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1.
Front Oncol ; 14: 1397855, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39386196

RESUMO

Background: Sarcomatoid urothelial carcinoma (SUC) is a rare renal malignancy. Its biological malignancy is high, the prognosis is poor, diagnostic and treatment options are few, and there is no standard treatment plan. Case presentation: In this case, a 64-year-old woman was hospitalized with fever and lower back pain one week previously. The preliminary diagnosis was a right kidney stone with a urinary tract infection. After the anti-infection treatment, a percutaneous right nephrostomy was performed. The intraoperative biopsy (renal pelvis) finding was infiltrating urothelial carcinoma with a sarcomatoid variation. Subsequently, radical surgery was performed for cancer of the right renal pelvis. Implant metastasis of the abdominal wall and adjacent abdominal cavity occurred half a month after the surgery. The lesion was resected again, and two cycles of doxorubicin plus carboplatin chemotherapy were administered. However, the disease progressed more rapidly after the chemotherapy. With the written consent of the patient, the treatment was altered to targeted immune therapy with toripalimab plus anlotinib. A clinical cure was achieved after nine cycles of treatment with no obvious lesions on imaging. The maintenance therapy was administered consecutively for over a year, and the patient is at present still in good condition with a disease-free survival exceeding two years. Conclusion: This case proves that the combination of toripalimab and anlotinib is effective in the treatment of recurrent renal SUC. To the best of our knowledge, this is the first reported case of a patient with advanced recurrent urothelial carcinoma of the renal pelvis sarcomatoid cured with this therapy.

2.
Theor Appl Genet ; 137(10): 223, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39278978

RESUMO

KEY MESSAGE: Mutations in TaCHLI impact chlorophyll levels and yield-related traits in wheat. Natural variations in TaCHLI-7A/B influence plant productivity, offering potential for molecular breeding. Chlorophyll is essential for plant growth and productivity. The CHLI subunit of the magnesium chelatase protein plays a key role inserting magnesium into protoporphyrin IX during chlorophyll biosynthesis. Here, we identify a novel wheat mutant chlorophyll (chl) that exhibits yellow-green leaves, reduced chlorophyll levels, and increased carotenoid content, leading to an overall decline in yield-related traits. Map-based cloning reveals that the chl phenotype is caused by a point mutation (Asp186Asn) in the TaCHLI-7D gene, which encodes subunit I of magnesium chelatase. Furthermore, the three TaCHLI mutants: chl-7b-1 (Pro82Ser), chl-7b-2 (Ala291Thr), and chl-7d-1 (Gly357Glu), also showed significant reductions in chlorophyll content and yield-related traits. However, TaCHLI-7D overexpression in rice significantly decreased thousand kernel weight, yield per plant, and germination. Additionally, natural variations in TaCHLI-7A/B are significantly associated with flag leaf, spike exsertion length, and yield per plant. Notably, the favorable haplotype, TaCHLI-7B-HapII, which displayed higher thousand kernel weight and yield per plant, is positively selected in wheat breeding. Our study provides insights on the regulatory molecular mechanisms underpinning leaf color and chlorophyll biosynthesis, and highlights TaCHLI functions, which provide useful molecular markers and genetic resources for wheat breeding.


Assuntos
Clorofila , Liases , Mutação de Sentido Incorreto , Fenótipo , Folhas de Planta , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Clorofila/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/genética , Liases/genética , Liases/metabolismo , Metanossulfonato de Etila , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oryza/genética , Oryza/crescimento & desenvolvimento , Mapeamento Cromossômico , Pigmentação/genética , Carotenoides/metabolismo , Clonagem Molecular , Melhoramento Vegetal
3.
Artigo em Inglês | MEDLINE | ID: mdl-39167500

