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Sulfur-containing amino acids have been proposed as drugs for lipid oxidation associated with diseases for a long time, but the molecular-level mechanism on the effectiveness of sulfur-containing amino acids against lipid oxidation remains elusive. In this work, with the interfacial sensitivity mass spectrometry method, oxidation of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG), a widely used model lipid, was significantly inhibited on hung droplet surface in presence of sulfur-containing amino acids, such as cysteine (Cys) and methionine (Met). Both the Cys and Met showed a self-sacrificing protection. The amino acids with -S-R tails (R referring to methyl or t-butyl group) showed more effective against POPG oxidation than those with -SH tails, and this process was not related to the conformations of amino acids. The low effectiveness of Cys during the interfacial chemistry was proved to arise from the formation of disulfide bond. This study extends the current understanding of chemistry of sulfur-containing amino acids and provides insights to aid the sulfur-containing amino acids against cell oxidation.
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The escalating use of artificial intelligence in marketing significantly impacts all aspects of consumer life. This research, grounded in attribution theory and S-O-R theory, employs scenario-based experimental methods to simulate two distinct purchasing contexts. The aim is to investigate consumers' psychological and behavioral responses to AI-initiated pricing. Through SPSS analysis of variance and Bootstrap analysis, the mechanisms of influence of AI-initiated pricing on consumer behavior are tested, revealing the mediating variables of mind perception and consumer perceived ethicality, as well as the mediating variables of perceived enterprise control. Data were collected from Chinese customers to test the model of this study. A total of 841 valid questionnaires were analyzed using ANOVA and Bootstrap analysis with SPSS. The results show that: (1) Consumers exhibit higher repurchase and word-of-mouth recommendation behaviors and lower complaint and switching behaviors for AI-initiated pricing compared to marketers; (2) AI-initiated pricing leads to diminished mind perceptions and augmented ethical perceptions among consumers. Ethical perceptions serve as a complete mediator, while mind perceptions play a less significant mediating role; (3) Perceived enterprise control plays a moderating role in the impact of AI-initiated pricing on consumer behavior. That is, when consumers know that the enterprise can control pricing agents, AI-initiated pricing leads to lower repurchase and word-of-mouth recommendation behaviors, and higher instances of complaining and switching behaviors than humans.
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Inteligencia Artificial , Comportamiento del Consumidor , Humanos , Femenino , Masculino , Adulto , Encuestas y Cuestionarios , Mercadotecnía , Persona de Mediana Edad , Adulto Joven , ChinaRESUMEN
As widely used alternative brominated flame retardants, tetrabromobisphenol S (TBBPS) and its derivatives have attracted increasing amounts of attention in the field of environmental science. Previous studies have shown that TBBPS and its derivatives easily accumulate in environmental media and may cause risks to environmental safety and human health. Therefore, to explore the environmental behaviours of TBBPS and its derivatives, in this paper, we summarized relevant research on the distribution of these compounds in water, the atmosphere, soil and food/biota, as well as their transformation mechanisms (biological and nonbiological) and toxic effects. The summary results show that TBBPS and its derivatives have been detected in water, the atmosphere, soil, and food/biota globally, making them a ubiquitous pollutant. These compounds may be subject to adsorption, photolysis or biological degradation after being released into the environment, which in turn increases their ecological risk. TBBPS and its derivatives can cause a series of toxic effects, such as neurotoxicity, hepatotoxicity, cytotoxicity, thyrotoxicity, genotoxicity and phytotoxicity, to cells or living organisms in in vitro and in vivo exposure. Toxicological studies suggest that TBBPS as an alternative to TBBPA is not entirely environmentally friendly. Finally, we propose future directions for research on TBBPS and its derivatives, including the application of new technologies in studies on the migration, transformation, toxicology and human exposure risk assessment of TBBPS and its derivatives in the environment. This review provides useful information for obtaining a better understanding of the behaviour and potential toxic effects of TBBPS and its derivatives in the environment.
