ABSTRACT
BACKGROUND: Zinc Finger Protein 337 (ZNF337) is a novel Zinc Finger (ZNF) protein family member. However, the roles of ZNF337 in human cancers have not yet been investigated. METHODS: In this study, with the aid of TCGA databases, GTEx databases, and online websites, we determined the expression levels of ZNF337 in pan-cancer and its potential value as a diagnostic and prognostic marker for pan-cancer and analyzed the relationship between ZNF337 expression and immune cell infiltration and immune checkpoint genes. We then focused our research on the potential of ZNF337 as a biomarker for diagnostic and prognostic in KIRC (kidney renal clear cell carcinoma) and validated in the E-MTAB-1980 database. Moreover, the expression of ZNF337 was detected through qRT-PCR and Western blotting (WB). CCK-8 experiment, colony formation experiment, and EDU experiment were performed to evaluate cell proliferation ability. Wound healing assay and transwell assay were used to analyze its migration ability. The qRT-PCR and WB were used to detect the expression of ZNF337 in tumor tissues and paracancerous tissues of KIRC patients. RESULTS: The pan-cancer analysis revealed that abnormal ZNF337 expression was found in multiple human cancer types. ZNF337 had a high diagnostic value in pan-cancer and a significant association with the prognosis of certain cancers, indicating that ZNF337 may be a valuable prognostic biomarker for multiple cancers. Further analysis demonstrated that the expression level of ZNF337 displayed significant correlations with cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes in many tumors. Additionally, ZNF337 was observed to have a high expression in KIRC. Its expression was significantly associated with poor prognosis [overall survival (OS), disease-specific survival (DSS)], age, TNM stage, histologic grade, and pathologic stage. The high ZNF337 expression was associated with poor prognosis in the E-MTAB-1980 validation cohort. The in vitro experiments suggested that the expression of ZNF337 in KIRC tumor tissues was higher than in adjacent tissues, and ZNF337 knockdown inhibited the proliferation and migration of KIRC cells, whereas overexpression of ZNF337 had the opposite effects. CONCLUSIONS: ZNF337 might be an important prognostic and immunotherapeutic biomarker for pan-cancer, especially in KIRC.
Subject(s)
Biomarkers, Tumor , Humans , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Prognosis , Cell Proliferation/genetics , Neoplasms/genetics , Neoplasms/immunology , Neoplasms/diagnosis , Neoplasms/mortality , Neoplasms/pathology , Cell Line, Tumor , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/diagnosis , Female , Gene Expression Regulation, Neoplastic , Male , Kidney Neoplasms/genetics , Kidney Neoplasms/immunology , Kidney Neoplasms/pathology , Kidney Neoplasms/mortality , Kidney Neoplasms/diagnosis , Cell Movement/geneticsABSTRACT
This study investigated the effect of different magnetic field treatments (0, 3, 6, 9, 12 mT) on the structure and emulsification properties of myofibrillar protein (MP). The results showed that the emulsion stabilized by MP with 3, 6, 9 mT magnetic field treatments possessed higher emulsifying ability, storage stability and apparent viscosity, since magnetic field induced the structural unfolding of MP and exposed the hydrophobic groups (the surface hydrophobic increased from 30.10 to 43.73⯵g). Meanwhile, the magnetic field treatments decreased the MP particle size from 1752.00 to 1278.67â¯nm, which was favorable for the diffusion and adsorption of proteins at the oil-water interface, thus improving the MP emulsification ability and stability. Furthermore, the 9 mT magnetic field-treated MP had the best ability to emulsify oil droplets with a more uniform and smaller emulsion size from 28.593 to 23.443⯵m. However, high-intensity magnetic field treatment (12 mT) caused MP particles to aggregate and the hydrophobic binding sites to be buried, which was not conducive to encapsulating oil droplets.
