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The spatial organization characteristics and redox status of the extracellular space (ECS) are crucial in the development of brain diseases. However, it remains a challenge to simultaneously capture dynamic changes in microstructural features and redox states at the submicron level within the ECS. Here, we developed a reversible glutathione (GSH)-responsive nanoprobe (RGN) for mapping the spatial organization features and redox status of the ECS in brain tissues with nanoscale resolution. The RGN is composed of polymer nanoparticles modified with GSH-responsive molecules and amino-functionalized methoxypoly(ethylene glycol), which exhibit exceptional single-particle brightness and excellent free diffusion capability in the ECS of brain tissues. Tracking single RGNs in acute brain slices allowed us to dynamically map spatial organizational features and redox levels within the ECS of brain tissues in disease models. This provides a powerful super-resolution imaging method that offers a potential opportunity to study the dynamic changes in the ECS microenvironment and to understand the physiological and pathological roles of the ECS in vivo.
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Encéfalo , Espacio Extracelular , Glutatión , Nanopartículas , Oxidación-Reducción , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Animales , Espacio Extracelular/metabolismo , Espacio Extracelular/química , Glutatión/química , Glutatión/metabolismo , Nanopartículas/química , Ratones , Polietilenglicoles/químicaRESUMEN
BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is a surgical procedure for treating pancreatic cancer; however, the risk of complications remains high owing to the wide range of organs involved during the surgery and the difficulty of anastomosis. Pancreatic fistula (PF) is a major complication that not only increases the risk of postoperative infection and abdominal hemorrhage but may also cause multi-organ failure, which is a serious threat to the patient's life. This study hypothesized the risk factors for PF after LPD. AIM: To identify the risk factors for PF after laparoscopic pancreatoduodenectomy in patients with pancreatic cancer. METHODS: We retrospectively analyzed the data of 201 patients admitted to the Fudan University Shanghai Cancer Center between August 2022 and August 2023 who underwent LPD for pancreatic cancer. On the basis of the PF's incidence (grades B and C), patients were categorized into the PF (n = 15) and non-PF groups (n = 186). Differences in general data, preoperative laboratory indicators, and surgery-related factors between the two groups were compared and analyzed using multifactorial logistic regression and receiver-operating characteristic (ROC) curve analyses. RESULTS: The proportions of males, combined hypertension, soft pancreatic texture, and pancreatic duct diameter ≤ 3 mm; surgery time; body mass index (BMI); and amylase (Am) level in the drainage fluid on the first postoperative day (Am > 1069 U/L) were greater in the PF group than in the non-PF group (P < 0.05), whereas the preoperative monocyte count in the PF group was lower than that in the non-PF group (all P < 0.05). The logistic regression analysis revealed that BMI > 24.91 kg/m² [odds ratio (OR) =13.978, 95% confidence interval (CI): 1.886-103.581], hypertension (OR = 8.484, 95%CI: 1.22-58.994), soft pancreatic texture (OR = 42.015, 95%CI: 5.698-309.782), and operation time > 414 min (OR = 15.41, 95%CI: 1.63-145.674) were risk factors for the development of PF after LPD for pancreatic cancer (all P < 0.05). The areas under the ROC curve for BMI, hypertension, soft pancreatic texture, and time prediction of PF surgery were 0.655, 0.661, 0.873, and 0.758, respectively. CONCLUSION: BMI (> 24.91 kg/m²), hypertension, soft pancreatic texture, and operation time (> 414 min) are considered to be the risk factors for postoperative PF.