RESUMO

Convolutional neural networks (CNNs) are widely used for embroidery feature synthesis from images. However, they are still unable to predict diverse stitch types, which makes it difficult for the CNNs to effectively extract stitch features. In this paper, we propose a multi-stitch embroidery generative adversarial network (MSEmbGAN) that uses a region-aware texture generation sub-network to predict diverse embroidery features from images. To the best of our knowledge, our work is the first CNN-based generative adversarial network to succeed in this task. Our region-aware texture generation sub-network detects multiple regions in the input image using a stitchclassifierandgeneratesastitchtextureforeachregionbasedonitsshapefeatures.Wealsoproposeacolorizationnetworkwitha color feature extractor, which helps achieve full image color consistency by requiring the color attributes of the output to closely resemble the input image. Because of the current lack of labeled embroidery image datasets, we provide a new multi-stitch embroidery dataset that is annotated with three single-stitch types and one multi-stitch type. Our dataset, which includes more than 30K high-quality multistitch embroidery images, more than 13K aligned content-embroidered images, and more than 17K unaligned images, is currently the largest embroidery dataset accessible, as far as we know. Quantitative and qualitative experimental results, including a qualitative user study, show that our MSEmbGAN outperforms current state-of-the-artembroiderysynthesisandstyle-transfermethodsonallevaluation indicators. Our demo and dataset sample can be found on the website https://csai.wtu.edu.cn/TVCG01/index.html.

4.
J Cancer Res Clin Oncol ; 150(8): 380, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39095579

RESUMO

PURPOSE: This study aims to determine whether Pokemon regulates Bim activity in colorectal carcinoma (CRC) carcinogenesis. METHODS: Clinical tissue samples were analyzed to detect the expression and clinicopathological significance of Pokemon and Bim in CRC. Proliferation, apoptosis, and invasion assays were conducted to identify the regulatory effect of Pokemon on Bim. The combined treatment effects of Pokemon knockdown and diamminedichloroplatinum (DDP) were also examined. RESULTS: Immunohistochemical analysis of 80 samples of colorectal epithelia (CRE), 80 cases of colorectal adenoma (CRA), and 160 of CRC samples revealed protein expression rates of 23.8%, 38.8%, and 70.6% for Pokemon, and 88.8%, 73.8%, and 31.9% for Bim, respectively. A significant negative correlation was observed between Pokemon and Bim expression across the CRE, CRA, and CRC lesion stages. In CRC, higher Pokemon and lower Bim expression correlated with higher histological grades, advanced Dukes stages, and increased cancer invasion. In both LoVo and HCT116 cells, overexpression of Pokemon significantly reduced Bim expression, leading to increased proliferation, resistance to anoikis, and cell invasion. Additionally, Pokemon overexpression significantly decreased DDP-induced Bim expression, reduction of anti-apoptosis and invasion, whereas Pokemon knockdown resulted in the opposite effects. CONCLUSION: These findings suggest that Pokemon inhibits Bim transcription, thereby promoting CRC proliferation, resistance to apoptosis, invasion, and advancing histological grade and Dukes staging. Pokemon knockdown enhances the therapeutic efficacy of DDP in the treatment of CRC.


Assuntos
Proteína 11 Semelhante a Bcl-2 , Proliferação de Células , Neoplasias Colorretais , Invasividade Neoplásica , Fatores de Transcrição , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Proteína 11 Semelhante a Bcl-2/genética , Proteína 11 Semelhante a Bcl-2/metabolismo , Feminino , Masculino , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Pessoa de Meia-Idade , Anoikis/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Estadiamento de Neoplasias , Idoso , Gradação de Tumores , Regulação Neoplásica da Expressão Gênica , Transcrição Gênica , Apoptose , Linhagem Celular Tumoral
5.
Cell Commun Signal ; 22(1): 308, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831451