ABSTRACT
A dual-mode fluorescence/visual aptasensor was developed for straightforward and accurate determination of aflatoxin B1 (AFB1) based on an Au/metal-organic framework (Au/MOF) composite. Aptamer-modified Au/Fe3O4 (Apt/Au/Fe3O4) served as the recognition element, and Au/MOF modified with complementary chains and 3,3',5,5'-tetramethylbenzidine (cDNA/TMB/Au/MOF) acted as the fluorescence and visual probes. These components are integrated to form conjugates (Apt/Au/Fe3O4-cDNA/TMB/Au/MOF). Upon the introduction of AFB1, some cDNA/TMB/Au/MOF dissociated from Apt/Au/Fe3O4, enabling the use of detached probes for visual detection. The undecomposed conjugates were isolated magnetically for use in fluorescence detection. As the AFB1 concentration increases, the visual signal intensifies and fluorescence intensity diminishes. Thus, the proposed aptasensor achieves the simultaneous fluorescence and visual determination of AFB1, obviating the need for material and reagent substitutions. The detection limits were established at 0.07 ng mL-1 for the fluorescence mode and 0.08 ng mL-1 for the visual mode. The effectiveness of the aptasensor was further validated by quantifying AFB1 in real samples.
Subject(s)
Aflatoxin B1 , Aptamers, Nucleotide , Biosensing Techniques , Gold , Limit of Detection , Metal-Organic Frameworks , Nanocomposites , Aflatoxin B1/analysis , Gold/chemistry , Aptamers, Nucleotide/chemistry , Metal-Organic Frameworks/chemistry , Biosensing Techniques/methods , Nanocomposites/chemistry , Spectrometry, Fluorescence/methods , Benzidines/chemistry , Food Contamination/analysis , Fluorescence , Fluorescent Dyes/chemistryABSTRACT
One-unit-cell FeSe films on SrTiO3 substrates are of great interest owing to significantly enlarged pairing gaps characterized by two coherence peaks at ±10 meV and ±20 meV. In-situ transport measurement is desired to reveal novel properties. Here, we performed in-situ microscale electrical transport and combined scanning tunneling microscopy measurements on continuous one-unit-cell FeSe films with twin boundaries. We observed two spatially coexisting superconducting phases in domains and on boundaries, characterized by distinct superconducting gaps ( Δ 1 ~15 meV vs. Δ 2 ~10 meV) and pairing temperatures (Tp1~52.0 K vs. Tp2~37.3 K), and correspondingly two-step nonlinear V ~ I α behavior but a concurrent Berezinskii-Kosterlitz-Thouless (BKT)-like transition occurring at T BKT ~28.7 K. Moreover, the onset transition temperature T c onset ~54 K and zero-resistivity temperature T c zero ~31 K are consistent with Tp1 and T BKT , respectively. Our results indicate the broadened superconducting transition in FeSe/SrTiO3 is related to intrinsic electronic inhomogeneity due to distinct two-gap features and phase fluctuations of two-dimensional superconductivity.