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Contaminantes Ambientales , Retardadores de Llama , Bifenilos Polibrominados , Retardadores de Llama/toxicidad , Bifenilos Polibrominados/toxicidad , Contaminantes Ambientales/toxicidad , Monitoreo del Ambiente , HumanosRESUMEN
Transcription factors (TFs) are major contributors to gene transcription, especially in controlling cell-specific gene expression and disease occurrence and development. Uncovering the relationship between TFs and their target genes is critical to understanding the mechanism of action of TFs. With the development of high-throughput sequencing techniques, a large amount of TF-related data has accumulated, which can be used to identify their target genes. In this study, we developed TFTG (Transcription Factor and Target Genes) database (http://tf.liclab.net/TFTG), which aimed to provide a large number of available human TF-target gene resources by multiple strategies, besides performing a comprehensive functional and epigenetic annotations and regulatory analyses of TFs. We identified extensive available TF-target genes by collecting and processing TF-associated ChIP-seq datasets, perturbation RNA-seq datasets and motifs. We also obtained experimentally confirmed relationships between TF and target genes from available resources. Overall, the target genes of TFs were obtained through integrating the relevant data of various TFs as well as fourteen identification strategies. Meanwhile, TFTG was embedded with user-friendly search, analysis, browsing, downloading and visualization functions. TFTG is designed to be a convenient resource for exploring human TF-target gene regulations, which will be useful for most users in the TF and gene expression regulation research.
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STUDY OBJECTIVES: Sleep disruption is prevalent and persistent among children who experience maltreatment/interpersonal trauma. Weighted blankets have gained popularity in recent years as a potential non-pharmacological intervention for improving sleep in various populations, but their efficacy has not been examined among maltreated children. The current study used a randomized, within-subjects, crossover design to examine whether the use of a weighted blanket improves objective and/or subjective indices of sleep among 30 children, ages 6 to 15 years (M = 9.7, SD = 2.9) adopted from foster care. METHODS: Participants used a weighted blanket for two weeks and their usual blanket for two weeks in a counterbalanced order. Sleep outcomes were measured using actigraphy and subjective sleep diaries. RESULTS: No differences in actigraphy-based or subjective estimates of total sleep time, sleep onset latency, wake after sleep onset, or sleep quality ratings were found based on blanket type. Child age, biological sex, timing of participation (school year versus summer months), and maltreatment/trauma history did not impact outcomes. CONCLUSIONS: Although we did not find evidence that weighted blankets improve sleep among children with a history of maltreatment/interpersonal trauma, additional well-controlled studies using larger samples of children are needed.
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PURPOSE: To assess the efficacy and safety of various intraocular lenses (IOLs), including standard monofocal, bifocal, trifocal, extended depth of focus (EDOF), and enhanced monofocal IOLs, post-cataract surgery through a network meta-analysis. METHODS: A systematic search of PubMed, Cochrane Library, and Web of Science was conducted to identify relevant studies from the past 5 years. Parameters such as binocular visual acuities, spectacle independence, contrast sensitivity (CS), and optical quality were used to evaluate efficacy and safety. Data from the selected studies were analyzed using Review Manager 5.4 and STATA 17.0 software. RESULTS: Twenty-eight Randomized Controlled Trials (RCTs) comprising 2465 subjects were included. Trifocal IOLs exhibited superior uncorrected near visual acuity (UNVA) compared to monofocal IOLs (MD: -0.35; 95% CI: -0.48, -0.22). Both trifocal (AcrySof IQ PanOptix IOLs group MD: -0.13; 95% CI: -0.21, -0.06) and EDOF IOLs (MD: -0.13; 95% CI: -0.17, -0.09) showed better uncorrected intermediate visual acuity (UIVA) than monofocal IOLs. Trifocal IOLs ranked highest in spectacle independence at various distances (AT LISAtri 839MP group: SUCRA 97.5% for distance, 80.7% for intermediate; AcrySof IQ PanOptix group: SUCRA 83.0% for near). CONCLUSIONS: For cataract patients who want to treat presbyopia, trifocal IOLs demonstrated better visual acuity and spectacle independence at near distances. Different types of trifocal IOL characteristics differ. EDOF and enhanced monofocal IOLs have improved visual quality at intermediate distances.Therefore, It is very important to select the appropriate IOLs based on the lens characteristics and patient needs.
