orientation of the (briefly presented) second grating. Stimulus contrast was titrated with adaptive staircases to assess visual performance. Expectedly, valid previews increased participants' postsaccadic contrast sensitivity. This preview benefit, however, was inversely related to polar angle perceptual asymmetries; largest at the upper, and smallest at the horizontal meridian. This finding reveals that the visual system compensates for peripheral asymmetries when integrating information across saccades, by selectively assigning higher weights to the less-well perceived preview information. Our study supports the recent line of evidence showing that perceptual dynamics around saccades vary with eye movement direction.


Asunto(s)
Movimientos Sacádicos , Campos Visuales , Percepción Visual , Humanos , Movimientos Sacádicos/fisiología , Adulto , Percepción Visual/fisiología , Femenino , Masculino , Campos Visuales/fisiología , Estimulación Luminosa/métodos , Adulto Joven , Sensibilidad de Contraste/fisiología
3.
Brief Bioinform ; 24(6)2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37930024

RESUMEN

Development of robust and effective strategies for synthesizing new compounds, drug targeting and constructing GEnome-scale Metabolic models (GEMs) requires a deep understanding of the underlying biological processes. A critical step in achieving this goal is accurately identifying the categories of pathways in which a compound participated. However, current machine learning-based methods often overlook the multifaceted nature of compounds, resulting in inaccurate pathway predictions. Therefore, we present a novel framework on Multi-View Multi-Label Learning for Metabolic Pathway Inference, hereby named MVML-MPI. First, MVML-MPI learns the distinct compound representations in parallel with corresponding compound encoders to fully extract features. Subsequently, we propose an attention-based mechanism that offers a fusion module to complement these multi-view representations. As a result, MVML-MPI accurately represents and effectively captures the complex relationship between compounds and metabolic pathways and distinguishes itself from current machine learning-based methods. In experiments conducted on the Kyoto Encyclopedia of Genes and Genomes pathways dataset, MVML-MPI outperformed state-of-the-art methods, demonstrating the superiority of MVML-MPI and its potential to utilize the field of metabolic pathway design, which can aid in optimizing drug-like compounds and facilitating the development of GEMs. The code and data underlying this article are freely available at https://github.com/guofei-tju/MVML-MPI. Contact:  jtang@cse.sc.edu, guofei@csu.edu.com or wuxi_dyj@csj.uestc.edu.cn.


Asunto(s)
Aprendizaje Automático , Redes y Vías Metabólicas
4.
Bioinformatics ; 40(9)2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39342389

RESUMEN

MOTIVATION: Retrosynthesis identifies available precursor molecules for various and novel compounds. With the advancements and practicality of language models, Transformer-based models have increasingly been used to automate this process. However, many existing methods struggle to efficiently capture reaction transformation information, limiting the accuracy and applicability of their predictions. RESULTS: We introduce RetroCaptioner, an advanced end-to-end, Transformer-based framework featuring a Contrastive Reaction Center Captioner. This captioner guides the training of dual-view attention models using a contrastive learning approach. It leverages learned molecular graph representations to capture chemically plausible constraints within a single-step learning process. We integrate the single-encoder, dual-encoder, and encoder-decoder paradigms to effectively fuse information from the sequence and graph representations of molecules. This involves modifying the Transformer encoder into a uni-view sequence encoder and a dual-view module. Furthermore, we enhance the captioning of atomic correspondence between SMILES and graphs. Our proposed method, RetroCaptioner, achieved outstanding performance with 67.2% in top-1 and 93.4% in top-10 exact matched accuracy on the USPTO-50k dataset, alongside an exceptional SMILES validity score of 99.4%. In addition, RetroCaptioner has demonstrated its reliability in generating synthetic routes for the drug protokylol. AVAILABILITY AND IMPLEMENTATION: The code and data are available at https://github.com/guofei-tju/RetroCaptioner.