Subject(s)
Glomerulonephritis , Kidney Transplantation , Humans , Male , Female , Adult , China , Middle Aged , Treatment Outcome , Young Adult , Adolescent , East Asian PeopleABSTRACT
Background: Renal ischemia-reperfusion injury (RIRI) is an inevitable complication in the process of kidney transplantation and lacks specific therapy. The study aims to determine the underlying mechanisms of RIRI to uncover a promising target for efficient renoprotection. Method: Four bulk RNA-seq datasets including 495 renal samples of pre- and post-reperfusion were collected from the GEO database. The machine learning algorithms were utilized to ascertain pivotal endoplasmic reticulum stress genes. Then, we incorporated correlation analysis and determined the interaction pathways of these key genes. Considering the heterogeneous nature of bulk-RNA analysis, the single-cell RNA-seq analysis was performed to investigate the mechanisms of key genes at the single-cell level. Besides, 4-PBA was applied to inhibit endoplasmic reticulum stress and hence validate the pathological role of these key genes in RIRI. Finally, three clinical datasets with transcriptomic profiles were used to assess the prognostic role of these key genes in renal allograft outcomes after RIRI. Results: In the bulk-RNA analysis, endoplasmic reticulum stress was identified as the top enriched pathway and three endoplasmic reticulum stress-related genes (PPP1R15A, JUN, and ATF3) were ranked as top performers in both LASSO and Boruta analyses. The three genes were found to significantly interact with kidney injury-related pathways, including apoptosis, inflammatory response, oxidative stress, and pyroptosis. For oxidative stress, these genes were more strongly related to oxidative markers compared with antioxidant markers. In single-cell transcriptome, the three genes were primarily upregulated in endothelium, distal convoluted tubule cells, and collecting duct principal cells among 12 cell types of renal tissues in RIRI. Furthermore, distal convoluted tubule cells and collecting duct principal cells exhibited pro-inflammatory status and the highest pyroptosis levels, suggesting their potential as main effectors of three key genes for mediating RIRI-associated injuries. Importantly, inhibition of these key genes using 4-phenyl butyric acid alleviated functional and histological damage in a mouse RIRI model. Finally, the three genes demonstrated highly prognostic value in predicting graft survival outcomes. Conclusion: The study identified three key endoplasmic reticulum stress-related genes and demonstrated their prognostic value for graft survival, providing references for individualized clinical prevention and treatment of postoperative complications after renal transplantation.
Subject(s)
Kidney Transplantation , Reperfusion Injury , Animals , Mice , Kidney Transplantation/adverse effects , Kidney , Reperfusion Injury/genetics , Disease Models, Animal , Endoplasmic Reticulum Stress/genetics , Ischemia , RNAABSTRACT
BACKGROUND AND OBJECTIVE: The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy. METHODS: Eligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework. RESULTS: Our study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P < 0.00001] compared with the full-dose corticosteroids group. Regarding serum creatinine (SCr), estimated glomerular filtration rate (eGFR), complete remission rate, and overall response rate, there was no difference between the groups (p > 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05). CONCLUSIONS: Low-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy. TRIAL REGISTRATION: The PROSPERO registration number is CRD42022361883.
Subject(s)
Glomerulonephritis, IGA , Humans , Leflunomide/adverse effects , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/chemically induced , Immunosuppressive Agents/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/pharmacology , Glomerular Filtration RateABSTRACT
Mycophenolate mofetil (MMF) is one of the most used immunosuppressive drugs in organ transplantation, but frequent gastrointestinal (GI) side effects through unknown mechanisms limit its clinical use. Gut microbiota and its metabolites were recently reported to play a vital role in MMF-induced GI toxicity, but the specific mechanism of how they interact with the human body is still unclear. Here, we found that secondary bile acids (BAs), as bacterial metabolites, were significantly reduced by MMF administration in the gut of mice. Microbiome data and fecal microbiota transfer model supported a microbiota-dependent effect on the reduction of secondary BAs. Supplementation of the secondary BA lithocholic acid alleviated MMF-induced weight loss, colonic inflammation, and oxidative phosphorylation damage. Genetic deletion of the vitamin D3 receptor (VDR), which serves as a primary colonic BA receptor, in colonic epithelial cells (VDRΔIEC) abolished the therapeutic effect of lithocholic acid on MMF-induced GI toxicity. Impressively, we discovered that paricalcitol, a Food and Drug Administration-approved VDR agonist that has been used in clinics for years, could effectively alleviate MMF-induced GI toxicity. Our study reveals a previously unrecognized mechanism of gut microbiota, BAs, and VDR signaling in MMF-induced GI side effects, offering potential therapeutic strategies for clinics.
