The predictive value of the thyroid nodule benign and malignant based on the ultrasound nodule-to-muscle gray-scale ratio.

OBJECTIVE: To investigate the efficacy of the ultrasonic nodule to muscle gray scale ratio as a predictive tool for distinguishing between benign and malignant thyroid nodules. METHODS: A retrospective study was undertaken at the First People's Hospital of Hangzhou, affiliated with the Zhejiang University School of Medicine, analyzing ultrasound and pathological data of patients with thyroid nodules between May 2020 and December 2022. The study extracted ultrasound features of nodules and employed univariate and multivariate logistic regression analyses to identify independent risk factors for malignant tumors in the nodules. Subsequently, a predictive model for distinguishing benign and malignant thyroid nodules was developed. RESULTS: A total of 466 patients were included in this retrospective study, of which 275 cases were malignant tumors. Univariate and multivariate logistic regression analyses showed that the nodular-muscle gray-scale ratio, nodule diameter, margin status, aspect ratio, and calcification were closely related to thyroid malignant tumors. The area under the curve (AUC) of training group was 0.832, with a sensitivity, specificity, and accuracy of 85.5%, 67.4%, and 76.6%, respectively. The AUC of the external validation group was 0.819, with a sensitivity, specificity, and accuracy of 76.4%, 74.5%, and 75.7%, respectively. The calibration and decision curves showed that the model had good diagnostic value. CONCLUSION: The research findings indicate that ratio is significantly associated with the malignant nature of thyroid nodules. The application of a line chart model based on these parameters exhibits a high level of predictive performance.

Critical review of the phytochemical profiles and health-promoting effects of the edible mushroom Armillaria mellea.

Research on the nutritional and medicinal properties of wild edible mushrooms has witnessed a significant surge in recent years. Among these mushrooms, Armillaria mellea (AM) stands out due to its abundant biologically active components. The presence of biological compounds in AM, including carbohydrates, sterols, fatty acids, sesquiterpenes, non-hallucinogenic indole compounds and adenosine derivatives, has been demonstrated in previous studies. Notably, specific bioactive substances isolated from AM, such as armillarikin, have exhibited promising anticancer effects. In vitro studies have elucidated the mechanisms behind these effects, further emphasizing the potential of AM in cancer treatment. Consequently, the objective of this study is to provide a comprehensive overview of the phytochemical profiles of AM while thoroughly investigating its therapeutic benefits. Moreover, this research has uncovered novel and effective treatments, including the utilization of ultrasonic disruption extraction in food processing. These findings highlight the potential of AM as a functional food with possible medical applications. By exploring AM's phytochemical composition and therapeutic effects, this study aims to contribute to a deeper understanding of its potential as a valuable natural resource.

HER2-targeting two-dimensional black phosphorus as a nanoplatform for chemo-photothermal therapy in breast cancer.

Trastuzumab (Tmab) targeted therapy or its combination with chemotherapy is normally insufficient to elicit a comprehensive therapeutic response owing to the inherent or acquired drug resistance and systemic toxicity observed in highly invasive HER2-positive breast cancer. In this study, we propose a novel approach that integrates photothermal therapy (PTT) with targeted therapy and chemotherapy, thereby achieving additive or synergistic therapeutic outcomes. We utilize PEGylated two-dimensional black phosphorus (2D BP) as a nanoplatform and photothermal agent to load chemotherapeutic drug mitoxantrone (MTO) and conjugate with Tmab (BP-PEG-MTO-Tmab). The in vitro and in vivo experiments demonstrated that the HER2-targeting BP-PEG-MTO-Tmab complexes exhibited desirable biocompatibility, safety and enhanced cancer cell uptake efficiency, resulting in increased accumulation and prolonged retention of BP and MTO within tumors. Consequently, the complex improved photothermal and chemotherapy treatment efficacy in HER2-positive cells in vitro and a subcutaneous tumor model in vivo, while minimized harm to normal cells and showed desirable organ compatibility. Collectively, our study provides compelling evidence for the remarkable efficacy of targeted and synergistic chemo-photothermal therapy utilizing all-in-one nanoparticles as a delivery system for BP and chemotherapeutic drug in HER2-positive breast cancer.