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Melatonin (N-acetyl-5-methoxytryptamine) is reported to improve mood disorders in perimenopausal women and gut microbiome composition is altered during menopausal period. The possible role of microbiome in the treatment effect of melatonin on menopausal depression remains unknown. Here, it is shown that melatonin treatment reverses the gut microbiota dysbiosis and depressive-like behaviors in ovariectomy (OVX) operated mice. This effect of melatonin is prevented by antibiotic cocktails (ABX) treatment. Transferring microbiota harvested from adolescent female mice to OVX-operated mice is sufficient to ameliorate depressive-like behaviors. Conversely, microbiota transplantation from OVX-operated mice or melatonin-treated OVX-operated mice to naïve recipient mice exhibits similar phenotypes to donors. The colonization of Alistipes Inops, which is abundant in OVX-operated mice, confers the recipient with depressive-like behaviors. Further investigation indicates that the expansion of Alistipes Inops induced by OVX leads to the degradation of intestinal tryptophan, which destroys systemic tryptophan availability. Melatonin supplementation restores systemic tryptophan metabolic disorders by suppressing the growth of Alistipes Inops, which ameliorates depressive-like behaviors. These results highlight the previously unrecognized role of Alistipes Inops in the modulation of OVX-induced behavioral disorders and suggest that the application of melatonin to inhibit Alistipes Inops may serve as a potential strategy for preventing menopausal depressive symptoms.
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OBJECTIVES: The aims of the present study were to compare the long-term outcomes for ascending aortic dilatation and adverse aortic events after isolated aortic valve replacement between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve ( TAV). METHODS: This retrospective study included 310 patients who had undergone isolated aortic valve replacement with an ascending aorta diameter ≤ 45 mm between January 2010 and September 2021. The patients were divided into BAV group (n=90) and TAV group (n=220). The differences in the dilation rate of the ascending aorta and long-term outcomes were analyzed. RESULTS: Overall survival was 89 ± 4% in the BAV group vs. 75 ± 6% in the TAV group at 10 years postoperatively (P=0.007), yet this difference disappeared after adjusting exclusively for age (P=0.343). The mean annual growth rate of the ascending aorta was similar between the two groups during follow-up (0.5 ± 0.6 mm/year vs. 0.4 ± 0.5 mm/year; P=0.498). Ten-year freedom from adverse aortic events was 98.1% in the BAV group vs. 95.0% in the TAV group (P=0.636). Multivariable analysis revealed preoperative ascending aorta diameter to be a significant predictor of adverse aortic events (hazard ratio: 1.76; 95% confidence interval: 1.33 to 2.38; P<0.001). CONCLUSION: Our study revealed that the long-term survival and the risks of adverse aortic events between BAV and TAV patients were similar after isolated aortic valve replacement. BAV was not a risk factor of adverse aortic events.
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Aorta , Válvula Aórtica , Enfermedad de la Válvula Aórtica Bicúspide , Enfermedades de las Válvulas Cardíacas , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Enfermedad de la Válvula Aórtica Bicúspide/cirugía , Enfermedad de la Válvula Aórtica Bicúspide/complicaciones , Persona de Mediana Edad , Válvula Aórtica/cirugía , Válvula Aórtica/anomalías , Anciano , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Aorta/cirugía , Enfermedades de las Válvulas Cardíacas/cirugía , Enfermedades de las Válvulas Cardíacas/complicaciones , Enfermedades de las Válvulas Cardíacas/mortalidad , Válvula Tricúspide/cirugía , Progresión de la Enfermedad , Factores de Riesgo , Resultado del Tratamiento , Complicaciones PosoperatoriasRESUMEN
BACKGROUND: A pragmatic randomised controlled trial has confirmed the effectiveness of Urinary Incontinence for Women (UIW) app-based intervention in improving postpartum urinary incontinence (UI) severity among pregnant women. However, the causal mechanisms underlying this intervention effect remain unclear. OBJECTIVE: To examine the mediating role of self-efficacy with pelvic floor muscle training (PFMT) on the effect of the UIW app-based intervention in improving postpartum UI severity. METHODS: This was a secondary causal mediation analysis of a single-center, 2-arm, unblinded pragmatic randomised controlled trial. Singleton pregnant women without UI before pregnancy aged ≥18 years and between 24 and 28 weeks of gestation were recruited from a tertiary public hospital in China and randomised to receive the UIW app intervention plus oral PFMT instructions (n = 63) or oral PFMT instructions alone (n = 63). The primary outcome was postpartum changes in UI severity at 6 weeks. Changes in self-efficacy with PFMT 2 months after randomisation were a hypothesised mediator. Causal mediation analysis was used to estimate the average causal mediation effect (ACME), average direct effect (ADE), average total effect (ATE), and proportion mediated. A sensitivity analysis was conducted to examine the robustness of the ACME in relation to potential unmeasured confounding. RESULTS: Data from 103 participants were analyzed. The ATE of UIW app-based intervention on postpartum UI severity was 2.91 points (95 % confidence intervals [CI] 1.69 to 4.12), with ADE of 1.97 points (95 % CI 0.63 to 3.41) and the ACME 0.94 points (95 % CI 0.27 to 1.72). The proportion of ATE mediated by self-efficacy with PFMT was 0.32 (95 % CI 0.08 to 0.67). Sensitivity analysis revealed the robust ACME with respect to the potential effects of unmeasured confounding. CONCLUSION: An increase in self-efficacy with PFMT partially mediated the effect of the UIW app intervention on improvements in postpartum UI severity. TRIAL REGISTRATION: The original trial was prospectively registered in the Chinese Clinical Trial Registry under the reference number ChiCTR1800016171 on 16/05/2018. Further details can be accessed at: http://www.chictr.org.cn/showproj.aspx?proj=27455.