Subject(s)
Bile Acids and Salts , Gastrointestinal Microbiome , Mycophenolic Acid , Receptors, Calcitriol , Animals , Mycophenolic Acid/pharmacology , Mice , Gastrointestinal Microbiome/drug effects , Receptors, Calcitriol/metabolism , Bile Acids and Salts/metabolism , Immunosuppressive Agents , Mice, Inbred C57BL , Male , Gastrointestinal Diseases/chemically induced , Lithocholic Acid , HumansABSTRACT
BACKGROUND: Antibody-mediated rejection (ABMR) emerged as a major cause of graft loss in renal transplantation. Needle biopsy is the gold standard for diagnosis of ABMR in renal allografts. Thus, noninvasive diagnosis methods of ABMR with high accuracy are urgently needed to prevent unnecessary biopsies. METHODS: We collected peripheral blood transcriptome data from two independent renal transplantation cohorts with patients with ABMR, stable well-functioning transplants (STA), and T-cell mediated rejection (TCMR). Differentially expressed genes (DEGs) were identified by comparing the ABMR group with the STA group. In addition, functional enrichment analysis and gene set enrichment analysis were performed to seek new key underlying mechanisms in ABMR. Subsequently, we utilized a Boruta algorithm and least absolute shrinkage and selection operator logistic algorithm to establish a diagnostic model which was then evaluated and validated in an independent cohort. RESULTS: According to functional enrichment analysis, autophagy was found to be the primary upregulated biological process in ABMR. Based on algorithms, three autophagy-associated genes, ubiquitin specific peptidase 33 (USP33), Ras homolog mTORC1 binding (RHEB), and ABL proto-oncogene 2 (ABL2), were selected to establish the diagnostic model in the training cohort. This autophagy-related gene model possessed good diagnostic value in distinguishing ABMR from STA blood samples in the training cohort (AUC = 0.907) and in the validation cohort (AUC = 0.972). In addition, this model also showed good discernibility in distinguishing ABMR from TCMR in the training and validation cohorts (AUCs = 0.908 and 0.833). CONCLUSION: We identified and validated an autophagy-associated diagnostic model with high accuracy for renal transplant patients with ABMR. Our study provided a new potential test for the non-invasive diagnosis of ABMR in clinical practice and highlighted the importance of autophagy in ABMR.
Subject(s)
Autophagy , Graft Rejection , Kidney Transplantation , Humans , Graft Rejection/diagnosis , Graft Rejection/immunology , Autophagy/immunology , Female , Male , Middle Aged , Adult , Proto-Oncogene Mas , Transcriptome , Isoantibodies/immunology , Isoantibodies/bloodABSTRACT
Clear cell renal cell carcinoma (ccRCC) is characterized by high heterogeneity and recurrence rates, posing significant challenges for stratification and treatment. Basement membrane-related genes (BMGs) play a crucial role in tumor initiation and progression. Clinical and transcriptomic data of ccRCC patients were extracted from TCGA and GEO databases. We employed univariate regression and LASSO-Cox stepwise regression analysis to construct a BMscore model based on BMGs expression level. A nomogram combining clinical features and BMscore was constructed to predict individual survival probabilities. Further enrichment analysis and immune-related analysis were conducted to explore the enriched pathways and immune features associated with BMGs. High-risk individuals predicted by BMscore exhibited poorer overall survival, which was consistent with the validation dataset. BMscore was identified as an independent risk factor for ccRCC. Functional analysis revealed that BMGs were related to cell-matrix and tumor-associated signaling pathways. Immune profiling suggests that BMGs play a key role in immune interactions and the tumor microenvironment. BMGs serve as a novel prognostic predictor for ccRCC and play a role in the immune microenvironment and treatment response. Targeting the BM may represent an alternative therapeutic approach for ccRCC.
