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BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH)-related fibrosis is reversible. However, the dynamic morphology change in fibrosis regression remains unclear. We aim to explore the morphological characteristics of fibrosis regression in advanced MASH patients. METHODS: Clinical and histological data of 79 biopsy-proved MASH patients with advanced fibrosis (F3-F4) were reviewed. The second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) image technology was used to quantitatively identify the R (regressive) septa from P (progressive) septa and PS (perisinusoidal) fibrosis. Non-invasive tests were used to compare the fibrosis level with and without R septa groups. Transcriptomics was used to explore hub genes and the underlying mechanism of the formation of R septa. RESULTS: The R septa were different from the P septa and PS fibrosis in detail collagen quantitation identified by SHG/TPEF technology. The R septa were found in MASH fibrosis-regressed patients, which met the definition of the "Beijing classification". Therefore, patients were divided into two groups according to septa morphology: with R septa (n = 10, 12.7%), and without R septa (n = 69, 87.3%). Patients with R septa had lower values in most non-invasive tests, especially for liver stiffness assessed by TE (12.3 vs. 19.4 kPa, p = 0.010) and FAST (FibroScan®-AST) score (0.43 vs. 0.70, p = 0.003). Transcriptomics analysis showed that the expressions of five hub fibrogenic genes, including Col3A1, BGN, Col4A1, THBS2, and Col4A2 in the R septa group, were significantly lower. CONCLUSIONS: The R septa can be differentiated from the P septa and PS fibrosis by quantitative assessment of SHG/TPEF, and it represents a tendency of fibrosis regression in MASH patients. TRIAL REGISTRATION: NCT03386890, 29/12/2017.
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It has long been known that T cells participate in wound healing, however, it is still enigmatic about the landscape of the signaling derived from T cells in the process of wound healing. With the advantages of scRNA-seq, in combination of immunofluorescent imaging, we identified activated T cells, cytotoxic T cells (CTLs), exhausting T cells and Tregs existing in inflammation phase of wound healing. Further analysis revealed each T cell population possess distinguished signals contributed to wound healing, some are critical for improving the wound healing quality. Besides, this study discovered and validated the exhistance of exhausting T cells among the T cells accumulated in skin duing wound healing, and the molecular mechanism(s) and contribution of exhausting T cells to wound healing deserves extensive studies in the future.
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INTRODUCTION: Postoperative ileus (POI) is a postoperative complication that can cause lingering recovery after colorectal resection and a heavy healthcare system burden. Acupuncture aims to prevent postoperative complications, reduce the duration of POI, help recovery and shorten hospital stays. We hypothesise that preoperative electroacupuncture (EA) can promote POI recovery under the enhanced recovery after surgery protocol after laparoscopic surgery in patients with POI. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 80 patients will be enrolled and randomly assigned to the EA or sham electroacupuncture (SA) group. The eligible patients will receive EA or SA for one session per day with treatment frequency starting on preoperative day 1 for four consecutive days. The primary outcome is the time to first defecation. The secondary outcomes include the time to first flatus, length of postoperative hospital stay, time to tolerability of semiliquid and solid food, postoperative nausea, vomiting, pain and extent of abdominal distention, time to first ambulation, preoperative anxiety, 30-day readmission rate, the usage of anaesthetics and analgesics during operation, length of postanaesthesia care unit stay. A mechanistic study by single-cell RNA sequencing in which postintervention normal intestinal tissue samples will be collected. The results of this study will provide evidence of the effects of acupuncture on POI and promote good clinical decision to millions of patients globally every year. ETHICS AND DISSEMINATION: This study has been approved by the ethical application of Beijing University of Chinese Medicine (2022BZYLL0401), Beijing Friendship Hospital Affiliated to Capital Medical University(2022-P2-368-02), Cancer Hospital Chinese Academy of Medical Science (23/175-3917), Huanxing Cancer Hospital (2023-002-02). The results will be published in a medical journal. In addition, we plan to present them at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300077633.
