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A long noncoding RNA (lncRNA) is longer than 200 bp. It regulates various biological processes mainly by interacting with DNA, RNA, or protein in multiple kinds of biological processes. Adenosine monophosphate-activated protein kinase (AMPK) is activated during nutrient starvation, especially glucose starvation and oxygen deficiency (hypoxia), and exposure to toxins that inhibit mitochondrial respiratory chain complex function. AMPK is an energy switch in organisms that controls cell growth and multiple cellular processes, including lipid and glucose metabolism, thereby maintaining intracellular energy homeostasis by activating catabolism and inhibiting anabolism. The AMPK signalling pathway consists of AMPK and its upstream and downstream targets. AMPK upstream targets include proteins such as the transforming growth factor ß-activated kinase 1 (TAK1), liver kinase B1 (LKB1), and calcium/calmodulin-dependent protein kinase ß (CaMKKß), and its downstream targets include proteins such as the mechanistic/mammalian target of rapamycin (mTOR) complex 1 (mTORC1), hepatocyte nuclear factor 4α (HNF4α), and silencing information regulatory 1 (SIRT1). In general, proteins function relatively independently and cooperate. In this article, a review of the currently known lncRNAs involved in the AMPK signalling pathway is presented and insights into the regulatory mechanisms involved in human ageing and age-related diseases are provided.
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The role of the aryl hydrocarbon receptor (AhR) in regulating oxidative stress and immune responses has been increasingly recognized. However, its involvement in depression and the underlying mechanisms remain poorly understood. This study aimed to investigate the effect of 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous AhR ligand, on a lipopolysaccharide (LPS)-induced depression model and the underlying mechanism. After being treated with FICZ (50 mg/kg), male C57BL/6J mice received intraperitoneal injection of LPS and underwent behavioral tests 24 h later. The levels of inflammatory cytokines, including IL-1ß, IL-6, and TNF-α, were measured in the hippocampus and serum using enzyme-linked immunosorbent assay (ELISA). The expression levels of CYP1A1, AhR and NLRP3 were analyzed using qPCR and Western blot. The results showed that, compared with control group, LPS alone significantly down-regulated the expression levels of CYP1A1 mRNA and AhR protein in the hippocampus of mice, reduced glucose preference, prolonged immobility time in forced swimming test, increased IL-6 and IL-1ß levels in the hippocampus, increased serum IL-1ß level, and up-regulated NLRP3 mRNA and protein expression levels in mouse hippocampus, while FICZ significantly reversed the aforementioned effects of LPS. These findings suggest that AhR activation attenuates the inflammatory response associated with depression and modulates the expression of NLRP3. The present study provides novel insights into the role of AhR in the development of depression, and presents AhR as a potential therapeutic target for the treatment of depression.
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Carbazoles , Citocromo P-450 CYP1A1 , Depresión , Hipocampo , Lipopolisacáridos , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Receptores de Hidrocarburo de Aril , Animales , Masculino , Ratones , Conducta Animal , Carbazoles/farmacología , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A1/genética , Citocinas/metabolismo , Depresión/metabolismo , Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/efectos adversos , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Peracetic acid (PAA) as emerging oxidant in advanced oxidation processes (AOPs) has attracted widespread attention in purifying water pollution. In this research, the removal of target contaminant (sulfamethoxazole, SMX) was investigated through PAA activation by a facile catalyst (Co@C), and the active sites of catalyst were identified as sp3-C, Oads, and Co0 by correlation analysis. Especially, different pH adjustment strategies were designed, including System A (adjusting pH after adding PAA) and System B (adjusting pH before adding PAA), to investigate the impact of oxidant acidity and alkalinity on solution microenvironment as well as effect and mechanism of pollutant removal. The results showed that HO· and CH3C(O)OO· dominated in System A, while Co(IV)O2+ was also observed in System B. Both systems showed optimal SMX degradation (98 %). However, System A exhibited excellent water quality tolerance (efficiency > 78 %), superior sustained catalyst activation (efficiency > 80 % in 40 h), less ion leaching (41 µg L-1), and lower products toxicity. Moreover, the pH of solution after reaction in System B was intensely acidic, requiring costly pH adjustments for discharge. This study unveils the strategy of adjusting pH after adding PAA is preferable for water purification, enriching the emerging research of PAA-based AOPs for the remediation of environments.
