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2.
IEEE Trans Image Process ; 33: 4116-4130, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38963735

RESUMO

Incomplete multiview clustering (IMVC) aims to reveal the underlying structure of incomplete multiview data by partitioning data samples into clusters. Several graph-based methods exhibit a strong ability to explore high-order information among multiple views using low-rank tensor learning. However, spectral embedding fusion of multiple views is ignored in low-rank tensor learning. In addition, addressing missing instances or features is still an intractable problem for most existing IMVC methods. In this paper, we present a unified spectral embedding tensor learning (USETL) framework that integrates the spectral embedding fusion of multiple similarity graphs and spectral embedding tensor learning for IMVC. To remove redundant information from the original incomplete multiview data, spectral embedding fusion is performed by introducing spectral rotations at two different data levels, i.e., the spectral embedding feature level and the clustering indicator level. The aim of introducing spectral embedding tensor learning is to capture consistent and complementary information by seeking high-order correlations among multiple views. The strategy of removing missing instances is adopted to construct multiple similarity graphs for incomplete multiple views. Consequently, this strategy provides an intuitive and feasible way to construct multiple similarity graphs. Extensive experimental results on multiview datasets demonstrate the effectiveness of the two spectral embedding fusion methods within the USETL framework.

3.
World J Gastrointest Oncol ; 16(6): 2769-2780, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38994173

RESUMO

BACKGROUND: Wnt/FZD-mediated signaling pathways are activated in more than 90% of hepatocellular carcinoma (HCC) cell lines. As a well-known secretory glycoprotein, Wnt3 can interact with FZD receptors on the cell surface, thereby activating the Wnt/ß-catenin signaling pathway. However, the N-glycosylation modification site of Wnt3 and the effect of this modification on the biological function of the protein are still unclear. AIM: To investigate the effect of Wnt3 N-glycosylation on the biological function of HCC cells. METHODS: Site-directed mutagenesis was used to verify the Wnt3 N-glycosylation sites, actinomycin D treatment was used to detect the stability of Wnt3 after site-directed mutation, the binding of the N-glycosylation site-directed mutant Wnt3 to FZD7 was observed by laser confocal microscopy, and the effects of the N-glycosylation site-directed mutation of Wnt3 on the Wnt/ß-catenin signaling pathway and the progression of HCC cells were detected by western blot and cell function experiments. RESULTS: Wnt3 has two N-glycosylation-modified sites (Asn90 and Asn301); when a single site at amino acid 301 is mutated, the stability of Wnt3 is weakened; the binding ability of Wnt3 to FZD7 decreases when both sites are mutated simultaneously; and the level of proteins related to the Wnt/ß-catenin signaling pathway is downregulated. Cell proliferation, migration and invasion are also weakened in the case of single 301 site and double-site mutations. CONCLUSION: These results indicate that by inhibiting the N-glycosylation of Wnt3, the proliferation, migration, invasion and colony formation abilities of liver cancer cells can be weakened, which might provide new therapeutic strategies for clinical liver cancer in the future.

4.
Nat Commun ; 15(1): 6120, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39033152

RESUMO

Extremely large magnetoresistance (XMR) is highly applicable in spintronic devices such as magnetic sensors, magnetic memory, and hard drives. Typically, XMR is found in Weyl semimetals characterized by perfect electron-hole symmetry or exceptionally high electric conductivity and mobility. Our study explores this phenomenon in a recently developed graphene moiré system, which demonstrates XMR owing to its topological structure and high-quality crystal formation. We investigate the electronic properties of three-dimensional intertwined twisted graphene spirals (TGS), manipulating the screw dislocation axis to achieve a rotation angle of 7.3°. Notably, at 14 T and 2 K, the magnetoresistance of these structures reaches 1.7 × 107%, accompanied by a metal-insulator transition as the temperature increases. This transition becomes noticeable when the magnetic field exceeds a minimal threshold of approximately 0.1 T. These observations suggest the possible existence of complex, correlated states within the partially filled three-dimensional Landau levels of the 3D TGS system. Our findings open up possibilities for achieving XMR by engineering the topological structure of 2D layered moiré systems.