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Neoplasias Colorretais , Eletroacupuntura , Íleus , Laparoscopia , Complicações Pós-Operatórias , Humanos , Eletroacupuntura/métodos , Laparoscopia/efeitos adversos , Íleus/etiologia , Íleus/terapia , Neoplasias Colorretais/cirurgia , Complicações Pós-Operatórias/terapia , Complicações Pós-Operatórias/etiologia , China , Tempo de Internação/estatística & dados numéricos , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Cuidados Pré-Operatórios/métodos , Feminino , Adulto , MasculinoRESUMO
Efficient and stable near-infrared silicon-based light source is a challenge for future optoelectronic integration and interconnection. In this paper, alkaline earth metal Ca2+ doped SiO2-SnO2: Er3+ films were prepared by sol-gel method. The oxygen vacancies introduced by the doped Ca2+ significantly increase the near-infrared luminescence intensity of Er3+ ions. It was found that the doping concentration of Sn precursors not only modulate the crystallinity of SnO2 nanocrystals but also enhance the luminescence performance of Er3+ ions. The stable electroluminescent devices based on SiO2-SnO2: Er3+/Ca2+ films exhibit the power efficiency as high as 1.04×10-2 with the external quantum efficiency exceeding 10%.
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Alkaline earth metal ions (Mg2+, Ca2+, Sr2+) have been introduced into Er3+:SnO2 nanocrystal co-doped silica thin films fabricated by a sol-gel method combined with a spin-coating technique. It is found that the incorporation of alkaline earth metal ions can enhance the light emission from Er3+ at the wavelength around 1540 nm and the strongest enhancement is observed in samples doped with 5 mol% Sr2+ ions. Based on X-ray diffraction, X-ray photoelectron spectroscopy and other spectroscopic measurements, the improved light emission can be attributed to more oxygen vacancies, better crystallinity and a stronger cross-relaxation process with the introduction of alkaline earth metal ions.
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Ferroptosis resistance is vital for B cell development, especially in inflammatory diseases, yet the underlying mechanism is still unclear. In this study, based on the scRNA-seq technique and flow cytometry, we discovered a proportion of neutrophils exhibited upregulated expression of the IL-6 and correlated with the expression of IL-6 receptor and SLC7A11 from B cells in lupus kidney. Moreover, we identified that in lupus kidney, neutrophils could provide IL-6 to facilitate ferroptosis resistance in B cells via SLC7A11, and inhibition of SLC7A11 could significantly enhance ferroptosis in B cells and could decrease B cell proliferation. This study helps understand the crosstalk between neutrophils and B cells in the kidney in the development of lupus.
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Ferroptose , Interleucina-6 , Nefrite Lúpica , Humanos , Rim , Neutrófilos , Linfócitos BRESUMO
While previous studies have explored the neurocognitive mechanism of novel word learning under sentential contexts, few studies have probed the potential effects of contextual emotions. The current study used behavioral methods and electroencephalography to elucidate the dynamic influences of contextual emotions while encoding abstract or concrete novel words on subsequent retrieval of the learned meanings. Enhanced N400 and smaller late positive components (LPC) were elicited when encoding abstract words in the positive context. Furthermore, negative contexts were found to hinder both abstract and concrete word learning, while positive contexts had a greater inhibitory effect on learning abstract words than concrete words. Taken together, these findings suggest that the effects of contextual emotions on novel word learning depend on the concreteness of the learned word and occur during the early and late processing stages while mapping abstract and concrete semantic concepts to novel words.