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Extracción de Catarata , Lentes Intraoculares , Presbiopía , Agudeza Visual , Humanos , Presbiopía/cirugía , Presbiopía/fisiopatología , Agudeza Visual/fisiología , Extracción de Catarata/métodos , Sensibilidad de Contraste/fisiología , Implantación de Lentes Intraoculares/métodos , Diseño de Prótesis , Visión Binocular/fisiología , Refracción Ocular/fisiologíaRESUMEN
Pathological cardiac hypertrophy often precedes heart failure due to various stimuli, yet effective clinical interventions remain limited. Recently, microRNAs (miRNAs) have been identified as critical regulators of cardiovascular development. In this study, we investigated the role of miR-146b-5p and its underlying mechanisms of action in cardiac hypertrophy. Isoprenaline (ISO) treatment induced significant hypertrophy and markedly enhanced the expression of miR-146b-5p in cultured neonatal rat cardiomyocytes and hearts of C57BL/6 mice. Transfection with the miR-146b-5p mimic led to cardiomyocyte hypertrophy accompanied by autophagy inhibition. Conversely, miR-146b-5p inhibition significantly alleviated ISO-induced autophagy depression, thereby mitigating cardiac hypertrophy both in vitro and in vivo. Our results showed that the autophagy-related mediator double FYVE domain-containing protein 1 (DFCP1) is a target of miR-146b-5p. MiR-146b-5p blocked autophagic flux in cardiomyocytes by suppressing DFCP1, thus contributing to hypertrophy. These findings revealed that miR-146b-5p is a potential regulator of autophagy associated with the onset of cardiac hypertrophy, suggesting a possible therapeutic strategy involving the inhibition of miR-146b-5p.
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Autofagia , Cardiomegalia , Isoproterenol , Ratones Endogámicos C57BL , MicroARNs , Miocitos Cardíacos , Animales , MicroARNs/genética , MicroARNs/metabolismo , Isoproterenol/farmacología , Cardiomegalia/genética , Cardiomegalia/inducido químicamente , Cardiomegalia/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Autofagia/efectos de los fármacos , Autofagia/genética , Ratas Sprague-Dawley , Ratas , Masculino , Ratones , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacos , Proteínas Relacionadas con la Autofagia/genética , Proteínas Relacionadas con la Autofagia/metabolismo , Secuencia de BasesRESUMEN
In recent years, gastric cancer (GC) is still one of the major public health burdens in the world. It is reported that exosome circular RNA (circRNA) is involved in the GC progression. However, the function and potential mechanism of circGMPS in GC remains unclear and needs further exploration. In this study, we isolated and identified exosomes from serum by TEM, NTA analysis and Western blot. RNA expression was evaluated by qRT-PCR. Western blot was employed to examine protein expression. Cell proliferation was measured using CCK-8. Transwell assay was adopted to analyze cell migration and invasion. The relationship between genes was explored through bioinformatics analysis, dual-luciferase reporter gene assay and spearman correlation coefficient. We found that circGMPS was elevated in GC exosomes, tissues and cells. Poor prognosis of GC patients was related to high circGMPS expression. Both exosome co-culture with cells and insertion of circGMPS clearly promoted cell progression. Mechanically, circGMPS sponged miR-144-3p to regulate PUM1. Inhibition of PUM1 or miR-144-3p overexpression inhibited the malignant GC cell progression. Our data confirmed that exosome-derived circGMPS boosted malignant progression by miR-144-3p/PUM1 axis in GC cells, providing strong evidences for circGMPS as a clinical biomarker of GC treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-023-00597-9.
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BV is a significant concern in women's health with a varying prevalence rate in different cities of China. The condition has been linked to the acquisition of STIs, including HIV and HPV, and can lead to infertility, adverse obstetric outcomes. We conducted a comprehensive literature search in the PubMed. The search was performed from 01/01/2018 to 01/09/2023. The following search terms were used: bacterial vaginosis and cytokine. We also manually searched the reference lists of included studies and relevant reviews to identify additional articles. The presence of Gardnerella spp. can lead to changes in cytokine levels. The immune system of the female reproductive tract consists of various immune cells and molecules that play a vital role in defending against infections. Cytokines, signaling molecules involved in immune cell recruitment and activation, have been identified as potential biomarkers for diagnosing BV and predicting STIs. Current treatments for BV primarily involve antibiotics, but there is a high recurrence rate posttreatment. BV is a complex condition that affects a significant number of women worldwide. The role of cytokines in the onset, progression, and treatment of BV offers promising avenues for future research and potential diagnostic and therapeutic advancements.
