RESUMO
BACKGROUND: Lumbar spondylolysis is a common cause of low back pain in adolescents. A lot of adolescent idiopathic scoliosis with concomitant spondylolysis has been reported before, but only two cases with acquired spondylolysis following long fusion for scoliosis were reported. We described another similar rare case and discussed its causes and treatment options in this paper. CASE PRESENTATION: A 17-year-old female underwent growing rod implantation, growing rod extension, and final long spinal fusion for idiopathic scoliosis. Then, she suffered from low back pain with a VAS of 1-2 points and gradually aggravated to a VAS of 7-8 points at 3.5 years after the final fusion. The X-ray images showed that there was L4-S1 instability. And the CT scan images showed new bilateral spondylolysis of L5. CONCLUSIONS: These findings suggested that distal mechanical stress might cause spondylolysis of the distal vertebra following long fusion for scoliosis. Surgeons should keep instrumentation as short as possible and avoid choosing a low lumbar as LIV when they decide on the fusion levels.
RESUMO
Background: Kawasaki disease (KD) has been considered as the most common required pediatric cardiovascular diseases among the world. However, the molecular mechanisms of KD were not fully underlined, leading to a confused situation in disease management and providing precious prognosis prediction. The disorders of gut microbiome had been identified among several cardiovascular diseases and inflammation conditions. Therefore, it is urgent to elucidate the characteristics of gut microbiome in KD and demonstrate its potential role in regulating intravenous immunoglobulin (IVIG) resistance and coronary artery injuries. Methods: A total of 96 KD children and 62 controls were enrolled in the study. One hundred forty fecal samples had been harvested from KD patients, including individuals before or after IVIG treatment, with or without early coronary artery lesions and IVIG resistance. Fecal samples had been collected before and after IVIG administration and stored at -80°C. Then, metagenomic analysis had been done using Illumina NovaSeq 6000 platform. After that, the different strains and functional differences among comparisons were identified. Results: First, significant changes had been observed between KD and their controls. We found that the decrease of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides uniformis, and Bacteroides ovatus and the increase of pathogenic bacteria Finegoldia magna, Abiotrophia defectiva, and Anaerococcus prevotii perhaps closely related to the incidence of KD. Then, metagenomic and responding functional analysis demonstrated that short-chain fatty acid pathways and related strains were associated with different outcomes of therapeutic efficacies. Among them, the reduction of Bacteroides thetaiotaomicron, the enrichment of Enterococcus faecalis and antibiotic resistance genes had been found to be involved in IVIG resistance of KD. Moreover, our data also revealed several potential pathogenetic microbiome of that KD patients with coronary artery lesions. Conclusion: These results strongly proved that distinct changes in the gut microbiome of KD and the dysfunction of gut microbiomes should be responsible for the pathogenesis of KD and significantly impact the prognosis of KD.