Safety and Efficacy of Anlotinib Hydrochloride Plus Temozolomide in Patients with Recurrent Glioblastoma.

PURPOSE: Glioblastoma (GBM) is a highly vascularized tumor with few treatment options after disease recurrence. Here, we report the efficacy and safety of anlotinib hydrochloride plus temozolomide in patients with recurrent GBM. PATIENTS AND METHODS: Patients with first definite postsurgical progression of histologically confirmed GBM preceded by standard radiotherapy and temozolomide chemotherapy were eligible for inclusion. All patients received temozolomide (150-200 mg/m2, orally, every day (QD) d1-5/4 wk) and anlotinib (10 mg, orally, QD, d1-14/3 wk) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate by the Response Assessment in Neuro-Oncology (RANO) criteria. RESULTS: Twenty-one patients were enrolled between May 2020 and July 2021, with a median age of 55 (range 27-68) years old. According to the Response Assessment in Neuro-Oncology (RANO) criteria, tumor response occurred in 17 patients, of which 9 patients had a complete response, and the objective response rate was 81.0% [95% confidence interval (CI), 62.6-99.3]. The disease control rate was 95.2% (95% CI, 76.2-99.9), with three additional patients achieving a stable disease without tumor progression. The median PFS was 7.3 months (95% CI, 4.9-9.7), and the 6-month PFS rate was 61.9% (95% CI, 39.3-84.6). The median overall survival was 16.9 months (95% CI, 7.8-26.0). The most common adverse events were leukocytopenia (66.7%), thrombocytopenia (38.1%), and hypertriglyceridemia (38.1%). Five patients had nine grade 3 adverse events, with a 23.8% incidence rate. Two patients discontinued therapy due to ischemic stroke (grade 3) and wound dehiscence (grade 1), respectively. No grade 4 or treatment-related deaths occurred in this study. CONCLUSIONS: Anlotinib combined with temozolomide is efficacious and tolerated in patients with recurrent GBM.

Nomogram model based on preoperative clinical characteristics of unilateral papillary thyroid carcinoma to predict contralateral medium-volume central lymph node metastasis.

Objectives: To explore the preoperative high-risk clinical factors for contralateral medium-volume central lymph node metastasis (conMVCLNM) in unilateral papillary thyroid carcinoma (uPTC) and the indications for dissection of contralateral central lymph nodes (conCLN). Methods: Clinical and pathological data of 204 uPTC patients who underwent thyroid surgery at the Hangzhou First People's Hospital from September 2010 to October 2022 were collected. Univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors for contralateral central lymph node metastasis (conCLNM) and conMVCLNM in uPTC patients based on the preoperative clinical data. Predictive models for conCLNM and conMVCLNM were constructed using logistic regression analyses and validated using receiver operating characteristic (ROC) curves, concordance index (C-index), calibration curves, and decision curve analysis (DCA). Results: Univariate and multivariate logistic regression analyses showed that gender (P < 0.001), age (P < 0.001), tumor diameter (P < 0.001), and multifocality (P = 0.008) were independent risk factors for conCLNM in uPTC patients. Gender(P= 0.026), age (P = 0.010), platelet-to-lymphocyte ratio (PLR) (P =0.003), and tumor diameter (P = 0.036) were independent risk factors for conMVCLNM in uPTC patients. A predictive model was established to assess the risk of conCLNM and conMVCLNM, with ROC curve areas of 0.836 and 0.845, respectively. The C-index, the calibration curve, and DCA demonstrated that the model had good diagnostic value. Conclusion: Gender, age, tumor diameter, and multifocality are high-risk factors for conCLNM in uPTC patients. Gender, age, tumor diameter, and PLR are high-risk factors for conMVCLNM in uPTC patients, and preventive conCLN dissection should be performed.

