Exposed Embolic Coils Observed in a 64-Year-Old Male With Head and Neck Cancer Following Transarterial Embolization for Carotid Blowout Syndrome.

Background: Delayed migration and exposure of embolic coils is a rare complication of endovascular therapy for carotid blowout syndrome. Methods: A 64-year-old man with recurrent tongue cancer noticed the presence of foreign body in the malignant wound on the right side of his neck. He had undergone transarterial embolization on his right vertebral artery, right common carotid artery (CCA), and internal carotid artery (ICA) for carotid blowout syndrome 1 month prior. On physical examination, exposed spring-like metallic coils were observed, covered in brownish granulation tissue, at the bottom of the malignant wound. Neck radiograph and computed tomography confirmed the extrusion and migration of the embolic coils. Results: In this case, the patient was managed by transection of the exposed coils at the wound surface with close monitoring. Conclusions: Computed tomography angiography is essential for assessing the condition of the remaining embolic coils. In cases with thrombosed parent arteries, a conservative approach, like the transection of exposed coils, can be employed as part of the management strategy.

Teaching Strategies in Psychiatric Nursing Based on Bloom's Taxonomy of Educational Objectives.

Bloom's Taxonomy of Educational Objective (BTEO), as a classic method for categorizing educational objectives, provides a clear and specific framework for formulating teaching goals in the global education field. Psychiatric nursing, as a highly specialized discipline, demands high requirements for students in both theoretical knowledge and practical skills. However, traditional teaching methods often focus excessively on knowledge impartation, neglecting the cultivation of students' practical abilities and emotional attitudes. Therefore, the purpose of this study was to Improve the existing psychiatric nursing curriculum by combining Bloom's educational goals theory, which emphasizes the comprehensive development of cognitive, affective, and psychomotor skills, providing new perspectives and methods for psychiatric nursing education. By applying BTEO, specific teaching goals at different levels can be defined more clearly, and corresponding teaching strategies and methods can be employed to achieve these goals. Furthermore, the application of BTEO requires effective interaction between teachers and students. Teachers need to monitor students' learning progress, adjust teaching strategies promptly, and ensure that students comprehensively grasp knowledge and skills. Thus, the application of this teaching strategy contributes to improving the quality of psychiatric nursing education and cultivating outstanding psychiatric nursing professionals. We hope to cultivate students' theoretical knowledge and practical skills in mental care by helping them develop their overall skills.

[Correlation of miR-155 Expression with Drug Sensitivity of FLT3-ITD+ Acute Myeloid Leukemia Cell Line and Its Mechanism].

OBJECTIVE: To investigate the correlation of miR-155 expression with drug sensitivity of FLT3-ITD+ acute myeloid leukemia (AML) cell line and its potential regulatory mechanism. METHODS: By knocking out miR-155 gene in FLT3-ITD+ AML cell line MV411 through CRISPR/Cas9 gene-editing technology, monoclonal cells were screened. The genotype of these monoclonal cells was validated by PCR and Sanger sequencing. The expression of mature miRNA was measured by RT-qPCR. The treatment response of doxorubicin, quizartinib and midostaurin were measured by MTT assay and IC50 of these drugs were calculated to identify the sensitivity. Transcriptome sequencing was used to analyze change of mRNA level in MV411 cells after miR-155 knockout, gene set enrichment analysis to analyze change of signaling pathway, and Western blot to verify expressions of key molecules in signaling pathway. RESULTS: Four heterozygotes with gene knockout and one heterozygote with gene insertion were obtained through PCR screening and Sanger sequencing. RT-qPCR results showed that the expression of mature miR-155 in the monoclonal cells was significantly lower than wild-type clones. MTT results showed that the sensitivity of MV411 cells to various anti FLT3-ITD+ AML drugs increased significantly after miR-155 knockout compared with wild-type clones. RNA sequencing showed that the mTOR signaling pathway and Wnt signaling pathway were inhibited after miR-155 knockout. Western blot showed that the expressions of key molecules p-mTOR, Wnt5α and ß-catenin in signaling pathway were down-regulated. CONCLUSION: Drug sensitivity of MV411 cells to doxorubicin, quizartinib and midostaurin can be enhanced significantly after miR-155 knockout, which is related to the inhibition of multiple signaling pathways including mTOR and Wnt signaling pathways.