Assuntos
Fezes , Microbioma Gastrointestinal , Metagenômica , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/microbiologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Microbioma Gastrointestinal/genética , Masculino , Metagenômica/métodos , Feminino , Pré-Escolar , Lactente , Fezes/microbiologia , Imunoglobulinas Intravenosas/uso terapêutico , Metagenoma , Criança , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Estudos de Casos e ControlesRESUMO
Background: Sepsis represents a severe manifestation of infection often accompanied by metabolic disorders and mitochondrial dysfunction. Notably, mitochondrial DNA copy number (mtDNA-CN) and the expression of specific mitochondrial genes have emerged as sensitive indicators of mitochondrial function. To investigate the utility of mitochondrial gene expression in peripheral blood cells for distinguishing severe infections and predicting associated outcomes, we conducted a prospective cohort study. Methods: We established a prospective cohort comprising 74 patients with non-sepsis pneumonia and 67 cases of sepsis induced by respiratory infections, aging from 2 to 6 years old. We documented corresponding clinical data and laboratory information and collected blood samples upon initial hospital admission. Peripheral blood cells were promptly isolated, and both total DNA and RNA were extracted. We utilized absolute quantification PCR to assess mtDNA-CN, as well as the expression levels of mt-CO1, mt-ND1, and mt-ATP6. Subsequently, we extended these comparisons to include survivors and non-survivors among patients with sepsis using univariate and multivariate analyses. Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic potential. Results: The mtDNA-CN in peripheral blood cells was significantly lower in the sepsis group. Univariate analysis revealed a significant reduction in the expression of mt-CO1, mt-ND1, and mt-ATP6 in patients with sepsis. However, multivariate analysis did not support the use of mitochondrial function in peripheral blood cells for sepsis diagnosis. In the comparison between pediatric sepsis survivors and non-survivors, univariate analysis indicated a substantial reduction in the expression of mt-CO1, mt-ND1, and mt-ATP6 among non-survivors. Notably, total bilirubin (TB), mt-CO1, mt-ND1, and mt-ATP6 levels were identified as independent risk factors for sepsis-induced mortality. ROC curves were then established for these independent risk factors, revealing areas under the curve (AUCs) of 0.753 for TB (95% CI 0.596-0.910), 0.870 for mt-CO1 (95% CI 0.775-0.965), 0.987 for mt-ND1 (95% CI 0.964-1.000), and 0.877 for mt-ATP6 (95% CI 0.793-0.962). Conclusion: MtDNA-CN and mitochondrial gene expression are closely linked to the severity and clinical outcomes of infectious diseases. Severe infections lead to impaired mitochondrial function in peripheral blood cells. Notably, when compared to other laboratory parameters, the expression levels of mt-CO1, mt-ND1, and mt-ATP6 demonstrate promising potential for assessing the prognosis of pediatric sepsis.
Assuntos
DNA Mitocondrial , Curva ROC , Sepse , Humanos , Sepse/sangue , Sepse/diagnóstico , Sepse/mortalidade , Pré-Escolar , Feminino , Masculino , DNA Mitocondrial/genética , Estudos Prospectivos , Prognóstico , Criança , Mitocôndrias/genética , Mitocôndrias/metabolismo , NADH Desidrogenase/genética , ATPases Mitocondriais Próton-Translocadoras/genética , Células Sanguíneas/metabolismo , Genes Mitocondriais , Expressão Gênica , Pneumonia/diagnóstico , Pneumonia/sangue , Valor Preditivo dos TestesRESUMO
INTRODUCTION: Liver fibrosis is primarily driven by the activation of hepatic stellate cells (HSCs), which involves various epigenetic modifications. OBJECTIVES: N6-methyladenosine (m6A), the most prevalent RNA modification in eukaryotic cells, influences numerous physiological and pathological processes. Nevertheless, the role of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), a reader gene mediating m6A modifications, in liver fibrosis remains unclear. METHODS AND RESULTS: This study demonstrated that IGF2BP3 knockout reduces liver fibrosis by promoting HSC ferroptosis (FPT) and inactivating HSCs. Multi-omics analysis revealed that HSC-specific IGF2BP3 knockout decreased m6A content in Jagged1 (Jag1), a key component of the Notch signalling pathway. Furthermore, IGF2BP3 deficiency significantly reduced the expression of hairy and enhancer of split-1 (Hes1), a transcription factor in the Notch/Jag1 signalling pathway, with mRNA levels declining to 35%-62% and protein levels to 28%-35%. Additionally, it suppressed glutathione peroxidase 4 (GPX4) (decreased to approximately 31%-38%), a negative regulator of FPT, thereby facilitating HSC FPT progression and reducing profibrotic gene expression. CONCLUSION: These findings uncover a novel IGF2BP3/Notch/Jag1 signalling pathway involving HSC FPT, suggesting promising targets for ameliorating liver fibrosis. KEY POINTS/HIGHLIGHTS: IGF2BP3 deficiency inactivates Jag1 signalling. IGF2BP3 deficiency-mediated m6A modifications promote HSC ferroptosis. IGF2BP3 inhibition facilitates ferroptosis in HSCs via the Hes1/GPX4 axis. IGF2BP3 deficiency inactivates Jag1/Notch1/3/Hes1 signalling pathway inactivation, leading to the decrease in GPX4, which contributes to HSC ferroptosis.