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Enfermedades de Transmisión Sexual , Vaginosis Bacteriana , Embarazo , Femenino , Humanos , Vaginosis Bacteriana/diagnóstico , Vaginosis Bacteriana/epidemiología , Vaginosis Bacteriana/microbiología , Citocinas , Vagina/microbiología , Enfermedades de Transmisión Sexual/diagnóstico , ChinaRESUMEN
Epidermolysis bullosa acquisita (EBA) rarely develops in childhood. This study retrospectively recruited paediatric patients with EBA (age ≤ 16 years), diagnosed by clinical and histopathological features and results of immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA), and reviews their clinical manifestations, histopathology, immunological features, and responses to various treatments. All 7 included patients presented with inflammatory EBA. Among them, 3 had a bullous pemphigoid-like phenotype. Pathologically, in addition to dermal-epidermal blistering, in all patients, the distribution of neutrophils was superficial perivascular or interstitial, or in the dermal papilla. Mixed neutrophils and eosinophils were detected in 2 of the 3 patients with bullous pemphigoid-like phenotypes. In addition to treatment with glucocorticoids, dapsone was administered in 4 patients, while thalidomide and sulfasalazine were administered in 1 patient. All patients responded to the these therapies. Relapse was mainly due to reduction and cessation of glucocorticoids. In conclusion, EBA in childhood may be unique, and thus distinct from its adult counterpart. Specific treatment and follow-up protocols are required for therapy of this rare autoimmune skin disease in children.
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Enfermedades Autoinmunes , Epidermólisis Ampollosa Adquirida , Penfigoide Ampolloso , Adulto , Humanos , Niño , Adolescente , Epidermólisis Ampollosa Adquirida/diagnóstico , Epidermólisis Ampollosa Adquirida/tratamiento farmacológico , Estudios Retrospectivos , Dapsona/uso terapéutico , Glucocorticoides/uso terapéuticoRESUMEN
Drought stress significantly affects crop productivity. Carotenoids are essential photosynthetic pigment for plants, bacteria, and algae, with signaling and antioxidant functions. Lutein is a crucial branch product in the carotenoid synthesis pathway, which effectively improves the stress tolerance of higher plants. lycopene cyclase, a central enzyme for lutein synthesis, holds great significance in regulating lutein production. This research establishes a correlation between lutein content and stress resistance by measuring the drought resistance and lutein content of various cotton materials. To identify which crucial genes are associated with lutein, the lycopene cyclase family (LCYs) was analyzed. The research found that LCYs form a highly conserved family divided into two subfamilies, LCY-ε (lycopene ε-cyclase) and LCY-ß (lycopene ß-cyclase). Most members of the LCY family contain photoresponsive elements and abscisic acid elements. qRT-PCR demonstrates showed that most genes responded positively to drought stress, and GhLCYε-3 was expressed significantly differently under drought stress. Virus-induced gene silencing (VIGS) assay showed that the content of GhLCYε-3 was significantly increased with MDA and PRO, and the contents of chlorophyll and lutein were significantly decreased in pYL156 plants. The decrease in GhLCYε-3 expression is speculated to lead to reduced lutein content in vivo, resulting in the accumulation of reactive oxygen species (ROS) and decreased drought tolerance. This research enriched the understanding of LCY gene family and lutein function, and provided a new reference for cotton planting in arid areas. Synopsis: Lycopene cyclase plays an important role in enhancing the ability of scavenging ROS and drought resistance of plants.
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Gene regulatory networks (GRNs) are interpretable graph models encompassing the regulatory interactions between transcription factors (TFs) and their downstream target genes. Making sense of the topology and dynamics of GRNs is fundamental to interpreting the mechanisms of disease etiology and translating corresponding findings into novel therapies. Recent advances in single-cell multi-omics techniques have prompted the computational inference of GRNs from single-cell transcriptomic and epigenomic data at an unprecedented resolution. Here, we present scGRN (https://bio.liclab.net/scGRN/), a comprehensive single-cell multi-omics gene regulatory network platform of human and mouse. The current version of scGRN catalogs 237 051 cell type-specific GRNs (62 999 692 TF-target gene pairs), covering 160 tissues/cell lines and 1324 single-cell samples. scGRN is the first resource documenting large-scale cell type-specific GRN information of diverse human and mouse conditions inferred from single-cell multi-omics data. We have implemented multiple online tools for effective GRN analysis, including differential TF-target network analysis, TF enrichment analysis, and pathway downstream analysis. We also provided details about TF binding to promoters, super-enhancers and typical enhancers of target genes in GRNs. Taken together, scGRN is an integrative and useful platform for searching, browsing, analyzing, visualizing and downloading GRNs of interest, enabling insight into the differences in regulatory mechanisms across diverse conditions.