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Background: Observational researches reported the underlying correlation of plasma myeloperoxidase (MPO) concentration with respiratory tract infections (RTIs), but their causality remained unclear. Here, we examined the cause-effect relation between plasma MPO levels and RTIs. Materials and Methods: Datasets of plasma MPO levels were from the Folkersen et al. study (n = 21,758) and INTERVAL study (n = 3,301). Summarized data for upper respiratory tract infection (URTI) (2,795 cases and 483,689 controls) and lower respiratory tract infection (LRTI) in the intensive care unit (ICU) (585 cases and 430,780 controls) were from the UK Biobank database. The primary method for Mendelian randomization (MR) analysis was the inverse variance weighted approach, with MR-Egger and weighted median methods as supplements. Cochrane's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers global test, funnel plots, and leave-one-out analysis were used for sensitivity analysis. Results: We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011-1.274; P=0.032) and LRTI (ICU) (OR = 1.323; 95% CI = 1.006-1.739; P=0.045). The consistent impact direction is shown when additional plasma MPO level genome-wide association study datasets are used (URTI: OR = 1.158; 95% CI = 1.072-1.251; P < 0.001; LRTI (ICU): OR = 1.216; 95% CI = 1.020-1.450; P=0.030). There was no evidence of a causal effect of URTI and LRTI (ICU) on plasma MPO concentration in the reverse analysis (P > 0.050). The sensitivity analysis revealed no violations of MR presumptions. Conclusions: Plasma MPO levels may causally affect the risks of URTI and LRTI (ICU). In contrast, the causal role of URTI and LRTI (ICU) on plasma MPO concentration was not supported in our MR analysis. Further studies are needed to identify the relationship between RTIs and plasma MPO levels.
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Estudio de Asociación del Genoma Completo , Infecciones del Sistema Respiratorio , Humanos , Análisis de la Aleatorización Mendeliana , Bases de Datos Factuales , PeroxidasaRESUMEN
Background: Previous observational studies have investigated the association between educational attainment and sepsis, pneumonia, and urinary tract infections (UTIs). However, their findings have been susceptible to reverse causality and confounding factors. Furthermore, no study has examined the effect of educational level on the risk of infections of the skin and subcutaneous tissue (SSTIs). Thus, we aimed to evaluate the causal relationships between educational level and the risk of four infectious diseases using Mendelian randomisation (MR) techniques. Methods: We used univariable MR analysis to investigate the causal associations between educational attainment (years of schooling (n = 766 345) and holding college or university degree (n = 334 070)) and four infectious diseases (sepsis (n = 486 484), pneumonia (n = 486 484), UTIs (n = 463 010), and SSTIs (n = 218 792)). We included genetic instrumental variables with a genome-wide significance (P < 5 × 10-8) in the study. We used inverse variance-weighted estimation in the primary analysis and explored the stability of the results using multivariable MR analysis after adjusting for smoking, alcohol consumption, and body mass index. Results: Genetically predicted years of schooling were associated with a reduced risk of sepsis (odds ratio (OR) = 0.763; 95% confidence interval (CI) = 0.668-0.870, P = 5.525 × 10-5), pneumonia (OR = 0.637; 95% CI = 0.577-0.702, P = 1.875 × 10-19), UTIs (OR = 0.995; 95% CI = 0.993-0.997, P = 1.229 × 10-5), and SSTIs (OR = 0.696; 95% CI = 0.605-0.801, P = 4.034 × 10-7). We observed consistent results for the correlation between qualifications and infectious diseases. These findings remained stable in the multivariable MR analyses. Conclusions: Our findings suggest that increased educational attainment may be causally associated with a decreased risk of sepsis, pneumonia, UTIs, and SSTIs.