Assuntos
Ferroptose , Células Estreladas do Fígado , Proteína Jagged-1 , Cirrose Hepática , Proteínas de Ligação a RNA , Receptores Notch , Transdução de Sinais , Ferroptose/genética , Células Estreladas do Fígado/metabolismo , Animais , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais/genética , Receptores Notch/metabolismo , Receptores Notch/genética , Camundongos Knockout , Masculino , HumanosRESUMO
OBJECTIVES: Blood cell-free DNA (cfDNA) can be a new reliable tool for detecting epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. However, the currently reported cfDNA assays have a limited role in detecting drug-resistant mutations due to their deficiencies in sensitivity, stability, or mutation detection rate. METHODS: We developed an Archaeoglobus fulgidus-derived flap endonuclease (Afu FEN)-based DNA-enhanced amplification system of mutated cfDNA by designing a pair of hairpin probes to anneal with wild-type cfDNA to form two 5'-flaps, allowing for the specific cleavage of wild-type cfDNA by Afu FEN. When the dominant wild-type somatic cfDNA fragments were cleaved by structure-recognition-specific Afu FEN, the proportion of mutated cfDNA in the reaction system was greatly enriched. As the amount of mutated cfDNA in the system was further increased by PCR amplification, the mutation status could be easily detected through first-generation sequencing. RESULTS: In a mixture of synthetic wild-type and T790M EGFR DNA fragments, our new assay still could detect T790M mutation at the fg level with remarkably high sensitivity. We also tested its performance in detecting low variant allele frequency (VAF) mutations in clinical samples from NSCLC patients. The plasma cfDNA samples with low VAF (0.1 and 0.5â¯%) could be easily detected by DNA-enhanced amplification. CONCLUSIONS: This system with enhanced amplification of mutated cfDNA is an effective tool used for the early screening and individualized targeted therapy of NSCLC by providing a rapid, sensitive, and economical way for the detection of drug-resistant mutations in tumors.
RESUMO
Rationale: Device implantation frequently triggers cardiac remodeling and fibrosis, with monocyte-driven inflammatory responses precipitating arrhythmias. This study investigates the role of m6A modification enzymes METTL3 and METTL14 in these responses and explores a novel therapeutic strategy targeting these modifications to mitigate cardiac remodeling and fibrosis. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from patients with ventricular septal defects (VSD) who developed conduction blocks post-occluder implantation. The expression of METTL3 and METTL14 in PBMCs was measured. METTL3 and METTL14 deficiencies were induced to evaluate their effect on angiotensin II (Ang II)-induced myocardial inflammation and fibrosis. m6A modifications were analyzed using methylated RNA immunoprecipitation followed by quantitative PCR. NF-κB pathway activity and levels of monocyte migration and fibrogenesis markers (CXCR2 and TGF-ß1) were assessed. An erythrocyte microvesicle-based nanomedicine delivery system was developed to target activated monocytes, utilizing the METTL3 inhibitor STM2457. Cardiac function was evaluated via echocardiography. Results: Significant upregulation of METTL3 and METTL14 was observed in PBMCs from patients with VSD occluder implantation-associated persistent conduction block. Deficiencies in METTL3 and METTL14 significantly reduced Ang II-induced myocardial inflammation and fibrosis by decreasing m6A modification on MyD88 and TGF-ß1 mRNAs. This disruption reduced NF-κB pathway activation, lowered CXCR2 and TGF-ß1 levels, attenuated monocyte migration and fibrogenesis, and alleviated cardiac remodeling. The erythrocyte microvesicle-based nanomedicine delivery system effectively targeted inflamed cardiac tissue, reducing inflammation and fibrosis and improving cardiac function. Conclusion: Inhibiting METTL3 and METTL14 in monocytes disrupts the NF-κB feedback loop, decreases monocyte migration and fibrogenesis, and improves cardiac function. Targeting m6A modifications of monocytes with STM2457, delivered via erythrocyte microvesicles, reduces inflammation and fibrosis, offering a promising therapeutic strategy for cardiac remodeling associated with device implantation.