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Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Análisis de la Célula Individual , Factores de Transcripción , Animales , Humanos , Ratones , Unión Proteica , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , TranscriptomaRESUMEN
Enhancer RNAs (eRNAs) transcribed from distal active enhancers serve as key regulators in gene transcriptional regulation. The accumulation of eRNAs from multiple sequencing assays has led to an urgent need to comprehensively collect and process these data to illustrate the regulatory landscape of eRNAs. To address this need, we developed the eRNAbase (http://bio.liclab.net/eRNAbase/index.php) to store the massive available resources of human and mouse eRNAs and provide comprehensive annotation and analyses for eRNAs. The current version of eRNAbase cataloged 10 399 928 eRNAs from 1012 samples, including 858 human samples and 154 mouse samples. These eRNAs were first identified and uniformly processed from 14 eRNA-related experiment types manually collected from GEO/SRA and ENCODE. Importantly, the eRNAbase provides detailed and abundant (epi)genetic annotations in eRNA regions, such as super enhancers, enhancers, common single nucleotide polymorphisms, expression quantitative trait loci, transcription factor binding sites, CRISPR/Cas9 target sites, DNase I hypersensitivity sites, chromatin accessibility regions, methylation sites, chromatin interactions regions, topologically associating domains and RNA spatial interactions. Furthermore, the eRNAbase provides users with three novel analyses including eRNA-mediated pathway regulatory analysis, eRNA-based variation interpretation analysis and eRNA-mediated TF-target gene analysis. Hence, eRNAbase is a powerful platform to query, browse and visualize regulatory cues associated with eRNAs.
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Bases de Datos Genéticas , ARN Potenciadores , Transcripción Genética , Animales , Humanos , Ratones , Cromatina/genética , Regulación de la Expresión GénicaRESUMEN
Long non-coding RNAs (lncRNAs) possess a wide range of biological functions, and research has demonstrated their significance in regulating major biological processes such as development, differentiation, and immune response. The accelerating accumulation of lncRNA research has greatly expanded our understanding of lncRNA functions. Here, we introduce LncSEA 2.0 (http://bio.liclab.net/LncSEA/index.php), aiming to provide a more comprehensive set of functional lncRNAs and enhanced enrichment analysis capabilities. Compared with LncSEA 1.0, we have made the following improvements: (i) We updated the lncRNA sets for 11 categories and extremely expanded the lncRNA scopes for each set. (ii) We newly introduced 15 functional lncRNA categories from multiple resources. This update not only included a significant amount of downstream regulatory data for lncRNAs, but also covered numerous epigenetic regulatory data sets, including lncRNA-related transcription co-factor binding, chromatin regulator binding, and chromatin interaction data. (iii) We incorporated two new lncRNA set enrichment analysis functions based on GSEA and GSVA. (iv) We adopted the snakemake analysis pipeline to track data processing and analysis. In summary, LncSEA 2.0 offers a more comprehensive collection of lncRNA sets and a greater variety of enrichment analysis modules, assisting researchers in a more comprehensive study of the functional mechanisms of lncRNAs.