RESUMO

Gasdermin D (GSDMD) is emerging as an important player in autoimmune diseases, but its exact role in lupus nephritis (LN) remains controversial. Here, we identified markedly elevated GSDMD in human and mouse LN kidneys, predominantly in CD11b+ myeloid cells. Global or myeloid-conditional deletion of GSDMD was shown to exacerbate systemic autoimmunity and renal injury in lupus mice with both chronic graft-versus-host (cGVH) disease and nephrotoxic serum (NTS) nephritis. Interestingly, RNA sequencing and flow cytometry revealed that myeloid GSDMD deficiency enhanced granulopoiesis at the hematopoietic sites in LN mice, exhibiting remarkable enrichment of neutrophil-related genes, significant increases in total and immature neutrophils as well as granulocyte/macrophage progenitors (GMPs). GSDMD-deficient GMPs and all-trans-retinoic acid (ATRA)-stimulated human promyelocytes NB4 were further demonstrated to possess enhanced clonogenic and differentiation abilities compared with controls. Mechanistically, GSDMD knockdown promoted self-renewal and granulocyte differentiation by restricting calcium influx, contributing to granulopoiesis. Functionally, GSDMD deficiency led to increased pathogenic neutrophil extracellular traps (NETs) in lupus peripheral blood and bone marrow-derived neutrophils. Taken together, our data establish that GSDMD deletion accelerates LN development by promoting granulopoiesis in a calcium influx-regulated manner, unraveling its unrecognized critical role in LN pathogenesis.


Assuntos
Cálcio , Nefrite Lúpica , Proteínas de Ligação a Fosfato , Nefrite Lúpica/patologia , Nefrite Lúpica/metabolismo , Nefrite Lúpica/genética , Animais , Humanos , Camundongos , Proteínas de Ligação a Fosfato/metabolismo , Proteínas de Ligação a Fosfato/genética , Proteínas de Ligação a Fosfato/deficiência , Cálcio/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Neutrófilos/metabolismo , Granulócitos/metabolismo , Células Mieloides/metabolismo , Camundongos Endogâmicos C57BL , Feminino , Armadilhas Extracelulares/metabolismo , Diferenciação Celular , Gasderminas
6.
Cell Death Dis ; 15(6): 397, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844455

RESUMO

Integrin αvß6 holds promise as a therapeutic target for organ fibrosis, yet targeted therapies are hampered by concerns over inflammatory-related side effects. The role of αvß6 in renal inflammation remains unknown, and clarifying this issue is crucial for αvß6-targeted treatment of chronic kidney disease (CKD). Here, we revealed a remarkable positive correlation between overexpressed αvß6 in proximal tubule cells (PTCs) and renal inflammation in CKD patients and mouse models. Notably, knockout of αvß6 not only significantly alleviated renal fibrosis but also reduced inflammatory responses in mice, especially the infiltration of pro-inflammatory macrophages. Furthermore, conditional knockout of αvß6 in PTCs in vivo and co-culture of PTCs with macrophages in vitro showed that depleting αvß6 in PTCs suppressed the migration and pro-inflammatory differentiation of macrophages. Screening of macrophage activators showed that αvß6 in PTCs activates macrophages via secreting IL-34. IL-34 produced by PTCs was significantly diminished by αvß6 silencing, and reintroduction of IL-34 restored macrophage activities, while anti-IL-34 antibody restrained macrophage activities enhanced by αvß6 overexpression. Moreover, RNA-sequencing of PTCs and verification experiments demonstrated that silencing αvß6 in PTCs blocked hypoxia-stimulated IL-34 upregulation and secretion by inhibiting YAP expression, dephosphorylation, and nuclear translocation, which resulted in the activation of Hippo signaling. While application of a YAP agonist effectively recurred IL-34 production by PTCs, enhancing the subsequent macrophage migration and activation. Besides, reduced IL-34 expression and YAP activation were also observed in global or PTCs-specific αvß6-deficient injured kidneys. Collectively, our research elucidates the pro-inflammatory function and YAP/IL-34/macrophage axis-mediated mechanism of αvß6 in renal inflammation, providing a solid rationale for the use of αvß6 inhibition to treat kidney inflammation and fibrosis.


Assuntos
Integrinas , Macrófagos , Camundongos Knockout , Insuficiência Renal Crônica , Animais , Macrófagos/metabolismo , Camundongos , Humanos , Integrinas/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Masculino , Antígenos de Neoplasias/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais , Modelos Animais de Doenças , Proteínas de Sinalização YAP/metabolismo , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Fibrose
7.
Immunity ; 57(6): 1306-1323.e8, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38815582

RESUMO

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues-like the kidneys-remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis.