Assuntos
Fibrose , Metiltransferases , Monócitos , NF-kappa B , Humanos , Metiltransferases/metabolismo , Metiltransferases/genética , Monócitos/metabolismo , Masculino , Animais , NF-kappa B/metabolismo , Eritrócitos/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Feminino , Metilação , Camundongos , Fator de Crescimento Transformador beta1/metabolismo , Micropartículas Derivadas de Células/metabolismo , Leucócitos Mononucleares/metabolismo , Angiotensina II/metabolismo , Receptores de Interleucina-8B/metabolismo , Receptores de Interleucina-8B/genética , Remodelação Ventricular , Miocárdio/metabolismo , Miocárdio/patologia , Nanomedicina/métodosRESUMO
Chronic pain can induce mood disorders and cognitive dysfunctions, such as anxiety, depression, and learning and memory impairment in humans. However, the specific neural network involved in anxiety- and depression-like behaviors and learning and memory impairment caused by chronic pain remains poorly understood. In this study, behavioral test results showed that chronic pain induced anxiety- and depression-like behaviors, and learning and memory impairment in male mice. c-Fos immunofluorescence and fiber photometry recording showed that glutamatergic neurons in the LH of mice with chronic pain were selectively activated. Next, the glutamatergic neurons of LH in normal mice were activated using optogenetic and chemogenetic methods, which recapitulates some of the depressive-like behaviors, as well as memory impairment, but not anxiety-like behavior. Finally, inhibition of glutamatergic neurons in the LH of mice with chronic pain, effectively relieved anxiety- and depression-like behaviors and learning and memory impairment. Taken together, our findings suggest that hyperexcitation of glutamatergic neurons in the LH is involved in depression-like behavior and learning and memory impairment induced by chronic pain.
RESUMO
The increasing prevalence and incidence of colorectal cancer (CRC), particularly in young adults, underscore the imperative to comprehend its fundamental mechanisms, discover novel diagnostic and prognostic markers, and enhance therapeutic strategies. Here, we integrated multi-omics data, including gene expression, somatic mutation data and DNA methylation data, to unravel the intricacies of tumor microenvironment (TME) in CRC and search for novel prognostic markers. By calculating the immune score for each patient from the expression profile, we delineated the differential immune cell fraction, constructed an immune-related multi-omics atlas, and identified molecular characteristics. The entire colorectal dataset (n = 343) was randomly divided into training (n = 249) and testing datasets (n = 94). We screened 144 immune-related genes, 6 mutant genes, and 38 methylation probes associated with overall survival (OS). These makers were then incorporated into a 10-gene prognostic model using Lasso and Cox regression in the training dataset, and the model's performance was evaluated in an independent validation dataset. The model exhibited satisfactory results (average concordance index [C-index] = 0.77), with the average 1-year, 3-year, and 5-year AUCs being 0.79, 0.76, and 0.76 in the training dataset and 0.74, 0.80, and 0.90 in the testing dataset. Furthermore, the prognostic model demonstrated applicability in guiding chemotherapy for CRC patients and exhibited a degree of pan-cancer utility in risk stratification. In conclusion, our integrated analysis of multi-omics data revealed immune-related genetic and epigenetic characteristics of the TME. We propose an integrative prognostic model that can stratify risk and guide chemotherapy for CRC patients. The generalizability of the model in risk stratification across different cancer types was validated in Pan-Cancer cohort.