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Bases de Datos de Ácidos Nucleicos , ARN Largo no Codificante , Bases de Datos de Ácidos Nucleicos/normas , ARN Largo no Codificante/genética , Análisis de DatosRESUMEN
Transcription factors (TFs), transcription co-factors (TcoFs) and their target genes perform essential functions in diseases and biological processes. KnockTF 2.0 (http://www.licpathway.net/KnockTF/index.html) aims to provide comprehensive gene expression profile datasets before/after T(co)F knockdown/knockout across multiple tissue/cell types of different species. Compared with KnockTF 1.0, KnockTF 2.0 has the following improvements: (i) Newly added T(co)F knockdown/knockout datasets in mice, Arabidopsis thaliana and Zea mays and also an expanded scale of datasets in humans. Currently, KnockTF 2.0 stores 1468 manually curated RNA-seq and microarray datasets associated with 612 TFs and 172 TcoFs disrupted by different knockdown/knockout techniques, which are 2.5 times larger than those of KnockTF 1.0. (ii) Newly added (epi)genetic annotations for T(co)F target genes in humans and mice, such as super-enhancers, common SNPs, methylation sites and chromatin interactions. (iii) Newly embedded and updated search and analysis tools, including T(co)F Enrichment (GSEA), Pathway Downstream Analysis and Search by Target Gene (BLAST). KnockTF 2.0 is a comprehensive update of KnockTF 1.0, which provides more T(co)F knockdown/knockout datasets and (epi)genetic annotations across multiple species than KnockTF 1.0. KnockTF 2.0 facilitates not only the identification of functional T(co)Fs and target genes but also the investigation of their roles in the physiological and pathological processes.
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Bases de Datos Genéticas , Factores de Transcripción , Transcriptoma , Animales , Humanos , Ratones , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Internet , Marcación de Gen , Arabidopsis , Zea maysRESUMEN
BACKGROUND: Bullous pemphigoid (BP) is a common subepidermal bullous disease. Dupilumab is a novel treatment for BP. However, its long-term efficacy and safety have not been demonstrated in prospective studies. OBJECTIVE: Evaluate the long-term efficacy and safety of dupilumab in treating severe BP. METHODS: Patients were divided into two groups: the methylprednisolone monotherapy group (M), and the methylprednisolone and dupilumab combination therapy group (D + M). This study consisted of two stages. The first stage focused on the initial treatment phase, where the early efficacy and safety was evaluated. The study then entered the 12-month maintenance treatment stage, where we assessed recurrence in both groups. Additionally, we evaluated the rate of healing of skin lesions, glucocorticoids burden and length of hospital stay and various laboratory test indicators. RESULTS: After four weeks of treatment, the Bullous Pemphigoid Disease Area Index (BPDAI) and pruritus Numerical Rating Scale scores of the D + M group decreased significantly more than those of the M group. The median BPDAI at week 4 was 0 (range: 0.0-3.0) in the D + M group and 10.0 (5.0-12.0) in the M group (P < 0.001). Patients treated with dupilumab experienced a faster cessation of new blisters, quicker glucocorticoid reduction, shorter healing times, and shorter hospital stays (P < 0.001). Additionally, after two weeks of treatment, the levels of eosinophils and immunoglobulin E also decreased (P < 0.001). Follow-up studies further demonstrated that dupilumab monotherapy was associated with a lower recurrence rate. Notably, no serious adverse effects were observed in the study. CONCLUSIONS: Our study provides evidence for the efficacy of dupilumab in the treatment of BP based on prospective studies. Additionally, our findings suggest that dupilumab can be considered a reliable single-agent maintenance treatment due to its good safety profile and lower relapse.
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Penfigoide Ampolloso , Humanos , Penfigoide Ampolloso/tratamiento farmacológico , Estudios Prospectivos , Anticuerpos Monoclonales Humanizados/efectos adversos , MetilprednisolonaRESUMEN
Background: Gastric cancer (GC) is one of the common and fatal cancers. Even though the Tumor, Node, Metastasis (TNM) staging system is the most classical staging system recognized worldwide, it has been controversial because there are various factors affecting the prognosis of GC patients. Objectives: The study aims to evaluate the relationship between interleukin-6 (IL-6) and several clinical indicators and construct a prognostic model to better predict the prognosis of GC. Design: A retrospective study. Methods: Data of 249 patients with GC diagnosed in GC center of West China Hospital were collected. Clinicopathological characteristics were analyzed to determine whether there were differences between IL-6 HIGH group and IL-6 LOW group. Besides, the association between the two groups and tumor marker levels was clarified. The K-M curves of 3- and 5-year were plotted with log-rank test. Afterward, we conducted univariate and multivariate analysis and a predicting nomogram. Significantly, C-index, and calibration were used to evaluate the value of nomogram in predicting prognosis. Results: The overall survival of GC in the IL-6 HIGH and IL-6 LOW groups were 47.8 months (95% CI: 42.1-53.4) and 57.9 months (95% CI: 54.1-61.7), respectively, with significant differences (p = 0.0046). Average tumor size of GC (p = 0.000) and nerve invasion (p = 0.018) were statistically significant between two groups. Multivariate analysis revealed that the factors affecting prognosis were IL-6 (<5.51 and ⩾5.51 pg/ml) (Hazard Ratio(HR): 1.665, 95% CI: 1.026-2.703, p = 0.039), N stage (HR: 1.336, 95% CI: 1.106-1.615, p = 0.003), and T stage (HR: 1.268, 95% CI: 0.998-1.611, p = 0.052), which were included in the nomogram with a C-index of 0.71. The current data calculated TNM staging C-index was 0.68, and the p-value for the difference between the two models was 0.08. Internal validation revealed that the predicted overall survival did not differ significantly from the actual observed patient survival. Conclusion: The differential expression of IL-6 has a tendency to differentiate the prognosis of GC patients. IL-6, N stage, and T stage are independent prognostic factors, and the new survival prognostic model consisting of the above three indicators is better than the classical TNM staging system. Trial registration: This study is a retrospective study, which does not require clinical registration.