Asunto(s)
Programas Informáticos , Algoritmos , Aprendizaje Automático
5.
Circ Res ; 133(3): 271-287, 2023 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-37409456

RESUMEN

BACKGROUND: Cardiomyopathy is characterized by the pathological accumulation of resident cardiac fibroblasts that deposit ECM (extracellular matrix) and generate a fibrotic scar. However, the mechanisms that control the timing and extent of cardiac fibroblast proliferation and ECM production are not known, hampering the development of antifibrotic strategies to prevent heart failure. METHODS: We used the Tcf21 (transcription factor 21)MerCreMer mouse line for fibroblast-specific lineage tracing and p53 (tumor protein p53) gene deletion. We characterized cardiac physiology and used single-cell RNA-sequencing and in vitro studies to investigate the p53-dependent mechanisms regulating cardiac fibroblast cell cycle and fibrosis in left ventricular pressure overload induced by transaortic constriction. RESULTS: Cardiac fibroblast proliferation occurs primarily between days 7 and 14 following transaortic constriction in mice, correlating with alterations in p53-dependent gene expression. p53 deletion in fibroblasts led to a striking accumulation of Tcf21-lineage cardiac fibroblasts within the normal proliferative window and precipitated a robust fibrotic response to left ventricular pressure overload. However, excessive interstitial and perivascular fibrosis does not develop until after cardiac fibroblasts exit the cell cycle. Single-cell RNA sequencing revealed p53 null fibroblasts unexpectedly express lower levels of genes encoding important ECM proteins while they exhibit an inappropriately proliferative phenotype. in vitro studies establish a role for p53 in suppressing the proliferative fibroblast phenotype, which facilitates the expression and secretion of ECM proteins. Importantly, Cdkn2a (cyclin-dependent kinase inhibitor 2a) expression and the p16Ink4a-retinoblastoma cell cycle control pathway is induced in p53 null cardiac fibroblasts, which may eventually contribute to cell cycle exit and fulminant scar formation. CONCLUSIONS: This study reveals a mechanism regulating cardiac fibroblast accumulation and ECM secretion, orchestrated in part by p53-dependent cell cycle control that governs the timing and extent of fibrosis in left ventricular pressure overload.


Asunto(s)
Cicatriz , Ventrículos Cardíacos , Ratones , Animales , Ventrículos Cardíacos/patología , Cicatriz/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Fibrosis , Fibroblastos/metabolismo , Proliferación Celular , Miocardio/metabolismo
6.
PLoS Comput Biol ; 20(6): e1012229, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38924082

RESUMEN

De novo drug design is crucial in advancing drug discovery, which aims to generate new drugs with specific pharmacological properties. Recently, deep generative models have achieved inspiring progress in generating drug-like compounds. However, the models prioritize a single target drug generation for pharmacological intervention, neglecting the complicated inherent mechanisms of diseases, and influenced by multiple factors. Consequently, developing novel multi-target drugs that simultaneously target specific targets can enhance anti-tumor efficacy and address issues related to resistance mechanisms. To address this issue and inspired by Generative Pre-trained Transformers (GPT) models, we propose an upgraded GPT model with generative adversarial imitation learning for multi-target molecular generation called MTMol-GPT. The multi-target molecular generator employs a dual discriminator model using the Inverse Reinforcement Learning (IRL) method for a concurrently multi-target molecular generation. Extensive results show that MTMol-GPT generates various valid, novel, and effective multi-target molecules for various complex diseases, demonstrating robustness and generalization capability. In addition, molecular docking and pharmacophore mapping experiments demonstrate the drug-likeness properties and effectiveness of generated molecules potentially improve neuropsychiatric interventions. Furthermore, our model's generalizability is exemplified by a case study focusing on the multi-targeted drug design for breast cancer. As a broadly applicable solution for multiple targets, MTMol-GPT provides new insight into future directions to enhance potential complex disease therapeutics by generating high-quality multi-target molecules in drug discovery.