RESUMO
OBJECTIVE: Relational job characteristics include perceived social worth and perceived social influence. Good relational job characteristics mean that nurses have high prosocial behavior. The purpose of this study was to explore the potential profile of nurses' relational job characteristics, influencing factors and their differences in turnover intention and subjective well-being, thus finding the most suitable clinical relationship job characteristics. METHODS: A cross-sectional survey was conducted among 1013 clinical nurses using the general demographic data questionnaire, Relational Job Characteristics scale, Turnover Intention Questionnaire and Campbell index of well-being. A latent profile analysis was performed to explore relational job characteristics latent profiles. Multinomial logistic regression analysis was conducted to examine the predictors of profile membership, and a one-way analysis of variance was applied to compare the turnover intention and subjective well-being in each latent profile. RESULTS: Five latent profiles were identified and labeled 'High prosocial job characteristics' profile (20.7%), 'Moderate prosocial job characteristics' profile (41.7%), 'High social worth-low social impact perceived' profile (6.3%), 'Low social worth-high social impact perceived' profile (18.8%) and 'Low prosocial job characteristics' profile (12.5%). Factors affecting the different types of nurse relationship job characteristics include age, marital status, hospital department, nursing years, professional title and hospital position. Among them, chief nurse, nurses with more than 20 years of nursing experience and obstetrics and gynecology nurses were more likely to be 'high prosocial job characteristics' profile. The turnover intention of nurses in 'high prosocial job characteristics' profile was significantly lower than that of other profiles, and their subjective well-being was significantly higher than that of other profiles. CONCLUSION: Improving nurses' perception of social worth and social impact on clinical work can improve nurses' prosocial behavior and subjective well-being, and reduce their turnover intention. Nursing managers or policy makers can formulate targeted intervention measures according to the influencing factors of potential profiles.
RESUMO
Fluorescent turn-on receptors are extensively employed for the detection of Zn ions contamination in the environment due to its simplicity, convenience and portability. However, developing highly sensitive and cell-imageable fluorescent turn-on probe for the recognition of Zn ions in living organisms remains a significant challenge. Herein, we have successfully synthesized a novel Schiff base probe (H2L) with a significant fluorescence turn-on response (Zn ions) by one-step synthetic method. In this work, H2L exhibited high sensitivity to Zn2+ ions upon interaction with various common metal ions in HEPES buffer solution. Its detection limit is 1.87 × 10-7 M, which is lower than the requirement of Environmental Protection Agency (EPA) and World Health Organization (WHO) guidelines. The fluorescence titration and Job's plot analysis suggested a 1:1 binding ratio between the probe and Zn ion, and the single-crystal structures obtained further confirmed this inference. In addition, the fluorescent sensor demonstrated recyclability, maintaining its fluorescence intensity for up to 6 cycles without significant decrease, which holds promise for future investigations on reversible fluorescent chemosensors. Notably, fluorescence imaging experiments demonstrated that H2L could be successfully used for the detection of Zn2+ in live cells.
RESUMO
Bos taurus is known for its tolerance of coarse grains, adaptability, high temperature, humidity, and disease resistance. Primarily, cattle are raised for their meat and milk, and pinpointing genes associated with traits relevant to meat production can enhance their overall productivity. The aim of this study was to identify the genome, analyze the evolution, and explore the function of the Pax gene family in B. taurus to provide a new molecular target for breeding in meat-quality-trait cattle. In this study, 44 Pax genes were identified from the genome database of five species using bioinformatics technology, indicating that the genetic relationships of bovids were similar. The Pax3 and Pax7 protein sequences of the five animals were highly consistent. In general, the Pax gene of the buffalo corresponds to the domestic cattle. In summary, there are differences in affinity between the Pax family genes of buffalo and domestic cattle in the Pax1/9, Pax2/5/8, Pax3/7, and Pax4/6 subfamilies. We believe that Pax1/9 has an effect on the growth traits of buffalo and domestic cattle. The Pax3/7 gene is conserved in the evolution of buffalo and domestic animals and may be a key gene regulating the growth of B. taurus. The Pax2/5/8 subfamily affects coat color, reproductive performance, and milk production performance in cattle. The Pax4/6 subfamily had an effect on the milk fat percentage of B. taurus. The results provide a theoretical basis for understanding the evolutionary, structural, and functional characteristics of the Pax family members of B. taurus and for molecular genetics and the breeding of meat-production B. taurus species.