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Eletroencefalografia , Potenciais Evocados , Humanos , Masculino , Feminino , Emoções , Semântica , AprendizagemRESUMO
OBJECTIVE: To explore the mechanism of electroacupuncture (EA) at "Zusanli" (ST36) on improving glucose metabolism disorder in chronic restraint induced depressed rats. METHODS: A total of 30 male SD rats were randomly divided into control, model and EA groups, with 10 rats in each group. The depression model was established by chronic restraint 2.5 h each day for 4 weeks. For rats in the EA group, EA stimulation (1 mA, 2 Hz, 30 min) was applied to bilateral ST36 during the modeling period, once a day for 4 weeks. The body weight of the rats was recorded before and after modeling. The behavior of rats was observed by sugar-water preference and forced swimming after modeling. The contents of glucose and glycosylated albumin in serum were determined by biochemical method. The histopathological morphology and liver glycogen content were observed by HE and PAS staining. The expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-PI3K (p-PI3K), protein kinase B (Akt), p-Akt, glycogen synthase kinase-3ß (GSK3ß) and p-GSK3ß proteins in liver were determined by Western blot. RESULTS: Compared with the control group, the weight increment and sugar-water preference index decreased (P<0.01), the immobile swimming time was prolonged (P<0.01), the glucose and glycosylated albumin contents in serum increased (P<0.05), the expression of p-Akt protein and the ratio of p-Akt/Akt in liver tissues decreased (P<0.001), the expression of p-GSK3ß protein and the ratio of p-GSK3ß/GSK3ß in liver tissues increased (P<0.01,P<0.001) in the model group. Compared with the model group, the weight increment and sugar-water preference index increased (P<0.05), the immobile swimming time was shortened (P<0.05), the glucose and glycosylated albumin contents in serum decreased (P<0.05), the expressions of p-PI3K and p-Akt proteins and the ratio of p-PI3K/PI3K and p-Akt/Akt in liver tissues increased (P<0.05), the expression of p-GSK3ß protein and the ratio of p-GSK3ß/GSK3ß in liver tissues decreased (P<0.01) in the EA group. HE staining showed that the structure of the hepatic lobule was intact, no obvious inflammatory cell infiltration or fibrosis was observed in the lobule and interstitium, and no abnormalities were observed in the small bile duct, portal vein and artery in the portal area. PAS staining showed that the intensity of staining from the center of the hepatic lobule to the periphery of the hepatic lobule was gradually enhanced in the blank group, that is, the glycogen-rich granules in the hepatic cells were gradually increased; most of the hepatocytes were light colored and glycogen was lost significantly in the model group; while the intensity of hepatocyte staining increased, the staining intensity of the perilobular zone was weaker than that in the blank group, and the glycogen particles partially recovered in the EA group. CONCLUSION: EA intervention can regulate glucose metabolism disorder in chronic restraint induced depressed rats through PI3K/Akt/GSK3ß signaling pathway.
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Eletroacupuntura , Transtornos do Metabolismo de Glucose , Ratos , Masculino , Animais , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinase/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Depressão/genética , Depressão/terapia , Transdução de Sinais , Glicogênio , Glucose , ÁguaRESUMO
The altered expression of ARMCX1 in patients with gastric cancer has been reported frequently, yet its correlation to prognosis and chemotherapy needs to be unveiled. In combination of the gene expression data retrieved from TCGA database and bioinformatic analysis, this study discovered 590 differentially expressed genes in the cancerous biopsies isolated from gastric patients, compared with controls. Among which, ARMCX1 exhibited great potential to serve as a prognostic biomarker for gastric patients; furthermore, patients with low expression of ARMCX1 could be more sensitive to these 9 chemotherapeutic agents: A-770041, AMG-706, ATRA, BEZ235, bortezomib, CGP60474, dasatinib, HG-64-1, and pazopanib, rather than the other chemotherapeutic agents. This study helps the improvement of evaluating the prognosis of gastric cancer patients, and would help optimize chemotherapeutic strategies in consideration of the expression of ARMCX1.
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Proteínas do Domínio Armadillo , Proteínas Oncogênicas , Neoplasias Gástricas , Humanos , Biomarcadores Tumorais/genética , Bortezomib/uso terapêutico , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Proteínas do Domínio Armadillo/genética , Proteínas Oncogênicas/genéticaRESUMO
BACKGROUND: Non-alcoholic steatohepatitis (NASH) had not yet been approved therapy. Electro-acupuncture (EA) has been reported to have potential efficacy. However, high-quality clinical evidence was still lacking. METHODS: NASH patients were randomized and allocated to either sham acupuncture (SA) or EA group in a 1:1 ratio, with the patient blinded. Each patient received 36 sessions of SA or EA treatment over 12 weeks, followed by additional 4 weeks. The primary outcome was the changes in relative liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF). RESULTS: A total of 60 patients were enrolled. From baseline to week 12, the reduction of relative liver fat content measured by MRI-PDFF in the EA group (- 33.6%, quantile range: - 52.9%, - 22.7%) was significantly more significant than that in the SA group (- 15.8%, quantile range: - 36.1%, - 2.7%) (p = 0.022). Furthermore, the EA group had more patients who achieved MRI-PDFF to 30% reduction at week 12 (53.3% vs. 25.9%, p = 0.035). EA treatment also significantly reduced body weight (- 3.0 vs. + 0.1 kg, p = 0.034) and BMI (- 1.5 vs. - 0.2 kg/m2, p = 0.013) at week 16. Except for AST (- 27.4 vs. - 16.2 U/L, p = 0.015), other biochemical varieties, including ALT, fasting-glucose, cholesterol, and triglyceride, showed no statistically significant difference. Both groups measured no significant changes in liver stiffness by magnetic resonance elastography (MRE). There were no serious adverse events in either group. CONCLUSIONS: Twelve weeks of EA effectively and safely reduces relative liver fat content in NASH patients. Further multicenter randomized controlled studies are needed. Trial registration Chinese Clinical Trial Registry, ChiCTR2100046617. Registered 23 May 2021, http://www.chictr.org.cn/edit.aspx?pid=127023&htm=4.