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Terapia por Ejercicio , Análisis de Mediación , Aplicaciones Móviles , Diafragma Pélvico , Autoeficacia , Incontinencia Urinaria , Humanos , Femenino , Adulto , Embarazo , Aplicaciones Móviles/normas , Incontinencia Urinaria/terapia , Incontinencia Urinaria/psicología , Diafragma Pélvico/fisiopatología , China , Terapia por Ejercicio/métodos , Terapia por Ejercicio/normas , Mujeres Embarazadas/psicología , Periodo PospartoRESUMEN
BACKGROUND: Autophagy is crucial for controlling the manifestation of tuberculosis. This study intends to discover autophagy-related molecular clusters as biomarkers for discriminating between latent tuberculosis (LTBI) and active tuberculosis (ATB) in children through gene expression profile analysis. METHODS: The expression of autophagy modulators was examined in pediatric patients with LTBI and ATB utilizing public datasets from the Gene Expression Omnibus (GEO) collection (GSE39939 and GSE39940). RESULTS: In a training dataset (GSE39939), patients with LTBI and ATB exhibited the expression of autophagy-related genes connected with their active immune responses. Two molecular clusters associated with autophagy were identified. Compared to Cluster 1, Cluster 2 was distinguished through decreased adaptive cellular immune response and enhanced inflammatory activation, according to single-sample gene set enrichment analysis (ssGSEA). Per the study of gene set variation, Cluster 2's differentially expressed genes (DEGs) played a role in synthesizing transfer RNA, DNA repair and recombination, and primary immunodeficiency. The peak variation efficiency, root mean square error, and area under the curve (AUC) (AUC = 0.950) were all lowered in random forest models. Finally, a seven-gene-dependent random forest profile was created utilizing the CD247, MAN1C1, FAM84B, HSZFP36, SLC16A10, DTX3, and SIRT4 genes, which performed well against the validation dataset GSE139940 (AUC = 0.888). The nomogram calibration and decision curves performed well in identifying ATB from LTBI. CONCLUSIONS: In summary, according to the present investigation, autophagy and the immunopathology of TB might be correlated. Furthermore, this investigation established a compelling prediction expression profile for measuring autophagy subtype development risks, which might be employed as possible biomarkers in children to differentiate ATB from LTBI.
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Autofagia , Tuberculosis Latente , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/genética , Autofagia/genética , Niño , Perfilación de la Expresión Génica , Tuberculosis/genética , Tuberculosis/diagnóstico , Diagnóstico Diferencial , Biomarcadores/metabolismo , Masculino , Preescolar , FemeninoRESUMEN
The surface morphology of perovskite films significantly influences the performance of perovskite light-emitting diodes (PeLEDs). However, the thin perovskite thickness (~10 nm) results in low surface coverage on the substrate, limiting the improvement of photoelectric performance. Here, we propose a molecular additive strategy that employs pentafluorophenyl diphenylphosphinate (FDPP) molecules as additives. P=O and Pentafluorophenyl (5F) on FDPP can coordinate with Pb2+ to slow the crystallization process of perovskite and enhance surface coverage. Moreover, FDPP reduces the defect density of perovskite and enhances the crystalline quality. The maximum brightness, power efficiency (PE), and external quantum efficiency (EQE) of the optimal device reached 24,230 cd m-2, 82.73 lm W-1, and 21.06%, respectively. The device maintains an EQE of 19.79% at 1000 cd m-2 and the stability is further enhanced. This study further extends the applicability of P=O-based additives.