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INTRODUCTION: A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. METHODS: All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. RESULTS: Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%-99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p < 0.0001). The SVR12 rates were similar regardless of most baseline characteristics. The most common adverse event (AE) (≥ 10%) was hypercholesterolemia. Serious adverse events (SAEs) were reported in 25 (7.7%) patients, none of which was judged to be related to the study drug. The majority of AEs were mild to moderate in severity. CONCLUSIONS: Alfosbuvir plus daclatasvir for 12 weeks was highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3, or 6, suggesting that this regimen could be a promising option for HCV treatment in China irrespective of genotype. TRIAL REGISTRATION: ClinicalTrial.gov identifier, NCT04070235.
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Although accumulating evidence has revealed that autophagy inhibition contributes to the development of pathological cardiac hypertrophy, the mechanisms leading to declined autophagy activity in the hypertrophic heart remain to be elucidated. Exosomes are known to be important mediators of intercellular communication, and the involvement of exosomes in cardiovascular abnormities has attracted increasing attentions. Cardiac fibroblasts (CFs) are the most abundant cell type in the heart. Here, we investigated the potential role of CFs-derived exosomes in regulating cardiomyocyte hypertrophy and autophagy. Exosomes from rat CFs treated with angiotensin II (Ang II-CFs-exosomes) were collected and characterized. Our experiments showed that these exosomes could induce hypertrophic responses and impair autophagy activity in primary neonatal rat cardiomyocytes (NRCMs). Ang II-CFs-exosomes blocked the autophagic flux of NRCMs via inhibiting the formation of autolysosomes. Moreover, the pro-hypertrophic effects and autophagy inhibition induced by Ang II-CFs-exosomes was validated in mice receiving injection of the exosomes. These findings highlight a novel role of Ang II-CFs-exosomes in suppressing cardiomyocyte autophagy, which may help to better understand the pathogenesis of cardiac hypertrophy.
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Exosomas , Miocitos Cardíacos , Ratas , Ratones , Animales , Miocitos Cardíacos/metabolismo , Angiotensina II/metabolismo , Exosomas/metabolismo , Cardiomegalia/metabolismo , Autofagia , Fibroblastos/metabolismoRESUMEN
As a receptor for plant melatonin, CAND2/PMTR plays an important role in melatonin signaling. Most of the CANDs are membrane proteins and play indispensable roles in signal transduction. In this study, the CANDs from four cotton species were characterized, and the phylogenetic relationships, expression patterns, stress responses of cotton CANDs were analyzed by bioinformatics. Through the analysis of phylogenetic and protein structure, it was found that the CANDs in clade â ¡ might function as cotton melatonin receptors, and most of the GhCANDs in clade â ¡ were induced by melatonin. A putative cotton melatonin receptor, GhCAND2-D5, was functionally probed by gene silencing. The plants with silenced expression of this gene exhibited decreased salt tolerance. Protein interaction prediction identified that GhCAND2-D5 interacted with several membrane proteins and played an important role in melatonin signaling. This study provided a theoretical reference for further investigation of melatonin signaling in cotton.