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Importance: Despite the adoption of the optimized Enhanced Recovery After Surgery (ERAS) protocol, postoperative ileus (POI) severely impairs recovery after colorectal resection and increases the burden on the health care system. Objective: To assess the efficacy of electroacupuncture (EA) in reducing the duration of POI with the ERAS protocol. Design, Setting, and Participants: This multicenter, randomized, sham-controlled trial was conducted in China from October 12, 2020, through October 17, 2021. There was a 1:1 allocation using the dynamic block random method, and analyses were by intention to treat. Patients 18 years or older undergoing laparoscopic resection of colorectal cancer for the first time were randomly assigned to treatment group by a central system. Interventions: Patients were randomly assigned to 4 sessions of EA or sham electroacupuncture (SA) after surgery. All patients were treated within the ERAS protocol. Main Outcomes and Measures: The primary outcome was the time to first defecation. Secondary outcomes included other patient-reported outcome measures, length of postoperative hospital stay, readmission rate within 30 days, and incidence of postoperative complications and adverse events. Results: A total of 249 patients were randomly assigned to treatment groups. After the exclusion of 1 patient because of a diagnosis of intestinal tuberculosis, 248 patients (mean [SD] age, 60.2 [11.4] years; 153 men [61.7%]) were included in the analyses. The median (IQR) time to first defecation was 76.4 (67.6-96.8) hours in the EA group and 90.0 (73.6-100.3) hours in the SA group (mean difference, -8.76; 95% CI, -15.80 to -1.73; P = .003). In the EA group compared with the SA group, the time to first flatus (median [IQR], 44.3 [37.0-58.2] hours vs 58.9 [48.2-67.4] hours; P < .001) and the tolerability of semiliquid diet (median [IQR], 105.8 [87.0-120.3] hours vs 116.5 [92.0-137.0] hours; P = .01) and solid food (median [IQR], 181.8 [149.5-211.4] hours vs 190.3 [165.0-228.5] hours; P = .01) were significantly decreased. Prolonged POI occurred in 13 of 125 patients (10%) in the EA group vs 25 of 123 patients (20%) in the SA group (risk ratio [RR], 0.51; 95% CI, 0.27-0.95; P = .03). Other secondary outcomes were not different between groups. There were no severe adverse events. Conclusions and Relevance: Results of this randomized clinical trial demonstrated that in patients undergoing laparoscopic surgery for colorectal cancer with the ERAS protocol, EA shortened the duration of POI and decreased the risk for prolonged POI compared with SA. EA may be considered as an adjunct to the ERAS protocol to promote gastrointestinal function recovery and prevent prolonged POI after surgery. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000038444.