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Escolaridad , Análisis de la Aleatorización Mendeliana , Neumonía , Sepsis , Infecciones Urinarias , Humanos , Neumonía/epidemiología , Sepsis/epidemiología , Infecciones Urinarias/epidemiología , Enfermedades Transmisibles/epidemiología , Causalidad , Masculino , Factores de Riesgo , FemeninoRESUMEN
Tragopogon dubius Scopoli is native to Europe and western Asia and is considered an invasive plant in China. In this study, the complete chloroplast genome of T. dubius was obtained using high-throughput next-generation sequencing technology. The whole chloroplast genome was 153,017 bp long with a GC content of 38% and comprised 130 genes (86 protein-coding genes, 36 tRNA genes, and 8 rRNA genes). Phylogenetic analysis based on the concatenated chloroplast protein-coding sequences showed that T. dubius is most closely related to Tragopogon pratensis. This study provides valuable genetic data for further phylogenetic analysis and molecular identification of species in the genus Tragopogon.
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The dysfunction of matriptase, a membrane-anchored protease, is highly related to the progression of skin and breast cancers. Epidermal growth factor (EGF)-induced matriptase activation and cancer invasion are known but with obscure mechanisms. Here, we demonstrate a vesicular-trafficking-mediated interplay between matriptase and EGF signaling in cancer promotion. We found that EGF induces matriptase to undergo endocytosis together with the EGF receptor, followed by acid-induced activation in endosomes. Activated matriptase is then secreted extracellularly on exosomes to catalyze hepatocyte growth factor precursor (pro-HGF) cleavage, resulting in autocrine HGF/c-Met signaling. Matriptase-induced HGF/c-Met signaling represents the second signal wave of EGF, which promotes cancer cell scattering, migration, and invasion. These findings demonstrate a role of vesicular trafficking in efficient activation and secretion of membrane matriptase and a reciprocal regulation of matriptase and EGF signaling in cancer promotion, providing insights into the physiological functions of vesicular trafficking and the molecular pathological mechanisms of skin and breast cancers.
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Neoplasias de la Mama , Invasividad Neoplásica , Serina Endopeptidasas , Transducción de Señal , Animales , Femenino , Humanos , Ratones , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular , Endocitosis , Endosomas/metabolismo , Factor de Crecimiento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Exosomas/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Precursores de Proteínas , Proteínas Proto-Oncogénicas c-met/metabolismo , Serina Endopeptidasas/metabolismo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismoRESUMEN
Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype of breast cancer, characterized by aggressiveness and high recurrence rate. As monotherapy provides limited benefit to TNBC patients, combination therapy emerges as a promising treatment approach. Gambogic acid (GA) is an exceedingly promising anticancer agent. Nonetheless, its application potential is hampered by low drug loading efficiency and associated toxic side effects. To overcome these limitations, using mesoporous polydopamine (MPDA) endowed with photothermal conversion capabilities is considered as a delivery vehicle for GA. Meanwhile, GA can inhibit the activity of heat shock protein 90 (HSP90) to enhance the photothermal effect. Herein, GA-loaded MPDA nanoparticles (GA@MPDA NPs) are developed with a high drug loading rate of 75.96% and remarkable photothermal conversion performance. GA@MPDA NPs combined with photothermal treatment (PTT) significantly inhibit the tumor growth, and effectively trigger the immunogenic cell death (ICD), which thereby increase the number of activated effector T cells (CD8+ T cells and CD4+ T cells) in the tumor, and hoist the level of immune-inflammatory cytokines (IFN-γ, IL-6, and TNF-α). The above results suggest that the combination of GA@MPDA NPs with PTT expected to activate the antitumor immune response, thus potentially enhancing the clinical therapeutic effect on TNBC.