6.
J Cancer Res Clin Oncol ; 150(7): 348, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39002018

RESUMO

BACKGROUND & AIMS: Patients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA. METHODS: scRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy. RNA-seq analysis and western blot assays were performed to examine the upstream and downstream signaling pathways of CD73. Subcutaneous tumor xenograft models were utilized to investigate the impact of CD73 on iCCA growth. Plasmid AKT/NICD-induced spontaneous murine iCCAs were used to explore the therapeutic efficacy of CD73 enzymatic inhibitor AB680 combined with PD-1 blockade. Time-of-flight mass cytometry (CyTOF) was conducted to identify the tumor-infiltrating immune cell populations and their functional changes in murine iCCAs treated with AB680 in combination with PD-1 antibody. RESULTS: scRNA-seq analysis identified elevated CD73 expression in malignant cells in response to ICBs therapy. Mechanistically, ICBs therapy upregulated CD73 expression in malignant cells via TNF-α/NF-κB signaling pathway. In vivo studies revealed that CD73 inhibition suppressed the growth of subcutaneous tumors, and achieved synergistic depression effects with gemcitabine and cisplatin (GC). Adenosine produced by CD73 activates AKT/GSK3ß/ß-catenin signaling axis in iCCA cells. CD73 inhibitor AB680 potentiates anti-tumor efficacy of PD-1 antibody in murine iCCAs. CyTOF analysis showed that AB680 combined with anti-PD-1 therapy promoted the infiltration of CD8+ T, CD4+ T cells, and NK cells in murine iCCAs, while simultaneously decreased the proportions of macrophages and neutrophils. Moreover, AB680 combined with anti-PD-1 significantly upregulated the expression of Granzyme B, Tbet and co-stimulatory molecule ICOS in infiltrating CD8+ T cells. CONCLUSIONS: CD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response.


Assuntos
5'-Nucleotidase , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1 , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Colangiocarcinoma/imunologia , Animais , 5'-Nucleotidase/antagonistas & inibidores , 5'-Nucleotidase/metabolismo , Camundongos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/imunologia , Neoplasias dos Ductos Biliares/metabolismo , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Progressão da Doença
7.
Sci Total Environ ; 949: 175126, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39084385

RESUMO

Tetracyclines (TCs) are the most common antibiotics in agricultural soil, due to their widespread usage and strong persistence. Biotic and abiotic degradation of TCs may generate toxic transformation products (TPs), further threatening soil ecological safety. Despite the increasing attention on the environmental behavior of TCs, a systematic review on the dissipation of TCs, evolution of TPs, and structure-toxicity relationship of TCs in agricultural soil remains lacking. This review aimed to provide a comprehensive overview of the environmental fate of TCs in agricultural soil. We first introduced the development history and structural features of different generations of TCs. Then, we comparatively evaluated the dissipation kinetics, transportation pathways, and ecological impacts of three representative TCs, namely tetracycline (TC), oxytetracycline (OTC), and chlortetracycline (CTC), in agricultural soil. The results showed that the dissipation kinetics of TCs generally followed the first-order kinetic model, with the median dissipation half-lives ranging from 20.0 to 38.8 days. Among the three TCs, OTC displayed the lowest dissipation rates due to its structural stability. The typical degradation pathways of TCs in soil included epimerization/isomerization, demethylation, and dehydration. Isomerization and dehydration reactions may lead to the formation of more toxic TPs, while demethylation was accompanied by the alteration of the minimal pharmacophore of TCs thus potentially reducing the toxicity. Toxicological experiments are urgently needed in future to comprehensively evaluate the ecological risks of TCs in agricultural soil.