Assuntos
Búfalos , Evolução Molecular , Fatores de Transcrição Box Pareados , Animais , Bovinos/genética , Fatores de Transcrição Box Pareados/genética , Búfalos/genética , Família Multigênica , Genoma/genética , Análise Mutacional de DNA , FilogeniaRESUMO
During myocardial ischaemiaâreperfusion injury (MIRI), the accumulation of damaged mitochondria could pose serious threats to the heart. The migrasomes, newly discovered mitocytosis-mediating organelles, selectively remove damaged mitochondria to provide mitochondrial quality control. Here, we utilised low-intensity pulsed ultrasound (LIPUS) on MIRI mice model and demonstrated that LIPUS reduced the infarcted area and improved cardiac dysfunction. Additionally, we found that LIPUS alleviated MIRI-induced mitochondrial dysfunction. We provided new evidence that LIPUS mechanical stimulation facilitated damaged mitochondrial excretion via migrasome-dependent mitocytosis. Inhibition the formation of migrasomes abolished the protective effect of LIPUS on MIRI. Mechanistically, LIPUS induced the formation of migrasomes by evoking the RhoA/Myosin II/F-actin pathway. Meanwhile, F-actin activated YAP nuclear translocation to transcriptionally activate the mitochondrial motor protein KIF5B and Drp1, which are indispensable for LIPUS-induced mitocytosis. These results revealed that LIPUS activates mitocytosis, a migrasome-dependent mitochondrial quality control mechanism, to protect against MIRI, underlining LIPUS as a safe and potentially non-invasive treatment for MIRI.
Assuntos
Modelos Animais de Doenças , Traumatismo por Reperfusão Miocárdica , Animais , Camundongos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/terapia , Ondas Ultrassônicas , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismoRESUMO
Meiosis is a specialized cell division process that generates gametes for sexual reproduction. However, the factors and underlying mechanisms involving meiotic progression remain largely unknown, especially in humans. Here, it is first showed that HSF5 is associated with human spermatogenesis. Patients with a pathogenic variant of HSF5 are completely infertile. Testicular histologic findings in the patients reveal rare postmeiotic germ cells resulting from meiotic prophase I arrest. Hsf5 knockout (KO) mice confirms that the loss of HSF5 causes defects in meiotic recombination, crossover formation, sex chromosome synapsis, and sex chromosome inactivation (MSCI), which may contribute to spermatocyte arrest at the late pachytene stage. Importantly, spermatogenic arrest can be rescued by compensatory HSF5 adeno-associated virus injection into KO mouse testes. Mechanistically, integrated analysis of RNA sequencing and chromatin immunoprecipitation sequencing data revealed that HSF5 predominantly binds to promoters of key genes involved in crossover formation (e.g., HFM1, MSH5 and MLH3), synapsis (e.g., SYCP1, SYCP2 and SYCE3), recombination (TEX15), and MSCI (MDC1) and further regulates their transcription during meiotic progression. Taken together, the study demonstrates that HSF5 modulates the transcriptome to ensure meiotic progression in humans and mice. These findings will aid in genetic diagnosis of and potential treatments for male infertility.