Asunto(s)
Biología Computacional , Descubrimiento de Drogas , Simulación del Acoplamiento Molecular , Humanos , Biología Computacional/métodos , Descubrimiento de Drogas/métodos , Diseño de Fármacos , Antineoplásicos/química , Antineoplásicos/farmacología , Algoritmos , Aprendizaje Profundo , Aprendizaje Automático
7.
BMC Biol ; 22(1): 119, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769511

RESUMEN

BACKGROUND: Many efforts have been made to improve the precision of Cas9-mediated gene editing through increasing knock-in efficiency and decreasing byproducts, which proved to be challenging. RESULTS: Here, we have developed a human exonuclease 1-based genome-editing tool, referred to as exonuclease editor. When compared to Cas9, the exonuclease editor gave rise to increased HDR efficiency, reduced NHEJ repair frequency, and significantly elevated HDR/indel ratio. Robust gene editing precision of exonuclease editor was even superior to the fusion of Cas9 with E1B or DN1S, two previously reported precision-enhancing domains. Notably, exonuclease editor inhibited NHEJ at double strand breaks locally rather than globally, reducing indel frequency without compromising genome integrity. The replacement of Cas9 with single-strand DNA break-creating Cas9 nickase further increased the HDR/indel ratio by 453-fold than the original Cas9. In addition, exonuclease editor resulted in high microhomology-mediated end joining efficiency, allowing accurate and flexible deletion of targeted sequences with extended lengths with the aid of paired sgRNAs. Exonuclease editor was further used for correction of DMD patient-derived induced pluripotent stem cells, where 30.0% of colonies were repaired by HDR versus 11.1% in the control. CONCLUSIONS: Therefore, the exonuclease editor system provides a versatile and safe genome editing tool with high precision and holds promise for therapeutic gene correction.


Asunto(s)
Exodesoxirribonucleasas , Edición Génica , Edición Génica/métodos , Humanos , Exodesoxirribonucleasas/genética , Exodesoxirribonucleasas/metabolismo , Sistemas CRISPR-Cas , Células HEK293 , Enzimas Reparadoras del ADN
8.
Nano Lett ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39352718

RESUMEN

The design and synthesis of nanomedicines capable of regulating programmed cell death patterns to enhance antitumor efficacy remain significant challenges in cancer therapy. In this study, we developed intelligent DNA nanospheres (NS) capable of distinguishing tiny pH changes between different endosomal compartments to regulate pyroptosis or apoptosis. These NS are self-assembled from two multifunctional DNA modules, enabling tumor targeting, acid-responsive disassembly, and photodynamic therapy (PDT) activation. By modifying the embedded i-motif sequence, the NS can be activated in early endosomes (EE) or lysosomes (Ly), producing singlet oxygen (1O2) at specific locations under laser irradiation. Our results demonstrate that EE-activated PDT induces gasdermin-E-mediated pyroptosis in tumor cells, enhancing antitumor efficacy and reducing systemic toxicity compared to Ly-activated apoptosis. This study offers new insights into the design of endosome-activated nanomedicines, advancing the biomedical applications of targeted cancer therapy.

9.
J Cell Physiol ; : e31460, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39402901

RESUMEN

Lithospermic acid (LA) is a water-soluble phenolic acid compound extracted and separated from the dried root and the rhizome of Salviamiltiorrhiza Bge (Labiatae), possessing multiple biological activities. Firstly, in terms of pharmacological activities, LA has been proven to possess anti-inflammatory, antioxidant, autophagy activation, and antiapoptotic properties. Secondly, the pharmacokinetic characteristics of LA show rapid and extensive distribution in various tissues after intravenous administration, followed by rapid elimination and excretion. Additionally, potential therapeutic effects of LA have been found in various diseases such as thrombosis, Parkinson's disease, hepatitis B, diabetes, and psoriasis, among others. Particularly, LA has shown promising prospects in the treatment of clinical heart diseases and has been included in new drug formulations for the treatment of chronic angina, demonstrating superior efficacy compared to current cardiovascular drugs. In conclusion, this review comprehensively introduces the pharmacological mechanisms, pharmacokinetics, and protective effects in diseases of LA. These information can lay a theoretical foundation for the future development and new clinical applications of LA.