Subject(s)
Carcinoma, Renal Cell , Carcinoma , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/genetics , Basement Membrane , Prognosis , Risk Factors , Tumor Microenvironment/genetics , Kidney Neoplasms/geneticsABSTRACT
Magnetic field combined with calcium chloride (CaCl2,) treatment is a highly promising technique for reducing sodium chloride (NaCl) in meat. Therefore, this paper investigated the effect of reducing NaCl addition (0-10%) by CaCl2 in combination with a magnetic field (3.8 mT) on the edible quality of low-salt pork mince. It is desired to drive the application of magnetic field and CaCl2 in low-sodium meat processing in this way. Results showed that the cooking yield, color, hardness, elasticity, mouthfeel, apparent texture, and orderliness of protein conformation of all minced pork were improved as compared to the control group, while the electron nose response values of their volatile sulfides and nitrogen oxides were decreased. In particular, the best edible quality and perceived salty intensity of minced pork gel was obtained by using CaCl2 in place of 5% NaCl under magnetic field mediation. In addition, energy dispersive X-ray spectroscopy scans showed that the reduced NaCl treatment by magnetic field combined with CaCl2 could increase the signal intensity of sodium in minced pork matrices to some extent. Magnetic field-mediated substitution of NaCl for CaCl2 treatment was also found to be favorable for inducing the transition of the protein secondary structure from an irregularly coiled to a ß-folded structure (demonstrated by infrared spectroscopy). In short, magnetic fields combined with CaCl2 instead of NaCl was a highly promising method of producing low-NaCl meats.
Subject(s)
Meat Products , Pork Meat , Red Meat , Animals , Swine , Sodium Chloride/chemistry , Calcium Chloride/chemistry , Meat Products/analysis , Proteins , Sodium , Gels/chemistryABSTRACT
Electronic processors are reaching the physical speed ceiling that heralds the era of optical processors. Multifunctional all-optical logic gates (AOLGs) of massively parallel processing are of great importance for large-scale integrated optical processors with speed far in excess of electronics, while are rather challenging due to limited operation bandwidth and multifunctional integration complexity. Here we for the first time experimentally demonstrate a reconfigurable all-in-one broadband AOLG that achieves nine fundamental Boolean logics in a single configuration, enabled by ultrabroadband (400-4000 nm) plasmon-enhanced thermo-optical nonlinearity (TONL) of liquid-metal Galinstan nanodroplet assemblies (GNAs). Due to the unique heterogeneity (broad-range geometry sizes, morphology, assembly profiles), the prepared GNAs exhibit broadband plasmonic opto-thermal effects (hybridization, local heating, energy transfer, etc.), resulting in a huge nonlinear refractive index under the order of 10-4-10-5 within visual-infrared range. Furthermore, a generalized control-signal light route is proposed for the dynamic TONL modulation of reversible spatial-phase shift, based on which nine logic functions are reconfigurable in one single AOLG configuration. Our work will provide a powerful strategy on large-bandwidth all-optical circuits for high-density data processing in the future.
ABSTRACT
The role of disulfidptosis in kidney renal clear cell carcinoma (KIRC) remains unknown. This study investigated disulfidptosis-related biomarkers for KIRC prognosis prediction and individualized treatment. KIRC patients were clustered by disulfidptosis profiles. Differential expression analysis, survival models, and machine learning were used to construct the disulfidptosis-related prognostic signature (DRPS). Characterizations of the tumor immune microenvironment, genetic drivers, drug sensitivity, and immunotherapy response were explored according to the DRPS risk stratification. Markers included in the signature were validated using single-cell, spatial transcriptomics, quantitative RT-qPCR, and immunohistochemistry. In the discovery cohort, we unveiled two clusters of KIRC patients that differed significantly in disulfidptosis regulator expressions and overall survival (OS). After multiple feature selection steps, a DRPS prognostic model with four features (CHAC1, COL7A1, FOXM1, SHOX2) was constructed and validated. Combined with clinical factors, the model demonstrated robust performance in the discovery and external validation cohorts (5-year AUC = 0.793 and 0.846, respectively). KIRC patients with high-risk scores are characterized by inferior OS, less tumor purity, and increased infiltrations of fibroblasts, M1 macrophages, and B cells. High-risk patients also have higher frequencies of BAP1 and AHNAK2 mutation. Besides, the correlation between the DRPS score and the chemotherapy-response signature indicated the potential effect of Gefitinib for high-risk patients. Among the signature genes, FOXM1 is highly expressed in cycling tumor cells and exhibits spatial aggregation, while others are expressed sparsely within tumor samples. The DRPS model enables improved clinical management and personalized KIRC therapy. The identified biomarkers and immune characteristics offer new mechanistic insight into disulfidptosis in KIRC.