RESUMO
Liver fibrosis can cause hepatitis B virus (HBV)-associated hepatocellular carcinoma. Menstrual blood-derived mesenchymal stem cells (MenSCs) can ameliorate liver fibrosis through paracrine. Single-cell RNA sequencing (scRNA-seq) may be used to explore the roadmap of activated hepatic stellate cell (aHSC) inactivation to target liver fibrosis. This study established HBV transgenic (HBV-Tg) mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis and demonstrated that MenSCs migrated to the injured liver to improve serological indices and reduce fibrotic accumulation. RNA-bulk analysis revealed that MenSCs mediated extracellular matrix accumulation and cell adhesion. Liver parenchymal cells and nonparenchymal cells were identified by scRNA-seq in the control, CCl4, and MenSC groups, revealing the heterogeneity of fibroblasts/HSCs. A CellChat analysis revealed that diminished intercellular adhesion molecule (ICAM) signaling is vital for MenSC therapy. Specifically, Icam1 in aHSCs acted on Itgal/Itgb2 and Itgam/Itgb2 in neutrophils, causing decreased adhesion. The expression of Itgal, Itgam, and Itgb2 was higher in CCl4 group than in the control group and decreased after MenSC therapy in neutrophil clusters. The Lcn2, Pglyrp1, Wfdc21, and Mmp8 had high expression and may be potential targets in neutrophils. This study highlights interacting cells, corresponding molecules, and underlying targets for MenSCs in treating HBV-associated liver fibrosis.
RESUMO
Objective: School age is a critical period for the development of individual gender equality consciousness. The purpose of this study was to explore the potential classes of school-age children's gender equality consciousness, influencing factors and their differences in gender role, thus providing targeted guidance for the formulation and implementation of gender equality education strategies. Methods: A cross-sectional survey was conducted among 1846 school-age children using the demographic information questionnaire, gender equality consciousness questionnaire and Bem Sex Role Inventory. A latent class analysis was performed to explore gender equality consciousness latent classes. Multinomial logistic regression analysis was conducted to examine the predictors of class membership, and chi-square test was used to compare the gender role of each latent class. Results: The average age of the included 1846 participants was 10.10 ± 1.82 years old. The proportion of boy, grade 6 and living in urban area, respectively, were 50.8, 25.3, and 60.2%. The only children was 16.3% and left-behind children was 22.5%. 60.5% of all children thought their parents had a good relationship. The core family structure in all participants was 54.1%. Mothers were the caregivers of most children (63.6%). The same-sex friends more than 3 was 73.5%, while opposite-sex friends ranged from 0 to 1 was 41.7%. Three latent classes were identified and labeled "high gender equality consciousness" class (20.6%), "moderate gender equality consciousness" class (42.3%) and "low high gender equality consciousness" class (37.1%). Factors affecting the different types of school-age children's gender equality consciousness include gender, grade, caregiver, place of residence, whether they are left-behind children and parental relationship. Rural and left-behind children are more likely to enter the "low gender equality consciousness" group. Children in the "low gender equality consciousness" group had a lower proportion of androgynous gender role. Conclusion: Rural children and left-behind children are the priority groups for gender equality education. Gender role is the important predictors and intervention targets of children's gender equality consciousness. Educators or policy makers can formulate targeted intervention measures according to the influencing factors of potential classes.
RESUMO
Doxorubicin (DOX) is a chemotherapy drug used for hepatocellular carcinoma (HCC) treatment, but its effectiveness can be dramatically dampened by cancer cell chemoresistance. Signal transducer and activator of transcription 3 (STAT3) is implicated with drug resistance in a range of cancers (e.g., HCC), and the STAT3 inhibition can reverse the resistance of cancer cells to chemotherapeutic drugs. In the present study, a combination regimen to improve the efficiency of DOX was provided via the STAT3 blockade using plumbagin (PLB). A poly(lactic-co-glycolic acid) decorated by polyethylene glycol and aminoethyl anisamide was produced in the present study with the hope of generating the nanoparticles for co-delivery of DOX and PLB. The resulting co-formulation suppressed the STAT3 activity and achieved the synergistic chemotherapy, which led to tumor inhibition in the mice with subcutaneous DOX-resistant HCC, without causing any toxicity. The present study reveals the synergism of DOX and PLB, and demonstrates a promising combinatorial approach for treating HCC.