Establishing national reference materials for genetic testing of cytochrome P450.

OBJECTIVES: Reference materials for in-vitro diagnostic reagents play a critical role in determining the quality of reagents and ensuring the accuracy of clinical test results. This study aimed to establish a national reference material (NRM) for detecting cytochrome P450 (CYP) genes related to drug metabolism by screening databases on the Chinese population to identify CYP gene polymorphism characteristics. METHODS: To prepare the NRM, we used DNA extracted from healthy human immortalized B lymphoblastoid cell lines as the raw material. Samples of these cell lines were obtained from the Chinese Population PGx Gene Polymorphism Biobank. Further, we used Sanger sequencing, next-generation sequencing, and commercial assay kits to validate the polymorphic genotypes. RESULTS: Among the CYP superfamily genes, we confirmed 24 riboswitch loci related to drug metabolism, with evidence levels of 1A, 2A, 3, and 4. We confirmed the polymorphic loci and validated their genotypes using various sequencing techniques. Our results were consistent with the polymorphism information of samples obtained from the biobank, thus demonstrating high precision and stability of the established NRM. CONCLUSION: An NRM (360 056-202 201) for CYP genetic testing covering 24 loci related to drug metabolism was established and approved to assess in-vitro diagnostic reagents containing CYP family gene polymorphisms and perform clinical inter-room quality evaluations.

Use of Dixon in magnetic resonance breast contrast-enhanced T1 weighted high-resolution imaging for mastectomy patients at 3T: A prospective study in single center.

BACKGROUND: For patients with complete breast resection, conventional contrast-enhanced T1-weighted imaging (CE-T1WI) with frequency-selective spectral attenuated inversion recovery (SPAIR) provides limited fat suppression on the postoperative side due to the uneven skin surface, inhomogeneous tissue environment, and frequency-selective feature of the SPAIR scheme, leading to difficulties in precise diagnosis. This study aimed to investigate the image quality and performance of the Dixon method compared with SPAIR in breast high-resolution CE-T1WI for mastectomy patients. MATERIALS AND METHODS: Sixty female patients who had not performed any breast surgeries were randomly selected retrospectively as the control group. Postmastectomy female patients were enrolled to undergone high-resolution CE-T1WI with SPAIR and Dixon breast scans. Subjective scores were rated using a 5-point scale. Objective parameters, including contrast-to-noise ratio (CNR), edge sharpness, and signal uniformity were measured and calculated. The Wilcoxon rank-sum test and Kappa statistic were used. RESULTS: A total of 114 consecutive postmastectomy patients were included. Subjective scores of T1WI-SPAIR in the control group were all significantly better than those with SPAIR on the postoperative side of mastectomy patients (P < 0.01). Dixon outperformed SPAIR with significantly better subjective scores in regards to uniformity and degree of fat-suppression, anatomical structures depiction, lesion conspicuity, and axillary visibility (p < 0.05) in both post- and non-operative sides and bilateral axillary areas through the paired comparison. The objective parameters of Dixon were significantly better than those of SPAIR. CONCLUSION: The Dixon method provided better image uniformity and higher fat suppression efficiency, and showed significant advantages in delineating the anatomical structures, with better axillary and lesion visibilities, especially on the completely removed breast side.

Observation of Nonlinear Exceptional Points with a Complete Basis in Dynamics.

The exotic physics associated with exceptional points (EPs) is always under the scrutiny of theoretical and experimental science. Recently, considerable effort has been invested in the combination of nonlinearity and non-Hermiticity. The concept of nonlinear EPs (NEPs) has been introduced, which can avoid the loss of completeness of the eigenbasis in dynamics while retaining the key features of linear EPs. Here, we present the first direct experimental demonstration of a NEP based on two non-Hermition coupled circuit resonators combined with a nonlinear saturable gain. At the NEP, the response of the eigenfrequency to perturbations demonstrates a third-order root law and the eigenbasis of the Hamiltonian governing the system dynamics is still complete. Our results bring this counterintuitive aspect of the NEP to light and possibly open new avenues for applications.