Critical review on chemical compositions and health-promoting effects of mushroom Agaricus blazei Murill.

Agaricus blazei Murrill (AbM) is a medical mushroom which has huge potential commercial value with various health-promoting functions. However, the chemical composition and therapeutic mechanisms of AbM have not been concluded systematically yet. Thus, this study aims to comprehensively summarize the phytochemical profiles and thoroughly characterize the health promotion effects such as the antitumor and antidiabetic impact of AbM in in vivo and in vitro. The AbM consists of abundant bioactive substances; polysaccharides, lipids including ergosterol, sterols, proteins, vitamin B, C and D, and phenolic compounds. Several studies have claimed that Agaricus blazei Murrill polysaccharides (AbMP) had immunoregulation, anti-inflammatory, hepatoprotective, and antitumor function both in vivo and in vitro. Meanwhile, AbM extracts were thought to cure diabetes and bacterial infection, exhibiting anticarcinogenic and antimutagenic functions. But some principles behind health-promoting effects have not been clarified. Additionally, AbM related clinical trials are limited and further discovery need to be conducted. Therefore, this paper has concluded the health promotion impact with corresponding mechanisms of AbM and indicated its potential medical usage as functional food in the future.

CD146 interaction with integrin ß1 activates LATS1-YAP signaling and induces radiation-resistance in breast cancer cells.

Radiotherapy is an indispensable modality in comprehensive treatment of breast cancer. However, inherent or acquired radiation resistance of tumors compromises the efficacy of radiotherapy. Herein, we found that CD146, a unique epithelial-to-mesenchymal transition (EMT) inducer particularly highly expressed in triple-negative breast cancer (TNBC), is dramatically induced by ionizing irradiation. Further study demonstrates that CD146 promotes tumor cell radioresistance in vitro and in vivo. Specifically, we report the underlying mechanism that CD146 activates YAP protein, and drives its relocation from plasma to nucleus by regulating LATS1, and promoting abnormal DNA damage repair, as well as inducing EMT and stemness. Moreover, CD146 can form a novel co-receptor complex with integrin ß1 and induces radiation-resistance in breast cancer. Dual inhibition of CD146 and integrin ß1 activity had a stronger inhibitory effect on breast cancer tumor growth and synergistically increased their sensitivity to radiotherapy. This study identifies a unique function of CD146 implicates with integrin ß1 and YAP signaling, contributing to radiation resistance. Targeted therapy against CD146 or inhibition of integrin ß1 is a potential strategy to overcome radiotherapeutic resistance of breast cancer.

Construction of a survival nomogram for gastric cancer based on the cancer genome atlas of m6A-related genes.

Objective: Based on TCGA database, a prediction model for 1-, 3-, and 5-year overall survival rates of gastric cancer (GC) patients was constructed by analyzing the critical risk factors affecting the prognosis of gastric cancer patients. Method: Clinicopathological features as well as gene signature of GC patients were obtained from TCGA database. Patients were randomly divided into a training cohort and an internal validation cohort. Independent predictors of GC prognosis were analyzed by univariate and multivariate Cox analyses to construct nomogram. The accuracy and reliability of the model was further validated by calibration curves, ROC curves, and C-indexes, and the clinical utility of the model was analyzed by decision analysis curves. Result: Age, sex, N stage, M stage, METTL16, RBM15, FMR1, IGFBP1, and FTO were significantly associated with the prognosis of GC patients, and these predictors were further included in the construction of nomogram. The C-indexes for the training cohort and validation set were 0.735 and 0.688, respectively. The results of the ROC curve analysis indicated that the area under the curve (AUC) exceeded 0.6 in training and validation sets at 1, 3, and 5 years. Conclusion: We have constructed and validated a nomogram that provides individual survival condition prediction for GC patients. The prognostic model integrating gene signatures and clinicopathological characteristics would help clinicians determine the prognosis of patients with GC and develop individualized treatment plans.