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In vivo real-time qualitative and quantitative analysis is essential for the diagnosis and treatment of diseases such as tumors. Near-infrared-II (NIR-II, 1000-1700 nm) bioimaging is an emerging visualization modality based on fluorescent materials. The advantages of NIR-II region fluorescent materials in terms of reduced photon scattering and low tissue autofluorescence enable NIR-II bioimaging with high resolution and increasing depth of tissue penetration, and thus have great potential for in vivo qualitative and quantitative analysis. In this review, we first summarize recent advances in NIR-II imaging, including fluorescent probe selection, quantitative analysis strategies, and imaging. Then, we describe in detail representative applications to illustrate how NIR-II fluorescence imaging has become an important tool for in vivo quantitative analysis. Finally, we describe the future possibilities and challenges of NIR-II fluorescence imaging.
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Colorantes Fluorescentes , Imagen Óptica , Colorantes Fluorescentes/química , Imagen Óptica/métodos , Humanos , Animales , Espectroscopía Infrarroja Corta/métodos , Neoplasias/diagnóstico por imagen , Rayos InfrarrojosRESUMEN
Background: Mounting evidence underscores the importance of cell communication within the tumor microenvironment, which is pivotal in tumor proliferation, invasion, and metastasis. Exosomes play a crucial role in cell-to-cell communication. Although single-cell RNA sequencing (scRNA-seq) provides insights into individual cell transcriptional characteristics, it falls short of comprehensively capturing exosome-mediated intercellular communication. Method: We analyzed Pancreatic Ductal Adenocarcinoma (PDAC) tissues, separating supernatant and precipitate for exosome purification and single-cell nucleus suspension. We then constructed Single-nucleus RNA sequencing (snRNA-seq) and small RNA-seq libraries from these components. Our bioinformatic analysis integrated these sequences with ligand-receptor analysis and public miRNA data to map the cell communication network. Results: We established intercellular communication networks using bioinformatic analysis to track exosome miRNA effects and ligand-receptor pairs. Significantly, hsa-miR-1293 emerged as a prognostic biomarker for pancreatic cancer, linked to immune evasion, increased myeloid-derived suppressor cells, and poorer prognosis. Targeting this miRNA may enhance anti-tumor immunity and improve outcomes. Conclusion: Our study offers a novel approach to constructing intercellular communication networks using snRNA-seq and exosome-small RNA sequencing. By integrating miRNA tracing with ligand-receptor analysis, we illuminate the complex interactions in the pancreatic cancer microenvironment, highlighting the pivotal role of miRNAs and identifying potential biomarkers and therapeutic targets.
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Currently, chemotherapy remains occupying a pivotal place in the treatment of pancreatic ductal adenocarcinoma (PDAC). Nonetheless, the emergence of drug resistance in recent years has limited the clinical efficacy of chemotherapeutic agents, especially gemcitabine (GEM). Through bioinformatics analysis, AT-rich Interactive Domain-containing Protein 3A (ARID3A), one of transcription factors, is discovered to possibly participate in this progress. This study thoroughly investigates the potential role of ARID3A in the malignant progression and GEM chemoresistance of PDAC and explores the underlying mechanisms. The results indicate that ARID3A knockdown suppresses tumor development and enhances the sensitivity of PDAC cells to GEM in vitro and vivo. Mechanically, CUT&Tag profiling sequencing, RNA-sequencing and functional studies demonstrates that decreased ARID3A expression alleviates the transcriptional inhibition of phosphatase and tensin homolog (PTEN), consequently leading to glutathione peroxidase 4 (GPX4) depletion and increased lipid peroxidation levels. Activated ferroptosis induced by the inhibition of GPX4 subsequently restricts tumor progression and reduces GEM resistance in PDAC. This research identifies the ferroptosis regulatory pathway of ARID3A-PTEN-GPX4 axis and reveals its critical role in driving the progression and chemoresistance of pancreatic cancer. Notably, both inhibition of ARID3A and enhancement of ferroptosis can increase chemosensitivity to GEM, which offers a promising opportunity for developing therapeutic strategies to combat acquired chemotherapy resistance in pancreatic cancer.