10.
J Am Chem Soc ; 146(20): 14357-14367, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38726589

RESUMEN

Introducing dynamic behavior into periodic frameworks has borne fruit in the form of flexible porous crystals. The detailed molecular design of frameworks in order to control their collective dynamics is of particular interest, for example, to achieve stimulus-induced behavior. Herein, by varying the degree of rigidity of ditopic pillar linkers, two isostructural flexible metal-organic frameworks (MOFs) with common rigid supermolecular building bilayers were constructed. The subtle substitution of single (in bibenzyl-4,4'-dicarboxylic acid; H2BBDC) with double (in 4,4'-stilbenedicarboxylic acid; H2SDC) C-C bonds in pillared linkers led to markedly different flexible behavior of these two MOFs. Upon the removal of guest molecules, both frameworks clearly show reversible single-crystal-to-single-crystal transformations involving the cis-trans conformation change and a resulting swing of the corresponding pillar linkers, which gives rise to Flex-Cd-MOF-1a and Flex-Cd-MOF-2a, respectively. Strikingly, a more favorable gas-induced dynamic behavior in Flex-Cd-MOF-2a was verified in detail by stepwise C3H6/C3H8 sorption isotherms and the corresponding in situ powder X-ray diffraction experiments. These insights are strongly supported by molecular modeling studies on the sorption mechanism that explores the sorption landscape. Furthermore, a consistency between the macroscopic elasticity and microscopic flexibility of Flex-Cd-MOF-2 was observed. This work fuels a growing interest in developing MOFs with desired chemomechanical functions and presents detailed insights into the origins of flexible MOFs.

11.
Apoptosis ; 29(9-10): 1361-1376, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38853204

RESUMEN

TRAF2 and NCK interacting kinase (TNIK), a critical interacting protein kinase, is currently receiving wide attention. TNIK is found in various human body organs and tissues and participates in cell motility, proliferation, and differentiation. On the one hand, its aberrant expression is related to the onset and progression of numerous malignant tumors. On the other hand, TNIK is important in neuronal growth, proliferation, differentiation, and synaptic formation. Thus, the novel therapeutic strategies for targeting TNIK offer a promising direction for cancer, neurological or psychotic disorders. Here, we briefly summarized the biological information of TNIK, reviewed the role and regulatory mechanism in cancer and neuropsychiatric diseases, and introduced the research progress of inhibitors targeting TNIK. Taken together, this review hopes to contribute to the in-depth understanding of the function and regulatory mechanism of TNIK, which is of great significance for revealing the role of TNIK in the occurrence and treatment of diseases.


Asunto(s)
Neoplasias , Humanos , Neoplasias/genética , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/terapia , Animales , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proliferación Celular/genética , Diferenciación Celular , Trastornos Mentales/genética , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/metabolismo , Trastornos Mentales/terapia , Terapia Molecular Dirigida
12.
J Transl Med ; 22(1): 512, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38807223

RESUMEN

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients' prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients' survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Neoplasias , Medicina de Precisión , Transcriptoma , Humanos , Transcriptoma/genética , Neoplasias/genética , Neoplasias/clasificación , Neoplasias/patología , Pronóstico , Perfilación de la Expresión Génica , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/clasificación , Carcinoma Hepatocelular/patología , Mutación/genética , Microambiente Tumoral/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/clasificación , Neoplasias Hepáticas/patología , Oncología Médica/métodos
13.
J Nutr ; 154(2): 535-542, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38072153