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Indoles , Polímeros , Neoplasias de la Mama Triple Negativas , Xantonas , Xantonas/química , Xantonas/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Indoles/química , Indoles/farmacología , Polímeros/química , Humanos , Animales , Línea Celular Tumoral , Femenino , Porosidad , Ratones , Nanopartículas/químicaRESUMEN
The plastid genomes (plastomes) of angiosperms are typically highly conserved, with extreme reconfiguration being uncommon, although reports of such events have emerged in some lineages. In this study, we conducted a comprehensive comparison of the complete plastomes from twenty-two species, covering seventeen genera from three subfamilies (Fumarioideae, Hypecooideae, and Papaveroideae) of Papaveraceae. Our results revealed a high level of variability in the plastid genome size of Papaveraceae, ranging from 151,864 bp to 219,144 bp in length, which might be triggered by the expansion of the IR region and a large number of repeat sequences. Moreover, we detected numerous large-scale rearrangements, primarily occurring in the plastomes of Fumarioideae and Hypecooideae. Frequent gene loss or pseudogenization were also observed for ndhs, accD, clpP, infA, rpl2, rpl20, rpl32, rps16, and several tRNA genes, particularly in Fumarioideae and Hypecooideae, which might be associated with the structural variation in their plastomes. Furthermore, we found that the plastomes of Fumarioideae exhibited a higher GC content and more repeat sequences than those of Papaveroideae. Our results showed that Papaveroideae generally displayed a relatively conserved plastome, with the exception of Eomecon chionantha, while Fumarioideae and Hypecooideae typically harbored highly reconfigurable plastomes, showing high variability in the genome size, gene content, and gene order. This study provides insights into the plastome evolution of Papaveraceae and may contribute to the development of effective molecular markers.
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Genoma de Plastidios , Papaveraceae , Filogenia , Papaveraceae/genética , Secuencias Repetitivas de Ácidos Nucleicos , Reordenamiento Génico , Evolución MolecularRESUMEN
INTRODUCTION: Ulcerative colitis (UC) is one of the most common diseases in the gastrointestinal tract related to abnormal inflammation. Pyroptosis, which is characterized by the formation of inflammasome, activation of caspase-1, and separation of N- and C-terminus of gasdermin D (GSDMD), and may be involved in the pathogenesis of IBD. Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor expressed in differentiated epithelial cells. KLF4 mediates proinflammatory signaling in macrophages. Here, we tested whether KLF4 is functional in pyroptosis of UC. METHODS: In human UC tissues and/or lipopolysaccharide (LPS)/adenosine 5-triphosphate (ATP) stimulation human colon epithelial cells, KLF4, TXNIP, Cleave-Caspase-1, and GSDMD expression were detected through quantitative reverse transcription polymerase chain reaction (PCR), immunohistochemical and western blot assay. Interleukin (IL)-1ß and IL-18 levels were quantified by enzyme-linked immunosorbent assay. We successfully constructed a KLF4-silenced colon epithelial cell line using an adenovirus vector. We apply the UCSC and JASPAR to predict the KLF4 binding sites in the promoter region of TXNIP. RESULTS: In human UC tissues and/or LPS/ATP stimulation human colon epithelial cells, KLF4, TXNIP, Caspase-1, and GSDMD expression level were significantly elevated via quantitative reverse transcription PCR, immunohistochemical and western blot assay. Moreover, We identified that there is an interaction between KLF4 and TXNIP through Yeast double hybrid assay and CO-IP assay. We successfully constructed a KLF4-silenced human intestinal epithelial cell line. In LPS/ATP stimulation KLF4-silenced human intestinal epithelial cells, KLF4, TXNIP, Cleave Caspase-1, ASC, and GSDMD expression level were significantly decreased via quantitative reverse transcription PCR. CONCLUSION: Our results confirm that KLF4 can positively regulate the expression of TXNIP and regulate the pyroptosis process of UC through the TXNIP/NLRP3 pathway.