Assuntos
Agricultura , Antibacterianos , Poluentes do Solo , Solo , Poluentes do Solo/química , Antibacterianos/química , Solo/química , Cinética , Monitoramento Ambiental , Tetraciclinas/química , Tetraciclina/química
8.
Huan Jing Ke Xue ; 45(6): 3614-3626, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38897781

RESUMO

The altitude distribution patterns of soil microorganisms and their driving mechanisms are crucial for understanding the consequences of climate change on terrestrial ecosystems. There is an obvious altitude difference in Datong River Basin in the Qilian Mountains. Two spatial scale transections were set up along the mountain slope (with altitude spanning 1 000 m) and the mainstream direction (with altitude spanning 300-500 m), respectively. The distribution characteristics of the soil bacterial community structure and diversity along the altitude gradients were examined using high-throughput sequencing technology. Based on the FAPROTAX database, the altitude distribution patterns of nitrogen cycling functional groups were analyzed to investigate the major environmental factors influencing the altitude distribution patterns of soil bacterial communities. The findings revealed that:① Soil physicochemical characteristics varied significantly with altitude. The content of total nitrogen (TN) and nitrate nitrogen (NO3-) were positively correlated with the altitude (P < 0.01), whereas the soil bulk density and pH were negatively connected (P < 0.001). ② The abundance of OTU increased significantly along the altitude (P < 0.01), and the richness and diversity indices increased along the altitude, although the trend was not statistically significant (P > 0.05). ③ The predominant bacterial communities were Acidobacteria, Proteobacteria, and Bacteroidetes, and as altitude climbed, their relative abundances varied between increasing, decreasing, and slightly decreasing, respectively. ④ The nitrogen cycling processes involved 13 functional groups, primarily nitrification, aerobic ammonia oxidation, aerobic nitrite oxidation, etc. As the altitude increased, the response law changed, with an increase in the abundance of nitrobacteria (P < 0.01), a slight increase in the abundance of aerobic ammonia-oxidizing bacteria and nitrite-oxidizing bacteria, and a hump-back tendency in bacteria abundance for nitrogen respiration. ⑤ Redundancy analysis revealed that the key determinants influencing soil bacterial populations at the phylum level were altitude, pH, and the content of NH4+. Mantel analysis showed that the dominant groups of soil bacterial nitrogen cycling were all statistically and significantly driven by altitude (P < 0.01). ⑥ The α-diversity of the bacterial community with increasing altitude were both increased along the mountain slope and the mainstream direction, but the soil properties, the abundance of N-cycling functional groups, and the main environmental factors differed. Therefore, it is of great significance to explore the altitude distribution pattern of soil microorganisms at different spatial scales.


Assuntos
Altitude , Bactérias , Nitrogênio , Rios , Microbiologia do Solo , China , Nitrogênio/análise , Bactérias/classificação , Bactérias/metabolismo , Rios/microbiologia , Ciclo do Nitrogênio , Solo/química , Ecossistema , Nitratos/análise
9.
Science ; 384(6700): 1100-1104, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38843317

RESUMO

One-dimensional transition metal dichalcogenides exhibiting an enhanced bulk photovoltaic effect have the potential to exceed the Shockley-Queisser limit efficiency in solar energy harvest within p-n junction architectures. However, the collective output of these prototype devices remains a challenge. We report on the synthesis of single-crystalline WS2 ribbon arrays with defined chirality and coherent polarity through an atomic manufacturing strategy. The chirality of WS2 ribbon was defined by substrate couplings into tunable armchair, zigzag, and chiral species, and the polarity direction was determined by the ribbon-precursor interfacial energy along a coherent direction. A single armchair ribbon showed strong bulk photovoltaic effect and the further integration of ~1000 aligned ribbons with coherent polarity enabled upscaling of the photocurrent.

10.
Acta Histochem ; 126(4): 152169, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38850586

RESUMO

Alveolar, the smallest structural and functional units within the respiratory system, play a crucial role in maintaining lung function. Alveolar damage is a typical pathological hallmark of respiratory diseases. Nevertheless, there is currently no simple, rapid, economical, and unbiased method for quantifying alveolar size for entire lung tissue. Here, firstly, we conducted lung sample slicing based on the size, shape, and distribution of airway branches of different lobes. Next, we performed HE staining on different slices. Then, we provided an unbiased quantification of alveolar size using free software ImageJ. Through this protocol, we demonstrated that C57Bl/6 mice exhibit varying alveolar sizes among different lobes. Collectively, we provided a simple and unbiased method for a more comprehensive quantification of alveolar size in mice, which holds promise for a broader range of respiratory research using mouse models.