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Neoplasias Colorretais , Eletroacupuntura , Recuperação Pós-Cirúrgica Melhorada , Íleus , Laparoscopia , Masculino , Humanos , Pessoa de Meia-Idade , Eletroacupuntura/efeitos adversos , Eletroacupuntura/métodos , Complicações Pós-Operatórias/epidemiologia , Laparoscopia/efeitos adversos , Íleus/etiologia , Íleus/terapia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/complicaçõesRESUMO
Post-stroke depression (PSD) is a common cerebrovascular complication characterized by complex pathogenesis and poor treatment effects. Here, we tested the influence of differentially expressed genes (DEGs), non-targeted metabolites, and intestinal microbes on the occurrence and development of PSD. We acquired gene expression profiles for stroke patients, depression patients, and healthy controls from the Gene Expression Omnibus database. After screening for DEGs using differential expression analysis, we identified common DEGs in stroke and depression patients that were considered to form the molecular basis of PSD. Functional enrichment analysis of DEGs also revealed that the majority of biological functions were closely related to metabolism, immunity, the nervous system, and microorganisms, and we also collected blood and stool samples from healthy controls, stroke patients, and PSD patients and performed 16S rDNA sequencing and untargeted metabolomics. After evaluating the quality of the sequencing data, we compared the diversity of the metabolites and intestinal flora within and between groups. Metabolic pathway enrichment analysis was used to identify metabolic pathways that were significantly involved in stroke and PSD, and a global metabolic network was constructed to explore the pathogenesis of PSD. Additionally, we constructed a global regulatory network based on 16S rDNA sequencing, non-targeted metabolomics, and transcriptomics to explore the pathogenesis of PSD through correlation analysis. Our results suggest that intestinal flora associates the dysregulation of cerebral cortex gene expression and could potentially promote the occurrence of depression by affecting the metabolism of stroke patients. Our findings may be helpful in identifying new targets for the prevention and treatment of PSD.
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Head and neck squamous cell carcinoma (HNSCC) usually has a poor prognosis and is associated with a high mortality rate. Its etiology is mainly the result from long-term exposure to either alcohol, tobacco or human papillomavirus (HPV) infection or a combination of these insults. However, HNSCC patients with HPV have been found to show a survival advantage over those without the virus, but the mechanism that confers this advantage is unclear. Due to the large number of HPV-independent HNSCC cases, there is a possibility that the difference in prognosis between HPV-positive (HPV+) and negative (HPV-) patients is due to different carcinogens. To clarify this, we used scRNA data and viral tracking methods in order to identify HPV+ and HPV- cells in the tumour tissues of patients infected with HPV. By comparing HPV+ and HPV- malignant cells, we found a higher level of tumour stemness in HPV- tumour cells. Using tumour stemness-related genes, we established a six-gene prognostic signature that was used to divide the patients into low- and high-risk groups. It was found that HPV patients who were at low-risk of contracting HNSCC had a higher number of CD8+ T-cells as well as a higher expression of immune checkpoint molecules. Correspondingly, we found that HPV+ tumour cells expressed higher levels of CCL4, and these were highly correlated with CD8+ T cells infiltration and immune checkpoint molecules. These data suggest that the stemness features of tumour cells are not only associated with the prognostic risk, but that it could also affect the immune cell interactions and associated signalling pathways.
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Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Linfócitos T CD8-Positivos , Papillomaviridae , Proteínas de Checkpoint ImunológicoRESUMO
A disintegrin and metalloprotease 10 (ADAM-10), a member of the ADAM protease family, has biological activities related to TNF-α activation, cell adhesion, and migration, among other functions. Macrophages are important immune cells that are involved in the inflammatory response of the body. ADAM-10 is involved in inflammatory responses, but the specific regulatory mechanisms are not fully understood. In this study, we investigated the regulatory mechanism of ADAM-10 in the lipopolysaccharide-promoted proliferation (LPS) of the macrophage inflammatory response. Differentially expressed or regulated proteins were identified in interfered ADAM-10 (sh ADAM-10) macrophages using tandem mass tag (TMT) proteomics. The changes and regulatory role of ADAM-10 during LPS-induced inflammatory response in normal, interfering, and overexpressing ADAM-10 (EX ADAM-10) cells were determined. Results indicated that ADAM-10 interference affected inflammation-related pathways and reduced matrix metalloproteinase 12 (MMP-12) protein levels, as identified by TMT proteomics. In normal cells, LPS decreased ADAM-10 gene expression, but promoted ADAM-10 secretion, MMP-12 and TNF-α gene expression, and MMP-12, iNOS, IL-10, and cyclinD1 protein expression. Additionally, ADAM-10 knockdown decreased macrophage viability in sh-ADAM-10 cells. Moreover, an MMP-12 inhibitor had no impact on the viability effect of LPS on cells or the expression of ADAM-10. iNOS expression decreased, whereas IL-10 expression increased after ADAM-10 depletion. ADAM-10 knockdown decreased MMP-12, iNOS, TNF-α, IL-1ß, and FKN, while overexpression had an opposite effect. ADAM-10 overexpression further increased MMP-12, iNOS, and TNF-α gene expression in response to LPS. Cell viability was increased in EX ADAM-10 cells, and ADAM-10 secretion was further increased in the EX and LPS groups. Flow cytometry and immunofluorescence staining revealed that EX-ADAM 10 cells had increased iNOS expression, which acted as an IL-6 expression driver. In summary, we found that ADAM-10 is activated by LPS and positively participates in LPS-stimulated macrophage inflammatory responses by positively regulating MMP-12 during the inflammatory process.