RESUMEN

BACKGROUND: Intrauterine growth restriction (IUGR) resulted in high mortality and many physiological defects of piglets, causing huge economic loss in the swine industry. Lactobacillus amylovorus (L. amylovorus) was identified as one of the main differential bacteria between IUGR and normal piglets. However, the effects of L. amylovorus on the growth performance and intestinal health in IUGR piglets remained unclear. OBJECTIVES: This study aimed to investigate the promoting effects of L. amylovorus Mafic1501, a new strain isolated from normal piglets, on the growth performance and intestinal barrier functions in IUGR piglets. METHODS: Newborn mice or piglets were assigned into 3 groups: CON (normal birth weight, control), IUGR (low birth weight), and IUGR+L. amy (low birth weight), administered with sterile saline or L. amylovorus Mafic1501, respectively. Growth performance, lactose content in the digesta, intestinal lactose transporter, and barrier function parameters were profiled. IPEC-J2 cells were cultured to verify the effects of L. amylovorus Mafic1501 on lactose utilization and intestinal barrier functions. RESULTS: L. amylovorus Mafic1501 elevated body weight and average daily gain of IUGR mice and piglets (P < 0.05). The lactose content in the ileum was decreased, whereas gene expression of glucose transporter 2 (GLUT2) was increased by L. amylovorus Mafic1501 in IUGR piglets during suckling period (P < 0.05). Besides, L. amylovorus Mafic1501 promoted intestinal barrier functions by increasing the villus height and relative gene expressions of tight junctions (P < 0.05). L. amylovorus Mafic1501 and its culture supernatant decreased the lactose level in the medium and upregulated gene expressions of transporter GLUT2 and tight junction protein Claudin-1 of IPEC-J2 cells (P < 0.05). CONCLUSION: L. amylovorus Mafic1501 improved the growth performance of IUGR piglets by promoting the lactose utilization in small intestine and enhancing intestinal barrier functions. Our results provided the new evidence of L. amylovorus Mafic1501 for its application in the swine industry.


Asunto(s)
Retardo del Crecimiento Fetal , Lactobacillus acidophilus , Femenino , Humanos , Animales , Porcinos , Ratones , Retardo del Crecimiento Fetal/metabolismo , Lactosa/farmacología , Lactosa/metabolismo , Peso al Nacer , Funcion de la Barrera Intestinal , Intestino Delgado/metabolismo , Animales Recién Nacidos
14.
J Org Chem ; 89(19): 14586-14590, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39298672

RESUMEN

In continuation of our research interest in the green oxidation of indoles, we further explore the direct oxidation of 2-methylindoles to 2-formyl indoles promoted by NCS and associated with H2O as the oxygen source. This methodology was demonstrated to be a robust protocol consisting of chlorination, SN2', and oxidation processes, and presents a reasonably broad substrate scope and excellent functional group tolerance, thus enabling the preparation of high added-value versatile building blocks susceptible to further functionalization.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38822974

RESUMEN

Vascular remodeling is the adaptive response of the vessel wall to physiological and pathophysiological changes, closely linked to vascular diseases. Vascular smooth muscle cells (VSMCs) play a crucial role in this process. Pyroptosis, a form of programmed cell death characterized by excessive release of inflammatory factors, can cause phenotypic transformation of VSMCs, leading to their proliferation, migration, and calcification-all of which accelerate vascular remodeling. Inhibition of VSMC pyroptosis can delay this process. This review summarizes the impact of pyroptosis on VSMCs and the pathogenic role of VSMC pyroptosis in vascular remodeling. We also discuss inhibitors of key proteins in pyroptosis pathways and their effects on VSMC pyroptosis. These findings enhance our understanding of the pathogenesis of vascular remodeling and provide a foundation for the development of novel medications that target the control of VSMC pyroptosis as a potential treatment strategy for vascular diseases.

16.
BMC Pregnancy Childbirth ; 24(1): 647, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39367375

RESUMEN

BACKGROUND: Surgery for adnexal mass does occur in pregnant women and therefore the choice of surgery during pregnancy needs to be carefully considered and studied. This study aimed to evaluate the safety and feasibility of Laparo-endoscopic Single-site Surgery (LESS) for adnexal mass during pregnancy and investigate the perioperative condition, pregnancy complications, and obstetric outcomes of operative women during pregnancy. METHODS: This study retrospectively collected medical records and surgery videos of 20 pregnant women who underwent LESS for adnexal mass between November 2019 and January 2022. Baseline characteristics, operative-related variables, and pregnancy outcomes were followed up. RESULTS: LESS for adnexal mass was successfully performed in 20 pregnant women, with very satisfactory surgery outcomes reported in all cases. The average gestational age at operation was 15+2 weeks (range, 5+1- 25+4 weeks). The median operative time was 80.8 min (range, 40 -185 min) and the average operative bleeding was 28.0 ml (range, 10-50 ml). The average VAS of 24 h postoperatively was 1 (range, 0-2), and the average length of hospital stay was 5.15 days (range, 3-7 days). All these women delivered a healthy newborn at full term except 1 woman induced abortion for her own reasons at 16+5 weeks gestational age (GA). The average GA of delivery was 39+1 weeks (range, 37-40+1 weeks), the average birth weight was 3228.95 g (range, 2740-3930 g), and the average Apgar score at 5 min was 9.95 (range, 9-10). CONCLUSIONS: LESS for adnexal mass is safe and feasible for pregnant women.