RNA modification patterns based on major RNA modifications define tumor microenvironment characteristics in glioblastoma.

RNA modifications play a major role in tumorigenicity and progression, but the expression and function in glioblastoma (GBM) have not been well described. In this study, we developed a GBM score based on the differentially expressed genes (DEGs) between groups showing RNA modification patterns. We assessed the association between the GBM score and tumor microenvironment (TME) characteristics. Based on the gene expression of these regulators, we identified two clusters with distinct RNA modification patterns. Kaplan-Meier survival curves showed that patients in cluster 1 had worse survival than those in cluster 2. Kaplan-Meier and multivariate Cox regression analyses showed that GBM scores (based on DEGs between RNA modification patterns) are an independent predictive biomarker for patient prognosis. Besides, we found that samples with high scores were significantly associated with epithelial-to-mesenchymal transition and immune checkpoints, while samples with low scores were associated with cell cycle regulation. Importantly, GBM-score markedly positively correlated drug resistance, while negatively correlated with drug sensitive. The responders of anti-PD-1/PD-L1 immunotherapy tend to have a lower GBM score than non-responders. In conclusion, our comprehensive analysis of multiple RNA modifications in GBM revealed that RNA modification regulators were closely correlated with TME.

Gold Nanocluster-Based Fluorometric Banoxantrone Assay Enabled by Photoinduced Electron Transfer.

Monitoring the blood concentration of banoxantrone (AQ4N) is important to evaluate the therapeutic efficacy and side effects of this new anticancer prodrug during its clinical applications. Herein, we report a fluorescence method for AQ4N detection through the modulation of the molecule-like photoinduced electron transfer (PET) behavior of gold nanoclusters (AuNCs). AQ4N can electrostatically bind to the surface of carboxylated chitosan (CC) and dithiothreitol (DTT) co-stabilized AuNCs and quench their fluorescence via a Coulomb interaction-accelerated PET process. Under optimized experimental conditions, the linear range of AQ4N is from 25 to 200 nM and the limit of detection is as low as 5 nM. In addition, this assay is confirmed to be reliable based on its successful use in AQ4N determination in mouse plasma samples. This work offers an effective strategy for AQ4N sensing based on fluorescent AuNCs and widens the application of AuNCs in clinical diagnosis and pharmaceutical analysis.

The progress of multimodal imaging combination and subregion based radiomics research of cancers.

In recent years, with the standardization of radiomics methods; development of tools; and popularization of the concept, radiomics has been widely used in all aspects of tumor diagnosis; treatment; and prognosis. As the study of radiomics in cancer has become more advanced, the currently used methods have revealed their shortcomings. The performance of cancer radiomics based on single-modality medical images, which based on their imaging principles, only partially reflects tumor information, has been necessarily compromised. Using the whole tumor as a region of interest to extract radiomic features inevitably leads to the loss of intra-tumoral heterogeneity of, which also affects the performance of radiomics. Radiomics of multimodal images extracts various aspects of information from images of each modality and then integrates them together for model construction; thus, avoiding missing information. Subregional segmentation based on multimodal medical image combinations allows radiomics features acquired from subregions to retain tumor heterogeneity, further improving the performance of radiomics. In this review, we provide a detailed summary of the current research on the radiomics of multimodal images of cancer and tumor subregion-based radiomics, and then raised some of the research problems and also provide a thorough discussion on these issues.

VX-765 ameliorates inflammation and extracellular matrix accumulation by inhibiting the NOX1/ROS/NF-κB pathway in diabetic nephropathy.