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Proteínas de Unión al ADN , Resistencia a Antineoplásicos , Ferroptosis , Regulación Neoplásica de la Expresión Génica , Fosfohidrolasa PTEN , Neoplasias Pancreáticas , Factores de Transcripción , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Humanos , Fosfohidrolasa PTEN/metabolismo , Fosfohidrolasa PTEN/genética , Resistencia a Antineoplásicos/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Ratones , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Gemcitabina , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genéticaRESUMEN
Eukaryotic chromatin is organized into functional domains, that are characterized by distinct proteomic compositions and specific nuclear positions. In contrast to cellular organelles surrounded by lipid membranes, the composition of distinct chromatin domains is rather ill described and highly dynamic. To gain molecular insight into these domains and explore their composition, we developed an antibody-based proximity biotinylation method targeting the RNA and proteins constituents. The method that we termed antibody-mediated proximity labelling coupled to mass spectrometry (AMPL-MS) does not require the expression of fusion proteins and therefore constitutes a versatile and very sensitive method to characterize the composition of chromatin domains based on specific signature proteins or histone modifications. To demonstrate the utility of our approach we used AMPL-MS to characterize the molecular features of the chromocenter as well as the chromosome territory containing the hyperactive X chromosome in Drosophila. This analysis identified a number of known RNA-binding proteins in proximity of the hyperactive X and the centromere, supporting the accuracy of our method. In addition, it enabled us to characterize the role of RNA in the formation of these nuclear bodies. Furthermore, our method identified a new set of RNA molecules associated with the Drosophila centromere. Characterization of these novel molecules suggested the formation of R-loops in centromeres, which we validated using a novel probe for R-loops in Drosophila. Taken together, AMPL-MS improves the selectivity and specificity of proximity ligation allowing for novel discoveries of weak protein-RNA interactions in biologically diverse domains.
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Cromatina , Espectrometría de Masas , ARN , Animales , Cromatina/metabolismo , Cromatina/química , ARN/metabolismo , ARN/química , Espectrometría de Masas/métodos , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Drosophila melanogaster/genética , Biotinilación , Centrómero/metabolismo , Anticuerpos/metabolismo , Anticuerpos/química , Cromosoma X/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/química , Coloración y Etiquetado/métodosRESUMEN
Objective To understand the differences in the demand,preference,and tendency for elderly care services between urban and rural areas in the Pearl River Delta (PRD),and to provide reference for the planning and balanced allocation of elderly care resources in urban and rural areas. Methods Using the multi-stage stratified random sampling method,we selected 7 community health service centers in 2 prefecture-level cities in the PRD and conducted a questionnaire survey on the elderly care service demand,preference,and tendency among 1919 regular residents aged 60 years and above who attended the centers. Results A total of 641 urban elderly residents (33.4%) and 1278 rural elderly residents (66.6%) were surveyed in the PRD.The urban and rural elderly residents showed differences in the child number (χ2=43.379,P<0.001),willingness to purchase socialized elderly care services (χ2=104.141,P<0.001),and attitudes to the concept of raising child to avoid elderly hardship (χ2=65.632,P<0.001).The proportion (71.8%) of rural elderly residents who prefer family-based elderly care was higher than that (57.1%) of urban elderly residents (χ2=41.373,P<0.001).The proportion (62.2%) of urban elderly residents clearly expressing their willingness to choose institutions for elderly care was higher than that (44.0%) of rural elderly residents (χ2=57.007,P<0.001).Compared with family-based elderly care,the willingness to choose institutional or community-based in-house elderly care was low among the urban elderly residents with surplus monthly household income or balanced income and expenditure;urban males,those with college education background or above,and those who purchased socialized elderly care services tended to prefer community-based in-house elderly care.In rural areas,the elderly residents who had local household registry were prone to choose institutional or community-based in-house elderly care,while those who had more than one child and those who were satisfied with the current living conditions were less willing to choose community-based in-house elderly care. Conclusions It is suggested that the urban-rural differences in the elderly care service demand,preference and tendency should be fully considered in the planning and allocation of urban and rural elderly care resources.Efforts remain to be made to develop diversified social elderly care services tailored to the characteristics of urban and rural areas.