Assuntos
Movimento Celular , Fibrose , Rim , Linfócitos , Receptor de Morte Celular Programada 1 , Receptores CXCR6 , Receptores de Interleucina , Transdução de Sinais , Animais , Fibrose/imunologia , Camundongos , Receptores CXCR6/metabolismo , Receptores CXCR6/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Transdução de Sinais/imunologia , Movimento Celular/imunologia , Humanos , Rim/patologia , Rim/imunologia , Rim/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Receptores de Interleucina/metabolismo , Receptores de Interleucina/imunologia , Camundongos Endogâmicos C57BL , Nefropatias/imunologia , Nefropatias/metabolismo , Nefropatias/patologia , Imunidade Inata/imunologia , Camundongos Knockout , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestinos/imunologia , Intestinos/patologia
8.
Theor Appl Genet ; 137(6): 131, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38748046

RESUMO

KEY MESSAGE: Identification of 337 stable MTAs for wheat spike-related traits improved model accuracy, and favorable alleles of MTA259 and MTA64 increased grain weight and yield per plant. Wheat (Triticum aestivum L.) is one of the three primary global, staple crops. Improving spike-related traits in wheat is crucial for optimizing spike and plant morphology, ultimately leading to increased grain yield. Here, we performed a genome-wide association study using a dataset of 24,889 high-quality unique single-nucleotide polymorphisms (SNPs) and phenotypic data from 314 wheat accessions across eight diverse environments. In total, 337 stable and significant marker-trait associations (MTAs) related to spike-related traits were identified. MTA259 and MTA64 were consistently detected in seven and six environments, respectively. The presence of favorable alleles associated with MTA259 and MTA64 significantly reduced wheat spike exsertion length and spike length, while enhancing thousand kernel weight and yield per plant. Combined gene expression and network analyses identified TraesCS6D03G0692300 and TraesCS6D03G0692700 as candidate genes for MTA259 and TraesCS2D03G0111700 and TraesCS2D03G0112500 for MTA64. The identified MTAs significantly improved the prediction accuracy of each model compared with using all the SNPs, and the random forest model was optimal for genome selection. Additionally, the eight stable and major MTAs, including MTA259, MTA64, MTA66, MTA94, MTA110, MTA165, MTA180, and MTA164, were converted into cost-effective and efficient detection markers. This study provided valuable genetic resources and reliable molecular markers for wheat breeding programs.


Assuntos
Fenótipo , Polimorfismo de Nucleotídeo Único , Triticum , Triticum/genética , Triticum/crescimento & desenvolvimento , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Alelos , Melhoramento Vegetal , Genoma de Planta , Estudos de Associação Genética , Seleção Genética , Genótipo , Marcadores Genéticos , Grão Comestível/genética , Grão Comestível/crescimento & desenvolvimento
9.
Front Immunol ; 15: 1342837, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487541

RESUMO

Diabetic kidney disease (DKD) is becoming the leading cause of chronic kidney disease, especially in the industrialized world. Despite mounting evidence has demonstrated that immunity and inflammation are highly involved in the pathogenesis and progression of DKD, the underlying mechanisms remain incompletely understood. Substantial molecules, signaling pathways, and cell types participate in DKD inflammation, by integrating into a complex regulatory network. Most of the studies have focused on individual components, without presenting their importance in the global or system-based processes, which largely hinders clinical translation. Besides, conventional technologies failed to monitor the different behaviors of resident renal cells and immune cells, making it difficult to understand their contributions to inflammation in DKD. Recently, the advancement of omics technologies including genomics, epigenomics, transcriptomics, proteomics, and metabolomics has revolutionized biomedical research, which allows an unbiased global analysis of changes in DNA, RNA, proteins, and metabolites in disease settings, even at single-cell and spatial resolutions. They help us to identify critical regulators of inflammation processes and provide an overview of cell heterogeneity in DKD. This review aims to summarize the application of multiple omics in the field of DKD and emphasize the latest evidence on the interplay of inflammation and DKD revealed by these technologies, which will provide new insights into the role of inflammation in the pathogenesis of DKD and lead to the development of novel therapeutic approaches and diagnostic biomarkers.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Insuficiência Renal Crônica , Humanos , Nefropatias Diabéticas/patologia , Rim/patologia , Inflamação/metabolismo , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/complicações , Genômica , Diabetes Mellitus/metabolismo
10.
Mol Cell Biochem ; 479(11): 2895-2906, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38217838