OBJECTIVE: This study explores the potential role of a highly selective caspase-1 inhibitor, VX-765, on extracellular matrix (ECM) accumulation and inflammation in diabetic nephropathy (DN) and the underlying mechanisms. METHODS: DN rats, induced via high-fat diet/streptozotocin, were used to assess the effects of VX-765. Parallel experiments were carried out on rat mesangial cell line HBZY-1 exposed to high glucose (HG) to reveal the molecular mechanism of VX-765 in preventing DN. Survival analysis, biochemical parameters and renal oxidative stress of rats were observed, and Western blotting and immunofluorescence were evaluated. In vitro, Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX)1 silencing by RNA interference and quantitative real-time PCR (qPCR) assays were conducted in HBZY-1 cells exposed to HG levels. KEY FINDINGS: In vivo, VX-765 significantly reduced the increase in urine albumin excretion and ECM accumulation. The phosphorylation of nuclear factor kappa-B (NF-κB) and the expression of pro-inflammatory cytokines IL-1ß, IL-6 and tumor necrosis factor (TNF)-α were significantly down-regulated. Furthermore, the generation of reactive oxygen species (ROS), phosphorylation of NF-κB and the expression of the NOX1 gene or protein were significantly decreased in HBZY-1 with VX-765 (5 µM) treatment in vitro. CONCLUSIONS: Our results demonstrated that VX-765 exerts favourable effects on DN via the simultaneous alleviation of systemic metabolic syndrome and down-regulating the renal NOX1/ROS/NF-κB pathway, suggesting that it has therapeutic potential for DN.

Metabolic Signature-Based Subtypes May Pave Novel Ways for Low-Grade Glioma Prognosis and Therapy.

Metabolic signatures are frequently observed in cancer and are starting to be recognized as important regulators for tumor progression and therapy. Because metabolism genes are involved in tumor initiation and progression, little is known about the metabolic genomic profiles in low-grade glioma (LGG). Here, we applied bioinformatics analysis to determine the metabolic characteristics of patients with LGG from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). We also performed the ConsensusClusterPlus, the CIBERSORT algorithm, the Estimate software, the R package "GSVA," and TIDE to comprehensively describe and compare the characteristic difference between three metabolic subtypes. The R package WGCNA helped us to identify co-expression modules with associated metabolic subtypes. We found that LGG patients were classified into three subtypes based on 113 metabolic characteristics. MC1 patients had poor prognoses and MC3 patients obtained longer survival times. The different metabolic subtypes had different metabolic and immune characteristics, and may have different response patterns to immunotherapy. Based on the metabolic subtype, different patterns were exhibited that reflected the characteristics of each subtype. We also identified eight potential genetic markers associated with the characteristic index of metabolic subtypes. In conclusion, a comprehensive understanding of metabolism associated characteristics and classifications may improve clinical outcomes for LGG.

Low-Dosage Bevacizumab Treatment: Effect on Radiation Necrosis After Gamma Knife Radiosurgery for Brain Metastases.

Cerebral radiation necrosis (RN), a complication of Gamma Knife radiosurgery, is difficult to treat, although bevacizumab seems to be effective. However, clinical data pertaining to bevacizumab treatment for RN are scarce, and its high price is problematic. This study explored the effectiveness of low-dose bevacizumab for RN caused by Gamma Knife. We retrospectively analyzed 22 patients who suffered cerebral RN post-Gamma Knife, and received bevacizumab treatment because of the poor efficacy of glucocorticoids. Low-dose bevacizumab (3 mg/kg) was administered for two cycles at 2-week intervals. T1- and T2-enhanced magnetic resonance imaging (MRI) images were examined for changes in RN status. We also monitored the dose of glucocorticoid, Karnofsky Performance Status (KPS) score, and adverse drug reactions. The mean volume of RN lesions decreased by 45% on T1-weighted images with contrast enhancement, and by 74% on T2-weighted images. All patients discontinued the use of glucocorticoids. According to the KPS scores, all patients showed an improvement in their symptoms and neurological function. No side effects were observed. Low-dosage bevacizumab at a dose of 3 mg/kg every 2 weeks is effective for treating cerebral RN after Gamma knife for brain metastases.

Long noncoding RNA GAS8-AS1: A novel biomarker in human diseases.