Assuntos
Carcinoma Hepatocelular , Doxorrubicina , Sinergismo Farmacológico , Neoplasias Hepáticas , Naftoquinonas , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/química , Naftoquinonas/administração & dosagem , Naftoquinonas/química , Naftoquinonas/farmacologia , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Humanos , Polietilenoglicóis/química , Polietilenoglicóis/administração & dosagem , Camundongos Endogâmicos BALB C , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Linhagem Celular Tumoral , Camundongos , Nanopartículas/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Camundongos Nus , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/farmacologia , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologiaRESUMO
SnSe2 with high theoretical capacity has been identified as an emerging anode candidate for lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). However, the rate performance and cycling performance of this material in practical applications are still limited by unavoidable volume expansion and low conductivity. In this work, we designed and synthesized nitrogen-doped carbon-coated SnSe2/C-N composites using 2-aminoterephthalic acid (C8H7NO4) as a nitrogen-containing compound for modification by hydrothermal and vacuum calcination methods to achieve efficient utilization of active sites and optimization of the electronic structure. The carbon skeleton inherited from the Sn-MOF precursor can effectively improve the electronic conduction properties of SnSe2. N-doping in the Sn-MOF can increase the positive and negative electrostatic potential energy regions on the molecular surface to further improve the electrical conductivity, and effectively reduce the binding energy with Li+/Na+ which was determined by Density Functional Theory (DFT) methods. In addition, the N-doped carbon skeleton also introduces a larger space for Li+/Na+ intercalation and enhances the mechanical properties. In particular, the post-synthetically modified MOF-derived SnSe2/C-N materials exhibit excellent cyclability, with a reversible capacity of 695 mA h g-1 for LIBs and 259 mA h g-1 for SIBs after 100 cycles at 100 mA g-1.
RESUMO
Four undescribed guaiane sesquiterpenes, aquisinenoids I-L (2-5) and five known compounds were isolated from the resins of Aquilaria sinensis. Their structures were deduced based on spectroscopic data analysis, X-ray crystallography and ECD calculations. Biologically, compounds 1, 5, 6 and 9 showed anti-renal fibrosis activity, significantly reducing the levels of fibronectin, collagen I, and α-SMA. Compounds 2-4, 7 and 8 could reduce one or two of these proteins at non-toxic concentrations in TGF-ß1 induced NRK-52E cells.
RESUMO
The origin of energetic charged particles in universe remains an unresolved issue. Astronomical observations combined with simulations have provided insights into particle acceleration mechanisms, including magnetic reconnection acceleration, shock acceleration, and stochastic acceleration. Recent experiments have also confirmed that electrons can be accelerated through processes such as magnetic reconnection and collisionless shock formation. However, laboratory identifying stochastic acceleration as a feasible mechanism is still a challenge, particularly in the creation of collision-free turbulent plasmas. Here, we present experimental results demonstrating kinetic turbulence with a typical spectrum k-2.9 originating from Weibel instability. Energetic electrons exhibiting a power-law distribution are clearly observed. Simulations further reveal that thermal electrons undergo stochastic acceleration through collisions with multiple magnetic islands-like structures within the turbulent region. This study sheds light on a critical transition period during supernova explosion, where kinetic turbulences originating from Weibel instability emerge prior to collisionless shock formation. Our results suggest that electrons undergo stochastic acceleration during this transition phase.
RESUMO
Here we report on a case of a 61-year-old female patient with 7-year history of major depressive disorder with shorter-duration hypomanic episodes who was prescribed with antidepressants which turned out to be ineffective. After a COVID-19 infection, the patient's clinical presentation became sufficient for the diagnosis of bipolar disorder and she was consistently effective on a mood stabilizer and an atypical antipsychotic. The course of treatment in this case suggests bipolar disorder is not a binary disorder, but a continuous spectrum disorder. For patients suffering from major depressive disorder with shorter-duration hypomanic episodes, mood stabilizers and atypical antipsychotics are possibly more suitable than antidepressants.