Subject(s)
Biomarkers, Tumor , Carcinoma, Renal Cell , Kidney Neoplasms , Precision Medicine , Humans , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/genetics , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/metabolism , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Tumor Microenvironment/genetics , Gene Expression Regulation, Neoplastic , Male , Female , TranscriptomeABSTRACT
Interferon-γ (IFN-γ) is an important cytokine in tissue homeostasis and immune response, while studies about it in antibody-mediated rejection (ABMR) are very limited. This study aims to comprehensively elucidate the role of IFN-γ in ABMR after renal transplantation. In six renal transplantation cohorts, the IFN-γ responses (IFNGR) biological process was consistently top up-regulated in ABMR compared to stable renal function or even T cell-mediated rejection in both allografts and peripheral blood. According to single-cell analysis, IFNGR levels were found to be broadly elevated in most cell types in allografts and peripheral blood with ABMR. In allografts with ABMR, M1 macrophages had the highest IFNGR levels and were heavily infiltrated, while kidney resident M2 macrophages were nearly absent. In peripheral blood, CD14+ monocytes had the top IFNGR level and were significantly increased in ABMR. Immunofluorescence assay showed that levels of IFN-γ and M1 macrophages were sharply elevated in allografts with ABMR than non-rejection. Importantly, the IFNGR level in allografts was identified as a strong risk factor for long-term renal graft survival. Together, this study systematically analyzed multi-omics from thirteen independent cohorts and identified IFN-γ and IFNGR as determinants of ABMR and clinical outcomes in patients after renal transplantation.
Subject(s)
Kidney Transplantation , Humans , Antibodies , Graft Rejection/etiology , Interferon-gamma , Risk FactorsABSTRACT
A nonlinear holographic technique is capable of processing optical information in the newly generated optical frequencies, enabling fascinating functions in laser display, security storage, and image recognition. One popular nonlinear hologram is based on a periodically poled lithium niobate (LN) crystal. However, due to the limitations of traditional fabrication techniques, the pixel size of the LN hologram is typically several micrometers, resulting in a limited field-of-voew (FOV) of several degrees. Here, we experimentally demonstrate an ultra-high-resolution LN hologram by using the laser poling technique. The minimal pixel size reaches 200 nm, and the FOV is extended above 120° in our experiments. The image distortions at large view angles are effectively suppressed through the Fourier transform. The FOV is further improved by combining multiple diffraction orders of SH fields. The ultimate FOV under our configuration is decided by a Fresnel transmission. Our results pave the way for expanding the applications of nonlinear holography to wide-view imaging and display.
ABSTRACT
Breast cancer is the most malignant subtype of gynecological tumors and with aggressive biological behavior and poor outcome. Ultra-conserved non-coding RNA (ucRNA) is a newly discovered class of long non-coding RNAs (lncRNAs) which involved in the regulation of interaction network of genes. However, the exact function and mechanism by which ucRNA modulates breast cancer aggressive has not yet to be completely elucidated. In the present study, we demonstrated that the expression of uc.246 was significantly upregulated in metastatic breast cancer patients and TNBC cell lines, compared with those in controls. Furthermore, overexpression of uc.246 in MCF-7 cell lines enhanced the capacity of breast cancer cells to induce tube formation and migration of HUVECs, and, finally, enhanced breast cancer cells metastasis. Meanwhile, uc.246 overexpressing enhances the EMT phenotype of TNBC cells. Mechanistically, we found that uc.246 promoted malignant progression of breast cancer via upregulating the levels of VEGF-C and increased the levels of mesenchymal marker protein. Our results demonstrated that uc.246 induced angiogenesis, migration, and EMT phenotype and may represent a novel prognostic biomarker and therapeutic target for patients with breast cancer.