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Lipopolissacarídeos , Metaloproteinase 12 da Matriz , Desintegrinas/metabolismo , Desintegrinas/farmacologia , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos , Metaloproteinase 12 da Matriz/genética , Metaloproteinase 12 da Matriz/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Although substantial progress has been made in the immunotherapy of kidney cancer, its efficacy varies from patient to patient, with many responding suboptimally or even developing metastases. Thus, research on the tumour immune microenvironment and immune cell heterogeneity is essential for kidney cancer treatment. In this study, natural killer (NK) cell populations were isolated using signature genes from the single-cell sequencing data of clear cell renal cell carcinoma (ccRCC) and normal kidney tissues and divided into three subpopulations according to the differences in gene expression profiles: NK(GZMH), NK(EGR1), and NK(CAPG). Gene set enrichment analysis revealed that NK(EGR1) and NK(CAPG) were closely related to tumour metastasis, as shown by kidney cancer metastasis to Hodgkin lymphoma, T-cell leukaemia, and Ki-1+ anaplastic large cell lymphoma. Thus, these two NK cell subpopulations are promising targets for inhibiting metastasis in ccRCC. Our findings revealed heterogeneity in the infiltrating NK cells of kidney cancer, which can serve as a reference for the mechanisms underlying metastasis in kidney cancer.
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Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/patologia , Humanos , Imunoterapia , Neoplasias Renais/patologia , Células Matadoras Naturais , Microambiente TumoralRESUMO
MicroRNAs (miRNAs) are vital post-transcriptional regulators that participate in host-pathogen interactions by modulating the expression of cellular factors. Previous studies have demonstrated that feline panleukopenia virus (FPV) alters miRNA expression levels within host cells. However, the relationship between FPV replication and host miRNAs remains unclear. Here, we demonstrated that FPV infection significantly altered cellular miR-92a-1-5p expression in F81 cells by upregulating the expression of specificity protein 1 (SP1). Furthermore, we observed that miR-92a-1-5p enhanced interferon (IFN-α/ß) expression by targeting the suppressors of cytokine signaling 5 (SOCS5) that negatively regulates NF-κB signaling and inhibits FPV replication in host cells. These findings revealed that miR-92a-1-5p plays a crucial role in host defense against FPV infection.
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MicroRNAs , Replicação Viral , Animais , Gatos , Vírus da Panleucopenia Felina/genética , Interações Hospedeiro-Patógeno/genética , Interferon beta , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Replicação Viral/genéticaRESUMO
Objective: Chaihu Shugan San (CSS) has a long history for treating major depressive disorder (MDD), which has been verified effectively and safely in clinical studies. Deficient angiogenesis plays important roles in MDD. However, the underlying mechanisms of CSS on angiogenesis remain poorly understood. Methods: Network pharmacology analysis was applied to explore the potential angiogenic targets and pathways between CSS and MDD. These targets would be validated in chronic unpredictable mild stress (CUMS)-induced depressive-like mice by Western blots, immunofluorescence, and immunohistochemistry. Then, the underlying molecular mechanisms were further investigated in brain microvascular endothelial cells (BMVECs) with CSS-containing serum by Western blots and immunofluorescence. Results: Network pharmacology analysis showed that the antidepressant role of CSS was closely associated with Silent information regulator protein 1 (SIRT1)/Forkhead box O1 (FOXO1) axis-mediated angiogenesis. This prediction was confirmed in the following experiments. CSS induced angiogenesis, increased SIRT1 expression, and decreased FOXO1 expression in the hippocampus of CUMS mice. Five percent CSS-containing serum produced a significant increase in BMVECs proliferation, migration, and tube formation, but these effects were reduced by SIRT1 silencing. CSS serum could also promote FOXO1 translocation to the cytoplasm through SIRT1 signaling, which triggered FOXO1 protein degradation. What is more, CSS upregulated VEGFA and BDNF expressions not only in the hippocampus of depressive mice but also in BMVECs supernatants. Of note, these trophic factors play important roles in promoting neurogenesis. Conclusion: The study showed that CSS could promote angiogenesis and neurogenesis in the hippocampus of CUMS-induced mice. The underlying molecular mechanism involves the SIRT1/FOXO1 axis and subsequent regulation of VEGFA and BDNF. These findings provide novel insight into CSS drug development, and targeting the SIRT1/FOXO1 axis might be a promising strategy to treat MDD.