Long non-coding RNAs (lncRNAs) represent a group of ncRNAs with more than 200 nucleotides. These RNAs can specifically regulate gene expression at both the transcriptional and the post-transcriptional levels, and increasing evidence indicates that they play vital roles in a variety of disease-related cellular processes. The lncRNA GAS8 antisense RNA 1 (GAS8-AS1, also known as C16orf3) is located in the second intron of GAS8 and has been reported to be both abnormally expressed in several diseases and closely correlated with many clinical characteristics. GAS8-AS1 has been shown to affect many biological functions, including cell proliferation, migration, invasiveness, and autophagy using several signaling pathways. In this review, we have summarized current studies on GAS8-AS1 roles in disease and discuss its potential clinical utility. GAS8-AS1 may be a promising biomarker for both diagnoses and prognoses, and a novel target for many disease therapies.

Identification of Immune Cell Infiltration and Immune-Related Genes in the Tumor Microenvironment of Glioblastomas.

Glioblastoma (GBM) is one of the most prevalent malignant brain tumors with poor prognosis. Increasing evidence has revealed that infiltrating immune cells and other stromal components in the tumor microenvironment (TME) are associated with prognosis of GBM. The aim of the present study was to identify immune cells and immune-related genes extracted from TME in GBM. RNA-sequencing and clinical data of GBM were downloaded from The Cancer Genome Atlas (TCGA). Four survival-related immune cells were identified via Kaplan-Meier survival analysis and immune-related differentially expressed genes (DEGs) screened. Functional enrichment and protein-protein interaction (PPI) networks for the genes were constructed. In addition, we identified 24 hub genes and the expressions of 6 of the genes were significantly associated with prognosis of GBM. Finally, the genes were validated in single-cell sequencing studies of GBM, and the immune cells validated in an independent GBM cohort from the Chinese Glioma Genome Atlas (CGGA). Overall, 24 immune-related genes infiltrating the tumor microenvironment were identified in the present study, which could serve as novel biomarkers and immune therapeutic targets.

Solid-state thiolate-stabilized copper nanoclusters with ultrahigh photoluminescence quantum yield for white light-emitting devices.

As a new emerging candidate for solid-state phosphors, copper nanoclusters (CuNCs) have gained tremendous interest in the field of white light-emitting devices (WLEDs). However, their further applications are impeded by the low photoluminescence quantum yield (PLQY) and poor emission color tunability of CuNCs. This work demonstrates the synthesis of cyan and orange emitting CuNCs, and their combination as color conversion phosphors in WLEDs. The cyan and orange emitting CuNCs were prepared employing 2-mercapto-1-methylimidazole (MMI) and N-acetyl-l-cysteine (NAC), respectively, as stabilizing-cum-reducing agents. The dispersions of MMI-CuNCs and NAC-CuNCs are weakly emissive. However, after processing into powders, they both possess ultrahigh PLQYs (45.2% for MMI-CuNCs, and 64.6% for NAC-CuNCs) owing to the effect of aggregation-induced emission (AIE). All-CuNC based WLEDs are then designed and developed using powdered MMI-CuNC and NAC-CuNC samples on commercially available 365 nm GaN LED chips. They display acceptable white light characteristics with a Commission Internationale de l'Eclairage coordinate value and color rendering index of (0.26, 0.30) and 83, respectively. We believe that these cost-effective and eco-friendly CuNCs with interesting AIE properties will vigorously promote the development of high-quality WLEDs for commercial applications.

Cell-Block cytology in diagnosis of primary central nervous system lymphoma: A case report.