Asunto(s)
Enfermedades de los Anexos , Laparoscopía , Resultado del Embarazo , Humanos , Femenino , Embarazo , Adulto , Estudios Retrospectivos , Laparoscopía/métodos , Enfermedades de los Anexos/cirugía , Estudios de Factibilidad , Tempo Operativo , Edad Gestacional , Tiempo de Internación/estadística & datos numéricos , Complicaciones Neoplásicas del Embarazo/cirugía
17.
Addict Biol ; 29(2): e13367, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38380757

RESUMEN

Alcohol use disorder (AUD) has been associated with attentional deficits and impairments of working memory. Meanwhile, attention and working memory are critical for time perception. However, it remains unclear how time perception alters in AUD patients and how attention and working memory affect their time perception. The current study aims to clarify the time perception characteristics of AUD patients and the cognitive mechanisms underlying their time perception dysfunction. Thirty-one patients (three of them were excluded) with AUD and thirty-one matched controls completed the Time Bisection Task, Attention Network Test and Digital Span Backward Test to assess their abilities in time perception, attention network and working memory, respectively. The results showed that, after controlling for anxiety, depression, and impulsivity, AUD patients had a lower proportion of 'long' responses at intervals of 600, 750, 900, 1050 and 1200 ms. Furthermore, they displayed higher subjective equivalence points and higher Weber ratios compared to controls. Moreover, AUD patients showed impaired alerting and executive control networks as well as reduced working memory resources. Only working memory resources mediated the impact of AUD on time perception. In conclusion, our findings suggested that the duration underestimation in AUD patients is predominantly caused by working memory deficits.


Asunto(s)
Alcoholismo , Percepción del Tiempo , Humanos , Memoria a Corto Plazo/fisiología , Función Ejecutiva/fisiología , Consumo de Bebidas Alcohólicas
18.
Nucleic Acids Res ; 50(9): 5384-5399, 2022 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-35544322

RESUMEN

Establishing saturated mutagenesis in a specific gene through gene editing is an efficient approach for identifying the relationships between mutations and the corresponding phenotypes. CRISPR/Cas9-based sgRNA library screening often creates indel mutations with multiple nucleotides. Single base editors and dual deaminase-mediated base editors can achieve only one and two types of base substitutions, respectively. A new glycosylase base editor (CGBE) system, in which the uracil glycosylase inhibitor (UGI) is replaced with uracil-DNA glycosylase (UNG), was recently reported to efficiently induce multiple base conversions, including C-to-G, C-to-T and C-to-A. In this study, we fused a CGBE with ABE to develop a new type of dual deaminase-mediated base editing system, the AGBE system, that can simultaneously introduce 4 types of base conversions (C-to-G, C-to-T, C-to-A and A-to-G) as well as indels with a single sgRNA in mammalian cells. AGBEs can be used to establish saturated mutant populations for verification of the functions and consequences of multiple gene mutation patterns, including single-nucleotide variants (SNVs) and indels, through high-throughput screening.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Animales , Mutación INDEL , Mamíferos/genética , Mutación , Uracil-ADN Glicosidasa/genética
19.
Australas J Dermatol ; 65(4): 328-336, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38419203