Designing Ultratough Single-Network Hydrogels with Centimeter-Scale Fractocohesive Lengths via Inelastic Crack Blunting.

Fractocohesive length, defined as the ratio of fracture toughness to work of fracture, measures the sensitivity of materials to fracture in the presence of flaws. The larger the fractocohesive length, the more flaw-tolerant and crack-resistant the hydrogel. For synthetic soft materials, the fractocohesive length is short, often on the scale of 1 mm. Here, highly flaw-insensitive (HFI) single-network hydrogels containing an entangled inhomogeneous polymer network of widely distributed chain lengths are designed. The HFI hydrogels demonstrate a centimeter-scale fractocohesive length of 2.21 cm, which is the highest ever recorded for synthetic hydrogels, and an unprecedented fracture toughness of ≈13 300 J m-2 . The uncommon flaw insensitivity results from the inelastic crack blunting inherent to the highly inhomogeneous network. When the HFI hydrogel is stretched, a large number of short chains break while coiled long chains can disentangle, unwind, and straighten, producing large inelastic deformation that substantially blunts the crack tip in a plastic manner, thereby deconcentrating crack-tip stresses and blocking crack extension. The flaw-insensitive design strategy is applicable to various hydrogels such as polyacrylamide and poly(N,N-dimethylacrylamide) hydrogels and enables the development of HFI soft composites.

Radiofrequency radiation reshapes tumor immune microenvironment into antitumor phenotype in pulmonary metastatic melanoma by inducing active transformation of tumor-infiltrating CD8+ T and NK cells.

Immunosuppression by the tumor microenvironment is a pivotal factor contributing to tumor progression and immunotherapy resistance. Priming the tumor immune microenvironment (TIME) has emerged as a promising strategy for improving the efficacy of cancer immunotherapy. In this study we investigated the effects of noninvasive radiofrequency radiation (RFR) exposure on tumor progression and TIME phenotype, as well as the antitumor potential of PD-1 blockage in a model of pulmonary metastatic melanoma (PMM). Mouse model of PMM was established by tail vein injection of B16F10 cells. From day 3 after injection, the mice were exposed to RFR at an average specific absorption rate of 9.7 W/kg for 1 h per day for 14 days. After RFR exposure, lung tissues were harvested and RNAs were extracted for transcriptome sequencing; PMM-infiltrating immune cells were isolated for single-cell RNA-seq analysis. We showed that RFR exposure significantly impeded PMM progression accompanied by remodeled TIME of PMM via altering the proportion and transcription profile of tumor-infiltrating immune cells. RFR exposure increased the activation and cytotoxicity signatures of tumor-infiltrating CD8+ T cells, particularly in the early activation subset with upregulated genes associated with T cell cytotoxicity. The PD-1 checkpoint pathway was upregulated by RFR exposure in CD8+ T cells. RFR exposure also augmented NK cell subsets with increased cytotoxic characteristics in PMM. RFR exposure enhanced the effector function of tumor-infiltrating CD8+ T cells and NK cells, evidenced by increased expression of cytotoxic molecules. RFR-induced inhibition of PMM growth was mediated by RFR-activated CD8+ T cells and NK cells. We conclude that noninvasive RFR exposure induces antitumor remodeling of the TIME, leading to inhibition of tumor progression, which provides a promising novel strategy for TIME priming and potential combination with cancer immunotherapy.

Organocatalytic enantioselective decarboxylative protonation of α-alkyl-α-aryl malonate monoesters.

In contrast to the well-established enzymatic enantioselective decarboxylative protonation (EDP), the corresponding chemocatalytic reactions of acyclic malonic acid derivatives remain challenging. Herein, we developed a biomimetic EDP of α-alkyl-α-aryl malonate monoesters using a chiral 1,2-trans-diaminocyclohexane-based N-sulfonamide as an organocatalyst. The method demonstrates excellent chemical yields, good enantioselectivity, mild reaction conditions, and the generation of only CO2 as waste.