Subject(s)
Breast Neoplasms , RNA, Long Noncoding , Triple Negative Breast Neoplasms , Humans , Female , Breast Neoplasms/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Triple Negative Breast Neoplasms/drug therapy , Angiogenesis , MCF-7 Cells , Phenotype , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Epithelial-Mesenchymal Transition/genetics , Cell Movement/genetics , Cell ProliferationABSTRACT
BACKGROUND: T cell-mediated rejection (TCMR) is a severe issue after renal transplantation, but research on its T cell-receptor (TCR) repertoire is lacking. This study intended to elucidate the TCR repertoire landscape in TCMR and hence identify novel potential targets. METHODS: A total of 12 multiomics data sets were collected. The TRUST4 algorithm was used to construct and analyze the TCR repertoire in renal allografts with TCMR and stable renal function. Then, novel TCR-related key genes were identified through various criteria and literature research. In bulk transcriptome, cell line, single-cell transcriptome data sets, multiple immune cell infiltration algorithms, and gene set enrichment analysis were used to analyze potential mechanisms of the identified key gene. Twenty-three pathological sections were collected for immunofluorescence staining in the clinical cohort. Finally, the diagnostic and prognostic values of ANXA2R were evaluated in multiple renal transplant data sets. RESULTS: Allografts with TCMR showed significantly increased clonotype and specific clonal expansion. ANXA2R was found to be a novel key gene for TCMR and showed strong positive connections with the TCR complex and lymphocyte cells, especially CD8 + T cells. Immunofluorescence staining confirmed the existence of ANXA2R + CD8 + T cells, with their percentage significantly elevated in TCMR compared with stable renal function. Finally, both mRNA and protein levels of ANXA2R showed promising diagnostic and prognostic value for renal transplant recipients. CONCLUSIONS: ANXA2R , identified as a novel TCR-related gene, had critical roles in clinicopathology, diagnosis, and prognosis in renal transplantation, which offered promising potential therapeutic targets.
Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Multiomics , Kidney/pathology , CD8-Positive T-Lymphocytes , Receptors, Antigen, T-Cell/genetics , Graft RejectionABSTRACT
The accurate and fast segmentation method of tumor regions in brain Magnetic Resonance Imaging (MRI) is significant for clinical diagnosis, treatment and monitoring, given the aggressive and high mortality rate of brain tumors. However, due to the limitation of computational complexity, convolutional neural networks (CNNs) face challenges in being efficiently deployed on resource-limited devices, which restricts their popularity in practical medical applications. To address this issue, we propose a lightweight and efficient 3D convolutional neural network SDS-Net for multimodal brain tumor MRI image segmentation. SDS-Net combines depthwise separable convolution and traditional convolution to construct the 3D lightweight backbone blocks, lightweight feature extraction (LFE) and lightweight feature fusion (LFF) modules, which effectively utilizes the rich local features in multimodal images and enhances the segmentation performance of sub-tumor regions. In addition, 3D shuffle attention (SA) and 3D self-ensemble (SE) modules are incorporated into the encoder and decoder of the network. The SA helps to capture high-quality spatial and channel features from the modalities, and the SE acquires more refined edge features by gathering information from each layer. The proposed SDS-Net was validated on the BRATS datasets. The Dice coefficients were achieved 92.7, 80.0 and 88.9% for whole tumor (WT), enhancing tumor (ET) and tumor core (TC), respectively, on the BRTAS 2020 dataset. On the BRTAS 2021 dataset, the Dice coefficients were 91.8, 82.5 and 86.8% for WT, ET and TC, respectively. Compared with other state-of-the-art methods, SDS-Net achieved superior segmentation performance with fewer parameters and less computational cost, under the condition of 2.52 M counts and 68.18 G FLOPs.