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Población Rural , Población Urbana , Humanos , Anciano , China , Masculino , Femenino , Persona de Mediana Edad , Encuestas y Cuestionarios , Servicios de Salud para Ancianos/estadística & datos numéricos , Anciano de 80 o más Años , Necesidades y Demandas de Servicios de SaludRESUMEN
BACKGROUND: The widespread involvement of tumor-infiltrating B cells highlights their potential role in tumor behavior. However, B cell heterogeneity in PDAC remains unexplored. Studying TIL-Bs in PDAC aims to identify new treatment strategies. METHODS: We performed single-cell RNA sequencing to study the heterogeneity of B cells in PDAC. The prognostic and immunologic value of the identified CD38+ B cells was explored in FUSCC (n = 147) and TCGA (n = 176) cohorts. Flow cytometry was conducted to characterize the relationship between CD38+ B cells and other immune cells, as well as their phenotypic features. In vitro and in vivo experiments were performed to assess the putative effect of CD38+ B cells on antitumor immunity. FINDINGS: The presence of CD38+ B cells in PDAC was associated with unfavorable clinicopathological features and poorer overall survival (p < 0.001). Increased infiltration of CD38+ B cells was accompanied by reduced natural killer (NK) cells (p = 0.021) and increased regulatory T cells (p = 0.016). Molecular profiling revealed high expression of IL-10, IL-35, TGF-ß, GZMB, TIM-1, CD5 and CD21, confirming their putative regulatory B cell-like features. Co-culture experiments demonstrated suppression of NK cell cytotoxicity by CD38+ B cell-derived IL-10 (p < 0.001). Finally, in vivo experiments suggested adoptive transfer of CD38+ B cells reduced antitumor immunity and administration of a CD38 inhibitor hampered tumor growth (p < 0.001). INTERPRETATION: We discovered regulatory B cell-like CD38+ B cell infiltration as an independent prognostic factor in PDAC. The use of CD38 inhibitor may provide new possibilities for PDAC immunotherapy. FUNDING: This study was supported by the National Natural Science Foundation of China (U21A20374), Shanghai Municipal Science and Technology Major Project (21JC1401500), Scientific Innovation Project of Shanghai Education Committee (2019-01-07-00-07-E00057), Special Project for Clinical Research in the Health Industry of the Shanghai Health Commission (No. 20204Y0265) and Natural Science Foundation of Shanghai (23ZR1479300).