Proof of concept in utilizing the peptidoglycan skeleton of pathogenic bacteria as antigen delivery platform for enhanced immune response.

Subunit vaccines are becoming increasingly important because of their safety and effectiveness. However, subunit vaccines often exhibit limited immunogenicity, necessitating the use of suitable adjuvants to elicit robust immune responses. In this study, we demonstrated for the first time that pathogenic bacteria can be prepared into a purified peptidoglycan skeleton without nucleic acids and proteins, presenting bacterium-like particles (pBLP). Our results showed that the peptidoglycan skeletons screened from four pathogens could activate Toll-like receptor1/2 receptors better than bacterium-like particles from Lactococcus lactis in macrophages. We observed that pBLP was safe in mouse models of multiple ages. Furthermore, pBLP improved the performance of two commercial vaccines in vivo. We confirmed that pBLP successfully loaded antigens onto the surface and proved to be an effective antigen delivery platform with enhanced antibody titers, antibody avidity, balanced subclass distribution, and mucosal immunity. These results indicate that the peptidoglycan skeleton of pathogenic bacteria represents a new strategy for developing subunit vaccine delivery systems.

Study on blasting fragmentation mechanism of burnt rock in open-pit coal mine.

A large number of burnt rocks in some open-pit mines in Xinjiang, Inner Mongolia and Ningxia have a great influence on the blasting effect. For this kind of rock, through the analysis of physical and chemical changes, combined with ANSYS/LS-DYNA and PFC 2D numerical simulation software, a burnt rock model with multiple joint cracks and irregular distribution is constructed to simulate the blasting process of burnt rock under the combined action of stress wave and detonation gas. The results show that the fracture of rock mass affects the propagation of blasting cracks in the fracture area, resulting in stress concentration and stress hindrance. The action time of stress wave is reduced, and the energy of blasting gas is partially absorbed by the fracture, resulting in uneven stress on the burnt rock bench and seriously affecting the bench blasting effect.

Tooth-Supported Overdentures Revisited.

The goal of prosthodontics is to provide a functional prosthesis to restore aesthetics, functions, and masticatory efficiencies. Tooth-supported overdentures are one of the treatment options for removable dentures. This article aims to discuss the advantages and disadvantages of tooth-supported overdentures and the principles of using various overdenture attachments, including non-attachment overdentures. The common treatment options in preparing the overdenture abutment are either with or without abutment coping with or without attachment systems, which were discussed and illustrated. A range of tooth-supported overdenture systems were addressed, from low to high financial implications and treatment complexities. The clinician can choose a system that best fits the patient's condition and expectations. This allows clinicians to decide and consider tooth-supported overdentures as a treatment option before full edentulism. A well-executed tooth-supported overdenture ensures the preservation of alveolar bone, optimizes patient satisfaction in denture treatment, and eventually improves the patient's adaptation when transitioning to complete dentures.

The haplotype-resolved genome assembly of autotetraploid rhubarb Rheum officinale provides insights into its genome evolution and massive accumulation of anthraquinones.

Rheum officinale, a member of the Polygonaceae family, is an important medicinal plant that is widely used in traditional Chinese medicine. Here, we report a 7.68-Gb chromosome-scale assembly of R. officinale with a contig N50 of 3.47 Mb, which was clustered into 44 chromosomes across four homologous groups. Comparative genomics analysis revealed that transposable elements have made a significant contribution to its genome evolution, gene copy number variation, and gene regulation and expression, particularly of genes involved in metabolite biosynthesis, stress resistance, and root development. We placed the recent autotetraploidization of R. officinale at ∼0.58 mya and analyzed the genomic features of its homologous chromosomes. Although no dominant monoploid genomes were observed at the overall expression level, numerous allele-differentially-expressed genes were identified, mainly with different transposable element insertions in their regulatory regions, suggesting that they functionally diverged after polyploidization. Combining genomics, transcriptomics, and metabolomics, we explored the contributions of gene family amplification and tetraploidization to the abundant anthraquinone production of R. officinale, as well as gene expression patterns and differences in anthraquinone content among tissues. Our report offers unprecedented genomic resources for fundamental research on the autopolyploid herb R. officinale and guidance for polyploid breeding of herbs.