Assuntos
Amarelo de Eosina-(YS) , Hematoxilina , Pulmão , Camundongos Endogâmicos C57BL , Alvéolos Pulmonares , Coloração e Rotulagem , Animais , Camundongos , Alvéolos Pulmonares/patologia , Coloração e Rotulagem/métodos , Pulmão/patologia , Masculino
11.
J Cancer Res Clin Oncol ; 150(6): 325, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38914802

RESUMO

PURPOSE: Hepatocellular carcinoma (HCC) is a critical global health concern, with existing treatments benefiting only a minority of patients. Recent findings implicate the chemokine ligand 17 (CCL17) and its receptor CCR4 as pivotal players in the tumor microenvironment (TME) of various cancers. This investigation aims to delineate the roles of CCL17 and CCR4 in modulating the tumor's immune landscape, assessing their potential as therapeutic interventions and prognostic markers in HCC. METHODS: 873 HCC patients post-radical surgery from 2008 to 2012 at Zhongshan Hospital, Fudan University were retrospectively examined. These individuals were stratified into a training cohort (n = 354) and a validation cohort (n = 519). Through immunohistochemical analysis on HCC tissue arrays, the expressions of CCL17, CCR4, CD73, CD47, HHLA2, and PD-L1 were quantified. Survival metrics were analyzed using the Cox model, and a prognostic nomogram was devised via R software. RESULTS: The investigation confirmed the presence of CCL17 and CCR4 within the cancerous and stromal compartments of HCC tissues, associating their heightened expression with adverse clinical markers and survival outcomes. Notably, the interplay between CD73 and CCR4 expression in tumor stroma highlighted a novel cellular entity, CCR4 + CD73 + stromal cells, impacting overall and relapse-free survival. A prognostic nomogram amalgamating these immunological markers and clinical variables was established, offering refined prognostic insights and aiding in the management of HCC. The findings suggest that reduced CCR4 and CCR4 + CD73 + cell prevalence may forecast improved outcomes post-TACE. CONCLUSION: This comprehensive evaluation of CCR4, CCL17, and associated markers introduces a nuanced understanding of the HCC immunological milieu, proposing CCR4 + CD73 + stromal cells as critical to HCC pathogenesis and patient stratification.


Assuntos
5'-Nucleotidase , Biomarcadores Tumorais , Carcinoma Hepatocelular , Quimiocina CCL17 , Proteínas Ligadas por GPI , Neoplasias Hepáticas , Receptores CCR4 , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/imunologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/imunologia , Quimiocina CCL17/metabolismo , Feminino , Masculino , Prognóstico , Receptores CCR4/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , 5'-Nucleotidase/metabolismo , Estudos Retrospectivos , Microambiente Tumoral/imunologia , Proteínas Ligadas por GPI/metabolismo , Idoso , Adulto
12.
JCI Insight ; 9(11)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38855868

RESUMO

Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) is not well defined. Urine lactate was measured in patients with type 2 diabetes (T2D) in 3 cohorts (HUNT3, SMART2D, CRIC). Urine and plasma lactate were measured during euglycemic and hyperglycemic clamps in participants with type 1 diabetes (T1D). Patients in the HUNT3 cohort with DKD had elevated urine lactate levels compared with age- and sex-matched controls. In patients in the SMART2D and CRIC cohorts, the third tertile of urine lactate/creatinine was associated with more rapid estimated glomerular filtration rate decline, relative to first tertile. Patients with T1D demonstrated a strong association between glucose and lactate in both plasma and urine. Glucose-stimulated lactate likely derives in part from proximal tubular cells, since lactate production was attenuated with sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney sections and in SGLT2-deficient mice. Several glycolytic genes were elevated in human diabetic proximal tubules. Lactate levels above 2.5 mM potently inhibited mitochondrial oxidative phosphorylation in human proximal tubule (HK2) cells. We conclude that increased lactate production under diabetic conditions can contribute to mitochondrial dysfunction and become a feed-forward component to DKD pathogenesis.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Glicólise , Ácido Láctico , Humanos , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Animais , Camundongos , Ácido Láctico/metabolismo , Ácido Láctico/sangue , Feminino , Masculino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/complicações , Mitocôndrias/metabolismo , Adulto , Taxa de Filtração Glomerular , Idoso , Túbulos Renais Proximais/metabolismo , Glucose/metabolismo , Fosforilação Oxidativa , Biomarcadores/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/genética , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
13.
J Transl Med ; 22(1): 596, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38926764