INTRODUCTION: Primary Central Nervous System Lymphoma (PCNSL) remains a diagnostic challenge due to the variable clinical manifestations. Liquid biopsies, particularly those involving cell-free DNA (cfDNA) from plasma, are rapidly emerging as important and minimally invasive adjuncts to traditional biopsies. However, conventional pathology may be still essential to obtain a diagnosis. PATIENT CONCERNS: A 56-year-old woman presented with a progressive headache, dizziness, blurred vision, and lower limbs weakness with dysesthesia. Atypical clinical and radiological presentations, previous empirical treatment in another hospital, together with the patient's refusal to stereotactic brain biopsy made it challenging to diagnose. Her status deteriorated continuously during hospitalization. DIAGNOSIS: Lumber punctual was performed, and CSF cytological analysis revealed malignancy cells with a high nuclear-cytoplasmic ratio. However, these cells were too loose to perform immunohistochemical stains. Genetic aberrations detections with CSF and peripheral blood sample were also inconclusive. We made a "cell-block" using the sedimentary cells collected from CSF collected through multiple aspirations via an Omaya reservoir. We further performed cytopathological and immunohistochemical analysis using this "cell-block," which finally confirmed the diagnosis of diffuse large-B cell PCNSL. INTERVENTIONS: Intracranial chemotherapy began afterwards (MTX 15 mg and dexamethasone 5 mg, twice per weeks). OUTCOMES: Unfortunately, this patient was dead 2 weeks later due to severe myelosuppression and secondary septic shock. CONCLUSION: We provided "cell-block" method, which collects cell components from large amount of CSF for cytology and immunohistochemical analysis. "Cell-block" cytology can be an alternative diagnostic method in diagnosis of PCNSL.

Rational Design of High-Performance Donor-Linker-Acceptor Hybrids Using a Schiff Base for Enabling Photoinduced Electron Transfer.

Donor-linker-acceptor (D-L-A)-based photoinduced electron transfer (PET) has been frequently used for the construction of versatile fluorescent chemo/biosensors. However, sophisticated and tedious processes are generally required for the synthesis of these probes, which leads to poor design flexibility. In this work, by exploiting a Schiff base as a linker unit, a covalently bound D-L-A system was established and subsequently utilized for the development of a PET sensor. Cysteamine (Cys) and N-acetyl-l-cysteine (NAC) costabilized gold nanoclusters (Cys/NAC-AuNCs) were synthesized and adopted as an electron acceptor, and pyridoxal phosphate (PLP) was selected as an electron donor. PLP can form a Schiff base (an aldimine) with the primary amino group of Cys/NAC-AuNC through its aldehyde group and thereby suppresses the fluorescence of Cys/NAC-AuNC. The Rehm-Weller formula results and a HOMO-LUMO orbital study revealed that a reductive PET mechanism is responsible for the observed fluorescence quenching. Since the pyridoxal (PL) produced by the acid phosphatase (ACP)-catalyzed cleavage of PLP has a weak interaction with Cys/NAC-AuNC, a novel turn-on fluorescent method for selective detection of ACP was successfully realized. To the best of our knowledge, this is the first example of the development of a covalently bound D-L-A system for fluorescent PET sensing of enzyme activity based on AuNC nanoprobes using a Schiff base.

MicroRNA-582-5p suppresses non-small cell lung cancer cells growth and invasion via downregulating NOTCH1.

Non-small cell lung cancer (NSCLC) is the most common cancer worldwide. MicroRNAs have been shown to be correlated with biological processes of various tumors. In this study, we observed that the expression of miR-582-5p was lower in NSCLC tissues than that in para-carcinoma tissues. Ectopic expression of miR-582-5p significantly inhibited NCI-H358 cell proliferation and invasion. Knockdown of miR-582-5p showed the opposite results, with cell growth rate and the invasive capacity of PC-9 cells enhanced. Furthermore, we elucidated that NOTCH1 is a target of miR-582-5p and there is an inverse correlation between miR-582-5p and NOTCH1 expression in NSCLC tissues. Overexpression of NOTCH1 in miR-582-5p-overexpressing NCI-H358 cells could partially reverse the inhibition of cell proliferation and invasion by miR-582-5p. Thus, our research demonstrated that miR-582-5p suppresses NSCLC cell lines' growth and invasion via targeting oncoprotein NOTCH1 and restoration of miR-582-5p might be feasible therapeutic strategy for NSCLC.