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Colitis Ulcerosa , Proteína con Dominio Pirina 3 de la Familia NLR , Humanos , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Piroptosis , Lipopolisacáridos/farmacología , Factor 4 Similar a Kruppel , Caspasas/metabolismo , Adenosina Trifosfato , Proteínas Portadoras/genéticaRESUMEN
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening syndrome induced by various diseases, including COVID-19. In the progression of ALI/ARDS, activated neutrophils play a central role by releasing various inflammatory mediators, including elastase. Sivelestat is a selective and competitive inhibitor of neutrophil elastase. Although its protective effects on attenuating ALI/ARDS have been confirmed in several models of lung injury, clinical trials have presented inconsistent results on its therapeutic efficacy. Therefore, in this report, we used a network pharmacology approach coupled with animal experimental validation to unravel the concrete therapeutic targets and biological mechanisms of sivelestat in treating ALI/ARDS. In bioinformatic analyses, we found 118 targets of sivelestat against ALI/ARDS, and identified six hub genes essential for sivelestat treatment of ALI/ARDS, namely ERBB2, GRB2, PTK2, PTPN11, ESR1, and CCND1. We also found that sivelestat targeted several genes expressed in human lung microvascular endothelial cells after lipopolysaccharide (LPS) treatment at 4 h (ICAM-1, PTGS2, RND1, BCL2A1, TNF, CA2, and ADORA2A), 8 h (ICAM-1, PTGS2, RND1, BCL2A1, MMP1, BDKRB1 and SLC40A1), and 24 h (ICAM-1). Further animal experiments showed that sivelestat was able to attenuate LPS-induced ALI by inhibiting the overexpression of ICAM-1, VCAM-1, and PTGS2 and increasing the phosphorylation of PTK2. Taken together, the bioinformatic findings and experimentative data indicate that the therapeutic effects of sivelestat against ALI/ARDS mainly focus on the early stage of ALI/ARDS by pharmacological modulation of inflammatory reaction, vascular endothelial injury, and cell apoptosis-related molecules.
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Lesión Pulmonar Aguda , Glicina/análogos & derivados , Síndrome de Dificultad Respiratoria , Sulfonamidas , Animales , Humanos , Molécula 1 de Adhesión Intercelular/uso terapéutico , Células Endoteliales , Lipopolisacáridos/uso terapéutico , Ciclooxigenasa 2/uso terapéutico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Pulmón , Proteínas de Unión al GTP rho/uso terapéuticoRESUMEN
The Himalaya-Hengduan Mountains (HHM), a renowned biodiversity hotspot of the world, harbors the most extensive habitats for alpine plants with extraordinary high levels of endemism. Although the general evolution pattern has been elucidated, the underlying processes driving spectacular radiations in many species-rich groups remain elusive. Corydalis DC. is widely distributed throughout the Northern Hemisphere containing more than 500 species, with high diversity in HHM and adjacent regions. Using 95 plastid genes, 3,258,640 nuclear single nucleotide polymorphisms (SNPs) and eight single-copy nuclear genes (SCNs) generated from genome skimming data, we reconstructed a robust time-calibrated phylogeny of Corydalis comprising more than 100 species that represented all subgenera and most sections. Molecular dating indicated that all main clades of Corydalis began to diverge in the Eocene, with the majority of extant species in HHM emerged from a diversification burst after the middle Miocene. Global pattern of mean divergence times indicated that species distributed in HHM were considerably younger than those in other regions, particularly for the two most species-rich clades (V and VI) of Corydalis. The early divergence and the recent diversification of Corydalis were most likely promoted by the continuous orogenesis and climate change associated with the uplift of the Qinghai-Tibetan Plateau (QTP). Our study demonstrates the effectivity of phylogenomic analyses with genome skimming data on the phylogeny of species-rich taxa, and sheds lights on how the uplift of QTP has triggered the evolutionary radiations of large plant genera in HHM and adjacent regions.
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Corydalis , Filogenia , Himalayas , Biodiversidad , Ecosistema , PlantasRESUMEN
Endosymbiotic fungi play an important role in the growth and development of insects. Understanding the endosymbiont communities hosted by the brown planthopper (BPH; Nilaparvata lugens Stål), the most destructive pest in rice, is a prerequisite for controlling BPH rice infestations. However, the endosymbiont diversity and dynamics of the BPH remain poorly studied. Here, we used circular consensus sequencing (CCS) to obtain 87,131 OTUs (operational taxonomic units), which annotated 730 species of endosymbiotic fungi in the various developmental stages and tissues. We found that three yeast-like symbionts (YLSs), Polycephalomyces prolificus, Ophiocordyceps heteropoda, and Hirsutella proturicola, were dominant in almost all samples, which was especially pronounced in instar nymphs 4-5, female adults, and the fat bodies of female and male adult BPH. Interestingly, honeydew as the only in vitro sample had a unique community structure. Various diversity indices might indicate the different activity of endosymbionts in these stages and tissues. The biomarkers analyzed using LEfSe suggested some special functions of samples at different developmental stages of growth and the active functions of specific tissues in different sexes. Finally, we found that the incidence of occurrence of three species of Malassezia and Fusarium sp. was higher in males than in females in all comparison groups. In summary, our study provides a comprehensive survey of symbiotic fungi in the BPH, which complements the previous research on YLSs. These results offer new theoretical insights and practical implications for novel pest management strategies to understand the BPH-microbe symbiosis and devise effective pest control strategies.