RESUMO

The metabolism of long-chain polyunsaturated fatty acids (LCPUFAs) is closely associated with the risk and progression of colorectal cancer (CRC). This paper aims to investigate the role of LCPUFA in the crosstalk between intestinal microflora and macrophages, as well as the effects of these three parties on the progression of CRC. The metabolism and function of LCPUFA play important roles in regulating the composition of the human gut microflora and participating in the regulation of inflammation, ultimately affecting macrophage function and polarization, which is crucial in the tumor microenvironment. The effects of LCPUFA on cellular interactions between the two species can ultimately influence the progression of CRC. In this review, we explore the molecular mechanisms and clinical applications of LCPUFA in the interactions between intestinal microflora and intestinal macrophages, as well as its significance for CRC progression. Furthermore, we reveal the role of LCPUFA in the construction of the CRC microenvironment and explore the key nodes of the interactions between intestinal flora and intestinal macrophages in the environment. It provides potential targets for the metabolic diagnosis and treatment of CRC.


Assuntos
Neoplasias Colorretais , Progressão da Doença , Ácidos Graxos Insaturados , Microbioma Gastrointestinal , Macrófagos , Microambiente Tumoral , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/microbiologia , Humanos , Macrófagos/metabolismo , Macrófagos/microbiologia , Macrófagos/patologia , Ácidos Graxos Insaturados/metabolismo , Animais
11.
Adv Sci (Weinh) ; 11(13): e2307850, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38240457

RESUMO

Kidney fibrosis is a common fate of chronic kidney diseases (CKDs), eventually leading to renal dysfunction. Yet, no effective treatment for this pathological process has been achieved. During the bioassay-guided chemical investigation of the medicinal plant Wikstroemia chamaedaphne, a daphne diterpenoid, daphnepedunin A (DA), is characterized as a promising anti-renal fibrotic lead. DA shows significant anti-kidney fibrosis effects in cultured renal fibroblasts and unilateral ureteral obstructed mice, being more potent than the clinical trial drug pirfenidone. Leveraging the thermal proteome profiling strategy, cell division cycle 42 (Cdc42) is identified as the direct target of DA. Mechanistically, DA targets to reduce Cdc42 activity and down-regulates its downstream phospho-protein kinase Cζ(p-PKCζ)/phospho-glycogen synthase kinase-3ß (p-GSK-3ß), thereby promoting ß-catenin Ser33/37/Thr41 phosphorylation and ubiquitin-dependent proteolysis to block classical pro-fibrotic ß-catenin signaling. These findings suggest that Cdc42 is a promising therapeutic target for kidney fibrosis, and highlight DA as a potent Cdc42 inhibitor for combating CKDs.


Assuntos
Diterpenos , Nefropatias , Proteína cdc42 de Ligação ao GTP , Animais , Camundongos , beta Catenina/efeitos dos fármacos , beta Catenina/metabolismo , Fibrose/tratamento farmacológico , Glicogênio Sintase Quinase 3 beta/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Rim/metabolismo , Nefropatias/tratamento farmacológico , Wikstroemia/química , Diterpenos/farmacologia , Proteína cdc42 de Ligação ao GTP/efeitos dos fármacos
12.
J Imaging ; 9(11)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37998098

RESUMO

To digital grade the staining color fastness of fabrics after rubbing, an automatic grading method based on spectral reconstruction technology and BP neural network was proposed. Firstly, the modeling samples are prepared by rubbing the fabrics according to the ISO standard of 105-X12. Then, to comply with visual rating standards for color fastness, the modeling samples are professionally graded to obtain the visual rating result. After that, a digital camera is used to capture digital images of the modeling samples inside a closed and uniform lighting box, and the color data values of the modeling samples are obtained through spectral reconstruction technology. Finally, the color fastness prediction model for rubbing was constructed using the modeling samples data and BP neural network. The color fastness level of the testing samples was predicted using the prediction model, and the prediction results were compared with the existing color difference conversion method and gray scale difference method based on the five-fold cross-validation strategy. Experiments show that the prediction model of fabric color fastness can be better constructed using the BP neural network. The overall performance of the method is better than the color difference conversion method and the gray scale difference method. It can be seen that the digital rating method of fabric staining color fastness to rubbing based on spectral reconstruction and BP neural network has high consistency with the visual evaluation, which will help for the automatic color fastness grading.