Aldosteronism is associated with more severe cerebral small vessel disease in hypertensive intracerebral hemorrhage.

Primary aldosteronism is associated with various types of cardiovascular and cerebrovascular damage independently of hypertension. Although chronic hypertension and related cerebral arteriosclerosis are the main risk factors for intracerebral hemorrhage, the effects of aldosteronism remain poorly understood. We enrolled 90 survivors of hypertensive intracerebral hemorrhage, 21 of them with aldosteronism and 69 with essential hypertension as controls in this study. Clinical parameters and neuroimaging markers of cerebral small vessel disease were recorded, and its correlations with aldosteronism were investigated. Our results showed that the aldosteronism group (55.2 ± 9.7 years, male 47.6%) had similar hypertension severity but exhibited a higher cerebral microbleed count (interquartile range) (8.5 [2.0‒25.8] vs 3 [1.0‒6.0], P = 0.005) and higher severity of dilated perivascular space in the basal ganglia (severe perivascular space [number >20], 52.4% vs. 24.6%, P = 0.029; large perivascular space [>3 mm], 52.4% vs. 20.3%, P = 0.010), compared to those with essential hypertension (53.8 ± 11.7 years, male 73.9%). In multivariate models, aldosteronism remained an independent predictor of a higher (>10) microbleed count (odds ratio = 8.60, P = 0.004), severe perivascular space (odds ratio = 4.00, P = 0.038); the aldosterone-to-renin ratio was associated with dilated perivascular space (P = 0.043) and large perivascular space (P = 0.008). In conclusions, survivors of intracerebral hemorrhage with aldosteronism showed a tendency towards more severe hypertensive arteriopathy than the essential hypertension counterparts independently of blood pressure; aldosteronism may contribute to dilated perivascular space around the deep perforating arteries. Aldosteronism is associated with more severe cerebral small vessel disease in hypertensive intracerebral hemorrhage.

CT radiomics in the identification of preoperative understaging in patients with clinical stage T1-2N0 esophageal squamous cell carcinoma.

Background: Predicting preoperative understaging in patients with clinical stage T1-2N0 (cT1-2N0) esophageal squamous cell carcinoma (ESCC) is critical to customizing patient treatment. Radiomics analysis can provide additional information that reflects potential biological heterogeneity based on computed tomography (CT) images. However, to the best of our knowledge, no studies have focused on identifying CT radiomics features to predict preoperative understaging in patients with cT1-2N0 ESCC. Thus, we sought to develop a CT-based radiomics model to predict preoperative understaging in patients with cT1-2N0 esophageal cancer, and to explore the value of the model in disease-free survival (DFS) prediction. Methods: A total of 196 patients who underwent radical surgery for cT1-2N0 ESCC were retrospectively recruited from two hospitals. Among the 196 patients, 134 from Peking University Cancer Hospital were included in the training cohort, and 62 from Henan Cancer Hospital were included in the external validation cohort. Radiomics features were extracted from patients' CT images. Least absolute shrinkage and selection operator (LASSO) regression was used for feature selection and model construction. A clinical model was also built based on clinical characteristics, and the tumor size [the length, thickness and the thickness-to-length ratio (TLR)] was evaluated on the CT images. A radiomics nomogram was established based on multivariate logistic regression. The diagnostic performance of the models in predicting preoperative understaging was assessed by the area under the receiver operating characteristic curve (AUC). Kaplan-Meier curves with the log-rank test were employed to analyze the correlation between the nomogram and DFS. Results: Of the patients, 50.0% (67/134) and 51.6% (32/62) were understaged in the training and validation groups, respectively. The radiomics scores and the TLRs of the tumors were included in the nomogram. The AUCs of the nomogram for predicting preoperative understaging were 0.874 [95% confidence interval (CI): 0.815-0.933] in the training cohort and 0.812 (95% CI: 0.703-0.912) in the external validation cohort. The diagnostic performance of the nomogram was superior to that of the clinical model (P<0.05). The nomogram was an independent predictor of DFS in patients with cT1-2N0 ESCC. Conclusions: The proposed CT-based radiomics model could be used to predict preoperative understaging in patients with cT1-2N0 ESCC who have undergone radical surgery.