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BACKGROUND: School bullying is a prevalent issue that threatens the psychological and social well-being of adolescents. However, little research has investigated how gender and family variables were related to bullying-involvement patterns among adolescents with siblings. OBJECTIVE: This study explored gender differences in the profiles of bullying involvement and the relationship between sibling, parental variables, and these profiles among Chinese adolescents. PARTICIPANTS AND SETTING: Participants (N = 1,060; 46.0 % boys; Mage = 15.53) were recruited from junior and senior high schools in Jiangxi and Guizhou Provinces, China. METHODS: Bullying involvement, sibling warmth and conflict, and parental psychological maltreatment and neglect were assessed by self-report questionnaire. Latent profile analysis was used to identify subgroups with distinct bullying involvement patterns, then multiple logistic regressions were performed to investigate the associations between family variables and bullying-involvement subgroups. RESULTS: We found gender differences in both the latent profiles of bullying involvement and the associations between profiles and family variables. Only boys were identified severe bully-victims (3.39 %), while only girls were categorized as relational bully-victims (20.18 %). Boys and girls were similarly represented among uninvolved students (70.76 % vs. 66.85 %), moderate bully-victims (15.25 % vs. 6.49 %), and victims (10.59 % vs. 6.49 %). Students with more sibling warmth manifested less likelihood of engaging in bullying-related profiles, with more parental psychological maltreatment, and more parental neglect manifested more likelihood of engaging in bullying-related profiles only among girls. While students with more sibling conflict were related to more bullying-related profiles among boys than girls. CONCLUSIONS: The findings emphasize the importance of developing gender-specific bullying intervention strategies that also consider relevant family factors.
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Acoso Escolar , Víctimas de Crimen , Masculino , Femenino , Adolescente , Humanos , Factores Sexuales , Acoso Escolar/psicología , Víctimas de Crimen/psicología , Instituciones Académicas , Encuestas y CuestionariosRESUMEN
Twenty-five percent of cervical cancers are classified as endocervical adenocarcinomas (EACs), which comprise a highly heterogeneous group of tumors. A histopathologic risk stratification system known as the Silva pattern system was developed based on morphology. However, accurately classifying such patterns can be challenging. The study objective was to develop a deep learning pipeline (Silva3-AI) that automatically analyzes whole slide image-based histopathologic images and identifies Silva patterns with high accuracy. Initially, a total of 202 patients with EACs and histopathologic slides were obtained from Qilu Hospital of Shandong University for developing and internally testing the Silva3-AI model. Subsequently, an additional 161 patients and slides were collected from seven other medical centers for independent testing. The Silva3-AI model was developed using a vision transformer and recurrent neural network architecture, utilizing multi-magnification patches, and its performance was evaluated based on a class-specific area under the receiver-operating characteristic curve. Silva3-AI achieved a class-specific area under the receiver-operating characteristic curve of 0.947 for Silva A, 0.908 for Silva B, and 0.947 for Silva C on the independent test set. Notably, the performance of Silva3-AI was consistent with that of professional pathologists with 10 years' diagnostic experience. Furthermore, the visualization of prediction heatmaps facilitated the identification of tumor microenvironment heterogeneity, which is known to contribute to variations in Silva patterns.