13.
Adv Sci (Weinh) ; 10(35): e2302804, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37915129

RESUMO

Group 3 innate lymphoid cells (ILC3s) represent a new population in immune regulation, yet their role in lupus nephritis (LN) remains elusive. In the present work, systemic increases in ILC3s, particularly in the kidney, are observed to correlate strongly with disease severity in both human and murine LN. Using MRL/lpr lupus mice and a nephrotoxic serum-induced LN model, this study demonstrates that ILC3s accumulated in the kidney migrate predominantly from the intestine. Furthermore, intestinal ILC3s accelerate LN progression, manifested by exacerbated autoimmunity and kidney injuries. In LN kidneys, ILC3s are located adjacent to B cells within ectopic lymphoid structures (ELS), directly activating B cell differentiation into plasma cells and antibody production in a Delta-like1 (DLL1)/Notch-dependent manner. Blocking DLL1 attenuates ILC3s' effects and protects against LN. Altogether, these findings reveal a novel pathogenic role of ILC3s in B cell activation, renal ELS formation and autoimmune injuries during LN, shedding light on the therapeutic value of targeting ILC3s for LN.


Assuntos
Nefrite Lúpica , Humanos , Animais , Camundongos , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Imunidade Inata , Linfócitos , Camundongos Endogâmicos MRL lpr , Rim
14.
Artigo em Inglês | MEDLINE | ID: mdl-37988217

RESUMO

Drug repositioning has emerged as a promising strategy for identifying new therapeutic applications for existing drugs. In this study, we present DRGBCN, a novel computational method that integrates heterogeneous information through a deep bilinear attention network to infer potential drugs for specific diseases. DRGBCN involves constructing a comprehensive drug-disease network by incorporating multiple similarity networks for drugs and diseases. Firstly, we introduce a layer attention mechanism to effectively learn the embeddings of graph convolutional layers from these networks. Subsequently, a bilinear attention network is constructed to capture pairwise local interactions between drugs and diseases. This combined approach enhances the accuracy and reliability of predictions. Finally, a multi-layer perceptron module is employed to evaluate potential drugs. Through extensive experiments on three publicly available datasets, DRGBCN demonstrates better performance over baseline methods in 10-fold cross-validation, achieving an average area under the receiver operating characteristic curve (AUROC) of 0.9399. Furthermore, case studies on bladder cancer and acute lymphoblastic leukemia confirm the practical application of DRGBCN in real-world drug repositioning scenarios. Importantly, our experimental results from the drug-disease network analysis reveal the successful clustering of similar drugs within the same community, providing valuable insights into drug-disease interactions. In conclusion, DRGBCN holds significant promise for uncovering new therapeutic applications of existing drugs, thereby contributing to the advancement of precision medicine.

15.
Technol Cancer Res Treat ; 22: 15330338231198348, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37981789

RESUMO

In recent years, genitourinary system tumors are common in people of all ages, seriously affecting the quality of life of patients, the pathogenesis and treatment of these diseases are constantly being updated and improved. Exosomes, with a lipid bilayer that enable delivery of their contents into body fluids or other cells. Exosomes can regulate the tumor microenvironment, and play an important role in tumor development. In turn, cellular and non-cellular components of tumor microenvironment also affect the occurrence, progression, invasion and metastasis of tumor. Non-coding RNAs have been shown to be able to be ingested and released by exosomes, and are seen as a potential tool in cancer diagnosis and treatment. Here, we summarize the effect of non-coding RNAs of exosome contents on the tumor microenvironment of genitourinary system tumor, expound the significance of non-coding RNAs of exosome in the occurrence, development, diagnosis and treatment of cancers.