Stereoelectronic Switches of Single-Molecule Junctions through Conformation-Modulated Intramolecular Coupling Approaches.

Stereoelectronic effects in single-molecule junctions have been widely utilized to achieve a molecular switch, but high-efficiency and reproducible switching remain challenging. Here, we demonstrate that there are three stable intramolecular conformations in the 9,10-diphenyl-9,10-methanoanthracen-11-one (DPMAO) systems due to steric effect. Interestingly, different electronic coupling approaches including weak coupling (through-space), decoupling, and strong coupling (through-bond) between two terminal benzene rings are accomplished in the three stable conformations, respectively. Theoretical calculations show that the molecular conductance of three stable conformations differs by more than 1 order of magnitude. Furthermore, the populations of the three stable conformations are highly dependent on the solvent effect and the external electric field. Therefore, an excellent molecular switch can be achieved using the DPMAO molecule junctions and external stimuli. Our findings reveal that modulating intramolecular electronic coupling approaches may be a useful manner to enable molecular switches with high switching ratios. This opens up a new route for building high-efficiency molecular switches in single-molecular junctions.

Dissecting telomerase RNA structural heterogeneity in living human cells with DMS-MaPseq.

Telomerase is a specialized reverse transcriptase that uses an intrinsic RNA subunit as the template for telomeric DNA synthesis. Biogenesis of human telomerase requires its RNA subunit (hTR) to fold into a multi-domain architecture that includes the template-containing pseudoknot (t/PK) and the three-way junction (CR4/5). These two hTR domains bind the telomerase reverse transcriptase (hTERT) protein and are thus essential for telomerase catalytic activity. Here, we probe the structure of hTR in living cells using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) and ensemble deconvolution analysis. Unexpectedly, approximately 15% of the steady state population of hTR has a CR4/5 conformation lacking features required for hTERT binding. Mutagenesis demonstrates that stabilization of the alternative CR4/5 conformation is detrimental to telomerase assembly and activity. We propose that this misfolded portion of the cellular hTR pool is either slowly refolded or degraded. Thus, kinetic traps for RNA folding that have been so well-studied in vitro may also present barriers for assembly of ribonucleoprotein complexes in vivo.

Klotho/FGF23 Axis Regulates Cardiomyocyte Apoptosis and Cytokine Release through ERK/MAPK Pathway.

Coronary artery disease (CAD) as a major cardiovascular disease is the leading global cause of mortality, Klotho/FGF23 axis involved in development of cardiovascular disease, while the function and underlying mechanism of Klotho/FGF23 axis in CAD is unclear. Blood samples from 67 CAD patients with coronary artery bypass graft (CABG) surgery were collected, and the level of Klotho and FGF23 of those patients was measured by using an ELISA kit. Cardiomyocyte was isolated from 0 to 3 days Sprague Dawley (SD) rats. Expression of Klotho, FGF23 and the cardiomyocyte marker α-sarcomeric actin (α-SA), myosin heavy chain (MHC) and cardiac troponin I (cTnI) was assessed by immunofluorescence staining. Expression of Klotho and FGF23 mRNA was detected by qRT-PCR. Apoptosis and cell cycle were measured by flow cytometry. Cell viability was detected by using CCK-8. The protein expression of ERK/MAPK pathway related protein and cytokines production was measured by western blotting. The levels of Klotho in CAD patients increased after CABG surgery, while FGF23 decreased. Isolated cardiomyocyte morphology and structure were completed, and with stabilized beating within culture for 15 days, besides, α-SA, MHC, and cTnI proved positive. After transfected Lenti-Klotho and Lenti-FGF23 into isolated cardiomyocyte, fluorescence staining showed that the transfection was successful, and qRT-PCR results showed that the expression levels of Klotho and FGF23 mRNA significant increased compared with NEG (empty vector) group. Immunofluorescence staining results showed that compared with NEG group, there was a higher Klotho positive rate and lower FGF23 positive rate in Klotho overexpression (Klotho) group, while, there was a higher FGF23 positive rate and lower Klotho positive rate in FGF23 overexpression (FGF23) group. In addition, the expression of p-ERK1/2 and p-P38 increased in Klotho group but decreased in FGF23 group. Furthermore, overexpression of Klotho inhibited cardiomyocyte apoptosis, increased S phase fraction, promoted proliferation and elevated expression of transforming growth factor ß1 (TGF-ß1), nuclear factor-kappa B (NF-κB), angiotensin-II (AT-II), and activator protein-1 (AP-1), overexpression of FGF23 showed the opposite effect, however, ERK agonist (TPA) and inhibitor (U0126) reversed the effect caused by overexpression of Klotho and FGF23 separately. Klotho/FGF23 axis play a critical role in CAD progression through regulating ERK/MAPK pathway in Cardiomyocyte.