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Adenocarcinoma , Aprendizaje Profundo , Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/patología , Redes Neurales de la Computación , Curva ROC , Adenocarcinoma/patología , Microambiente TumoralRESUMEN
OBJECTIVES: To understand the growth and development status and differences between small for gestational age (SGA) and appropriate for gestational age (AGA) preterm infants during corrected ages 0-24 months, and to provide a basis for early health interventions for preterm infants. METHODS: A retrospective study was conducted, selecting 824 preterm infants who received regular health care at the Guangzhou Women and Children's Medical Center from July 2019 to July 2022, including 144 SGA and 680 AGA infants. The growth data of SGA and AGA groups at birth and corrected ages 0-24 months were analyzed and compared. RESULTS: The SGA group had significantly lower weight and length than the AGA group at corrected ages 0-18 months (P<0.05), while there were no significant differences between the two groups at corrected age 24 months (P>0.05). At corrected age 24 months, 85% (34/40) of SGA and 79% (74/94) of AGA preterm infants achieved catch-up growth. Stratified analysis by gestational age showed that there were significant differences in weight and length at corrected ages 0-9 months between the SGA subgroup with gestational age <34 weeks and the AGA subgroups with gestational age <34 weeks and 34 weeks (P<0.05). In addition, the weight and length of the SGA subgroup with gestational age 34 weeks showed significant differences compared to the AGA subgroups with gestational age <34 weeks and 34 weeks at corrected ages 0-18 months and corrected ages 0-12 months, respectively (P<0.05). Catch-up growth for SGA infants with gestational age <34 weeks and 34 weeks mainly occurred at corrected ages 0-12 months and corrected ages 0-18 months, respectively. CONCLUSIONS: SGA infants exhibit delayed early-life physical growth compared to AGA infants, but can achieve a higher proportion of catch-up growth by corrected age 24 months than AGA infants. Catch-up growth can be achieved earlier in SGA infants with a gestational age of <34 weeks compared to those with 34 weeks.
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Recien Nacido Prematuro , Recién Nacido Pequeño para la Edad Gestacional , Recién Nacido , Niño , Lactante , Femenino , Humanos , Preescolar , Edad Gestacional , Estudios Longitudinales , Estudios RetrospectivosRESUMEN
BACKGROUND: Neurodegenerative disease is a collective term for a category of diseases that are caused by neuronal dysfunction, such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Circular RNAs (circRNAs) are a class of non-coding RNAs without the 3' cap and 5' poly(A) and are linked by covalent bonds. CircRNAs are highly expressed in brain neurons and can regulate the pathological process of neurodegenerative diseases by affecting the levels of various deposition proteins. AIMS: This review is aiming to suggest that the majority of circRNAs influence neurodegenerative pathologies mainly by affecting the abnormal deposition of proteins in neurodegenerative diseases. METHODS: We systematically summarized the pathological features of neurodegenerative diseases and the regulatory mechanisms of circRNAs in various types of neurodegenerative diseases. RESULTS: Neurodegenerative disease main features include intercellular ubiquitin-proteasome system abnormalities, changes in cytoskeletal proteins, and the continuous deposition of insoluble protein fragments and inclusion bodies in the cytoplasm or nucleus, resulting in impairment of the normal physiological processes of the neuronal system. CircRNAs have multiple mechanisms, such as acting as microRNA sponges, binding to proteins, and regulating transcription. CircRNAs, which are highly stable molecules, are expected to be potential biomarkers for the pathological detection of neurodegenerative diseases such as AD and PD. CONCLUSIONS: In this review, we describe the regulatory roles and mechanisms of circRNAs in neurodegenerative diseases and aim to employ circRNAs as biomarkers for the diagnosis and treatment of neurodegenerative diseases.