RESUMEN

BACKGROUND: Atopic dermatitis (AD) often arises in infancy, and gut microbial dysbiosis is associated with the development of AD. However, less is known about specific changes in early-life gut microbiome associated with AD and AD severity. This study aims to reveal the gut microbial composition and function profiles associated with the severity of AD in infants. METHODS: Sixty-two infants (mean [SD] age, 4.7[1.9] months) with different severities of AD were enrolled and divided into three groups (mild, moderate and severe) according to the Scoring Atopic Dermatitis (SCORAD) index. The profiles of gut microbial composition and function were analysed by sequencing 16S ribosomal RNA amplicons. Quality of life on children and the family was evaluated using published questionnaires. RESULTS: Decreased levels of Clostridium sensu stricto, Collinsella and increased level of Parabacteroides presented in the severe AD group compared with the mild AD group after adjusting potential confounders (p < 0.05). There were strong positive correlations between the Scoring Atopic Dermatitis (SCORAD) index and the relative abundance (RA) of Bacteroides and functional pathways for metabolism of sphingolipids and glycosphingolipids (p < 0.05). The SCORAD index was negatively correlated with the RA of Clostridium sensu stricto (p < 0.05), and was also positively correlated with the index of quality of life on children and the family (p < 0.05). CONCLUSION: Discrepancies in gut microbial composition and functional pathways were observed in infants with mild-to-severe AD. Alterations in butyrate-producing bacteria (Clostridium sensu stricto), sphingolipid-producing bacteria (Parabacteroides, Bacteroides), and related functional pathways were associated with the severity of AD infants.


Asunto(s)
Dermatitis Atópica , Microbioma Gastrointestinal , Calidad de Vida , Índice de Severidad de la Enfermedad , Humanos , Dermatitis Atópica/microbiología , Lactante , Masculino , Femenino , Disbiosis/microbiología , Heces/microbiología
20.
J Sci Food Agric ; 104(14): 8593-8603, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38923536

RESUMEN

BACKGROUND: Dendrobium officinale flos (DOF), a novel food raw material, is used in Chinese folk medicine to nourish the stomach. However, there is still no available study to evaluate the effects of DOF on animal models of acute gastric injury and its mechanism by modern pharmacological research. RESULTS: Herein, we characterized the major components of an aqueous extract of DOF and assessed its potential ameliorative effects in a rat model of acute gastric mucosal injury. The DOF water extract showed significant protective effects on the gastric mucosa and exhibited excellent antioxidant and anti-inflammatory activities. Acute gastric injury rat models induced by ethanol (6 mL kg-1) were pretreated with different doses of DOF water extract (50-100 mg kg-1 day-1), and the biological effects of DOF extract in gastric tissues were evaluated. DOF extract alleviated the symptoms of ethanol-stimulated acute gastric mucosal injury, as evidenced by a significant reduction in gastric injury index and the degree of gastric pathological changes. Additionally, treatment with DOF extract upregulated mucin expression in the gastric mucosa, attenuated oxidative stress, decreased the release of inflammatory mediators (TNF-α, IL-6), suppressed the expression of key proinflammatory enzymes (COX-2 and iNOS), reduced the phosphorylation of p38 MAPK and p65 NF-κB and increased the level of PGE2 in gastric tissues. CONCLUSION: DOF exerts protective effects against ethanol-induced acute gastric mucosal injury, mainly by inhibiting inflammation and oxidative stress. © 2024 Society of Chemical Industry.


Asunto(s)
Dendrobium , Etanol , Mucosa Gástrica , Estrés Oxidativo , Extractos Vegetales , Ratas Sprague-Dawley , Animales , Dendrobium/química , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/lesiones , Mucosa Gástrica/patología , Estrés Oxidativo/efectos de los fármacos , Ratas , Extractos Vegetales/farmacología , Extractos Vegetales/química , Extractos Vegetales/administración & dosificación , Masculino , Etanol/efectos adversos , Antiinflamatorios/farmacología , Humanos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/inducido químicamente , Flores/química , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/tratamiento farmacológico , Úlcera Gástrica/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Antioxidantes/farmacología , Interleucina-6/metabolismo , Interleucina-6/genética , FN-kappa B/metabolismo , FN-kappa B/genética
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