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Transtorno Depressivo Maior , Sirtuína 1 , Animais , Antidepressivos/metabolismo , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtorno Depressivo Maior/metabolismo , Células Endoteliais/metabolismo , Proteína Forkhead Box O1/metabolismo , Hipocampo , Medicina Tradicional Chinesa , Camundongos , Neovascularização Patológica/metabolismo , Sirtuína 1/metabolismoRESUMO
Against the backdrop of China's growing market economy, small- and medium-sized enterprises (SMEs) have taken advantage of this opportunity to develop rapidly. At present, SMEs have become an important part of the market economy. Accounting system information management system is an advanced form of management, and improving the degree of accounting information is the key to improving the management mode of SMEs. This study applies cloud computing to enterprise accounting management systems. The results show that realizing SME accounting information management can effectively improve economic settlements. With the development of cloud computing, its improvement of accounting management efficiency cannot be ignored. Besides, the risks of accounting informatization, enterprises can make their development by establishing a secure network protection wall and relying on strict relevant laws and regulations.
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Inteligência Artificial , Computação em NuvemRESUMO
BACKGROUND: Genomic and epigenomic dynamics both play critical roles during embryogenesis. Zfp57 maintains genomic imprinting with both maternal and zygotic functions. In our previous study, we found that maternal and zygotic Zfp57 modulate NOTCH signaling during cardiac development. In this study, we investigated Zfp57 mutants from E11.5 to E13.5 to delineate its function during cardiac development. RESULTS: Here, we describe novel roles of maternal and zygotic Zfp57 during cardiovascular system development. We found that maternal and zygotic Zfp57 was required for coronary vascular development. Maternal and zygotic loss of Zfp57 perturbed the sprouting of the sinus venosus-derived endothelial cells and led to underdeveloped coronary vasculature, meanwhile, there was an ectopic overproduction of blood islands over the ventricles. Furthermore, loss of Zfp57 and failed vasculature disturbed myocardium maturation. Loss of maternal and zygotic Zfp57 resulted in hyper trabeculation and failed myocardium compaction. Zfp57 zygotic mutant (M+ Z- ) hearts displayed noncompaction cardiomyopathy at E18.5. CONCLUSIONS: Our results suggest that maternal and zygotic ZFP57 are essential for coronary vascular formation and myocardium maturation in mice. Our research provides evidence for the role of genomic imprinting during embryogenesis.
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Clear cell renal cell carcinoma (ccRCC) usually affects multiple organs (e.g., bone and brain), and patient prognosis is usually poor. Although it is known that CD8+ T cell infiltration can potentially alleviate ccRCC progression, few studies have concentrated on the correlation between CD8+ T cell infiltration and ccRCC prognosis. In this study, ten genes expressed by infiltrated CD8+ T cells (i.e., AMD1, CCSER2, CIB1, DRAP1, HMGB2, HMGN1, NPIPB5, PTP4A2, RORA, and SAP18) were suggested as potential ccRCC prognostic biomarkers, by using next-generation sequencing (i.e. bulk sequencing and single-cell sequencing) of ccRCC, papillary renal cell carcinoma (papRCC), and control kidney biopsies. Specifically, we identified four genes (i.e., CCSER2, DRAP1, NPIPB5, and SAP18) as potential novel prognostic biomarkers for ccRCC. It is noteworthy that SAP18 derived from CD8+ T cells negatively correlates to Atg7+ neutrophils in ccRCC, compared with papRCC, indicating a potential decreased neutrophil metabolic function in autophagy and fatty acids. This study elucidated the protective role of infiltrated CD8+ T cells in ccRCC and identified ten candidate genes related to an improved prognosis in patients with ccRCC.