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Enfermedad de Alzheimer , MicroARNs , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/genética , ARN Circular/metabolismo , MicroARNs/genética , Enfermedad de Alzheimer/genética , BiomarcadoresRESUMEN
Esophageal cancer (EC) treatment via anti-angiogenic therapy faces challenges due to non-cytotoxicity and non-specific biodistribution of the anti-angiogenic agents. Hence, the quest for a synergistic treatment modality and a targeted delivery approach to effectively address EC has become imperative. In this study, an acid-responsive release nanosystem (Bev-IR820@FeIII TA) that involves the conjugation of bevacizumab, an anti-angiogenic monoclonal antibody, with TA and Fe3+ to form a metal-phenolic network, followed by loading with the near-infrared photothermal agent (IR820) to achieve combinational therapy, is designed. The construction of Bev-IR820@FeIII TA can be realized through a facile self-assembly process. The Bev-IR820@FeIII TA exhibits tumor-targeting capabilities and synergistic therapeutic effects, encompassing anti-angiogenic therapy, photothermal therapy (PTT), and ferroptosis therapy (FT). Bev-IR820@FeIII TA exhibits remarkable proficiency in delivering drugs to EC tissue through its pH-responsive release properties. Consequently, bevacizumab exerts its therapeutic effects by obstructing tumor angiogenesis, thereby impeding tumor growth. Meanwhile, PTT facilitates localized thermal ablation at the tumor site, directly eradicating EC cells. FT synergistically collaborates with PTT, giving rise to the formation of a reactive oxygen species (ROS) storm, subsequently culminating in the demise of EC cells. In summary, this amalgamated treatment modality carries substantial promise for synergistically impeding EC progression and showcases auspicious prospects for future EC treatment.
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Neoplasias Esofágicas , Ferroptosis , Humanos , Terapia Fototérmica , Bevacizumab/farmacología , Bevacizumab/uso terapéutico , Compuestos Férricos , Distribución Tisular , Neoplasias Esofágicas/tratamiento farmacológicoRESUMEN
Ageing is an evolutionarily conserved and irreversible biological process in different species. Numerous studies have reported that taking medicine is an effective approach to slow ageing. Lemon extract (LE) is a natural extract of lemon fruit that contains a variety of bioactive phytochemicals. Various forms of LE have been shown to play a role in anti-ageing and improving ageing-related diseases. However, studies on the molecular mechanism of LE in Drosophila ageing have not been reported. In this study, we found that 0.05 g/L LE could significantly extend Drosophila lifespan and greatly improve antioxidative and anti-heat stress abilities. Furthermore, transcriptome and metabolome analyses of 10 d flies between the LE-fed and control groups suggested that the differentially expressed gene ppo1 (Prophenoloxidase 1) and metabolite L-DOPA (Levodopa) were co-enriched in the tyrosine metabolism pathway. Overall, our results indicate that affecting metabolism was the main reason for LE extending Drosophila lifespan.
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Drosophila , Longevidad , Animales , Drosophila/genética , Longevidad/genética , Drosophila melanogaster/genética , Transcriptoma , Perfilación de la Expresión Génica , Extractos Vegetales/farmacologíaRESUMEN
Background: Gastroblastoma is an extremely rare stomach tumor with a biphasic cell morphology of epithelioid and spindle cells. Due to the low incidence rate and the lack of specific clinical characteristics, it is easy to misdiagnose. Detailed imaging analysis is also unavailable. At present, we reported a case of gastroblastoma to analyze its clinical and imaging characteristics. In addition, we reviewed the imaging findings, current diagnosis, treatment, and outcome of gastroblastoma. Case presentation: A 5-year-old girl was admitted to our hospital with upper abdominal pain and melena. Endoscopic examination showed a protuberant submucosal mass on the greater curvature of the gastric body. Abdominal ultrasonography and an abdominal enhanced computed tomography further confirmed the mass. The patient was pathologically diagnosed with gastroblastoma after radical surgery in February 2021. Conclusion: We described a rare case of gastroblastoma and may provide a new perspective on imaging diagnosis, treatment, and outcome of this tumor. Gastroblastoma tends to occur in male patients, typically affects young people, and has low malignant potential and a low rate of recurrence and metastasis. Gastroblastoma usually arises in the gastric muscularis propria with hypoecogenic and submucosal characteristics in ultrasound examination and significant enhancement in computed tomography (CT) scan. Surgical resection and regular follow-up after surgery are the main management of the disease. Clinicians should strengthen the understanding of this rare tumor for early detection and treatment.