Assuntos
Neoplasias , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Qualidade de Vida , Sistema Urogenital , RNA não Traduzido/genética
16.
Foods ; 12(20)2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37893714

RESUMO

The synthesis of tea fatty acids plays a crucial role in determining the oil content of tea seeds and selecting tea tree varieties suitable for harvesting both leaves and fruits. However, there is limited research on fatty acid synthesis in tea trees, and the precise mechanisms influencing tea seed oil content remain elusive. To reveal the fatty acid biosynthesis mechanism, we conducted a photosynthetic characteristic and targeted metabolomics analysis in comparison between Jincha 2 and Wuniuzao cultivars. Our findings revealed that Jincha 2 exhibited significantly higher net photosynthetic rates (Pn), stomatal conductance (Gs), and transpiration rate (Tr) compared with Wuniuzao, indicating the superior photosynthetic capabilities of Jincha 2. Totally, we identified 94 metabolites with significant changes, including key hormone regulators such as gibberellin A1 (GA1) and indole 3-acetic acid (IAA). Additionally, linolenic acid, methyl dihydrojasmonate, and methylthiobutyric acid, precursors required for fatty acid synthesis, were significantly more abundant in Jincha 2 compared with Wuniuzao. In summary, our research suggests that photosynthetic rates and metabolites contribute to the increased yield, fatty acid synthesis, and oil content observed in Jincha 2 when compared with Wuniuzao.

17.
Sci Rep ; 13(1): 12657, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37542076

RESUMO

The neutron capture cross section of [Formula: see text]Ta is relevant to s-process of nuclear astrophysics, extraterrestrial samples analysis in planetary geology and new generation nuclear energy system design. The [Formula: see text]Ta([Formula: see text]) cross section had been measured between 1 eV and 800 keV at the back-streaming white neutron facility (Back-n) of China spallation neutron source(CSNS) using the time-of-flight (TOF) technique and [Formula: see text] liquid scintillator detectors. The experimental results are compared with the data of several evaluated libraries and previous experiments in the resolved and unresolved resonance region. Resonance parameters are extracted using the R-Matrix code SAMMY in the 1-700 eV region. The astrophysical Maxwell average cross section(MACS) from kT = 5 to 100 keV is calculated over a sufficiently wide range of neutron energies. For the characteristic thermal energy of an astrophysical site, at kT = 30keV the MACS value of [Formula: see text]Ta is 834 ± 75 mb, which shows an obvious discrepancy with the Karlsruhe Astrophysical Database of Nucleosynthesis in Stars (KADoNiS) recommended value 766 ± 15 mb. The new measurements strongly constrain the MACS of [Formula: see text]Ta([Formula: see text]) reaction in the stellar s-process temperatures.

18.
Front Immunol ; 14: 1078310, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36860851

RESUMO

Background: There is a complex interaction between chronic kidney disease (CKD) and ulcerative colitis (UC), but the pathophysiological mechanisms underlying the coexistence of CKD and UC are unclear. This study aimed to investigate the key molecules and pathways that may mediate the co-occurrence of CKD and UC through quantitative bioinformatics analysis based on a public RNA-sequencing database. Methods: The discovery datasets of CKD (GSE66494) and UC (GSE4183), as well as validation datasets of CKD (GSE115857) and UC (GSE10616), were downloaded from the Gene Expression Omnibus (GEO) database. After identifying differentially expressed genes (DEGs) with GEO2R online tool, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for the DEGs were performed. Next, protein-protein interaction network was constructed with Search Tool for the Retrieval of Interacting Genes (STRING) and visualized by Cytoscape. Gene modules were identified by the plug-in MCODE and hub genes were screened using the plug-in CytoHubba. Then, correlation between immune cell infiltration and hub genes was analyzed, and the receiver operating characteristic curves were used to assess the predictive value of hub genes. Finally, immunostaining of human specimens was used to validate the relevant findings. Results: A total of 462 common DEGs were identified and selected for further analyses. GO and KEGG enrichment analyses indicated that these DEGs were primarily enriched in immune- and inflammation-related pathways. Among them, the PI3K-Akt signaling pathway ranked top in both discovery and validation cohorts, and the key signal molecule phosphorylated Akt (p-Akt) was shown to be significantly overexpressed in human CKD kidneys and UC colons, and further elevated in CKD-UC comorbidity specimens. Moreover, nine candidate hub genes, including CXCL8, CCL2, CD44, ICAM1, IL1A, CXCR2, PTPRC, ITGAX, and CSF3, were identified, of which ICAM1 was validated as a common hub gene. Besides, immune infiltration analysis revealed that neutrophils, macrophages, and CD4+ T memory cells significantly accumulated in both diseases, and ICAM1 was remarkably associated with neutrophil infiltration. Furthermore, intercellular adhesion molecule1 (ICAM1)-mediated neutrophil infiltration was validated to be upregulated in kidney and colon biopsies of CKD and UC patients, and further increased in patients diagnosed with both CKD and UC. Finally, ICAM1 had shown critical value as a diagnostic marker for the co-occurrence of CKD and UC. Conclusions: Our study elucidated that immune response, PI3K-Akt signaling pathway, and ICAM1-mediated neutrophil infiltration might be the common pathogenesis of CKD and UC, and identified ICAM1 as a key potential biomarker and therapeutic target for the comorbidity of these two diseases.