Development of a Rare Earth Nanoprobe Enables In Vivo Real-Time Detection of Sentinel Lymph Node Metastasis of Breast Cancer Using NIR-IIb Imaging.

Sentinel lymph node (SLN) biopsy plays a critical role in axillary staging of breast cancer. However, traditional SLN mapping does not accurately discern the presence or absence of metastatic disease. Detection of SLN metastasis largely hinges on examination of frozen sections or paraffin-embedded tissues post-SLN biopsy. To improve detection of SLN metastasis, we developed a second near-infrared (NIR-II) in vivo fluorescence imaging system, pairing erbium-based rare-earth nanoparticles (ErNP) with bright down-conversion fluorescence at 1,556 nm. To visualize SLNs bearing breast cancer, ErNPs were modified by balixafortide (ErNPs@POL6326), a peptide antagonist of the chemokine receptor CXCR4. The ErNPs@POL6326 probes readily drained into SLNs when delivered subcutaneously, entering metastatic breast tumor cells specifically via CXCR4-mediated endocytosis. NIR fluorescence signals increased significantly in tumor-positive versus tumor-negative SLNs, enabling accurate determination of SLN breast cancer metastasis. In a syngeneic mouse mammary tumor model and a human breast cancer xenograft model, sensitivity for SLN metastasis detection was 92.86% and 93.33%, respectively, and specificity was 96.15% and 96.08%, respectively. Of note, the probes accurately detected both macrometastases and micrometastases in SLNs. These results overall underscore the potential of ErNPs@POL6326 for real-time visualization of SLNs and in vivo screening for SLN metastasis. SIGNIFICANCE: NIR-IIb imaging of a rare-earth nanoprobe that is specifically taken up by breast cancer cells can accurately detect breast cancer macrometastases and micrometastases in sentinel lymph nodes.

Transcription activation of SPINK4 by ELF-1 augments progression of colon cancer by regulating biological behaviors.

BACKGROUND: SPINK4 was highly expressed in colorectal cancer and resulted in worse prognosis of colorectal cancer patients. However, the expression and function of SPINK4 in colon cancer have not been revealed. METHODS: Analysis from GEPIA website showed the expression and function of SPINK4 in colon cancer samples. Colon cancer cell lines were applied to detect the biological function of SPINK4. Functionally, the transcriptional factor of SPINK4 has been predicted and verified. Finally, the associations between transcriptional factor and SPINK4 have been confirmed. RESULTS: SPINK4 expression was obviously increased in colon cancer samples. HCT-116 and DXH-1 cells in si-SPINK4-1 or si-SPINK4-2 group displayed an obvious reduction in its proliferation, cell cycle, invasion and migration compared to those in the si-control group. Moreover, transcriptional factor ELF-1 bound to the promoter of SPINK4 and affected its expression in colon cancer cells. High ELF-1 expression was presented in colon cancer samples and resulted in worse prognosis of colon cancer patients. Additionally, si-SPINK4 antagonized the function of ELF-1 overexpression in modulating colon cancer cell proliferation, cell cycle and mobility. CONCLUSIONS: Our findings afforded a theoretical basis for further research on the treatment of colon cancer based on the control of ELF-1/SPINK4 expression.