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ADP-Ribosil Ciclasa 1 , Carcinoma Ductal Pancreático , Humanos , ADP-Ribosil Ciclasa 1/metabolismo , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/terapia , Animales , Ratones , Pronóstico , Antígenos CD19/metabolismo , Antígenos CD19/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidad , Femenino , Masculino , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Línea Celular Tumoral , Microambiente Tumoral/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Linfocitos B/inmunología , Linfocitos B/metabolismo , Persona de Mediana Edad , Subgrupos de Linfocitos B/inmunología , Subgrupos de Linfocitos B/metabolismo , Terapia de InmunosupresiónRESUMEN
BACKGROUND: The McKeown minimally invasive esophagectomy (McMIE) procedure has various limitations, including surgical contraindications and a high rate of postoperative pulmonary complications. A novel mediastinoscopic esophagectomy procedure was described in this study by using esophageal invagination and a transhiatal and bilateral cervical approach (EITHBC). METHODS: According to the mode of operation, a total of 259 patients were divided into two groups, among which 106 underwent EITHBC and 153 underwent McMIE. The number of lymph nodes dissected, intraoperative outcomes, and postoperative outcomes were compared between the two groups of patients. RESULTS: The results revealed that the average number of resected lymph node in the EITHBC group was significantly higher in the recL106 and TbL106 stations (recL106: 1.75 vs. 1.51, p = 0.016, TbL106: 1.53 vs. 1.19, p = 0.016) and significantly lower in the 107 stations (1. 74 vs. 2. 07, p < 0.001) than in the McMIE group. The intraoperative blood loss in the EITHBC group was significantly lower than that in the McMIE group (63.30 vs. 80.45 mL, p < 0.001). The incidence of postoperative pulmonary complications in the EITHBC group was lower than that in the McMIE group (14.15% vs. 27.45%, p = 0.008). The incidence of recurrent laryngeal nerve paralysis in the EITHBC group was significantly higher than that in the McMIE group (26.41% vs. 10.46%, p = 0.003). CONCLUSION: Compared with the McMIE procedure, the EITHBC procedure has advantages in terms of removing the upper mediastinal lymph nodes and reducing postoperative pulmonary complications.
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Neoplasias Esofágicas , Esofagectomía , Mediastinoscopía , Humanos , Esofagectomía/métodos , Femenino , Estudios Retrospectivos , Masculino , Mediastinoscopía/métodos , Persona de Mediana Edad , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/patología , Anciano , Complicaciones Posoperatorias/epidemiología , Escisión del Ganglio Linfático/métodos , Resultado del Tratamiento , Adulto , Estudios de CohortesAsunto(s)
Carcinoma de Células Escamosas , ADN Tumoral Circulante , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/diagnóstico , ADN Tumoral Circulante/sangre , ADN Tumoral Circulante/genética , Estadificación de Neoplasias , Biomarcadores de Tumor/sangreRESUMEN
Dental calculi can cause gingival bleeding and periodontitis, yet the mechanism underlying the formation of such mineral build-ups, and in particular the role of the local microenvironment, are unclear. Here we show that the formation of dental calculi involves bacteria in local mature biofilms converting the DNA in neutrophil extracellular traps (NETs) from being degradable by the enzyme DNase I to being degradation resistant, promoting the nucleation and growth of apatite. DNase I inhibited NET-induced mineralization in vitro and ex vivo, yet plasma DNases were ineffective at inhibiting ectopic mineralization in the oral cavity in rodents. The topical application of the DNA-intercalating agent chloroquine in rodents fed with a dental calculogenic diet reverted NET DNA to its degradable form, inhibiting the formation of calculi. Our findings may motivate therapeutic strategies for the reduction of the prevalence of the deposition of bacteria-driven calculi in the oral cavity.
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We investigated the effects and mechanisms of nitrogen additions (0, 1, 2, 4, 8, 16, 24, 32 g N·m-2·a-1) on contents of anion and cation in rhizosphere soil, bulk soil, and mixed rhizosphere and bulk soil in the heavily salinized grassland in the agro-pastoral ecotone of North China. The results showed that pH of rhizosphere, mixed and bulk soils decreased significantly with the increases of nitrogen addition levels. Moreover, pH of three soil types under the 32 g N·m-2·a-1 treatment decreased by 1.2, 0.9, and 0.6, respectively, while pH of rhizosphere soil decreased by 0.44 compared with the bulk soil. Na+ content of rhizosphere, mixed and bulk soils significantly decreased, while the NO3- content significantly increased. The proportion of Na+ content in total soluble salt content in rhizosphere soil decreased by 14% and that in bulk soil decreased by 12% after the 32 g N·m-2·a-1 addition. NO3- content increased by 29% in rhizosphere soil and by 26% in bulk soil. There was significant negative correlation between pH and NO3- content, and significant positive correlation between pH and Na+ content. The total soluble salt content of rhizosphere soil under the 32 g N·m-2·a-1 treatment was significantly reduced by 31.5%. Collectedly, nitrogen deposition could reduce soil pH and total soluble salt content of rhizosphere soil and alleviate saline-alkali stress.