RESUMO

BACKGROUND: Existing studies have found that circular RNAs (circRNAs) act as sponges for micro RNAs (miRNAs) to control downstream genes. However, the specific functionalities and mechanisms of circRNAs in human clear cell renal cell carcinoma (ccRCC) have yet to be thoroughly investigated. METHODS: Patient cohorts from online databases were used to screen candidate circRNAs, while another cohort from our hospital was obtained for validation. CircSOD2 was identified as a potential oncogenic target, and its relevant characteristics were investigated during ccRCC progression through various assays. A positive feedback loop containing downstream miRNA and its target gene were identified using bioinformatics and validated by luciferase reporter assays, RNA pull-down, and high-throughput sequencing. RESULTS: CircSOD2 expression was elevated in tumor samples and significantly correlated with overall survival (OS) and the tumor stage of ccRCC patients, which appeared in the enhanced proliferation, invasion, and migration of tumor cells. Through competitive binding to circSOD2, miR-532-3p can promote the expression of PAX5 and the progression of ccRCC, and such regulation can be salvaged by miR-532-3p inhibitor. CONCLUSION: A novel positive feedback loop, PAX5/circSOD2/miR-532-3p/PAX5 was identified in the study, indicating that the loop may play an important role in the diagnosis and prognostic prediction in ccRCC patients.


Assuntos
Carcinoma de Células Renais , Proliferação de Células , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , MicroRNAs , RNA Circular , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Pessoa de Meia-Idade , Masculino , Carcinogênese/genética , Carcinogênese/patologia , Movimento Celular/genética , Fator de Transcrição PAX5/metabolismo , Fator de Transcrição PAX5/genética , Oncogenes/genética , Sequência de Bases , Progressão da Doença , Invasividade Neoplásica , Reprodutibilidade dos Testes
14.
Wei Sheng Yan Jiu ; 53(3): 455-464, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38839588

RESUMO

OBJECTIVE: To establish an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 11 nutritional components(thiamine, riboflavin, nicotinamide, nicotinic acid, pantothenic acid, pyridoxine, pyridoxal, pyridoxamine, biotin, choline, L-carnitine) in liquid milk. METHODS: Milk samples were shaken with 20 mmol/L ammonium formate solution and heated in a water bath at 100 ℃ for 30 min, then incubated with papain and acid phosphatase at 45 ℃ for 16 h, the lower liquid was collected after centrifugation for analysis. UPLC separation was performed on an ACQUITY~(TM) HSS T3(3.0 mm×150 mm, 1.8 µm) column, 2 mmol/L ammonium formate(containing 0.1% formic acid) solution and acetonitrile(containing 0.1% formic acid) were used as mobile phase. Quantitative detection was performed by internal standard method. RESULTS: 11 nutritional components can be effectively separated and detected in 12 min, and the linear correlation coefficients(R~2) were all above 0.995. The limits of detection(LODs) were between 0.05 and 0.50 µg/L, and the limits of quantification(LOQs) were between 0.20 and 1.25 µg/L. The recovery rates of three-level addition were 85.6%-119.3%, and the precision RSDs were between 3.68% and 7.82%(n=6). Based on the detection of 60 liquid milk samples from 5 different animals, it was found that the contents of 11 nutrients in liquid milk from different milk sources were significantly different, but pyridoxine could not be detected. CONCLUSION: The method can quantitatively detect 11 water-soluble nutrients, including free and bound forms, by effective enzymolysis. It is sensitive, reproducible and can meet the needs of quantitative detection.