Assuntos
Colite Ulcerativa , Insuficiência Renal Crônica , Humanos , Colite Ulcerativa/genética , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/genética , Insuficiência Renal Crônica/genética , Bases de Dados de Ácidos Nucleicos
19.
Adv Mater ; 35(12): e2210658, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36641734

RESUMO

CO2 utilization and conversion are of great importance in alleviating the rising CO2 concentration in the atmosphere. Here, a single-atom catalyst (SAC) is reported for electrochemical CO2 utilization in both aqueous and aprotic electrolytes. Specifically, atomically dispersed Mn-N4 sites are embedded in bowl-like mesoporous carbon particles with the functionalization of epoxy groups in the second coordination spheres. Theoretical calculations suggest that the epoxy groups near the Mn-N4 site adjust the electronic structure of the catalyst with reduced reaction energy barriers for the electrocatalytic reduction of CO2 to CO. The resultant Mn-single-atom carbon with N and O doped catalyst (MCs-(N,O)) exhibits extraordinary electrocatalytic performance with a high CO faradaic efficiency of 94.5%, a high CO current density of 13.7 mA cm-2 , and a low overpotential of 0.44 V in the aqueous environment. Meanwhile, as a cathode catalyst for aprotic Li-CO2 batteries, the MCs-(N,O) with well-regulated active sites and unique mesoporous bowl-like morphology optimizes the nucleation behavior of discharge products. MCs-(N,O)-based batteries deliver a low overpotential and excellent cyclic stability of 1000 h. The findings in this work provide a new avenue to design and fabricate SACs for various electrochemical CO2 utilization systems.

20.
Front Neurosci ; 16: 1031546, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325480

RESUMO

The surface spectral reflectance of an object is the key factor for high-fidelity color reproduction and material analysis, and spectral acquisition is the basis of its applications. Based on the theoretical imaging model of a digital camera, the spectral reflectance of any pixels in the image can be obtained through spectral reconstruction technology. This technology can avoid the application limitations of spectral cameras in open scenarios and obtain high spatial resolution multispectral images. However, the current spectral reconstruction algorithms are sensitive to the exposure variant of the test images. That is, when the exposure of the test image is different from that of the training image, the reconstructed spectral curve of the test object will deviate from the real spectral to varying degrees, which will lead to the spectral data of the target object being accurately reconstructed. This article proposes an optimized method for spectral reconstruction based on data augmentation and attention mechanisms using the current deep learning-based spectral reconstruction framework. The proposed method is exposure invariant and will adapt to the open environment in which the light is easily changed and the illumination is non-uniform. Thus, the robustness and reconstruction accuracy of the spectral reconstruction model in practical applications are improved. The experiments show that the proposed method can accurately reconstruct the shape of the spectral reflectance curve of the test object under different test exposure levels. And the spectral reconstruction error of our method at different exposure levels is significantly lower than that of the existing methods, which verifies the proposed method's effectiveness and superiority.

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