Assuntos
Leite , Espectrometria de Massas em Tandem , Leite/química , Espectrometria de Massas em Tandem/métodos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Niacinamida/análise , Riboflavina/análise , Nutrientes/análise , Ácido Pantotênico/análise , Bovinos , Piridoxina/análise , Niacina/análise , Carnitina/análise
15.
Cell Death Discov ; 10(1): 304, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926350

RESUMO

Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples. Tumor-infiltrating DCs correlated with increased CD8+ T cell infiltration and better prognoses in ICC patients. Mechanistically, ß-catenin-mediated CXCL12 suppression accounted for the impaired DC recruitment in ICC with LNM. Two mouse ICC cell lines MuCCA1 and mIC-23 cells were established from AKT/NICD or AKT/YAP-induced murine ICCs respectively and were utilized to construct the footpad tumor LNM model. We found that expansion and activation of conventional DCs (cDCs) by combined Flt3L and poly(I:C) (FL-pIC) therapy markedly suppressed the metastasis of mIC-23 cells to popliteal LNs. Moreover, ß-catenin inhibition restored the defective DC infiltration into primary tumor sites and reduced the incidence of LNM in ICC. Collectively, our findings identify tumor cell intrinsic ß-catenin activation as a key mechanism for subverting DC-mediated anti-tumor immunity in ICC with LNM. FL-pIC therapy or ß-catenin inhibitor could merit exploration as a potential regimen for mitigating ICC cell metastasis to LNs and achieving effective tumor immune control.

16.
Cancer Immunol Immunother ; 73(8): 143, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832955

RESUMO

This study investigates the role of USP47, a deubiquitinating enzyme, in the tumor microenvironment and its impact on antitumor immune responses. Analysis of TCGA database revealed distinct expression patterns of USP47 in various tumor tissues and normal tissues. Prostate adenocarcinoma showed significant downregulation of USP47 compared to normal tissue. Correlation analysis demonstrated a positive association between USP47 expression levels and infiltrating CD8+ T cells, neutrophils, and macrophages, while showing a negative correlation with NKT cells. Furthermore, using Usp47 knockout mice, we observed a slower tumor growth rate and reduced tumor burden. The absence of USP47 led to increased infiltration of immune cells, including neutrophils, macrophages, NK cells, NKT cells, and T cells. Additionally, USP47 deficiency resulted in enhanced activation of cytotoxic T lymphocytes (CTLs) and altered T cell subsets within the tumor microenvironment. These findings suggest that USP47 plays a critical role in modulating the tumor microenvironment and promoting antitumor immune responses, highlighting its potential as a therapeutic target in prostate cancer.


Assuntos
Linfócitos do Interstício Tumoral , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Microambiente Tumoral
17.
PLoS One ; 19(6): e0305357, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38917065

RESUMO

Increasing the yield of maize F1 hybrid is one of the most important target for breeders. However, as a result of the genetic complexity and extremely low heritability, it is very difficult to directly dissect the genetic basis and molecular mechanisms of yield, and reports on genetic analysis of F1 hybrid yield are rare. Taking F1 hybrid as the research object and dividing the yield into different affect factors, this approach may be the best strategy for clarifying the genetic mechanism of yield. Therefore, in this study, a maize F1 population consisting of 300 hybrids with 17,652 single nucleotide polymorphisms (SNPs) markers was used for genome-wide association study (GWAS) to filtrate candidate genes associated with the four yield-related traits, i.e., kernel row number (KRN), kernel number per row (KNPR), ear tip-barrenness (ETB), and hundred kernel weight (HKW). Combined with the results of previous studies and functional annotation information of candidate genes, a total of six candidate genes were identified as being associated with the four traits, which were involved in plant growth and development, protein synthesis response, phytohormone biosynthesis and signal transduction. Our results improve the understanding of the genetic basis of the four yield-related traits and may be provide a new strategy for the genetic basis of maize yield.


Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Zea mays , Zea mays/genética , Zea mays/crescimento & desenvolvimento , Fenótipo , Locos de Características Quantitativas , Genes de Plantas
18.
Rev Esp Enferm Dig ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832596

RESUMO

The inverted hyperplastic polyp (IHP) is known as hyperplastic gastric mucosa growth into submucosa and endoscopically presented as sessile or pedunculated submucosa lesion. It occurs in between 3.1% to 20.1% of cases, while its malignant transformation rate is just 0.02%. A male underwent esophagogastroduodenoscopy (EGD) and discovered a submucosal lesion with a pinhole-like orifice in the fundus. And endoscopic ultrasound (EUS) showed it was a heterogenous hypoechoic lesion located in the submucosa. After endoscopic resection, the pathological findings and immunohistochemical staining revealed it was inverted hyperplastic polyp (IHP) with adenocarcinoma. The measurement of the cancerous IHP depth of invasion is controversial. Thus, how to define the depth of lesion invasion in this patient needs to be seriously considered. To manage IHP with adenocarcinoma better, the depth of lesion invasion cancerous IHP needs to be seriously considered.

19.
Water Sci Technol ; 89(10): 2839-2850, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38822618

RESUMO

Antibiotics release into the water environment through sewage discharge is a significant environmental concern. In the present study, we investigated the removal of ciprofloxacin (CIP) in simulated sewage by biological aeration filter (BAF) equipped with Fe3O4-modified zeolite (Fe3O4@ZF). Fe3O4@ZF were prepared with impregnation method, and the Fe3O4 particles were successfully deposited on the surface of ZF in an amorphous form according to the results of XPS and XRD analysis. The modification also increased the specific surface area (from 16.22 m²/g to 22 m²/g) and pore volume (from 0.0047 cm³/g to 0.0063 cm³/g), improving the adsorption efficiency of antibiotics. Fe3O4 modified ZF improved the treatment performance significantly, and the removal efficiency of CIP in BAF-Fe3O4@ZF was 79%±2.4%. At 10ml/L CIP, the BAF-Fe3O4@ZF reduced the relative abundances of antibiotics resistance genes (ARGs) int, mexA, qnrB and qnrS in the effluent by 57.16%, 39.59%, 60.22%, and 20.25%, respectively, which effectively mitigate the dissemination risk of ARGs. The modification of ZF increased CIP-degrading bacteria abundance, such as Rhizobium and Deinococcus-Thermus, and doubled bacterial ATP activity, promoting CIP degradation. This study offers a viable, efficient method to enhance antibiotic treatment and prevent leakage via sewage discharge.


Assuntos
Antibacterianos , Ciprofloxacina , Águas Residuárias , Poluentes Químicos da Água , Zeolitas , Zeolitas/química , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Águas Residuárias/química , Antibacterianos/farmacologia , Antibacterianos/química , Filtração/métodos , Purificação da Água/métodos , Eliminação de Resíduos Líquidos/métodos , Adsorção , Resistência Microbiana a Medicamentos/genética , Genes Bacterianos , Farmacorresistência Bacteriana/genética
20.
Biomed Chromatogr ; 38(7): e5894, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38777624

RESUMO

Verbena officinalis L. as a medical plant has been used to treat many diseases. However, the quality control underlying V. officinalis remains to be studied. HPLC fingerprint analysis and the qualitative and quantitative analysis of water extract from V. officinalis were carried out, and it was found that the quality varies according to habitat and batch. Verbenalin could be a crucial component in the quality evaluation of V. officinalis. This study contributes to better understanding of quality control for V. officinalis.


Assuntos
Extratos Vegetais , Verbena , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Extratos Vegetais/análise , Verbena/química , Reprodutibilidade dos Testes , Espectrometria de Massas/métodos , Modelos Lineares , Limite de Detecção , Espectrometria de Massa com Cromatografia Líquida
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